electrophilic iodination of organic compounds using ......review 1487 electrophilic iodination of...

REVIEW 1487

Electrophilic Iodination of Organic Compounds Using Elemental Iodine or IodidesElectrophilic Iodination of Organic CompoundsStojan Stavber,*a Marjan Jereb,b Marko Zupana,b

a Laboratory for Organic and Bioorganic Chemistry, ‘Jozef Stefan’ Institute, Jamova 39, 1000 Ljubljana, SloveniaFax +386(1)4235400; E-mail: [email protected]

b Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, 1000 Ljubljana, SloveniaE-mail: [email protected]; E-mail: [email protected]

Received 20 December 2007; revised 1 February 2008

SYNTHESIS 2008, No. 10, pp 1487–1513xx.xx.2008Advanced online publication: 29.04.2008DOI: 10.1055/s-2008-1067037; Art ID: E20407SS© Georg Thieme Verlag Stuttgart · New York

Abstract: Synthetic methods for electrophilic iodination of organiccompounds using elemental iodine or various iodides are compiledin this review, and literature data for the last 10–15 years is organ-ised according to the type of organic compound.

1 Introduction2 Iodination of Aromatic Hydrocarbons2.1 Unsubstituted Aromatic Hydrocarbons2.2 Phenols and Aromatic Ethers2.3 Aromatic Amines2.4 Alkyl-Substituted Aromatic Hydrocarbons2.5 Deactivated Aromatic Hydrocarbons3 Iodination of Alkenes and Alkynes4 Iodination of Aliphatic Hydrocarbons5 Iodination of Organic Compounds Bearing an Enolisable

Carbonyl Group 6 Iodination of Heteroatom-Containing Organic Compounds 6.1 Organoboron and Organometallic Compounds 6.2 Heterocyclic Compounds7 Conclusions and Perspectives

Key words: iodination, iodine, iodide

1 Introduction

As the iodine atom is an excellent leaving group, iodo-substituted organic compounds have for a long time beenrecognised as valuable synthons or precursors in organicsynthesis, above all in carbon–carbon, carbon–nitrogen orcarbon–oxygen bond formation.1 In addition, owing totheir use in medicine as drugs or radioactively labelleddiagnostic markers,2 iodinated organic compounds andmethods for their preparation have received significant at-tention from the scientific community.

The basic natural source of iodine is the iodide anion, butsince this species is a weak nucleophile, iodide is an in-convenient agent for the introduction of an iodine atominto organic molecules. Nature solved this problem withan enzymatically generated formation of the carbon io-dine bond, in conjunction with vanadium, iron or flavinco-catalysis, and use of hydrogen peroxide or molecularoxygen as oxidants for the transformation of inactive io-dide to an active iodonium species.3 In view of this, elec-

trophilic iodination has long been recognised as the mostconvenient approach to the selective introduction of an io-dine atom into organic compounds. Many electrophilic io-dinating reagents have been developed and subsequentlyused in organic synthesis,4 including N-iodosuccinimide5

and other N–I compounds,6 bis(pyridinium)iodonium(I)tetrafluoroborate (IPy2BF4),

7 or iodochloride (ICl) as aneat6,8 or polymer-supported material.9 All of these are ex-cellent iodine atom donating reagents, but each also has itsdisadvantages. Protocols for their preparation are oftenchemical- and energy-consuming processes, while manyof them produce a considerable amount of waste materialafter iodine transfer. In view of green trends in modernorganic chemistry, there is a great need to reduce theseinconveniences as far as possible, such that now, iodideanion (I–) or elemental iodine (I2) seem to be the logicalchoices.

Scheme 1

I

I

I

I I

I

I

I

A

A

δ+ δ–I I

AA

path a path c

path b

S SI I

HH

S I

or

S H

S HS H

S H

A

1488 S. Stavber et al. REVIEW

Synthesis 2008, No. 10, 1487–1513 © Thieme Stuttgart · New York

Oxidative iodination is the only choice when the iodideanion is used as the source of an iodine atom for electro-philic transfer into an organic molecule; that is, I– shouldbe first oxidised to the iodonium species (I+), which fur-ther collapses with an organic molecule electron donor.On the other hand, two disadvantages must be overcomewhen iodine (I2) is used as an iodinating reagent. The firstis the low electrophilicity of I2 and thus its low reactivitytowards the majority of organic compounds, while thesecond is the release of HI during the iodination process,which ordinarily causes the rupture of carbon–iodinebonds. Except in the case of alkynes, where sufficient ac-tivation for iodine attack can already be achieved by thechoice of an appriopriate solvent, activation of iodine andtrapping, or, even better, regeneration of released hydro-gen iodide is thus necessary in order to obtain efficientand selective iodofunctionalisation. Activation of iodineby modifying its electrophilicity can be achieved follow-ing three main scenarios (Scheme 1). The first is the po-larisation of the I–I bond by an electron-deficient species(A) such as a Brönsted or Lewis acid (path a). Protons,metal ions, proper solvent or an excess of I2 are some ofthe corresponding choices. The other two primary pro-cesses are essentially electron transfers. Electron-defi-cient activator A could interact with organic substrate (S–

H) generating its radical cation (S–H+), which after col-lapse with iodine leads to iodinated substrate S–I (path b).Following path c, an interaction of A with a molecule ofiodine, generating an iodine radical cation (I2

+), is consid-ered and its collapse with S–H follows, resulting in S–I asthe final product. The reaction scenario path c enables ahigher atom economy for iodine, often as high as 100%iodine atom economy, while in the other two primary pro-cesses, half of the iodine atoms are lost for desired func-tionalisation. In practice, all three pathways couldoverlap, especially paths b and c. These basic processeshave resulted in three main synthetic methodologies (i–iii)or combinations thereof, and their applications over thelast two decades are summarised in Table 16 in the con-cluding chapter of this review:

(i) Hydrogen iodide trapping by a base, or iodide trappingby formation of insoluble metal iodides;

(ii) Use of a Lewis or Brönsted acid which polarises theiodine molecule, thus increasing its electrophilicity;

(iii) Oxidative activation producing iodonium species orregenerating released iodide.

Modes (i) and (ii) enable no more than 50% iodine atomeconomy since half of the iodine atoms are lost, while ox-

Stojan Stavber obtainedhis BSc, MSc, and, in 1987,his PhD degrees from theUniversity of Ljubljana,Slovenia. He is a member of

the ‘Jozef Stefan’ Institute,Ljubljana, Slovenia and cur-rently Head of the Labora-tory for Organic andBioorganic Chemistry. His

main scientific interests areconnected with organohalo-gen chemistry and greenorganic chemistry.

Marjan Jereb obtained hisBSc degree and in 2001completed his PhD at theUniversity of Ljubljana un-der the supervision of Prof.Zupan and Dr. Stavber. In2004–2005, he spent a year

at the ETH Zurich in Prof.Antonio Togni’s group. Heis currently an Assistant atthe Faculty of Chemistryand Chemical Technologyof the University of Ljublja-na. His main research

interest is dedicated toorganohalogen chemistry,stressing the green chemicalapproach to the synthesis oforganohalogen compounds.

Marko Zupan received hisBSc and MSc degrees fromthe University of Ljubljanaand also obtained his doc-torate there in 1974. He is aProfessor of organic chem-istry at the Faculty of Chem-

istry and Chemical Tech-nology of the University ofLjubljana and a member ofthe ‘Jozef Stefan’ Institute.He is one of the pioneers ofmodern organohalogenchemistry, which remains

his main scientific interestalong with research in thefields of polymer-supportedreagents and catalysts, pho-tochemistry of organic com-pounds and organic greenchemistry.

Biographical Sketches

REVIEW Electrophilic Iodination of Organic Compounds 1489


idative iodination methodologies (iii) enable higher io-dine atom economy to be achieved. This mode is a betterchoice, especially from the green chemistry point of view.A variety of oxidants have been used for this purpose,such as a metal in its higher valency state in the form ofmetal cations, oxides or oxometalates, compounds of io-dine(III) or its higher valency state, N–F reagents, variousperoxides, and oxygen.

The primary literature dealing with the electrophilic iodi-nation of organic compounds has not been reviewed for along time.10 Some relevant partial data were included inrecently published secondary literature,6,11–17 such as inreview papers dealing with direct iodination of aromaticcompounds,6 iodine(I, III, and V) organic chemistry,11,12

synthetic use of molecular iodine for organic synthesis,13

and electrophilic halocyclisation reactions in organic syn-thesis.14–17 Achievements in the field of iodoorganic syn-

thetic chemistry for the period of the last 10 to 15 years arethus worth collecting and evaluating.

2 Iodination of Aromatic Hydrocarbons

2.1 Unsubstituted Aromatic Hydrocarbons

Benzene and naphthalene were directly iodinated to iodo-benzene (2) or 1-iodonaphthalene (4) using several iodi-nating systems (Table 1). Transformations using iodineand the oxidants chromium(VI) oxide,18 sodium percar-bonate (SPC)19 or iodopentoxide20 under anhydrous andstrongly acidic conditions gave moderate to good yields of2 (entries 1–3), while oxidative activation with polyvi-nylpyrrolidone-supported hydrogen peroxide (PVP-H2O2) catalysed by tungstophosphoric acid,21 the char-coal-supported complex Fe(NO3)3·1.5N2O4,

22a xenon di-

Table 1 Iodination of Benzene (1) and Naphthalene (3)

Reagent Conditions Temp (°C) Yield (%) Ref.

1 I2, CrO3 AcOH–Ac2O–H2SO4 65 77 18

2 I2, SPCa AcOH–Ac2O–H2SO4 40 40 19

3 I2, I2O5 AcOH–H2SO4 60 56 20

4 I2 or KI, PVP–H2O2b H3PW12O40 (cat.), CH2Cl2 reflux 15–22 21

5 I2 or NaI, Fe(NO3)3·N2O4 on charcoal CH2Cl2 r.t. 74 22a

6 NaI Ce(OH)3OOH SDSc (8.1 × 10–3 M aq soln) r.t. 80 22b

7 KI, KBrO3, H+ 60% aq AcOH/HCl 80 91 22c

8 I2, XeF2 CH2Cl2 r.t. 90 23

9 I2, Hg(NO3)2 CH2Cl2 r.t. 52 24

10 I2, AgOTf CH2Cl2 r.t. 100 25

11 I2 or NaI, Fe(NO3)3·N2O4 on charcoal CH2Cl2 r.t. 50 22a

12 NaI, Ce(OH)3OOH SDS (8.1 × 10–3 M aq soln) r.t. 78 22b

13 KI, KBrO3, H+ 60% aq AcOH/HCl 80 90 22c

14 I2 or KI, PVP–H2O2 H3PW12O40 (cat.), CH2Cl2 reflux 80 21

15 NaI or KI, H2SO4 (concd) 60 75 26

16 I2, PS–I(OAc)2 EtOAc 60 63 27

a SPC = sodium percarbonate.b PVP = polyvinylpyrrolidone.c SDS = sodium dodecyl sulfate.

I

1 2

I

3 4



fluoride,23 or with poly[styrene-(iodosodiacetate)]27 couldbe performed under milder reaction conditions (entries 4,5, 8, 11, 16). Activation following iodide trapping by mer-cury(II)24 or silver(I)25 ions was also applied (entries 9,10) and moderate to excellent yields obtained, while oxi-dative iodination by alkali metal iodides and potassiumbromate under acidic conditions22c (entries 7 and 13), con-centrated sulfuric acid,26 (entry 15), cerium(IV) trihydrox-ide hydroperoxide in aqueous sodium dodecyl sulfate(SDS),22b (entries 6 and 12) or polymer-supported hydro-gen peroxide21 (entries 4 and 14) were also used for thisderivatisation of benzene or naphthalene.

2.2 Phenols and Aromatic Ethers

Phenolic or arylalkoxy moieties are important buildingblocks in bioactive organic molecules. A variety of io-dine- or iodide-containing iodinating systems were testedon phenol 5 or anisole 7 (Table 2) and further applied tothe iodofunctionalisation of various substituted deriva-tives of both compounds, and other more complex organicmolecules bearing the hydroxy or alkoxyaryl moiety. Thesurvival of hydroxy and methoxy functional groups wasalso reported in the case when strong oxidants or strong

acids were present in the iodination system. Iodinationsystems include metal oxides, metal ions, or the nitrate an-ion as oxidative mediators (entries 4–11) or iodide trap(entries 2, 3), various oxidants from the group of io-dine(III, V or VII), chlorine(V), or bromine(V) com-pounds (entries 12–18), N–F compounds like 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octanebis(tetrafluoroborate) (Selectfluor® F-TEDA-BF4; entries24–26), derivatives of peroxosulfates (entries 20–23), hy-drogen peroxide (entries 27, 28), and, finally, oxygen inthe presence of various catalysts (entries 29–32).

The regioselectivity of iodine atom introduction usingthese iodinating systems is shown in Scheme 2 andScheme 3. High para regioselectivity was observed forthe majority of the systems used, while when the para po-sition is occupied (9 or 19) iodofunctionalisation of posi-tion 2 takes place (10 or 20) and in most cases 2,6-diiodination resulting in 11 or 21 was observed as themain process. Two exceptions from this general observa-tion were reported. High degrees of ortho iodination wereobserved when phenol derivatives were treated with io-dine in the presence of thallium(I) acetate,54 and this find-

Scheme 2 Iodination of phenol and naphthol derivatives; reagentsand conditions are described in the corresponding references

OH

R1

‘I+’

OH

R1

I

9 10

10a: R1 = Me (66%;46 82%51)10b: R1 = t-Bu (60%;47 73%;48 85%52)10c: R1 = C2H4OMe (92%51)10d: R1 = Ph (90%21)10e: R1 = Cl (93%;37 87%51)10f: R1 = Br (85%51)10g: R1 = NO2 (42%;47 80%53)

OH

R2

OH

R2

I

‘I+’

11

12

13a: R2 = Me (77%;26 85%53)13b: R2 = COOH (74%;37 70%42)13c: R2 = NO2 (88%;37 84%53)13d: R2 = Cl (45%40a)

OH

II

R1

11a (83%19)11e (99%36)11f (95%38)11g (72%;19 99%;36 90%47)

OH

R2

I

I

13 14

14c (80%19)14d (98%38)

OHI

OH

OH OH

I

15 16

17 18

(92%;22c 86%;26 74%;36 90%;37

100%;43 93%;47 87%52)

(100%43)

‘I+’

‘I+’

‘I+’

‘I+’

Scheme 3 Iodination of derivatives of phenyl and naphthyl alkylethers; reagents and conditions are described in the correspondingreferences

OMe

R1

OMe

I

R1

OMe

I

R1

I‘I+’ ‘I+’

‘I+’ ‘I+’

19 20 21

20a: R1 = Me (75–99%)29,31,32,33,41,49,51

20b: R1 = t-Bu (92%)44

20c: R1 = CH2Ac (65–79%)45,55

20d: R1 = Ac (90%)44,55

20e: R1 = COPh (67–90%)18,23,33,55

20f: R1 = CHO (83–85%)22d,44,45

20g: R1 = COOH (73–80%)18,19

20h: R1 = NO2 (73–92%)18,19

20i: R1 = Hal (75–92%)44, 55

OR2

R3

OR2

R3

I

OR2

I

R3I

22 23 24

23a: R2 = alkyl; R3 = H (68–94%)18, 29, 31, 32, 33, 34, 44, 50

23b: R2 = R3 = Me (82–100%)22a,29,31,32,33,42,50

23c: R2 = Me; R3 = Hal (46–84%)31,32

23d: R2 = Me; R3 = NO2 (40%)55

23e: R2 = Me; R3 = CHO (95–97%)22d

OR4I

OR4

OMe OMe

I

25 26

27

‘I+’

‘I+’

26a: R4 = Me (65–99%)40,43,47

26b: R4 = Et (52–99%)34,50

28 (62–95%)33,40a,c,43,47,49,50,51



Table 2 Iodination of Phenol (4) and Anisole (7)

Reagent Conditions Temp (°C) Yield (%) 6 Yield (%) 8 Ref.

