comprehensive organic synthesis ii || 7.26 glycol cleavage reactions

7.26 Glycol Cleavage ReactionsAWH Wong and TKM Shing, The Chinese University of Hong Kong, Shatin, Hong Kong, China

r 2014 Elsevier Ltd. All rights reserved.

7.26.1 Introduction 801
7.26.2 Metallic Reagents 801 7.26.2.1 Bismuth(V) and Bismuth(III) Derivatives 801 7.26.2.2 Calcium Hypochlorite 801 7.26.2.3 Cerium(IV) Reagents 802 7.26.2.4 Chromium(VI) Reagents 802 7.26.2.5 Cobalt(II) Reagents 802 7.26.2.6 Lead Tetraacetate (LTA) 802 7.26.2.7 Manganese Dioxide 802 7.26.2.8 Manganese(III) Complexes 802 7.26.2.9 Potassium Permanganate 802 7.26.2.10 Ruthenium Reagents 803 7.26.2.11 Tin(IV) Porphyrin Complexes 803 7.26.2.12 Vanadium Reagents 804 7.26.3 Nonmetallic Reagents 804 7.26.3.1 Ammonium Type Reagents 804 7.26.3.2 Hydrogen Peroxide 804 7.26.3.3 Iodo Reagents 805 7.26.3.4 Periodate 806 7.26.4 Applications in Organic Syntheses 806 References 816
Co

GlossaryAldol reaction An addition reaction between twoaldehydes (or an aldehyde and a ketone) resulting in a β-hydroxy aldehyde. Similar reaction between two ketonesgives a β-hydroxy ketone. Subsequent dehydration producesan α,β-unsaturated aldehyde or ketone. The combination ofan aldol reaction with subsequent dehydration is an aldolcondensation which can be promoted by base or acid.α-Glycol A diol with two hydroxyl groups bonded to twoadjacent carbons.

mprehensive Organic Synthesis II, Volume 7 doi:10.1016/B978-0-08-097742-3.

INOC Intramolecular nitrile oxide cycloaddition. A 1,3-dipolar cycloaddition between a nitrile oxidation and analkene.Ionic liquid A salt in liquid state which are largely madeof ions and short-lived ion pairs.Oxidative fission The oxidative splitting of an atomicnucleus into two or more lighter nuclei accompanied byenergy release.Spiro A molecule containing two or more rings where twoadjoined rings share exactly the same atom.

7.26.1 Introduction

This chapter discusses the development of oxidative carbon–carbon bond cleavage of vicinal diol (α- or 1,2-glycols) and relatedfunctional groups after the 1990s. The glycol fission reactions usually are very rapid, clean quantitative, and specific. Nowadays,sodium periodate is the most common reagent of choice because of its reactivity under neutral and mild conditions which iscompatible with a wide range of functional groups, its stability, and its low cost. The studies of other reagents have been mainlyexploratory or mechanistic. Some have shown promise for specific application but none has been as popular as lead tetraacetate(LTA) or periodate in organic synthesis. Several reviews of glycol cleavage were published.1–7

7.26.2 Metallic Reagents

7.26.2.1 Bismuth(V) and Bismuth(III) Derivatives

The synthetic potential of sodium bismuthate for cleavage of vicinal diols and conversion of acyloins to α-diketone was discoveredfirst by Rigby in 1950. Arylbismuth(V) reagents has been known for many years with their oxidizing ability. However, no furtherdevelopment of this reagent was carried out after the twentieth century. For details, please refer back to the review reported before.5

00731-X 801

dx.doi.org/10.1016/B978-0-08-097742-3.00731-X

802 Glycol Cleavage Reactions

7.26.2.2 Calcium Hypochlorite

Calcium hypochlorite, Ca(OCl)2, is an inexpensive and easily stored oxidizing agent, which is able to cleave α-glycols to itscorresponding carbonyls. Apart from α-glycols, it is also feasible to fragmented α-diones, α-hydroxy ketones, and α-hydroxy andα-keto acids. However, it is not popular in synthetic application nowadays and no development anymore nowadays.5