1 NR4I oleum 60–120 85 82a 28

2 I2, HgCl2 CH2Cl2 r.t. 71 92 24

3 I2, HgO CH2Cl2 r.t. 84 29

4 I2, NaNO3 AcOH r.t. 92 30

5 I2, CrO3 AcOH–Ac2O–H2SO4 60 90 18

6 I2, Fe(NO3)3·N2O4 on charcoal CH2Cl2 r.t. 96 22a

7 NaI, Ce(OH)3OOH SDS (aq) r.t. 97 22b

8 I2, silica–Fe(NO3)3 CH2Cl2 20 95 31

9 I2, Fe(NO3)3 H3PW12O40 (cat.), CH2Cl2 r.t. 79 92 32

10 I2, silica–Bi(NO3)3 SFRCb r.t. 92 33

11 I2, Pb(OAc)4 AcOH–Ac2O 60 85 34

12 I2, H5IO6 EtOH 60 89 35

13 KI, KIO3, HCl MeOH r.t. –c 81 36

14 KI, KClO3, HCl H2O 80 95 37

15 KI, NaIO4, NaCl AcOH–H2O 25 –c 87 38

16 KI, KBrO3, HCl AcOH–H2O 60 80 94 22c

17 I2, PhI(OAc)2 SFRCb r.t. 96 39

18 I2, PS–I(OAc)2 EtOAc 60 56d 27

19 I2, SPC AcOH–Ac2O–H2SO4 10–40 64 19

20 KI or NH4I, Oxone® MeOH r.t. 51e 95 40a,b

21 I2, (Bu4N)2S2O8 MeCN r.t. 92 41

22 I2, (n-BuPPh3)2S2O8 MeCN reflux 100 42

23 I2, PVP–S2O8 MeCN reflux 66 100 43

24 I2, F-TEDA-BF4 MeCN 22 89 44

25 I2, F-TEDA-BF4 H2O r.t. 83 45

26 I2, F-TEDA-BF4 [bmin][PF6] 80 72 71 46

27 KI, 30% H2O2, H+ MeOH r.t. 93 47

28 I2, PVP–H2O2 H3PW12O40 (cat.), CH2Cl2 reflux 85 92 21

29 I2, O2 H5PV2Mo10O40 (cat.); MeCN 80 98 98 49

30 I2, air Bi(NO3)3 (cat.); MeCN r.t. 90 50

31 I2, air CAN (cat.); MeCN r.t. –f 94 51

32 I2, air, H+ NaNO2 (cat.); MeCN r.t. 96 52

a 17% of 4-iodophenol was also formed.b SFRC = solvent-free reaction conditions.c Phenol was quantitatively transformed to 2,4,6-triiodophenol.d 2,4-Diiodoanisole (99%) was formed using a fivefold molar excess of the reagent.e Ratio of 2-iodo:4-iodo:2,4-diodo = 42:51:7.f A 7:3 mixture of 2- and 4-iodophenol was isolated.

OROR

I

5: R = H7: R = OMe

68



ing could be explained by possible coordination of thethallium(I) ion with phenolic oxygen. The second casewas the iodination of phenol in water with iodine, activat-ed by 30% hydrogen peroxide, which resulted in the for-mation of 2-iodophenol, further transforming to 2,6-diodophenol, while 4-iodophenol was not formed.48 2-Hy-droxynapthalene (15)53 or 2-alkoxynaphthalenes 25 wereregioselectively iodinated at position 1 (16, 26), while 1-naphthol (17) or its methyl ether analogue, 27, were trans-formed into their 4-iodo derivatives (18, 28).

Polyalkoxy-substituted benzene derivatives were oftenused as starting materials for iodofunctionalisation sincethis kind of moiety is a frequent building block in bioac-tive compounds. 1,2-, 1,3-, and 1,4-dimethoxybenzene(29, 32, and 35, respectively) or three isomers of tri-methoxy-substituted benzene (38, 41, and 43) were readi-ly and efficiently iodinated to their mono- or dioiododerivatives by various iodinating systems (Table 3).

The presence of a carbonyl functional group bearing anenolisable carbonyl could represent a certain inconve-nience regarding the regioselectivity of iodination. Sever-al phenols or alkoxyaryls bearing an alkyl carbonyl group

bonded to an aromatic ring were iodinated with iodine andthe appropriate oxidant (Scheme 4). In the case of iodicacid (HIO3)

60,61 or bis(trifluoroacetoxy)iodobenzene[PhI(O2CCF3)2]

62 mediated iodinations, the functionalisa-tion of the aromatic ring was found to be exclusive, whilein the case of F-TEDA-BF4 mediation, the regioselectivityof the iodination could be regulated by the solvent used.In acetonitrile, ring iodination took place, while in metha-nol the a-carbonyl position was exclusively iodinated.63

2.3 Aromatic Amines

Amino-substituted aromatics, as electron-rich molecules,were readily iodinated using various iodinating systems(Table 4 and Scheme 5). The course of these reactions isvery similar to that for iodination of phenols or aryl ethers,in that a high degree of para regioselectivity was observedand the amino group ordinarily remained unchanged un-der the reaction conditions. Aniline (54) was mainly or ex-clusively iodinated at the para position, while in the casethat this position was already occupied, ortho iodofunc-tionalisation took place.

Table 3 Iodination of Di- and Trimethoxybenzenes

Reaction Substrate Product Yield (%) Ref.

2929

3031

68–10078–81

29,39a,42,45,49,56,59

18,29

3232

3334

84–9972–99

22,29,39a,41,45,47,48,52

29,43,55

3535

3637

67–9272

29,31,39a,41,45,49,56,58

29

3838

3940

82–10076

29,43,56,57

29

41 42 72–100 29,43,56

4343

4445

76–9092

29,48,56,57,58

29

OMe

OMe

OMe

OMe

OMe

OMe

I I

I29 30

31

OMe

OMe

OMe

OMe

OMe

OMe

I I

I

32 33

34

OMe

OMe

OMe

OMe

OMe

OMe

I I

I35 3637

OMe

OMe

OMe

OMe

OMe

OMe

OMe

OMe

OMe

I I

I

38 39 40

OMe

OMe

OMe

OMe

OMe

OMe

I41 42

OMe

OMeMeO

OMe

OMeMeO

OMe

OMeMeO

I

I

I

43 44 45



Several N,N-dialkyl-substituted anilines 56 (Scheme 5),useful precursors in the materials sciences, were almostquantitatively iodinated by iodine in a pyridine/dioxanesolvent mixture, thus forming 4-iodo substituted deriva-tives 57.64 Interesting results were observed following ox-idative iodination of dimethyl-substituted acetanilides 58,60, and 63. 2,3-Dimethylacetanilide (58) was transformedinto the expected 4-iodo derivative 59 with both iodinat-ing systems studied [(ii)68 KI, 30% aq H2O2, H2SO4, cat.Na2WO4 in glacial AcOH; or (iii)69 HI, AcOOH, H2SO4 inAcOH–Ac2O], the 2,4-dimethyl isomer 60 was reportedto give the expected 6-iodo-2,4-dimethylacetanilide (61)under conditions (ii) but 5-iodo-2,4-dimethylacetanilide(62) with (iii), while 2,6-dimethyl derivative 63 gave un-expectedly 3-iodo-2,6-dimethylacetanilide (64) with both

reagents. On the other hand, 2,6-dimethylaniline wasreadily transformed to 4-iodo-2,6-dimethyl aniline withiodine in alkaline media.70

2.4 Alkyl-Substituted Aromatic Hydrocarbons

The regioselectivity of iodination of monosubstitutedalkyl benzene derivatives depends on the structure of thealkyl group and the iodinating system used. In Table 5 arecollected data regarding the iodination of toluene (65)with various iodinating systems. A mixture of 2-iodotolu-ene (66) and 4-iodotoluene (67) was ordinarily obtained,while iodination of isopropylbenzene or tert-butylben-zene gave only the 4-iodo isomer.26,55,71,72

Dimethyl (68, 71, 75), trimethyl (79, 82, 86), and tetra-methyl benzene derivatives (89, 92, 95) were also readilyiodinated by a variety of iodinating systems (Table 6) andprogressive iodination to poly(iodo-substituted) com-pounds was selectively achieved.

Sterically hindered alkyl-substituted benzene derivatives(98, 102, 106, 109, 111, and 114; Scheme 6) were pro-gressively iodinated using the iodine and F-TEDA-BF4

iodinating system.72

Scheme 4 Iodination of phenols and aromatic ethers bearing a car-bonyl group bonded to the aromatic ring

OH

R1

OH

R1

O

CH2R2

O

CH2R2

I

I2, HIO3

EtOH–H2O; 40 °C

46 47

OH

Cl COCH2Cl

I

OH

COEt

Me

I

OH

COEt

Br

I

47a (81%) 47b (86%) 47c (82%)

OMe

COCH2R4

I

OMe

R3 COCH2R4

MeCN or MeOH

48 49

OMe

I OOMe

COMe

I

OMe

OMe

I

MeOC

49a (80%) 49b (68%) 49c (81%)

Ar

O

CH2

I2

F-TEDA-BF4

MeCN

MeOH

OH

COMe

OH

COCH2I

I

O

O

OMe

OMe

I

I

50 (72%)

51 (78%)

52 (68%)

53 (86%)

I2, PhI(O2CCF3)2R3

Scheme 5 Iodination of N,N-dialkyl anilines and dimethyl acetani-lides. Reagents and conditions: (i)64 56 (5 mmol) dissolved in dioxane(30 mL) and pyridine (30 mL), I2 (20 mmol), 0 °C to r.t for 2 h; (ii)68

substrate 58, 60 or 63 (10 mmol), KI (10 mmol), 30% aqueous H2O2

(3 mL) dissolved in glacial AcOH (20 mL) and H2SO4 (1 mL),NaWO4 (10 mol%), 0–50 °C, 1 h; (iii)69 substrate 58, 60 or 63 (7.5mmol), dissolved in glacial AcOH (15 mL) and Ac2O (10 mL), 40%HI (2 mL) and concd H2SO4 (2 mL) added, followed by 35% AcOOHin AcOH (3 mL), r.t., 24 h.

N

I

N

(i)

R1 R2R1 R2

56

57a: R1 = R2 = Me (98%)57b: R1 = R2 = n-hexyl (80%)57c: R1 = R2 = C2H4OH (94%)57d: R1 = Et; R2 = C2H4OH (96%)

NHAc

Me

Me

NHAc

Me

Me

I

58

59 (60–69%)

(ii) or (iii)

NHAc

Me

Me

NHAc

Me

Me

I

NHAc

Me

Me

I

(ii) (iii)

60

61 (56%) 62 (70%)

NHAc

MeMe

NHAc

MeMe

I

(ii) or (iii)

63

64 (72–90%)



Table 4 Iodination of Aniline

Entry Reagent Conditions Temp (°C) Yield (%) Ref.

1 NaI or KI oleum 60–120 82 26

2 I2, HgCl2 CH2Cl2 r.t. 44a 24

3 I2, pyridine dioxane 0 85 64

4 I2, Fe(NO3)3 H3PW12O40 (cat.), CH2Cl2 r.t. 82 32

5 HI, KMnO4 MeCN r.t. 76 65

6 KI, KBrO3, HCl AcOH–H2O 60 81 22c

7 KI, KClO3, HCl MeOH–H2O 80 81b 37

8 I2, H5IO6 CH2Cl2 reflux or MW 68 66

9 KI, KIO3, HCl MeOH–H2O r.t. 65b 36

10 I2, F-TEDA-BF4 [bpy][BF4] 80 56 46

11 I2, SPC AcOH–Ac2O–H2SO4 10–40 53 19

12 I2, urea–H2O2 AcOH–Ac2O–H2SO4 10–40 64 67

13 KI, 30% H2O2, H+ MeOH r.t. 96 47

14 I2, 30% H2O2 H2O r.t. 87 48

15 I2, O2 H5PV2Mo10O40 (cat.), MeCN 80 83b 49

a An excess of aniline was used.b 2-Iodoaniline was also formed (10%).

NH2NH2

I

54 55

Table 5 Ring Iodination of Toluene

Entry Reagent Conditions Temp (°C) Ratio 66/67 Yield (%) Ref.

1 NaI or KI oleum 60–120 0:100 76 26

2 I2, AgOTf CH2Cl2 r.t. 25:75 100 25

3 I2, Hg(NO3)2 CH2Cl2 r.t. 35:65 92 24

4 I2, Fe(NO3)3 H3PW12O40 (cat.), CH2Cl2 20 0:100 59 32

5 I2, Fe(NO3)3·N2O4 on charcoal CH2Cl2 r.t. 40:60 93 22a

6 NaI, Ce(OH)3OOH aq. SDS r.t. 0:100 87 22b

7 I2, NO2 H2SO4 (cat.), CHCl3 60 40:60 –a 59

8 I2, H5IO6 EtOH 60 8:92 44 35

9 I2, F-TEDA-BF4 [bmim][PF6] 80 35:65 40 46

10 I2, O2 H5PV2Mo10O40 (cat.), MeCN 80 15:85 99 49

a Yield not reported.

Me Me Me

I

I

+

65 66 67



2.5 Deactivated Aromatic Hydrocarbons

Direct iodination of an electron-poor aromatic ring is adifficult task, but many methods developed recently(Table 7) represent good alternatives to the classical indi-rect approach using the Sandmeyer reaction.77 Substitu-ents providing a strong electron-withdrawing effect (NO2,

CF3, COR, SO2R) decrease the electron density on thearomatic ring, thus demanding a very high concentrationof the electrophilic species in order to introduce it into themolecule. A very strong oxidant in an anhydrous andstrongly acidic medium is ordinarily necessary for thiskind of functionalisation when molecular iodine or theiodide anion is used as the source of iodine, while meta

Table 6 Iodination of Di-, Tri-, and Tetramethyl-Substituted Benzenes

Reaction Substrate Product Yield (%) Ref.

6868

6970

40–9345

22b,32,35,39a,59,73

74

717171

727374

62–9940–8165

22b,30,33,35,50,71,73 18,74,75

71

757575

767778

43–9068–9665

31,33,39a,46,73

71,74,75

71

7979

8081

88–9869

23,24,71

71

828282

838485

81–9579–9980–83

21,30,31,33,46,47,49,76

27,55,71,75

71,74

8686

8788

8868

40,71

71

8989

9091

8567

71

71

9292

9394

65–8768–78

30,33,50,71,76

71,74

9595

9697

8868

71

71

Me

Me

Me

Me

Me

Me

I I

I68 69 70

Me

Me

Me

Me

Me

Me

Me

Me

I I

I I

I

I

71 72 73 74

Me

Me

Me

Me

Me

Me

Me

Me

I I

I II

I

75 76 77 78

Me

Me

Me

Me

Me

Me

I I

I

79 80 81

Me Me Me

I

Me

MeMe

Me

MeMe

Me

Me Me

Me

MeMe

I I

I

I

I

I

83 84 8582

Me

Me

Me

Me

Me

Me

I

II86 88

Me

Me

Me87I

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

I I

I

89 90 91

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

MeI I

I

92 93 94

Me

MeMe

Me

Me

MeMe

Me

Me

MeMe

Me

I I I95 96 97



regioselectivity of iodination was observed in these reac-tions. A variety of benzene derivatives bearing a stronglydeactivated aromatic ring were selectively and efficientlyiodinated by iodine in concentrated sulfuric acid in thepresence of strong oxidants like sodium percarbonate(SPC),19 manganese(IV) oxide or potassiumpermanganate78 (entry 4), sodium iodate or sodiumperiodate79,80 (entries 5 and 6), diluted fluorine81 (entry 8)or urea–hydrogen peroxide adduct67 (entry 9), while foroxidative iodination by potassium iodide and potassiumbromate in the presence of hydrochloric acid22c was ap-plied (entry 7). For the synthesis of 4-iodo-2,3,5,6-tetrafluorobenzaldehyde from the corresponding highlydeactivated tetrafluorobenzaldehyde precursor, an arylcarbanion was primarily formed and treated later withmolecular iodine.82

3 Iodination of Alkenes and Alkynes

Electrophilic iodofunctionalisation of a double bond(Scheme 7) proceeds through a cyclic iodonium ion. This,

following the addition process after collapse with an ex-ternal nucleophile, transforms into vicinal-substituted io-dides (B), or a cyclisation takes place with theparticipation of an internal nucleophile (C), while an ad-dition–elimination pathway results in the formation of io-doalkenes (A). Iodocyclisation reactions represent animportant synthetic methodology, but since this topic hasrecently been the subject of many reviews,14–17 it is notdiscussed in the present work.

In Table 8 are collected data on iodination of styrene(119) as the most frequently used test compound for eval-uation of new iodinating systems. Markovnikov-type vic-inal iodohydrins, iodoethers or iodoacetates (120) wereobtained by treatment with molecular iodine in the pres-ence of sources of various nucleophiles (OH, OR, OAc,F). Its activation was performed by different metallic ionsin salts83a or natural clay84 (entries 1, 2), by itself inexcess83b (entry 3), acetic acid86 (entry 4), ultrasound87

(entry 5), or anionic surfactant88 (entry 6), while oxidativeactivation using cerium(IV)89a (entry 7), zinc(II) chloride(entry 8),89b hypervalent iodine(III) derivatives90 (entries9–11), or 30% aqueous hydrogen peroxide91,92 (entries 12,13) was also employed.

These iodinating systems were used for iodohydroxyla-tion or iodoalkoxylation of a variety of aryl-substitutedalkenes. The corresponding Markovnikov-type adductswere obtained, while the regioselectivity of iodination inthe case of alkyl-substituted terminal alkenes depended onthe structure of the alkene and the iodinating system used(Table 9). Products of Markovnikov-type addition (122)were predominatly formed, except in the case of 3,3-di-methylbut-1-ene (entry 12), where the bulky tert-butylgroup prevented nucleophilic attack on the the C-2 atomand C-1 thus remained the only possible approach.91

The stereochemical course of iodohydroxylation, iodo-peroxylation,85 and iodoalkoxylation reactions has beeninvestigated on a variety of acyclic (124) or cyclic alkenes(126, 128, 130, 132, Scheme 8) and anti addition wasfound to be the exclusive process,83–93 thus proving theformation of the cyclic iodonium ion as the reactive inter-mediate. Remarkable diastereoselectivity was also ob-

Scheme 6 Progressive iodination of sterically hindered alkyl-substituted benzene derivatives.72 Reagents and conditions: I2,F-TEDA-BF4, MeCN, 55–70 °C, 1–24 h.

t-Bu t-Bu t-Bu t-Bu

98 I I

I

I

II99 100 101

i-Pr

Me

i-Pr

Me

i-Pr

Me

i-Pr

Me

I I

I

II

I

102 103 (72%) 104 (77%) 105 (70%)

(90%) (87%) 73%)

t-Bu t-Bu t-Bu

Me Me Me

I II

106 107 (88%) 108 (80%)

t-Bu t-Bu

t-Bu t-BuI

109 110 (83%)

i-Pr

i-Pr

i-Pr

i-Pr

i-Pr

i-Pr

I I

I

111 112 (89%) 113 (71%)

t-Bu

t-BuMe

t-Bu

t-BuMe

t-Bu

IMe

I I114 115 (58%) 116 (77%)

Scheme 7 Iodofunctionalisation of a carbon–carbon double bond

‘I+’

I+

additionaddition–elimination

Nu

I

external Nu internal Nu

I

A

B C

I

Nu



served in the case of iodohydroxylation of tri-O-benzyl-D-glucal (134) with the sodium iodide, hydrogen peroxideand tetrafluoroboric acid iodinating system, where pre-dominantly the manno isomer 135 (manno/gluco = 14:1)was formed in the ratio of 4:1 for a/b epimers.92

Iodination of monoterpenes was investigated92,94,95 andthe use of the system sodium iodide/hydrogen peroxide/tetrafluoroboric acid for functionalisation of (+)-3-carene136 afforded the trans adduct 137,92 while iodination witha mixture of iodine and (dichloroiodo)benzene in metha-nol gave the corresponding trans-configured iodo-meth-

Table 7 Iodination of Deactivated Aromatic Hydrocarbons

Entry R Reagent Conditions Temp (°C) Yield (%) Ref.

1 NO2 or COOR1 I2, CrO3 AcOH–Ac2O–H2SO4 60 71–86 18

2 COR1 I2, SPC AcOH–Ac2O–H2SO4 40 51–93 19

3 NO2 or COOH I2, (BuPPh3)2S2O8 MeCN reflux 70–80 42

4 NO2 or COR1 I2, MnO2 or KMnO4 AcOH–Ac2O–concd H2SO4 60 63–89 78

5 NO2 or COR1 I2, NaIO3 concd H2SO4 60 57–85 79

6 NO2 or COR1 I2 or KI, NaIO4 concd H2SO4 60 63–87 80

7 NO2 or COOH KI, KBrO3, HCl AcOH–H2O 60 71–82 22c

8 NO2 or CF3 I2, 10% F2 in N2 concd H2SO4a r.t. 70–83 81

9 COR1 I2, urea–H2O2 (1:1) AcOH–Ac2O–H2SO4 10–40 46–84 67

a Perfluorodecalin (C10F18) or C2Cl3F3 was used as co-solvent.

R R

I

117 118

Table 8 Iodination of Styrene in the Presence of an External Nucleophile

Entry Reagent Conditions Temp (°C) Nu Yield (%) Ref.

1 (i) I2, Fe3+ dioxane–H2O r.t. OH 89 83a

2 (ii) I2, clay dioxane–H2O r.t. OH 67 84

3 (iii) I2 excess dioxane–ROH r.t. OR 75 83b

4 (iv) I2 NH4OAc, AcOH 25 OAc 82 86

5 (v) I2 ROH, ultrasound 25 OR 85 87

6 (vi) I2 H2O, SDSa 60 OH 67 88

7 (vii) I2, Ce(OTf)4 ROH r.t. OR 80 89a

8 (viii) I2, ZnCl2 ROH reflux OR 98 89b

9 (ix) I2, PhI(O2CCF3)2 MeCN–H2O r.t. OH 95 90a

10 (x) I2, PhICl2 MeCN–H2O r.t. OH 88 90b

11 (xi) I2, 4-MeC6H4IF2 CH2Cl2 0–5 F 72 90c

12 (xii) I2, H2O2 ROH–MeCN r.t. OR 93–96 91

13 (xiii) NaI, H2O2, H+ THF–H2O 25 OH 72 92

a SDS = sodium dodecyl sulfate (an anionic surfactant).

Ph Ph

Nu

I‘I+’

Nu–

119 120



oxy derivative.94 Treating limonene with the latter systemgave a complex reaction mixture as the result of function-alisation of both double bonds in the substrate,94 but theuse of the system iodine and copper(II) acetate in diox-ane–water resulted in the regio- and diastereoselectiveformation of trans-2-iodo-4-isopropenyl-1-methylcyclo-hexanol in 82% yield.95 Reactions of cyclic and acyclic1,3-diene derivatives with iodine and ammonium ceri-um(IV) nitrate (CAN) in alcohols or acetonitrile–watergave the corresponding regiospecific trans-2-hydroxy- ortrans-2-alkoxy-1-iodo compounds as major products, ac-companied by 1,4-dialkoxy derivatives as by-products.96

This reaction, improved by further treatment of primarilyformed trans-iodonitrate or trans-iodoacetate with aque-ous potassium hydroxide, was used as a new selective andefficient method for preparation of cis-diols.97 Organotel-luride compounds were used as water soluble catalysts forthe regio and stereo selective oxidative iodination of alk-enes with the sodium iodide and hydrogen peroxide sys-tem.98

Iodination of allenyl phenyl sulfoxides (138a, Scheme 9),allenyl phenyl sulfides 138b or allenyl phenyl selenides138c with molecular iodine was studied. Iodohydroxyla-tion of 138a in aqueous acetonitrile in the presence of lith-ium acetate smoothly regio- and stereoselectivelygenerated (E)-2-iodo-3-hydroxy-1-alkenyl phenyl sulfox-ides 139a.99a,b The corresponding sulfides 138b undersimilar reaction conditions gave Z-configured analogues140a,99c while selenides 138c in the presence of watergave Z-configured product 140b, and under anhydrousconditions a Ritter-type iodoamidation took place,forming N-[2-iodo-3-phenylseleno-2(Z)-propenyl]alkylamides 141.100 On the other hand, sulfoxide 138a in anhy-drous acetonitrile in the presence of benzyl thiol stereose-lectively gave E-isomer 139b.99d By using an acetonitrile–alcohol solvent mixture, stereoselective Z-iodoalkoxyla-tion of 1,2-allenyl sulfides or selenides was observed.99e

a-Iodoenones are versatile intermediates in organic syn-thesis.101 The iodination of enones with molecular iodinein the presence of organic amines has been found to be a

Scheme 8 Stereochemistry of iodohydroxylation and iodoalkoxylation of alkenes with molecular iodine or sodium iodide mediated with hy-drogen peroxide. Reagents and conditions: (i)91 alkene (1 mmol), I2 (0.5 mmol), 30% aq H2O2 (0.5 mmol), 10 mL of MeCN and H2O (15 mmol),or 10 mL of MeOH, 20 °C, 20 h; (ii)92 alkene (5 mmol), NaI (5 mmol), 33% aq H2O2 (15 mmol), 35% aq HBF4 (30 mmol), THF–H2O (12 mL/5 mL), ice-water bath, 15 min; (iii)85 alkene (1 mmol), I2 (0.5–4 mmol), R4OOH as 5–6% (or 50%, in the case of t-BuOOH) solution in Et2O(1.2–5 mmol), Et2O (5 mL), r.t., 3–72 h.

PhR1

OH

I124 125

OR2

I

126 n = 1128 n = 2

127129

Y YR3 R3

OR4

I

130 131

125a: R1 = Me (67%)125b: R1 = COOMe (81%)

127a: R2 = H (83–95%)127b: R2 = Me (92%)129a: R2 = H (85%)129b: R2 = Me (76%)

(i) or (ii)

(i) or (ii)

(i) or (ii)

131a: n = 0, Y = CH2, R3 = R4 = H (69%)131a': n = 0, Y = CH2, R3 = H, R4 = Me (40%)131b: n = 1, Y = CH2, R3 = R4 = H (64%)131b': n = 1, Y = CH2, R3 = H, R4 = Me (68%)131c: n = 1, Y = CH2, R3 = R4 = Me (71%)131d: n = 0, Y = O, R3 = H, R4 = Me (48%)131e: n = 1, Y = O, R3 = H, R4 = Me (61%)

(ii)OH

I

O

CH2OBn

BnO

BnOO

BnO

BnOBnO

IOH

(ii)

135 (manno/gluco =14:1; α/β = 4:1)

136 137

OOR5

I

132 133

(iii)

134

133a: n = 0, R5 = H (61%)133b: n = 1, R5 = H (62%)133c: n = 3, R5 = H (51%)133d: n = 0, R5 = t-Bu (68%)133e: n = 1, R5 = t-Bu (61%)133f: n = 3, R5 = t-Bu (67%)

( )n( )n

( )n ( )n

( )n ( )n

Ph

R1



very efficient method for their preparation. The use of anexcess of iodine in pyridine–carbon tetrachloride (1:1)solvent [protocol (i), Scheme 10] was originally proposedby Johnson.102 The idea was later improved by the use ofan equivalent of pyridine in dichloromethane [protocol(ii)],103 or triethylamine [protocol (iii)],104 and finally op-timised by the use of a catalytic amount of 4-dimethylami-nopyridine (0.2 equiv) and potassium carbonate (1.2equiv) in aqueous tetrahydrofuran [protocol (iv)]. Proto-cols (i), (ii), and (iii) were successful only for the a-iodi-nation of cyclic enones (142, 144, 146), while protocol(iv) was also useful for linear enones 148.105 The crucial

role of organic amines in these valuable iodofunctionali-sations was postulated and a reaction pathway followingthe Baylis–Hillman-type pathway [i.e., nucleophilic(amine) addition/electrophilic (iodine) capture/elimina-tion (amine)], was proposed. The efficiency of the reac-tion was found to be considerably lower when theiodinating system of iodine and bis(tetra-n-butylammoni-um)peroxydisulfate in acetonitrile was used [protocol(v)],106 while application of the iodine and bis(trifluoro-acetoxy)iodobenzene system in the presence of pyridine(1:1:2 molar ratio) in dichloromethane [protocol (vi)]gave almost quantitative formation of 2-iodoenones

Scheme 9 Iodination of allenyl phenyl sulfoxides and allenyl phenyl sulfides and allenyl phenyl selenides with molecular iodine. Reagentsand conditions: (i)99a 138a (0.5 mmol), I2 (2.4 mmol), LiOAc (1 mmol), MeCN–H2O (7:1, 1 mL), r.t., 1 h; product 139a; (ii)99d 138a (0.5 mmol),I2 (0.75 mmol), PhCH2SH (0.5 mmol), anhyd MeCN (6 mL), 5 °C; 2 h; product 139b; (iii)99c 138b (0.25 mmol), I2 (0.5 mmol), MeCN–H2O(7:2; 9 mL), N2, 15 °C, 16 h; product 140a; (iv)100 138c (1 mmol), I2 (2 mmol), H2O (16 mmol), MeCN–n-hexane (1:1; 10 mL), N2, 25 °C, 9h; product 140b; (v)100 138c (1 mmol), I2 (2 mmol), R1CN–n-hexane (1:1; R1 = Me or n-Pr; 10 mL), N2, 25 °C, 10 h; product 141.

YC C CR2

H+ I2

(iii) or (iv)

(v)

(i) or (ii)Y

I

OHPh

Y I

CR2OH

Ph

Se IPh

NH

OR1

138a: Y = SO138b: Y = S138c: Y = Se

139a: Y = SO (96%)139b: Y = S (50%)

140a: Y = S, R = Me (63%)140b: Y = Se, R = H (63%)

141: R1 = Me (59%)

Ph

Table 9 Regioselectivity of Iodohydroxylation and Iodoalkoxylation of Alkyl-Substituted Terminal Alkenes

Entry Iodinating systema R1 R2 Ratio 122/123 Yield (%) Ref.

1 (i) Bu H 100:0 70 83a

2 (ii) Hex H 80:20 66 84

3 (iii) Bu H 80:20 80 83b

4 (iii) Bu Et 85:15 65 83b

5 (iv) Hex Ac 100:0b 91 86

6 (v) Bu Me 100:0 92 87

7 (vi) Hex H 67:33 95 88

8 (vii) Hex H 80:20 72 89a

9 (vii) Hex Me 70:30 70 89a

10 (vii) Hex Ac 70:30 70 89a

11 (xii) Hex H 83:17 54 91

12 (xii) t-Bu H 0:100 61 91

13 (xiii) Bu H 83:17 76 92

a Iodinating systems from Table 8.b The same results were reported in the case of dodec-1-ene, undec-1-ene, hept-1-ene and hex-1-ene.