7.26.2.3 Cerium(IV) Reagents

Cerium(IV) is an efficient reagent for α-glycol cleavage. Recently, Tandon et al. has reported that addition of rhodium(III) chlorideand further enhance the cleavage rate of propane-1,2-diols and butane-2,3-diols under acidic medium.8

7.26.2.4 Chromium(VI) Reagents

Chromic acid and pyridinium chlorochromate (PCC) are two reagents usually employed for glycol cleavage oxidation. However,chromic acid receives less attention because of its harsh conditions used as well as the newly formed aldehydes easily furtheroxidized to its corresponding carboxylic acids.5 Apart from PCC, Maki et al. also reported using pyridinium dichromate to cleavethe vicinal diols.9 It is believed that the intermediate should consist of a chromate ester.

7.26.2.5 Cobalt(II) Reagents

Cobalt(II) salts are effective catalysts for glycol cleavages with molecular oxygen in aprotic polar solvents. The aldehydic productsare usually further oxidized to carboxylic acids, so it is very useful to convert vicinal diols into carboxylic acids industrially.10

7.26.2.6 Lead Tetraacetate (LTA)

LTA is one of the most widely used reagents for the oxidative cleavage of vicinal diols nowadays. It was first discovered by Criegee,and has been demonstrated to cleave the carbon–carbon bond of 1,2-diols efficiently in 1931.11 The reactions are very clean, efficient,and give high yields. A stoichiometric amount of the oxidant is required for each mole of carbon–carbon cleaved. The carbonylcompounds generated are inert toward further oxidation. The reaction is usually conducted in acetic acid or aprotic solvents such asbenzene, ethyl acetate, and dichloromethane. For mechanistic details, please refer to the review published by Shing.5

7.26.2.7 Manganese Dioxide

Excess activated manganese dioxide can cleave α-glycols to their corresponding carbonyls smoothly under neutral conditions.12

The reaction conditions are extremely mild (stirring at room temperature in dichloromethane) and neutral. However, only1,2-cis-diols and trans-diols with flexible backbones are able to be cleaved. No further development is reported on the oxidativefission using MnO2 after the 1990s.

7.26.2.8 Manganese(III) Complexes

In recent years, the oxidative fission of vicinal diols by molecular oxygen accompanied by catalytic amount of manganese(III)complexes has been investigated. Barroso et al. reported that using trans-dipyridine manganese(III) complex (1) with a tetradentateo-phenylenedioxamate ligand to cleave the mono-, di-, tri-, and tetra-substituted vicinal diols.13 The complex catalyzes theoxidative cleavage of α,β-disubstituted diols such as 2-phenyl-1,2-propanediol, 1,1-diphenyl-1,2-ethanediol, and 1-p-nitrophenyl-1-phenyl-1,2-ethanediol to the corresponding ketones, acetophenone, benzophenone, and p-nitrobenzophenone, respectively,with very good yields. Besides, Fernández et al. have discovered the positive effect of ionic liquid toward the manganese(III)-catalyzed oxidative cleavage of vicinal diols.14

N N

O O

O

O

O

OMn

py

py

7.26.2.9 Potassium Permanganate

Ferreira et al. used the silica-gel supported potassium permanganate for the oxidative carbon–carbon bond cleavage of vicinal diolsto give either ketonic compounds or carboxylic acids. The advantages of this reaction includes: (1) mild conditions, efficient and

Glycol Cleavage Reactions 803

simple work-up procedures; (2) the ketone compounds formed are eluted with the solvent which makes its isolation exceedingeasy; and (3) the reagent is cheap.15