R1 R1

R2O

I R1

I

OR2

+

121 122 123

iodinatingsystem

R2OH



143.107 Iodination of 1,4-naphthoquinones using the mor-pholine–iodine complex in an aqueous solution of potas-sium carbonate gave high yields of 2-iodo-substitutedproducts.108 Johnson’s method or its modification hasbeen used in sequences of total synthesis of many naturalproducts.109–112 a-Carboxylates of a-cinnamoyl ketene cy-clic dithioacetals 150 were treated with iodine under basicconditions [protocol (vii)], resulting in an iododecarboxy-lation reaction to give 151.113a Similar results were ob-tained with acyclic dithioacetal derivatives.113b

Iodination of alkynes by molecular iodine results in theformation of (E)-1,2-diodoalkenes and could be per-formed without special activation of iodine. The use of ac-tivators, however, accelerates the transformation andoften improves its efficiency. In Table 10 are collecteddata for the iodination of phenyl acetylene (152) to (E)-1,2-diiodophenylethene (153). In acetonitrile, iodinationwith molecular iodine in the presence of copper(I) iodide(5 mol%) gave 153 in high yield114 (entry 1), while in thepresence of an equimolar amount of cerium(III) ions in

aqueous media, quantitative conversion was reported115

(entry 2), as was the case when the reaction was per-formed in an aqueous solution of carbon dioxide116 (entry3). In pure water48 or under solvent-free reaction condi-tions (SFRC),57,117a the transformation into 153 occurredin moderate to high yields, while a recent report suggestedthe use of the iodine with hydrogen peroxide pair in tet-rahydrofuran.117b

Iodination protocols for the transformation of substitutedalkynes using molecular iodine under different reactionconditions are shown in Scheme 11. Various alkynes154a–i were readily transformed to the corresponding(E)-1,2-diiodoalkenes 155a–i under reaction conditionsfrom Table 10, while the formation of 1,2-iodotosyloxy-lated alkenes 157 was observed when molecular iodinewas used in the presence of 1-(p-toluenesulfonyloxy)ben-ziodoxolone (159).75 Treatment of alkynes with the iodineand sodium nitrate system in acetic acid resulted in theformation of 1-iodo-2-nitroalkenes 158, but in this casethe transformation was not stereospecific.118 Various ter-

Scheme 10 Iodination of enones or enaminones with molecular iodine. Reagents and conditions: (i)102 substrate (5.21 mmol), I2 (22 mmol),Py–CCl4 (1:1, 40 mL), argon, 0 °C to r.t., 24 h; (ii)103 substrate (2 mmol), I2 (2.4 mmol), Py (1.6 mmol), CH2Cl2 (15 mL), r.t., 24 h; (iii)104

substrate (2 mmol), I2 (2 mmol), Et3N (2 mmol), CH2Cl2 (5 mL), r.t., 5 min; (iv)105 substrate (1 mmol), I2 (1.5 mmol), DMAP (0.2 mmol), K2CO3

(1.2 mmol), THF–H2O (1:1, 5 mL), r.t., 2 h; (v)106 substrate (1 mmol), I2 (1 mmol), (n-Bu4N)2S2O8 (1 mmol), MeCN (10 mL), r.t., 5 h; (vi)107

substrate (1 equiv), I2 (0.6 equiv), PhI(OCOCF3)2 (0.6 equiv), pyridine (1.2 equiv), CH2Cl2, r.t.; (vii)113a substrate (1 mmol), I2 (1.5 mmol), sat.aq NaHCO3 (1 mL), CH2Cl2 (5 mL), r.t., 0.5–4 h.

O

(i), (ii), (iv), (v) or (vi)

O

R1

I

142

a: R1 = H; i (60%), ii (92%), iv (99%), v (60%), vi (96%)b: R1 = Me; i (70%), iv (16%), vi (82%)

143

O

NH

R2

O

NH

R2

I(iii)

R3

R4

144 145

a: R2 = Ph, R3 = R4 = H (95%)b: R2 = 4-ClC6H4, R3 = R4 = H (93%)c: R2 = Bn, R3 = R4 = H (96%)d: R2 = c-hexyl, R3 = R4 = H (94%)e: R2 = Ph, R3 = R4 = Me (91%)f: R2 = Ph, R3 = H, R4 = Me (96%)g: R2 = Ph, R3 = H, R4 = Ph (92%)

R3

R4

O

O

O

O

O

O

(i)I

146

147 (100%)

O

R5

R6

R7O

R5

R6

R7

I(iv)

148 149

a: R5 = Me, R6 = R7 = H (68%)b R5 = Ph, R6 = R7 = H (92%)c: R5 = Me, R6 = R7 = Me (27%)d: R5 = Me, R6 = Me, R7 = H (85%)e: R5 = Et, R6 = Me, R7 = H (90%)f: R5 = H, R6 = Me, R7 = H (99%)g: R5 = Me, R6 = Ph, R7 = H (32%)

Ar

S

S

OHOOC

Ar

SS

OI

(vii)

150 151

a: n = 1, Ar = Ph (90%)b: n = 1, Ar = 4-MeOC6H4 (95%)c: n = 1, Ar = 4-O2NC6H4 (96%)d: n = 1, Ar = 2-furanoyl (82%)e: n = 2, Ar = Ph (77%)f: n = 2, Ar = 4-MeOC6H4 (95%)g: n = 2, Ar = 4-O2NC6H4 (89%)h: n = 2, Ar = 2-furanoyl (85%)

( )n( )n

OTBSOTBS

R1



minal alkynes 160 were transformed into substituted 1-io-doalkynes 161 by cesium carbonate catalysedtransformation with molecular iodine in the presence ofpotassium hydroxide,119 or copper(I) iodide catalysedtreatment with the iodinating system of potassium iodideand (diacetoxyiodo)benzene in acetonitrile in the pres-ence of triethylamine.120 Similar results were also ob-tained by anodic oxidation of alkynes in the presence ofsodium iodide.121

4 Iodination of Aliphatic Hydrocarbons

The selective and efficient transformation of unreactivecarbon–hydrogen bonds in aliphatic hydrocarbons is oneof the most challenging tasks in organic chemistry. Radi-cal halogenations of aliphatic hydrocarbons using molec-

ular halogens are probably the simplest way tofunctionalise them, but the process in the case of iodine isendothermic and does not allow a chain reaction to occur.

In Table 11 are collected some modern methods for directiodination of saturated hydrocarbons with molecular io-dine tested on cyclohexane (162). The diacetoxyiodoben-zene-promoted reaction in the presence of tert-butylalcohol under photochemical conditions gave iodocyclo-hexane (163), while under thermal conditions, trans-1-acetoxy-2-iodocyclohexane was formed.122 A similarmethod using molecular iodine and sodium tert-butoxidealso gave 163; in both cases, in situ formed tert-butyl hy-poiodide was supposed to act as the iodinating reagent.123

Following another approach the system involving molec-ular iodine and 1-acetoxy-1,2-benziodoxol-3(1H)-one or30% aqueous hydrogen peroxide as oxidant in the pres-ence of an azide was used for this transformation,124 whileinitiation with a superelectrophile moiety, such as thecomplex between carbon tetrachloride and aluminium(III)

Scheme 11 Iodination of substituted alkynes with molecular iodine

R1 R2

R1 I

I155

R2

‘I+’

154

a: R1 = Ph, R2 = Me (92%;48 72%57)b: R1 = COOEt, R2 = H (100%115,116)c: R1 = Bu, R2 = H (90%114)d: R1 = C5H11, R2 = H (76–80%48,117b)e: R1 = CH2OMe, R2 = H (75%117b)f: R1 = R2 = Et (89%117b)g: R1 = R2 = Pr (88–100%115,116,117b)h: R1 = Me, R2 = COOMe (100115,116)i: R1 = R2 = COOMe (75%117b)

R3 R4

156a: R3 = R4 = Ph b: R3 = R4 = n-Pr c: R3 = H, R4 = n-Bu

R3 OTs

I157a (93%) b (73%) c (83%)

R4

R3 NO2

I158a (72%; E/Z = 3:1) b (13%; E/Z = 2:1)R4

I2

NaNO3, AcOH

OI

O

OTs

159

DCE

R5

160R5 I

161

I2, cat. Cs2CO3

KOH, THF–HMPA, r.t.

a: R5 = CH2OMe (89%)b: R5 = CH2OH (86%)c: R5 = CH2OPh (78%)d: R5 = CH2OC10H7 (93%)

(iodination protocolsfrom Table 10)

Table 10 Iodination of Phenyl Acetylene

Entry Reagent Conditions Temp (°C)

Yield(%)

Ref.

1 I2, CuI (cat.) MeCN 60 95 114

2 I2, Ce2(SO4)3 H2O r.t. 100 115

3 I2 H2O, CO2 r.t. 100 116

4 I2 H2O r.t. 83 48

5 I2 SFRC r.t. 52–90 57,117a

6 HI, KMnO4 MeCN r.t. 71 65

7 KI, HNO3 SFRC 20 50a 117a

8 I2, H2O2 THF r.t. 85 117b

a (E)-1-Iodo-2-nitro-1-phenylethene (28%) was also formed.

PhI

Ph I

152 153

Table 11 Iodination of Cyclohexane


1 (i) I2, PhI(OAc)2, t-BuOH C6H12, hn r.t. 97 122

2 (ii) I2, t-BuONa C6H12 40 84–94 123

3 (iii) I2, l3-iodane, TMSN3 (cat.) C6H12 60 0.91a 124

4 (iv) I2, 30% aq H2O2, NaN3 Ac2O–H2O 0–40 1.31a 124

5 (v) I2, CCl4·2AlI3 CH2Cl2 –20 75 125

a Yield given as the ratio of mmol of isolated 163 per mmol of iodine used.

I

162 163



iodide, also gave 163 in good yield.125 These methodswere applied for the iodination of various cyclic (164), bi-cyclic (166) and linear alkanes (168), as well as for side-chain functionalisation of alkylbenzenes (172a–e)(Scheme 12). Selective terminal C–H bond activation oflinear alkanes was achieved through the tungsten allyl-nitrosyl-n-alkyl complex, but iodination of this specieswith I2 was so far tested only on n-pentane, thus forming1-iodopentane.126

Asymmetric iodination of an inactivated carbon–hydro-gen bond with molecular iodine was achieved under pal-ladium(II) catalysis. The strategy involved the installationof a palladium s-chelating auxiliary with an oxazoline de-rivative in order to facilitate the assembly of the pre-tran-sition state for cyclometallation through a square–planarcomplex, thus activating a carbon–hydrogen bond. Ox-azolines were readily prepared from the correspondingderivatives of carboxylic acids and amino alcohol (S)-tert-butylleucinol, palladium(II) acetate was used as the cata-lyst, and diacetoxyiodobenzene as the catalyst turnoverreagent.127,128 Some examples of the application of thismethodology are shown in Table 12, while its use for thesynthesis of gem-dimethyleniodo compounds was also re-ported.129

5 Iodination of Organic Compounds Bearing an Enolisable Carbonyl Group

The position a to a carbonyl functional group is a strategicpart of an organic compound and many synthetic benefitscan be achieved through its halofunctionalisation, in par-ticular its iodofunctionalisation.

Classical synthetic approaches to a-iodination of carbonylcompounds, such as the halogen interchange reaction orelectrophilic iodination of enol derivatives, have beensubstituted by modern methods for the direct introductionof an iodine atom into this position. In Table 13 are col-lected examples of these methods tested in the direct iodi-nation of acetophenone (174) to a-iodoacetophenone(175). Molecular iodine in dimethoxyethane (entry 1),130

or in the presence of various oxidants such as N–F reagent(entry 4),63 copper(II) oxide (entry 3),133a 30% aqueoushydrogen peroxide (entry 6)134 and urea–hydrogen perox-ide (1:1 complex) (entry 7),57 or air oxygen (entries 8,9)52,,135 was used as the iodinating reagent, while protocolsincluding oxidation of the iodide anion with potassium io-date (entry 2),131 or 30% aqueous hydrogen peroxide (en-try 5)133b were also applied for this transformation. Thesemethods were also used for side-chain iodination of deriv-atives bearing other aryl moieties (naphthyl, phenanthryl,pyrenyl), substituents on an aromatic ring or longer alkylchain bonded to a carbonyl carbon atom.

Special attention was paid to aryl alkyl ketones bearing astrongly activated aromatic ring, since in this case theelectron-rich aryl part of the molecule represents a com-petitive reaction site for the iodination. In Scheme 4 arecollected methods for regioselective iodination of the arylpart of these compounds, while in Scheme 13 those for theregioselective iodofunctionalisation of the a-carbonyl po-sition are shown. Iodination protocols were ordinarilytested on 4¢-methoxyacetophenone (176b) by its transfor-mation into 1-(4¢-methoxyphenyl)-2-iodoethanone(177b). Further useful application of these methods wasachieved in the case of dimethoxy- and trimethoxy-substi-tuted acetophenone derivatives 178, and alkoxy-substitut-ed 1-indanone or 1-tetralone derivatives 180, where

Scheme 12 Direct iodination of saturated hydrocarbons. Reagentsand conditions: (i) – (v) from Table 11. Yield and distribution of pro-ducts 169/170/171: (i)122 85%, 171/170 = 1:1.5, 169/171+170 = 1:15;(ii)123b 90%, 1:5:4; (ii) 50%, 1:3:2; (iii)124 50%, 0:1:1.1.

(i)–(v) I

164n = 1, 3, 4

16565–98%

I(v)

166 167 78%

Pr Pr Pr Pr+ +I

I

I168 169 170 171

Me

R

CH2I

R

(i)–(iii)

(i)–(iii)

172 173

a: R = Hb: R = 2-Mec: R = 3-Med: R = 4-Mee: R = 3,5-di-Me

( )n( )n

Table 12 Palladium-Catalysed Diastereoselective Iodination of an Inactivated Carbon–Hydrogen Bond a

Entry Substrate Product Yield (%) de (%)

1 92 –

2 91 26

3 60 35

4 83 82

5 65 99

a Reaction conditions:127,128 substrate (1 equiv), I2 (1 equiv), PhI(OAc)2 (1 equiv), Pd(OAc)2 (0.1 equiv), CH2Cl2, 24–50 °C, 24–96 h; Oxa = (S)-4-tert-butyloxazoline-2-yl.

Oxa

Me

Me

MeMe Oxa

Me

I

Oxa

Me

Me

EtMe Oxa

Et

I

Oxa

Me

Me

CH2ClMe Oxa

CH2Cl

I

Oxa

Me

Me

t-BuMe Oxa

t-Bu

I

Me

Oxa

Me

OxaI



regiospecific formation of side-chain-iodinated product179 or 181 was observed. For the oxidative activation ofmolecular iodine, 30% aqueous hydrogen peroxide wasused in aqueous solution [protocol (i) in Scheme 13]56 ormethanolic media [protocol (ii)]134, F-TEDA-BF4 inmethanol [protocol (iii)],136,137 or selenium dioxide in ace-tic acid [protocol (iv)].138 In these cases, a half-equivalentof the oxidant was sufficient for total atom economy of io-dine, ordinarily achieved where both iodine atoms wereinvolved in the iodination process, while activation withmanganese(IV) oxide in butan-1-ol needed a 50% molarexcess of molecular iodine for successful transformation

of the starting compound into its corresponding iodo de-rivatives.139

Various dialkyl or cycloalkyl ketones were also readily io-dinated using the mentioned iodinating systems.48,52,130–135

Unsymmetrical ketones were preferentially iodinated atthe most occupied a-carbon atom, but in the case of iodi-nation with the molecular iodine and ammonium ceri-um(IV) nitrate tandem in alcohol, the regioselectivity offunctionalisation could be regulated by the structure of thealcohol and reaction temperature (Table 14).140 At lowertemperature, the C3-position in alkan-2-ones 184 waspreferentially iodinated in methanol and isopropyl alcohol(entries 1, 3, 5, and 7), in methanol the functionalisationbeing more regiospecific and efficient. At higher reactiontemperature in methanol, the same regioselectivity wasobserved (entries 2 and 6), while in isopropyl alcohol theC1-position was preferentially iodinated (entries 4 and 8).These observations were explained by the known fact thatthe cerium(IV) ion in alcohols forms the cerium(IV)–al-cohol complex which is assumed to be coordinated to theoxygen of the carbonyl group. At higher temperatures,formation of the complex is faster and attack of the iodo-nium ion occurs at the less hindered position, which in thecase of more bulky alkoxy groups, is the C1-position.140

The molecular iodine and ammonium cerium(IV) nitratesystem in acetonitrile or aqueous acetic acid was also usedfor efficient a,a¢-diodination of ketones.141

b-Dicarbonyl compounds were also efficiently iodinatedat the a-position using molecular iodine48,106 or the iodideanion52,132 as the iodine atom source. Following a recentreport, a few minutes of grinding in a mortar at room tem-perature of a reaction mixture of various b-dicarbonyls(187, Scheme 14) with molecular iodine and a catalyticamount of Oxone® gave excellent yields of the corre-sponding monoiodo derivatives 188.135 A critical evalua-tion of this method should be made, since data concerningthe experimental procedure were scant and the nature ofOxone® catalysis of the iodination process has not yetbeen investigated.

Selective a-iodination of unsaturated amides or lactamswith molecular iodine in the presence of 2,6-dimethylpy-ridine or 2,4,6-trimethylpyridine was reported. The allylicpart of the substrate was found to be essential for this re-action and could be bonded to the carbonyl carbon atom(193, Scheme 15)142 or to the amide nitrogen atom (197 or199).143

The reaction pathway that was proposed assumes the for-mation of a cationic iodocyclisation intermediate, whichafter a-deprotonation gives the cyclic ketene N,O-acetal.This acetal, after subsequent a-iodination and ring open-ing of the a-iodonium intermediate, gives rise to the cor-responding a-iodoamide. It was thus expected that thereaction of 4-alkenamides with a b-chiral centre shouldproceed with high diastereoselectivity to give syn-config-ured a-iodoalkenamides, since a-iodination from the op-posite side of a b-substituent in the cyclic ketene N,O-acetal intermediate is preferential. The realisation of this

Scheme 13 Side-chain iodination of aryl alkyl ketones with an acti-vated aryl moiety. Reagents and conditions: (i)56 ketone (1 mmol), I2

(0.5 mmol), 30% aq H2O2 (0.6 mmol of active oxidant), H2SO4 (0.1mmol), H2O (10 mL), 50 °C, 2–18 h; (ii)134 ketone (2 mmol), I2 (1mmol), 30% aq H2O2 (1.2 mmol of active oxidant), H4[Si(W3O10)4](0.03 mmol), MeOH (5 mL), 65 °C, 1.5–3 h; (iii)136,137 ketone (2mmol), I2 (1 mmol), F-TEDA-BF4 (425 mg, 1.2 mmol), MeOH (20mL), 22 °C, 20–48 h; (iv)138 ketone (0.1 mol), I2 (0.055 mol), SeO2

(0.055 mol), AcOH or MeCN (50 mL), 70 °C, 3–4 h; (v)139 ketone (1mmol), I2 (1.5 mmol), MnO2 (1.1 mmol), n-BuOH (1 mL), MW(78 °C, 10 min).

R1O

O

R1O

O

176 177a: R1 = H (64–78%)63,130

177b: R1 = Me (62–99%)45,57,130,131,133a,134

(OMe)n (OMe)n

178 179

179a: 2,4-di-OMe (71%)56

179b: 2,5-di-OMe (76%)56

179c: 2,6-di-OMe (54%)56

179d: 3,4-di-OMe (76–95)56,134,136

179e: 2,3,4-tri-OMe (74–82%)56,136

179f: 3,4,5-tri-OMe (83%)136

(i), (ii) or (iii)

O

OR2

O

OR2

180 181a: n = 0; 5-OMe (86%)137

181b: n = 0; 6-OMe (85%)137

181c: n = 0; 4,5-di-OMe (86%)137

181d: n = 0; 5,6-di-OMe (84%)137

181e: n = 0; 4,7-di-OMe (85%)137

181f: n = 1; 5-OH (69%)137

181g: n = 1; 5-OMe (79–87%)137-139

181h: n = 1; 6-OMe (85%)138, 139

181i: n = 1; 7-OMe (82–92%)137-139

181j: n = 1; 6,7-di-OMe (85%)137

181k: n = 1; 5,8-di-OMe (87%)137

181l: n = 1; 6-OAllyl (80%)139

181m: n = 1; 6-OPiv (70%)139

181n: n = 1; 6-OH (73)137

OMe

HO

O

OMe

HO

O

182 183 (84%)136

(iii), (iv) or (v)

(iii)

I

IOO

( )n( )n

I

I



assumption is given in Table 15.144 The highest diastereo-selectivity was achieved in N,N-dimethylformamide,while the best substrates seemed to be N-benzyl-2¢-cyclo-hexenyl acetamide (entry 4) or N-benzyl-2¢-cyclopentenylacetamide (entry 5).

6 Iodination of Heteroatom-Containing Organic Compounds

6.1 Organoboron and Organometallic Com-pounds

Selective introduction of an iodine atom through organo-metallic precursors is an often-used synthetic strategy for

iodofunctionalisation of organic compounds. Iodinationof organotrifluoroborates (203, 205, and 207,Scheme 16), with the combination of sodium iodide andchloramine-T as the oxidant, was used for the synthesis ofvarious aryl iodides145 (204) or vinyl (206) and alkynyl io-dides (208),146 while the same reagent was used for thepreparation of radiolabelled aryl iodides via arylboronateester precursors.147 Fluoroalkenylboranes were used asprecursors for iodination with molecular iodine, resultingin the stereoselective synthesis of (E)- or (Z)-fluoro-iodoalkenes.148 Hydroboration or hydrozirconation of ter-minal alkenes (209) followed by iodination of the thus insitu formed terminal alkyl borane (210) or zirconane wasused as a strategy for the regioselective conversion ofthese alkenes into the terminal alkyl iodides 211.149 Orga-nometallic methodology was also used in the case ofstereoselective synthesis of iodinated selenoalkenes. Hy-droboration followed by iodination was used for regio-and stereoselective transformation of terminal alkylsele-noalkynes 212 to (E)-2-alkylseleno-1-iodoethenes 213,150

while (E)-1-iodo-1-selenoalkenes 215 were efficientlyobtained via the hydroalumination–iodination reactionprotocol.151 Addition of tri-n-butyltin hydride to the ethy-nyl group and iodination of the thus-formed (E)-tributyl-stannylethenyl-substituted precursor with the moleculariodine or sodium iodide and hydrogen peroxide combina-tion was often used for regio- and stereoselective intro-duction of an iodine atom into complex bioactive organiccompounds, also in the case of radiolabelling of these ma-terials.152–154 Nonsymmetrically substituted internal alke-nyl iodides were regio- and stereoselectively prepared bytreatment of (E)-[2¢-(tributyltin)alkenyl]dialkylboraneswith iodine.155 An efficient method based on directedortho-lithiation followed by low-temperature iodinationof the resulting substituted ortho-lithiated phenol deriva-tives with molecular iodine was recently developed, offer-ing an efficient alternative for selective ortho-iodinationof phenols.156

Table 13 Side-Chain Iodination of Acetophenone


1 I2 (excess) DME 90 74 130

2 KI, KIO3, H2SO4 AcOH r.t. 86 131

3 I2, CuO MeOH reflux 96 133a

4 I2, F-TEDA-BF4 MeOH r.t. 85 63

5 NaI, 30% H2O2, H2SO4 H2O 60 85 133b

6 I2, 30% H2O2, H4[Si(W3O10)4] (cat.) MeOH r.t. 95 134

7 I2, urea–H2O2 SFRC 45 89 57

8 I2, air, NaNO2 (cat.), H2SO2 (cat.) MeCN r.t. 91 52

9 I2, air, Oxone® (cat.) SFRC r.t. 91 135

Ph

O

Ph

O

I

174 175

Table 14 Regioselectivity of the Iodination of 2-Alkanones with Iodine and Ammonium Cerium(IV) Nitrate in Alcoholsa

Entry R1 R2 Temp(°C)

Yield (%)

Ratio 185/186

1 n-Pr Me 25 83 4:96

2 n-Pr Me 50 58 9:91

3 n-Pr i-Pr 25 46 32:68

4 n-Pr i-Pr 50 91 73:27

5 n-Bu Me 25 62 0:100

6 n-Bu Me 50 73 8:92

7 n-Bu i-Pr 25 49 7:93

8 n-Bu i-Pr 50 97 72:28

a Reaction conditions:140 2-alkanone 184 (5 mmol), I2 (2.5 mmol), CAN (2.5 mmol), ROH (50 mL), 15 h.

R1

O

R1

O

R1

O

I I184 185 186

I2, CAN

R2OH



6.2 Heterocyclic Compounds

Iodinated heterocyclic compounds are valuable buildingblocks in organic synthesis and their direct iodination isone of the options available for the preparation of theseuseful compounds.

Pyrrole derivative 216 was iodinated to its 5-iodoanalogue 217 and 4,5-diodo analogue 218 using mole-cular iodine and bis(trifluoroacetoxy)iodobenzene(Scheme 17).157 This method was also used for monoiod-ination of calix[4]pyrroles158 and indole derivatives.107

Substituted indole derivatives 219 were also iodinatedwith the mercury(I) oxide and molecular iodine combina-tion to 3-iodo-substituted derivatives 220,159 while 2,2¢-

biindole was iodinated to its 3,3¢-diiodo derivative by mo-lecular iodine in the presence of ethanolic potassium hy-droxide.160 Iodination of 5-nitroindole (221a) with thesodium iodide, sodium chlorite and hydrochloric acid sys-tem yielded 3-iodo derivative 222, while the same proto-col in the case of 5,6-diacetoxyindole (221b) afforded 2,3-diiodo derivative 223 in a moderate yield.161 The carbocy-clic derivatives of 4-chloro-5-iodopyrrolopyrimidine 225were prepared using molecular iodine and silver trifluoro-acetate as the iodinating system,162 while the same reagentat low temperature was used for selective iodination of3,4-bis(trimethylsilyl)-1H-pyrrole to the 3-iodo-substitut-ed derivative.163 Carbazole (226) was efficiently iodinatedto 3-iodocarbazole (227) or 3,6-diiodocarbazole (228)with hydroiodic acid and hydrogen peroxide under micro-wave irradiation.164 5,15-Diaryl zinc-porphyrins were se-lectively iodinated at the meso position using themolecular iodine and silver hexafluorophosphate combi-nation,165 or the molecular iodine and bis(trifluoro-acetoxy)iodobenzene system.166

Pyrazole derivatives were iodinated using the iodine–io-dide method (I2, KI),167 oxidative iodination by moleculariodine and iodic acid168 or the molecular iodine withlead(IV) acetate34 combination, but the efficiency as wellas the selectivity of these efforts were poor. Better resultsresulting in efficient formation of the desired 4-iodo-sub-

Scheme 14 Iodination of 1,3-dicarbonyl compounds under solvent-free reaction conditions with I2 in the presence of a catalytic amountof Oxone®. Reagents and conditions: (i)135 1,3-dicarbonyl (1 mmol),I2 (0.5 mmol), Oxone® (0.1 mmol or 0.25 mmol in the case of diethyl-malonate 187i), grinding in a mortar for 1–5 min at r.t.

R1

O O

R1

O O

I

(i)

187

a: R1 = R2 = Me (92%)b: R1 = Me, R2 = Ph (94%)c: R1 = Me, R2 = OMe (96%)d: R1 = Me, R2 = OEt (93%)e: R1 = Me, R2 = t-BuO (91%)f: R1 = Me; R2 = OBz (90%)g: R1 = R2 = Ph (95%)h: R1 = Ph; R2 = OEt (92%)i: R1 = R2 = OEt (94%)

188

O

OEt

O O

OEt

O

I

189 190 (93%)

O O O O

I191 192 (90%)

R2 R2

(i)

(i)

Table 15 Diastereoselective a-Iodination of 4-Alkenylamides with a b-Chiral Centrea

R1 R2 Temp (°C)

Time (h)

Yield (%)

Ratio syn/anti

1 H OH 40 14 67 15:1

2 H Me 22 60 55 2.5:1

3 H Ph 50 36 43 13:1

4 (CH2)3 22 22 65 45:1

5 (CH2)2 22 24 84 44:1

a Reaction conditions: amide (1 mmol), I2 (1.0–1.5 mmol), 2,6-di-methylpyridine (1.5–3 mmol), DMF (6–14 mL).

O

NHBn

R1 R2 O

NHBn

R1 R2

I201 202

Scheme 15 Iodination of unsaturated amides and lactams. Reagentsand conditions: (i)142 amide (1 mmol), I2 (1.5 mmol), 2,4,6-trimethyl-pyridine (1.5), CH2Cl2 (6–7 mL), r.t., 14–40 h; (ii)143 amide (1 mmol),I2 (1.5 mmol), 2,6-dimethylpyridine (1.5 mmol), CH2Cl2 (8 mL), r.t.,15–20 h.

O

NEt2

R2 O

NEt2

R2

I

R1 R1

193194a: n = 1, R1 = R2 = H (81%)194b: n = 2, R1 = R2 = H (57%)194c: n = 3, R1 = R2 = H (44%)194d: n = 1, R1 = CH2Bn, R2 = H (84%)194e: n = 1, R1 = R2 = Me (81%)

O

NH

COOEt

O

NH

COOEt

I

195 196 (42%)

O

NR3

R4Bn

O

NR3

R4BnI

197198a: R3 = Me, R4 = H (61%)198b: R3 = R4 = Me (73%)198c: R3 = Bn, R4 = Me (73%)

NO N

O

I

199 200a: n = 3 (76%)200b: n = 4 (64%)

( )n( )n

( )n( )n

(i)

(i)

(ii)

(ii)



stituted pyrazole derivatives were obtained using the mo-lecular iodine with bismuth(III) nitrate combination33 ormolecular iodine and m-iodosylbenzoic acid pair.55 Acomprehensive range of substituted pyrazole derivatives(229, Scheme 18) were transformed into their 4-iodo de-

rivatives 230 by molecular iodine and ammonium ceri-um(IV) nitrate in acetonitrile media,169 or by moleculariodine and diacetoxyiodobenzene or its polymer-support-ed analogue as the oxidant in dichloromethane solvent.170

Imidazole (231) was efficiently transformed into 2,4,5-tri-iodoimidazole (232) using the molecular iodine andbis(trifluoroacetoxy)iodobenzene pair107 or in moderateyield using the sodium iodide, sodium chlorite and hydro-chloric acid system.161 For the selective iodination of ox-azole derivatives, the iodo-delithiation methodology wasapplied.171

Scheme 16 Selective introduction of an iodine atom into organiccompounds through organoboron and organometallic precursors.Reagents and conditions: (i)145, 146 trifluoroborate (1 mmol), NaI (1.05mmol), chloramine-T (1 mmol), THF (50% aq), r.t., 30 min; (ii) and(iii)149 hydroboration step: dicyclohexylborane (130 mol%) in anhydTHF, r.t., 30 min; iodination step: I2 (2.5–7.0 equiv), NaOAc (2.5–7.0equiv), MeOH, r.t., 5 h to overnight; (iv) and (v)150 terminal alkyl-selenoacetylene 212 (5 mmol), catecholborane (0.6 mL, 5.5 mmol),Pd(PPh3)4 (0.15 mmol), THF (15 mL), r.t., 20 h, resulting mixturecooled to –10 °C, then NaOH (6 N aq, 6 mL), followed by I2 (10mmol in 3 mL of THF) and stirred for 2 h at 10 °C; (vi) and (vii)151 1-alkynyl selenide 214 (37.8 mmol in 80 mL of n-hexane), DIBAL-H(39.6 mmol, 1.5 M in toluene), 0 °C, 1 h and r.t., 3 h; cooled to–78 °C, I2 (94.5 mmol in 45 mL of THF) added dropwise, stirred for30 min, slowly reached 0 °C and stirred 1 h at r.t.