7.26.2.10 Ruthenium Reagents

Ruthenium pyrochlore oxide is a well-known catalyst for glycol cleavage reactions with oxygen gas as oxidant. It was first reportedby Felthouse which 1,6-hexanediol, 1,2-cis-cyclohexanediol and its trans-isomer were successfully converted into their corre-sponding carbonyl compounds with high conversions.16 Ruthenium(III) chloride catalyzed hypochlorite oxidation of cyclohex-ane-1,2-diols were also reported by Wolfe in 1970.17 Later on, Emons et al. modified the method, making it become useful to awide range of acetal-protected sugars (Scheme 1).18

OO

OH

OHO

O

RuCl3, NaOCl O

O

O

OH

95%

Scheme 1

In 1999, Takezawa discovered the usage of a catalytic amount of the commercially available dichlorotris(triphenylphosphine)ruthenium(II) loaded on the activated charcoal (Ru(PPh3)3Cl2/C), with molecular oxygen to perform the oxidative fissionof various kinds of vicinal diols. Good conversion and selectivity was observed when treating of 1,2-octanediol and1,2-cyclooctanediol with dioxygen in the presence of the catalyst in benzotrifluoride at 60 °C for 15 h to furnish 1,8-octanedial in77% and 76% yield, respectively.19 Recently, Schmidt et al. discovered the cleavage of vicinal diols by tetrapropylammoniumperruthenate (TPAP) with N-methylmorpholine N-oxide (NMO). However, this method is only useful to synthesize ketoniccompounds or carboxylic acids as the aldehydic products would be further oxidized.20 Two mechanistic pathways are proposed forthe cleavage by TPAP. The first involves initial formation of a cyclic perruthenate diester (path a)21 which then oxidativelycollapses under cleavage of the C–C bond to give the corresponding carbonyl compounds (Scheme 2). Hydration of the latter andsubsequent oxidation give the desired carboxylic acid (or diacid).22 It is also conceivable that the diol is first oxidized to thehydroxy ketone (or diketone) which, after hydration, could also form a cyclic perruthenate diester (path b). The oxidativefragmentation of this Ru(VII) diester would result in a carboxylic acid (two carboxylic acids in the case of a diketone precursor)and an aldehyde which could then be oxidized further.22

R1 R2

HO OH RuO4

R1 R2

ORu

O

O OO

R1 H

H R2

O

O+ H2O R1 H

H R2

+

HO OH

HO OH

RuO4

Path a

RuO4

R1 R2

O OHor

R1 R2

O O

R1 R2

HO OH

H2O

OHRuO4

R1 R2

ORu

O

O OO

R1 H

HO R2

O

O+

OH

R1 OH

HO R2

O

O+RuO4

H2O

Path b

Scheme 2

7.26.2.11 Tin(IV) Porphyrin Complexes

Tin(IV) porphyrin complexes have been reported by Du et al. to cleave vicinal diols. They used a catalytic amount of the tinphophyrin complexes with air as oxidant and examined the reactivity of the catalysts toward the oxidative fission reaction. It wasfound that (TTP)Sn(CCPh)2 (2) and (TTP)Sn(OH)2 (3) gave good to excellent yields of benzophenone from benzopinacol.23

MAC_ALT_TEXT Scheme 1



The mechanism starts with (TTP)Sn(CCPh)2 (2), with which the diols reacted to form the cyclic tin intermediates (4), whichbreaks down to provide the desired carbonyl compounds. The inactive tin(II) porphyrins complex is oxidized back to active tin(IV)phophyrin complex (3) by air (Scheme 3).