BF3K

R1

I

R1(i)

203 204 (54–94%)

R1 = H, 4-OMe, 4-Me, 2,6-di-Me, 4-Cl, 4-Br, 2,6-di-F, 3-NO2

R2

BF3KR2

I

205 206 (90–95%)

(i) R2 = Ph, 4'-ClC6H4, 4'-MeC6H4, C7H15

R3 BF3K R3 I(i)

207 208 (93–96%)

R3 = Ph, 4'-MeC6H4, C3H6Cl, C6H13

R4 R4 B(Chx)2 R4 I209 210 211 (83–90%)

209a: 209b:O

BnO

209c:

O

Et

BnO TBSO

Et

209d:

(ii) (iii)

R5Se

R5Se

B

O

OR5Se

I212 213(57–70%)R5 = Me, Et; i-Pr,

n-Bu, n-hexyl

(iv) (v)

R6 SeTIPPR6

Al(i-Bu)2

SeTIPP R6

I

SeTIPP

214 215 (82–95%)

(vi) (vii)

R6 = Me, n-Bu, i-Bu, c-hexylTIPP = 2,4,6-triisopropylphenyl

( )7

Ph

Scheme 17 Iodination of pyrrole, indole and carbazole derivatives.Reagents and conditions: (i)157 216 (2 mmol), I2 (1 mmol),PhI(O2CCF3)2 (1 mmol), CCl4 (3 mL), r.t., 24 h; (ii)159 219 (1 mmol),I2 (1 mmol), HgO (1 mmol), CH2Cl2 (20 mL), r.t., 20 min; (iii)161 221a(2 mmol) in MeOH (100 mL), NaI (4 mmol) and NaClO2 (2 mmol) inH2O (100 mL), HCl (12 M; 6 mmol), r.t., 0.5–3 h; (iv)162 224 (4.65mmol), I2 (5.6 mmol), AgO2CCF3 (7.46 mmol), CH2Cl2 (20 mL), r.t.,1.5 h; (v)164 226 (3 mmol), 58% aqueous HI (3.3–6.6 mmol), 30% aqH2O2 (3.3–6.6 mmol), 85% aq AcOH (25 mL), MW at 100 °C for 30min.

HN

216 217 218

(i) (i)

N N(ii)

219 220

220a: R1 = H (84%)220b: R1 = Me (86%)

N

NNR4O

Cl

N

NNR4O

ClI

(iv)

224 225a: R4 = Ac (74%)225b: R4 = TBS (76%)

HN

HN

HN

(v)

(v)

I I

226 227 (80%)

228 (88%)

HNR2

R3

HN

HNAcO

AcO221a: R2 = NO2, R3 = H221b: R2 = R3 = OAc

(iii)

222 (75%)

223 (47%)

CHOHN

HN

CHOI CHOI

I

I

R1 R1

O2NI

I

I

I



Scheme 18 Iodination of substituted pyrazoles and imidazole.Reagents and conditions: (i)169 229 (1 mmol), I2 (0.6 mmol), CAN(0.6 mmol), MeCN (10 mL), r.t. to reflux, 1–3 h; (ii)170 229 (1 mmol),I2 (0.5 mmol), PhI(OAc)2 (0.5 mmol), CH2Cl2 (10 mL), r.t., 15–40min; (iii)107 231 (1 mmol), I2 (0.6 mmol), PhI(O2CCF3)2 (0.6 mmol),py (1.2 mmol), CH2Cl2, r.t., 3 h.

Only a few examples of iodination of a pyridine ring withmolecular iodine have been reported. 2-Hydroxy-3-cy-anopyridine (233) was iodinated to its 5-iodo derivative234 by the molecular iodine and potassium carbonate cou-ple in N,N-dimethylformamide (Scheme 19),172 and thesame protocol was used for the preparation of 5-hydroxy-2-iodopyridine.173 Quinoline (235) was iodinated to 3,6-diiodoquinoline (236) by oxidative iodination with themolecular iodine, potassium periodate and sulfuric acidsystem,174 while for selective preparation of 4-iodo-sub-stituted quinoline derivatives, an iodo-delithiation meth-odology was applied.175 Monocyclic enaminones 237 andbicyclic enaminones 239 with a ring-fused nitrogen wereselectively and efficiently transformed into the a-iodo-enaminones 238 and 240 using standard or modifiedJohnson conditions.176

Uracil and its derivatives were readily iodinated followingoxidative iodination methodology using moleculariodine48,106,107 or potassium iodide.47

Thiophene and benzothiophene were iodinated at the 5-position following an aerobic oxidative process by molec-ular iodine catalysed with H5PV2Mo10O40 polyoxometal-late.49 The series of 2-substituted thiophene derivatives(241, Scheme 20) were efficiently iodinated at the 5-posi-tion (242) using the molecular iodine and bis(trifluoroac-etoxy)iodobenzene system in carbon tetrachloridesolvent.177 3-Substituted thiophene derivatives 243 wereiodinated to 2-iodo substituted products 244 by the molec-ular iodine and mercury(II) oxide couple,178–180 while inthe case of 2,3-substituted derivatives, the iodo-delithia-tion procedure was used in order to obtain the 5-iodo de-rivative.178 The 3-position in the 1,2-oxathiole-2,2-dioxide ring in TSAO nucleosides was readily iodinatedusing the molecular iodine and ammonium cerium(IV) ni-trate pair.181

7 Conclusions and Perspectives

Table 16 summarises the methods and reagents – pro-moted, developed or applied in the last 10–15 years – forthe electrophilic iodination of organic compounds usingmolecular iodine as the source of an iodine atom. Entries1 to 19 show the methods where either an iodide-trap or aLewis acid activation was used. Demand for at least oneequivalent of molecular iodine is the common character-istic of these protocols, and except in the case of additionto a carbon–carbon double bond, half of the iodine atomsare thus lost for iodofunctionalisation. Oxidative iodina-tion methods are collected in entries 20 to 46. Various ox-idants, metals (entries 20–32) or nonmetals (entries 33–43) were used for these tasks, but the most acceptable arethe methods where hydrogen peroxide (entries 44–46) oroxygen (entries 47, 48) were used as oxidants. According

229

230

(i) or (ii)

a: R1 = R2 = R3 = H (98%)b: R1 = H, R2 = R3 = Me (93%)c: R1 = R2 = H, R3 = Me (90%)d: R1 = H, R2 = R3 = CO2Et (80%)e: R1 = Bn, R2 = R3 = H (79%)f: R1 = Bn, R2 = R3 = Me (80%)g: R1 = H, R2 = R3 = Ph (91%)h: R1 = H, R2 = Me, R3 = Ph (88%)i: R1 = R2 = R3 = Ph (86%)j: R1 = 2,4-(NO2)2C6H3, R2 = R3 = Me (90%)k: R1 = 4-ClC6H4, R2 = Me, R3 = Ph (91%)

231 232 (95%)(iii)

N

HN

N

HN

I

I

I

R1

R2

R3

R1

R2

R3

I

Scheme 19 Iodination of pyridine and quinoline rings and cyclicenaminones with ring-fused nitrogen. Reagents and conditions: (i)174

quinoline (50 g, 0.389 mol), I2 (100g, 0.394 mol), KIO4 (50 g, 0.217mol), AcOH (200 mL), CHCl3 (150 mL), concd H2SO4 (60 mL), H2O(60 mL), 90 °C, 96 h; (ii)176 enaminone (1 mmol), I2 (1 mmol), Et3N(1 mmol), CH2Cl2 (3 mL), r.t., 5 min.

N

O

R1

R2 N

O

R1

R2

I

I2, K2CO3233 234 (50%)

a: R1 = H, R2 = Bn (85%)b: R1 = Me, R2 = H (88%)c: R1 = Bn, R2 = H (94%)

N

O

R3

N

O

R3

iia: n = 1, R3 = H (99%)b: n = 2, R3 = H (97%)c: n = 2, R3 = Ph (85%)I( )n

( )n

N OH

CN

N OH

CN I

N N

II

235i

ii

237 238

239 240

DMF, 60 °C

236 (18%)

Scheme 20 Iodination of thiophene derivatives. Reagents and con-ditions: (i)177 241 (1.2 mmol), I2 (0.6 mmol), PhI(O2CCF3)2 (0.65mmol), CCl4 (1.5 mL), r.t., 2 h; (ii)178 243 (42 mmol), I2 (43.1 mmol),HgO (38.9 mmol), benzene (10 mL), r.t., overnight.

S R1

S R1I

241

242

a: R1 = H (83%)b: R1 = Br (87%)c: R1 = Cl (85%)d: R1 = I (87%)e: R1 = Me (78%)f: R1 = CHO (59%)g: R1 = Ac (69%)h: R1 = CO2Me (78%)i: R1 = CN (71%)j: R1 = NO2 (50%)

S S

243 244

a: R2 = Et (84%)b: R2 = n-Bu (72%)c: R2 = C2H4OH (81%)

i

ii

R2 R2

I



to current green and sustainable trends in organic chemis-try, further investigation of these methods is promisingand welcome, especially when aqueous reaction media or

solvent-free reaction conditions (SFRC) are used for syn-thetic protocols.

Table 16 Methods and Reagent Systems for Electrophilic Iodination of Organic Compounds Using Molecular Iodine

Iodine Activator (A)

Catalyst;mol%

StoichiometryS/I2/A

Solvent; Temp (°C)

Applications:iodination of

Ref.

1 AgOTf – 1:1:1 CH2Cl2; r.t. arenes 25

2 AgO2CCF3 – 1:1–1.2:1–1.6 CH2Cl2; r.t heterocycles 162,163

3 AgPF6 – 1:1:1 CHCl3–Py (60:1); r.t. porphyrins 165

4 HgX2 – 1:1:1 CH2Cl2; r.t. arenes 24

5 HgO – 1:1:1 CH2Cl2; r.t. arenes, thiophenes 29,159,178–180

6 Fe2(SO4)3 – 1:2:1 dioxane (aq); r.t alkenes 83a

7 I2 – 1:2 dioxane (aq or alc); r.t. alkenes 83b

8 I2 – 1:4 DME; 90 ketones 130

9 clay – 1:2:0.2 g dioxane (aq); r.t. alkenes 84

10 Ce2(SO4)3 – 1:1:1 H2O; r.t. alkynes 115

11 – CuI; 5 1:1.5 MeCN; 60 alkynes 114

12 NH4OAc – 1:1:0.5 AcOH; 25 alkenes 86

13 LiOAc – 1:2.4:2 MeCN (aq); r.t allenes 99a,b

14 Py or Et3N – 1:1:1 CH2Cl2; r.t. enones, enaminones 103,104,176

15 K2CO3 DMAP; 20 1:1.5:1.2 THF (aq); r.t enones 105

16 K2CO3 – 1:0.6:2 DMF; 60 pyridines 172,173

17 KOH Cs2CO3; 20 1:1:2 THF–HMPA; r.t terminal alkynes 119

18 KOH – 1:2:5 EtOH; r.t. biindoles 160

19 2,6-lutidine – 1:1.5:3 CH2Cl2; r.t. unsaturated amides 142–144

20 CrO3 – 1:0.5:0.3 AcOH–Ac2O–H2SO4;30

arenes 18

21 Pb(OAc)4 – 1:0.5:0.6 AcOH–Ac2O; 60 arenes 34

22 KMnO4 – 1:0.6:0.7 AcOH–Ac2O–H2SO4;35

deactivated arenes 78

23 Fe(NO3)3·1.5N2O4 – 1:0.55:0.25 CH2Cl2; r.t. arenes 22a

24 SiO2–Fe(NO3)3 1:0.55:0.5 CH2Cl2; 20 arenes 31

25 Fe(NO3)3 H3PW12O40;10

1:0.6:0.4 CH2Cl2; r.t. arenes 32

26 SiO2-Bi(NO3)3 – 1:0.6:0.35 SFRC; r.t. arenes 33

27 – Ce(OTf)4; 25 1:0.75 ROH; r.t. alkenes 89a

28 CAN – 1:0.5–1.0:0.5 AcOH or MeCN; reflux alkenes, ketones, TSAO 96,140,141,181

29 ZnCl2 or EPZ-10 1:0.5:0.5 ROH; reflux alkenes 89b

30 CuO – 1:1:1 MeOH; reflux aryl ketones 133a

31 MnO2 – 1:1.5:1.1 EtOH; reflux or MW aryl ketones 139



The same suggestion holds for the oxidative iodinationmethods collected in Table 17, where the iodide anionwas used as the source of iodine atoms. Since the iodideanion is a natural source of iodine atoms, these effortsseem to be the most reasonable perspective for the issueof iodination of organic compounds.

Acknowledgment

The authors are grateful to the Slovenian Research Agency (ARRS)for financial support.

References

(1) (a) Diederich, F.; Stang, P. J. Metal-Catalysed Cross-Coupling Reactions; Wiley-VCH: Weinheim, 1998. (b) Hassan, J.; Sévignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359. (c) Bellina, F.; Carpita, A.; Rossi, R. Synthesis 2004, 2419.

(2) Handbook of Radiopharmaceuticals: Radiochemistry and Applications; Welch, M. J.; Redvanly, C. S., Eds.; Wiley: Chichester, 2003.

(3) (a) Vaillancourt, F. H.; Yeh, E.; Vosburg, D. A.; Garneau-Tsodikova, S.; Walsh, C. T. Chem. Rev. 2006, 106, 3364. (b) van Pée, K.-H. Arch. Microbiol. 2001, 175, 250.

(4) Sasson, Y. In The Chemistry of Functional Groups, Supplement D2: The Chemistry of Halides, Pseudohalides

32 SeO2 – 1:0.55:0.55 AcOH or MeCN; 80 ketones 138

33 NO2 H+; 5 1:0.5:excess CHCl3; 60 arenes 59

34 NaNO3 – 1:0.55:0.4 AcOH; 85 arenes, alkynes 30,118

35 H5IO6 – 1:0.4:0.14 CH2Cl2 or EtOH; MW arenes 35,66

36 NaIO3 – variable 90% H2SO4; 30 deactivated arenes 79

37 HIO3 – 1:0.4:0.2 EtOH; 40 phenols 60,61

38 ArI(OAc)2

ArI(O2CCF3)2

ArICl2

ArIF2

Pd(II); 10––––––––

1:1:11:1.1:11:0.6:0.71:1.8:1.81:0.5:0.51:0.6:1.21:0.6:11:0.55:0.551:0.5:0.7

CH2Cl2; 25t-BuOH; 40CHCl3; r.t.EtOAc; 60CH2Cl2; r.t.MeCN; r.t.MeCN–H2O; r.t.ROH; r.t.CH2Cl2; 0–5

sat. hydrocarbonssat. hydrocarbons porphyrinsarenesthiophenes, pyrazolesaryl ketonesalkenesalkenesalkenes

126–128

122

166

27

170,177

62

90a

90b

90c

39 l3-iodane TMSN3; 10–

excess:1:1.11:0.6:1.2

CH-substrate; 60MeCN; r.t.

sat. hydrocarbonsarenes

124

75

40 F-TEDA-BF4 – 1:0.5–1.0:0.55–1.0 MeCN, MeOH or IL;70

arenes, ketones 44–46,63,72,

136,137

41 S2O8– – 1:1:1 MeCN; r.t. arenes, enones 41–43,106

42 Oxone® – 1:0.5:0.1 SFRC; r.t. ketones 135

43 SPC – 1:0.5:0.5–1.0 AcOH–Ac2O–H2SO4;40

arenes 19

44 30% aq H2O2 H+; 3–5H+; 3–5NaN3

1:0.5:0.61:0.5–1.0:0.6–1.0excess :1:1

MeOH or MeCN–ROH; r.t.H2O; 50CH substrate; 0–40

ketones, alkenesarenes, ketonessat. hydrocarbons

134,91

56

124

45 urea–H2O2 (1:1) – 1:0.5–1.0:0.6–1.0 AcOH or SFRC; 40 arenes, ketones 57,67

46 PVP–H2O2 (25.5%) H3PW12O40; 20 1:1:3 CH2Cl2; reflux arenes 21

47 O2 H5PV2Mo10O40 1:0.5:excess MeCN; 80 arenes 49

48 air Bi(III); 5CAN; 10NaNO2, H

+; 5

1:0.55:excess1:1:excess1:0.5:excess

MeCN; r.t.MeCN; r.t.MeCN; r.t.

arenesarenesarenes, ketones, aldehydes

50

51

52

Table 16 Methods and Reagent Systems for Electrophilic Iodination of Organic Compounds Using Molecular Iodine (continued)

Iodine Activator (A)

Catalyst;mol%

StoichiometryS/I2/A

Solvent; Temp (°C)

Applications:iodination of

Ref.



and Azides, Part 2; Patai, S.; Rappoport, Z., Eds.; Wiley: Chichester, 1995, 535–620.

(5) Virgil, S. C. In Encyclopedia of Reagents for Organic Synthesis, Vol. 4; Paquette, L. A., Ed.; Wiley: Chichester, 1995, 2845–2846.

(6) Hanson, J. R. J. Chem. Res. 2006, 277; and references therein.

(7) Barluenga, J. Pure Appl. Chem. 1999, 71, 431; and references therein.

(8) Johnsson, R.; Meijer, A.; Ellervik, U. Tetrahedron 2005, 61, 11657; and references therein.

(9) Šket, B.; Zupet, P.; Zupan, M. J. Chem. Soc., Perkin Trans. 1 1989, 2279.

(10) Merkushev, E. B. Synthesis 1988, 923.(11) Kryska, A.; Skulski, L. J. Chem. Res., Miniprint 1999, 2501.(12) Skulski, L. Molecules 2000, 5, 1331.(13) (a) Togo, H.; Iida, S. Synlett 2006, 2159. (b) Wang, H. S.;

Miao, J. Y.; Zhao, L. F. Chin. J. Org. Chem. 2005, 25, 615.(14) French, A. N.; Bissmire, S.; Wirth, T. Chem. Soc. Rev. 2004,

33, 354.(15) Ranganathan, S.; Muraleedharan, K. M.; Vaish, N. K.;

Jayaraman, N. Tetrahedron 2004, 60, 5273.(16) Kitagawa, O.; Taguchi, T. Synlett 1999, 1191.(17) Robin, S.; Rousseau, G. Tetrahedron 1998, 54, 13681.

(18) Luliński, P.; Skulski, L. Bull. Chem. Soc. Jpn. 1997, 70, 1665.

(19) Zielinska, A.; Skulski, L. Molecules 2005, 10, 1307.(20) Brazdil, L. C.; Cutler, C. J. J. Org. Chem. 1996, 61, 9621.(21) Pourali, A. R.; Ghanei, M. Chin. J. Chem. 2006, 24, 1077.(22) (a) Firouzabadi, H.; Iranpoor, N.; Shiri, M. Tetrahedron Lett.

2003, 44, 8781. (b) Firouzabadi, H.; Iranpoor, N.; Garzan, A. Adv. Synth. Catal. 2005, 347, 1925. (c) Sathiyapriya, R.; Karunakaran, R. J. J. Chem. Res. 2006, 575.

(23) Shellhamer, D. F.; Jones, B. C.; Pettus, B. J.; Pettus, T. L.; Stringer, J. M.; Heasley, V. L. J. Fluorine Chem. 1998, 88, 37.

(24) Bachki, A.; Foubelo, F.; Yus, M. Tetrahedron 1994, 50, 5139.

(25) Mulholland, G. K.; Zheng, Q.-H. Synth. Commun. 2001, 31, 3059.

(26) Pasha, M. A.; Myint, Y. Y. Synth. Commun. 2004, 34, 2829.(27) (a) Togo, H.; Nogami, G.; Yokoyama, M. Synlett 1998, 534.

(b) Togo, H.; Abe, S.; Nogami, G.; Yokoyama, M. Bull. Chem. Soc. Jpn. 1999, 72, 2351.

(28) Myint, Y. Y.; Pasha, M. A. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 2004, 43, 357.

(29) Orito, K.; Hatakeyama, T.; Takeo, M.; Suginome, H. Synthesis 1995, 1273.

Table 17 Methods and Reagent Systems for Electrophilic Iodination of Organic Compounds Using the Iodide Anion as the Source of an Iodine Atom

Entry Iodination system: iodide; oxidant Solvent; Temp (°C) Application: iodination of

Ref.

1 NaI, KI or NMe4I; 98% H2SO4 H2SO4 (98%); 60 arenes 26,28

2 KI; 63% HNO3 SFRC; r.t. alkynes 117a

3 NaI; Fe(NO3)3·1.5N2O4 on charcoal CH2Cl2; r.t. arenes 22a

4 HI; KMnO4 MeCN; r.t. anilines, alkynes 65

5 [AcMIm]Ia; CAN [AcMIm]Ia; r.t. ketones 132

6 NaI; Ce(OH)3OOH SDS (0.008 M, aq); r.t. arenes 22b

7 NaI; NaClO2, HCl (12 M) MeOH; r.t. arenes 161

8 KI; KClO3 or KIO3, HCl or H2SO4 H2O–MeOH (9:1) or AcOH; r.t. arenes, ketones 36,37,131

9 KI; NaIO4 H2SO4 (95%); 30 deactivated arenes 80

10 KI; NaIO4, NaCl AcOH (90% aq); 25 arenes 38

11 KI; KBrO3; HCl (35% aq) AcOH (aq) or MeOH, 60 arenes 22c

12 NaI; chloramine-T THF (50% aq); r.t. arenes,b alkenes,b alkynesb 145–147

13 KI; 30% aq H2O2 or SPBc; NaWO4 (cat.) AcOH–Ac2O–H2SO4 (3:2:1); 50 acetanilides 68

14 HI; AcOOH; NaWO4 (cat.) AcOH–Ac2O–H2SO4 (15:10:1); r.t. acetanilides 69

15 NaI; H2O2 (2 M, aq), 0.8 mol% Te(II) catalyst phosphate buffer (pH 6); r.t. arenes, alkenes 98

16 KI; PVP–H2O2, H3PW12O40 (cat.) CH2Cl2; reflux arenes 21

17 HI; 30% aq H2O2 AcOH (80% aq); 100 (MW) arenes, carbazole 164

18 NaI or KI; 30% aq H2O2, H2SO4 or HBF4 MeOH, H2O or THF (aq); r.t. to 50 arenes, ketones, alkenes 47,92,133b

19 NH4I; 30% aq H2O2 AcOH; r.t. arenes 40c

a [AcMIm]I = acetylmethylimidazolium iodide (an ionic liquid).b Through organoboron precursors.c SPB: sodium perborate.



(30) Yusubov, M. S.; Filimonov, V. D.; Jin, H.-W.; Chi, K.-W. Bull. Korean Chem. Soc. 1998, 19, 400.

(31) Tilve, R. D.; Alexander, V. M.; Khadilkar, B. M. Tetrahedron Lett. 2002, 43, 9457.

(32) Jafarzadeh, M.; Amani, K.; Nikpour, F. Can. J. Chem. 2005, 83, 1808.

(33) Alexander, V. M.; Khandekar, A. C.; Samant, S. D. Synlett 2003, 1895.

(34) Krassowska-Świebocka, B.; Luliński, P.; Skulski, L. Synthesis 1995, 926.

(35) Sosnowski, M.; Skulski, L. Molecules 2005, 10, 401.(36) Adimurthy, S.; Ramachandraiah, G.; Ghosh, P. K.; Bedekar,

A. V. Tetrahedron Lett. 2003, 44, 5099.(37) Sathiyapriya, R.; Karunakaran, R. J. Synth. Commun. 2006,

36, 1915.(38) Emmanuvel, L.; Shukla, R. K.; Sudalai, A.; Gurunath, S.;

Sivaram, S. Tetrahedron Lett. 2006, 47, 4793.(39) (a) Karade, N. N.; Tiwari, G. B.; Huple, D. B.; Siddiqui, T.

A. J. J. Chem. Res. 2006, 366. (b) Krasnokutskaya, E. A.; Trusova, M. E.; Filimonov, V. D. Russ. J. Org. Chem. 2005, 41, 1750.

(40) (a) Krishna-Mohan, K. V. V.; Narender, N.; Kulkarni, S. J. Tetrahedron Lett. 2004, 45, 8015. (b) Narender, N.; Srinivasu, P.; Kulkarni, S. J.; Raghavan, K. V. Synth. Commun. 2002, 32, 2319. (c) Narender, N.; Reddy, K. S. K.; Krishna-Mohan, K. V. V.; Kulkarni, S. J. Tetrahedron Lett. 2007, 48, 6124.

(41) Yang, S. G.; Kim, Y. H. Tetrahedron Lett. 1999, 40, 6051.(42) Tajik, H.; Esmaeili, A. A.; Mohammadpoor-Baltork, I.;

Ershadi, A.; Tajmehri, H. Synth. Commun. 2003, 33, 1319.(43) Tajik, H.; Mohammadpoor-Baltork, I.; Rasht-Abadi, H. R.

Synth. Commun. 2004, 34, 3579.(44) Zupan, M.; Iskra, J.; Stavber, S. Tetrahedron Lett. 1997, 38,

6305.(45) Pavlinac, J.; Zupan, M.; Stavber, S. J. Org. Chem. 2006, 71,

1027.(46) Chiappe, C.; Pieraccini, D. ARKIVOC 2002, (xi), 249.(47) Iskra, J.; Stavber, S.; Zupan, M. Synthesis 2004, 1869.(48) Jereb, M.; Zupan, M.; Stavber, S. Chem. Commun. 2004,

2614.(49) Branytska, O. V.; Neumann, R. J. Org. Chem. 2003, 68,

9510.(50) Wan, S.; Wang, S. R.; Lu, W. J. Org. Chem. 2006, 71, 4349.(51) Das, B.; Krishnaiah, M.; Venkateswarlu, K.; Reddy, V. S.

Tetrahedron Lett. 2007, 48, 81.(52) Iskra, J.; Stavber, S.; Zupan, M. Tetrahedron Lett. 2007, 49,

893.(53) Hajipour, A. R.; Adibi, H. J. Chem. Res. 2004, 294.(54) (a) Cambie, R. C.; Larsen, D. S.; Rutledge, P. S.; Woodgate,

P. D. Aust. J. Chem. 1997, 50, 767. (b) Cambie, R. C.; Rutledge, P. S.; Smith-Palmer, T.; Woodgate, P. D. J. Chem. Soc., Perkin Trans. 1 1976, 1161.

(55) Kirschning, A.; Yusubov, M. S.; Yusubova, R. Y.; Chi, K.-W.; Park, J. Y. Beilstein J. Org. Chem. 2007, 3, 19.

(56) Pavlinac, J.; Zupan, M.; Stavber, S. Synthesis 2006, 2603.(57) Pavlinac, J.; Zupan, M.; Stavber, S. Org. Biomol. Chem.

2007, 5, 699.(58) Midorikawa, K.; Suga, S.; Yoshida, J. Chem. Commun.

2006, 3794.(59) Noda, Y.; Kashima, M. Tetrahedron Lett. 1997, 38, 6225.(60) Patil, B. R.; Bhusare, S. R.; Pawar, R. P.; Vibhute, Y. B.

Tetrahedron Lett. 2005, 46, 7179.(61) Patil, B. R.; Bhusare, S. R.; Pawar, R. P.; Vibhute, Y. B.

ARKIVOC 2006, (i), 104.(62) Panunzi, B.; Rotiroti, L.; Tingoli, M. Tetrahedron Lett.

2003, 44, 8753.

(63) Stavber, S.; Jereb, M.; Zupan, M. Chem. Commun. 2002, 488.

(64) Monnereau, C.; Blart, E.; Odobel, F. Tetrahedron Lett. 2005, 46, 5421.

(65) Chen, J.-A.; Lin, C.-S.; Liu, L.-K. J. Chin. Chem. Soc. 1996, 43, 95.

(66) Sosnowski, M.; Skulski, L.; Wolowik, K. Molecules 2004, 9, 617.

(67) Lulinski, P.; Kryska, A.; Sosnowski, M.; Skulski, L. Synthesis 2004, 441.

(68) Beinker, P.; Hanson, J. R.; Meindl, N.; Rodriguez-Medina, I. C. J. Chem. Res., Synop. 1998, 204.

(69) Rodriguez-Medina, I. C.; Hanson, J. R. J. Chem. Res., Synopsis 2003, 428.

(70) Jovanović, M. S.; Popović, G.; Kapetanović, V.; Orlić, M.; Vladimirov, S. J. Pharm. Biomed. Anal. 2004, 35, 1257.

(71) Stavber, S.; Kralj, P.; Zupan, M. Synlett 2002, 598.(72) Stavber, S.; Kralj, P.; Zupan, M. Synthesis 2002, 1513.(73) Sy, W.-W.; Lodge, B. A. Tetrahedron Lett. 1989, 30, 3769.(74) Kryska, A.; Skulski, L. J. Chem. Res., Synop. 1999, 590.(75) Muraki, T.; Togo, H.; Yokoyama, M. J. Org. Chem. 1999,

64, 2883.(76) Yusubov, M. S.; Tveryakova, E. N.; Krasnokutskaya, E. A.;

Perederyna, I. A.; Zhdankin, V. V. Synth. Commun. 2007, 37, 1259.

(77) Galli, C. Chem. Rev. 1988, 88, 765.(78) Luliński, P.; Skulski, L. Bull. Chem. Soc. Jpn. 1999, 72, 115.(79) Kraszkiewicz, L.; Sosnowski, M.; Skulski, L. Tetrahedron

2004, 60, 9113.(80) Kraszkiewicz, L.; Sosnowski, M.; Skulski, L. Synthesis

2006, 1195.(81) Chambers, R. D.; Skinner, C. J.; Atherton, M.; Moilliet, J. S.

Chem. Commun. 1995, 19.(82) Leroy, J.; Schöllhorn, B.; Syssa-Magalé, J.-L.; Boubekeur,

K.; Palvadeau, P. J. Fluorine Chem. 2004, 125, 1379.(83) (a) de Mattos, M. C. S.; Sanseverino, A. M. J. Chem. Res.,

Synop. 1994, 440. (b) Sanseverino, A. M.; de Mattos, M. C. S. Synthesis 1998, 1584.

(84) Villegas, R. A. S.; de Aguiar, M. R. M. P.; de Mattos, M. C. S.; Guarino, A. W. S.; Barbosa, L. M.; Assumpçăo, L. C. F. N. J. Braz. Chem. Soc. 2004, 15, 150.

(85) Terent’ev, A. O.; Krylov, I. B.; Borisov, D. A.; Nikishin, G. I. Synthesis 2007, 2979.

(86) Myint, Y. Y.; Pasha, M. A. Synth. Commun. 2004, 34, 4477.(87) Rama, K.; Pasha, M. A. Ultrasonics Sonochem. 2005, 12,

437.(88) Cerritelli, S.; Chiarini, M.; Cerichelli, G.; Capone, M.;

Marsili, M. Eur. J. Org. Chem. 2004, 623.(89) (a) Iranpoor, N.; Shekarriz, M. Tetrahedron 2000, 56, 5209.

(b) Mahajan, V. A.; Shinde, P. D.; Gajare, A. S.; Karthikeyan, M.; Wakharkar, R. D. Green Chem. 2002, 4, 325.

(90) (a) De Corso, A. R.; Panunzi, B.; Tingoli, M. Tetrahedron Lett. 2001, 42, 7245. (b) Yusubov, M. S.; Yusubova, R. J.; Filimonov, V. D.; Chi, K.-W. Synth. Commun. 2004, 34, 443. (c) Conte, P.; Panunzi, B.; Tignoli, M. Tetrahedron Lett. 2006, 47, 273.

(91) Jereb, M.; Zupan, M.; Stavber, S. Green Chem. 2005, 7, 100.(92) Barluenga, J.; Marco-Arias, M.; González-Bobes, F.;

Ballesteros, A.; González, J. M. Chem. Eur. J. 2004, 10, 1677.

(93) Villegas, R. A. S.; Espírito Santo, J. L.; Sanseverino, A. M.; de Mattos, M. C. S.; de Aguiar, M. R. M. P.; Guarino, A. W. S. Synth. Commun. 2005, 35, 1627.

(94) Yusubov, M. S.; Drygunova, L. A.; Tkachev, A. V.; Zhdankin, V. V. ARKIVOC 2005, (iv), 179.



(95) Sanseverino, A. M.; da Silva, F. M.; Jones, J.; de Mattos, M. C. S. J. Braz. Chem. Soc. 2000, 11, 381.

(96) Horiuchi, C. A.; Hosokawa, H.; Kanamori, M.; Muramatsu, Y.; Ochiai, K.; Takahashi, E. Chem. Lett. 1995, 13.

(97) Horiuchi, C. A.; Dan, G.; Sakamoto, M.; Suda, K.; Usui, S.; Sakamoto, O.; Kitoh, S.; Watanabe, S.; Utsukihara, T.; Nozaki, S. Synthesis 2005, 2861.

(98) Higgs, D. E.; Nelen, M. I.; Detty, M. R. Org. Lett. 2001, 3, 349.

(99) (a) Ma, S.; Wei, Q.; Wang, H. Org. Lett. 2000, 2, 3893. (b) Ma, S.; Ren, H.; Wei, Q. J. Am. Chem. Soc. 2003, 125, 4817. (c) Ma, S.; Hao, X.; Huang, X. Org. Lett. 2003, 5, 1217. (d) Fu, C.; Huang, X.; Ma, S. Tetrahedron Lett. 2004, 45, 6063. (e) Fu, C.; Chen, G.; Liu, X.; Ma, S. Tetrahedron 2005, 61, 7768.

(100) Ma, S.; Hao, X.; Huang, X. Chem. Commun. 2003, 1082.(101) Negishi, E. J. Organomet. Chem. 1999, 576, 179.(102) Johnson, C. R.; Adams, J. P.; Braun, M. P.; Senanayake, C.

B. W.; Wovkulich, P. M.; Uskoković, M. R. Tetrahedron Lett. 1992, 33, 917.

(103) Djuardi, E.; Bovonsombat, P.; McNelis, E. Synth. Commun. 1997, 27, 2497.

(104) Kim, J. M.; Na, J. E.; Kim, J. N. Tetrahedron Lett. 2003, 44, 6317.

(105) Krafft, M. E.; Cran, J. W. Synlett 2005, 1263.(106) Whang, J. P.; Yang, S. G.; Kim, Y. H. Chem. Commun.

1997, 1355.(107) Benhida, R.; Blanchard, P.; Fourrey, J.-L. Tetrahedron Lett.

1998, 39, 6849.(108) Perez, A. L.; Lamoureux, G.; Herrera, A. Synth. Commun.

2004, 34, 3389.(109) Negishi, E.; Tan, Z.; Liou, S.-Y.; Liao, B. Tetrahedron 2000,

56, 10197.(110) Barros, M. T.; Maycock, C. D.; Ventura, M. R. Chem. Eur.

J. 2000, 6, 3991.(111) Barros, M. T.; Maycock, C. D.; Ventura, M. R. J. Chem.

Soc., Perkin Trans. 1 2001, 166.(112) William, A. D.; Kobayashi, Y. J. Org. Chem. 2002, 67,

8771.(113) (a) Wang, M.; Xu, X.-X.; Liu, Q.; Xiong, L.; Yang, B.; Gao,

L.-X. Synth. Commun. 2002, 32, 3437. (b) Zhao, Y.-L.; Liu, Q.; Sun, R.; Zhang, Q.; Xu, X.-X. Synth. Commun. 2004, 34, 463.

(114) Duan, J.; Dolbier, W. R.; Chen, Q.-Y. J. Org. Chem. 1998, 63, 9486.

(115) Li, J.-H.; Xie, Y.-X.; Yin, D.-L. Chin. J. Org. Chem. 2002, 22, 894.

(116) Li, J.-H.; Xie, Y.-X.; Yin, D.-L. Green Chem. 2002, 4, 505.(117) (a) Tveryakova, E. N.; Miroshnichenko, Y. Y.; Perederina, I.

A.; Yusubov, M. S. Russ. J. Org. Chem. 2007, 43, 152. (b) Terent’ev, A. O.; Borisov, D. A.; Krylov, I. B.; Nikishin, G. I. Synth. Commun. 2007, 37, 3151.

(118) (a) Yusubov, M. S.; Perederina, I. A.; Filimonov, V. D.; Park, T.-H.; Chi, K.-W. Synth. Commun. 1998, 28, 833. (b) Yusubov, M. S.; Perederina, I. A.; Kulmanakova, Y. Y.; Filimonov, V. D.; Chi, K.-W. Russ. J. Org. Chem. 1999, 35, 1264.

(119) He, G.-W.; Liu, F.-W.; Xu, X.-H. Chin. J. Org. Chem. 2007, 27, 663.

(120) Yan, J.; Li, J.; Cheng, D. Synlett 2007, 2442.(121) Nishiguchi, I.; Kanbe, O.; Itoh, K.; Maekawa, H. Synlett

2000, 89.(122) Barluenga, J.; González-Bobes, F.; González, J. M. Angew.

Chem. Int. Ed. 2002, 41, 2556.(123) (a) Montoro, R.; Wirth, T. Org. Lett. 2003, 5, 4729.

(b) Montoro, R.; Wirth, T. Synthesis 2005, 1473.

(124) Barluenga, J.; Campos-Gómez, E.; Rodríguez, D.; González-Bobes, F.; González, J. M. Angew. Chem. Int. Ed. 2005, 44, 2808.

(125) Akhrem, I.; Orlinkov, A.; Vitt, S.; Chistyakov, A. Tetrahedron Lett. 2002, 43, 1333.

(126) Tsang, J. Y. K.; Buschhaus, M. S. A.; Legzdins, P. J. Am. Chem. Soc. 2007, 129, 5372.

(127) Giri, R.; Chen, X.; Yu, J.-Q. Angew. Chem. Int. Ed. 2005, 44, 2112.

(128) Giri, R.; Chen, X.; Hao, X.-S.; Li, J.-J.; Liang, J.; Fan, Z.-P.; Yu, J.-Q. Tetrahedron: Asymmetry 2005, 16, 3502.

(129) Giri, R.; Wasa, M.; Breazzano, S. P.; Yu, J.-Q. Org. Lett. 2006, 8, 5685.

(130) Rao, M. L. N.; Jadhav, D. N. Tetrahedron Lett. 2006, 47, 6883.

(131) Okamoto, T.; Kakinami, T.; Nishimura, T.; Hermawan, I.; Kajigaeshi, S. Bull. Chem. Soc. Jpn. 1992, 65, 1731.

(132) Ranu, B. C.; Adak, L.; Banerjee, S. Aust. J. Chem. 2007, 60, 358.

(133) (a) Yin, G.; Gao, M.; She, N.; Hu, S.; Wu, A.; Pan, Y. Synthesis 2007, 3113. (b) Barluenga, J.; Marco-Arias, M.; González-Bobes, F.; Ballesteros, A.; González, J. M. Chem. Commun. 2004, 2616.

(134) Jereb, M.; Iskra, J.; Zupan, M.; Stavber, S. Lett. Org. Chem. 2005, 2, 465.

(135) Goswami, P.; Ali, S.; Khan, M.; Khan, A. T. ARKIVOC 2007, (xv), 82.

(136) Jereb, M.; Stavber, S.; Zupan, M. Synthesis 2003, 853.(137) Jereb, M.; Stavber, S.; Zupan, M. Tetrahedron 2003, 59,

5935.(138) Bekaert, A.; Barberan, O.; Gervais, M.; Brion, J.-D.

Tetrahedron Lett. 2000, 41, 2903.(139) Le Bras, G.; Provot, O.; Bekaert, A.; Peyrat, J.-F.; Alami,

M.; Brion, J.-D. Synthesis 2006, 1537.(140) Horiuchi, C. A.; Kiji, S. Bull. Chem. Soc. Jpn. 1997, 70, 421.(141) Horiuchi, C. A.; Takahashi, E. Bull. Chem. Soc. Jpn. 1994,

67, 271.(142) Kitagawa, O.; Hanano, T.; Hirata, T.; Inoue, T.; Taguchi, T.

Tetrahedron Lett. 1992, 33, 1299.(143) Kitagawa, O.; Kikuchi, N.; Hanano, T.; Aoki, K.; Yamazaki,

T.; Okada, M.; Taguchi, T. J. Org. Chem. 1995, 60, 7161.(144) Okada, M.; Kitagawa, O.; Hanano, T.; Taguchi, T.

Tetrahedron 1997, 53, 6825.(145) Kabalka, G. W.; Mereddy, A. R. Tetrahedron Lett. 2004, 45,

343.(146) Kabalka, G. W.; Mereddy, A. R. Tetrahedron Lett. 2004, 45,

1417.(147) Kabalka, G. W.; Akula, M. R.; Zhang, J. Nucl. Med. Biol.

2002, 29, 841.(148) Hara, S.; Guan, T.; Yoshida, M. Org. Lett. 2006, 8, 2639.(149) Freixas, G.; Urpí, F.; Vilarrasa, J. Lett. Org. Chem. 2006, 3,

183.(150) Yang, D.-Y.; Huang, X. Synth. Commun. 1996, 26, 4617.(151) Pérez-Balado, C.; Markó, I. E. Tetrahedron 2006, 62, 2331.(152) Dubois, E. A.; van den Bos, J. C.; Doornbos, T.;

van Doremalen, P. A. P. M.; Somsen, G. A.; Vekemans, J. A. J. M.; Janssen, A. G. M.; Batink, H. D.; Boer, G. J.; Pfaffendorf, M.; van Royen, E. A.; van Zwieten, P. A. J. Med. Chem. 1996, 39, 3256.

(153) Hoyte, R. M.; Labaree, D. C.; Fede, J.-M.; Harris, C.; Hochberg, R. B. Steroids 1998, 63, 595.

(154) Goodman, M. M.; Chen, P.; Plisson, C.; Martarello, L.; Galt, J.; Votaw, J. R.; Kilts, C. D.; Malveaux, G.; Camp, V. M.; Shi, B.; Ely, T. D.; Howell, L.; McConathy, J.; Nemeroff, C. B. J. Med. Chem. 2003, 46, 925.

(155) Zou, M.-F.; Deng, M.-Z. J. Org. Chem. 1996, 61, 1857.



(156) (a) Kauch, M.; Hoppe, D. Synthesis 2006, 1578. (b) Ganta, A.; Snowden, T. S. Synlett 2007, 2227.

(157) D’Auria, M.; De Luca, E.; Mauriello, G.; Racioppi, R.; Sleiter, G. J. Chem. Soc., Perkin Trans. 1 1997, 2369.

(158) Miyaji, H.; Sato, W.; Sessler, J. L.; Lynch, V. M. Tetrahedron Lett. 2000, 41, 1369.

(159) Orito, K.; Hatakeyama, T.; Takeo, M.; Uchiito, S.; Tokuda, M.; Suginome, H. Heterocycl. Commun. 1997, 3, 207.

(160) Roy, S.; Gribble, G. W. Synth. Commun. 2006, 36, 3487.(161) Lista, L.; Pezzella, A.; Napolitano, A.; d’Ischia, M.

Tetrahedron 2008, 64, 234.(162) Gudmundsson, K. S.; Wang, Z.; Daluge, S. M.; Feldman, P.

L. Nucleosides, Nucleotides Nucleic Acids 2001, 20, 1823.(163) Liu, J.-H.; Chan, H.-W.; Wong, H. N. C. J. Org. Chem.

2000, 65, 3274.(164) Bogdal, D.; Lukasiewicz, M.; Pielichowski, J. Green Chem.

2004, 6, 110.(165) Nakano, A.; Shimidzu, H.; Osuka, A. Tetrahedron Lett.

1998, 39, 9489.(166) (a) Boyle, R. W.; Johnson, C. K.; Dolphin, D. J. Chem. Soc.,

Chem. Commun. 1995, 527. (b) Shultz, D. A.; Gwaltney, K. P.; Lee, H. J. Org. Chem. 1998, 63, 769. (c) Odobel, F.; Suzenet, F.; Blart, E.; Quintard, J.-P. Org. Lett. 2000, 2, 131.

(167) Holzer, W.; Gruber, H. J. Heterocycl. Chem. 1995, 32, 1351.(168) Tretyakov, E. V.; Vasilevsky, S. F. Mendeleev Commun.

1995, 6, 233.

(169) Rodríguez-Franco, M. I.; Dorronsoro, I.; Hernández-Higueras, A. I.; Antequera, G. Tetrahedron Lett. 2001, 42, 863.

(170) Cheng, D.-P.; Chen, Z.-C.; Zheng, Q.-G. Synth. Commun. 2003, 33, 2671.

(171) Vedejs, E.; Luchetta, L. M. J. Org. Chem. 1999, 64, 1011.(172) Lavecchia, G.; Berteina-Raboin, S.; Guillaumet, G.

Tetrahedron Lett. 2004, 45, 6633.(173) Sheldrake, P. W.; Powling, L. C.; Slaich, P. K. J. Org. Chem.

1997, 62, 3008.(174) Bangcuyo, C. G.; Rampey-Vaughn, M. E.; Quan, L. T.;

Angel, S. M.; Smith, M. D.; Bunz, U. H. F. Macromolecules 2002, 35, 1563.

(175) Comins, D. L.; Nolan, J. M.; Bori, I. D. Tetrahedron Lett. 2005, 46, 6697.

(176) Wang, X.; Turunen, B. J.; Leighty, M. W.; Georg, G. I. Tetrahedron Lett. 2007, 48, 8811.

(177) D’Auria, M.; Mauriello, G. Tetrahedron Lett. 1995, 36, 4883.

(178) Pearson, D. L.; Tour, J. M. J. Org. Chem. 1997, 62, 1376.(179) Liu, L.; Liu, Z.; Xu, W.; Xu, H.; Zhang, D.; Zhu, D.

Tetrahedron 2005, 61, 3813.(180) Li, G.; Wang, X.; Li, J.; Zhao, X.; Wang, F. Tetrahedron

2006, 62, 2576.(181) Lobatón, E.; Rodríguez-Barrios, F.; Gago, F.; Pérez-Pérez,

M.-J.; De Clercq, E.; Balzarini, J.; Camarasa, M.-J.; Velázquez, S. J. Med. Chem. 2002, 45, 3934.

electrophilic iodination of organic compounds using ......review 1487 electrophilic iodination of...

Documents