Sn

OH

OH

O O

Ph

Ph

Ph

Ph

Sn

HO OH

PhPh

PhPh

2 X H2O

Sn

C

C

C

C

(2)(4)

(3)

Ph

Ph

Diol

2 X H Ph

SnII

H2O + 1/2 O2

Ph

O

2 X Ph

Scheme 3

7.26.2.12 Vanadium Reagents

In recent years, Kirihara et al. has reported the effective cleavage of ditertiary glycols via vanadium(V) catalyzed aerobic oxidation.VOCl3 was selected as a catalyst to furnish good to excellent yields of the carbonyl compounds. However, this reaction does notproceed for secondary-tertiary glycols as only the ketonic products can be obtained quantitatively, but the aldehydic compoundwould lead to a complex mixture.24

7.26.3 Nonmetallic Reagents

7.26.3.1 Ammonium Type Reagents

Tetrabutylammonium tribromide (TBATB) has been used for the bromination of some selected organic substrates, but only a fewreports regarding their use as oxidizing and brominating agents in synthetic chemistry have been reported. This reagent is moresuitable than molecular halogens because of its solid nature, ease of handling, stability, selectivity, and excellent product yields.There were no reports on the oxidation of diols by TBATB until the discovery by Gosain. TBATB can oxidize ethanediol, propane-1,2-diol, butane-2,3-diol, butane-1,2-diol, and pinacol to their corresponding carbonyl compounds in excellent yields. Thereaction conditions are mild and efficient as well.25 Tetraethylammonium superoxide, generated in situ by the phase-transferreaction of potassium superoxide and tetraethylammonium bromide in dimethylformamide (DMF) efficiently cleaved carbon–carbon bond of vicinal diols and related dihydroxy arenes under mild conditions at room temperature (Scheme 4).26

OH

OH

orOH

OHNEt4Br, KO2

DMF

COOH

COOH

R1 R1

R2HO OH

R2 NEt4Br, KO2

DMF R2 R1

O2 X

Scheme 4

7.26.3.2 Hydrogen Peroxide

This method employs an inexpensive catalyst and readily available, cheap, and nonpolluting oxidizing agent, which is particularlyuseful in large-scale experiments. Recently, the presence of iron tetrasulfophthalocyanine (FePcS) catalyst (5) with H2O2 wasemployed for oxidative fission of vicinal diols in polysaccharides to give their carbonyl and carboxylic derivatives.27




N

NN

N

N

NN N

O3S

SO3

SO3

O3S

FeIII

7.26.3.3 Iodo Reagents

Beebe has shown that vicinal diols are cleaved to their corresponding carbonyl compounds on treatment with N-iodosuccinimide(NIS) and UV light. Products produced from this oxidation are ketones, aldehydes, iodine and succinimide.28 However, the iodineproduced may pose some complication with substrates with sensitive functional groups. McDonald has extended the applicationof NIS to cleave vicinal and monoprotected diols to a mixed acetal and carbonyl compounds.29

Dess–Martin periodinane (DMP) is a well known oxidant to cleave vicinal diols into the corresponding carbonyl compounds.This high reactivity is because of the irreversible formation of intermediate (6) when the diol reacts with DMP and rapidly undergodecomposition into dicarbonyl compounds (Scheme 5).30

HOR1

R2

OHR1

R2

O

I

O

OAc

OAcAcO

DMPO

I

O

O

O(6)

(7)

R2R1

R2

R1AcO

OI

O

OAcO

I

O

OH

O

IBX

OI

O

O

O

R2R1

AcO OH

R2

R1

R1=H ≠ R2

OI

O

OH

X

XR1 R2

O

R2 R2

O

OH

or R2 R2

O

O

Scheme 5

IBX has been found to have the same effect as DMP by Moorthy if trifluoroacetic acid (TFA) was used as solvent. TFA canpromote the formation of intermediate (16) rather than intermediate (7) for all types of 1,2-diols, leading to effective oxidativefragmentation.30



The use of phenyliododiacetate [PhI(OAc)2] to cleave 1,2-diols was rare until Nicolaou's extensive study on it.31,32 The reactionconditions are very mild by mixing the 1,2-diols and PhI(OAc)2 in dichloromethane at room temperature. He further extended theuse of PhI(OAc)2 to cleave olefinic bond in the presence of osmium tetraoxide OsO4 (cat.) and 2,6-lutidine to yield the corre-sponding carbonyl compounds, albeit, in some cases, with α-hydroxy ketones as a byproduct. A more practical and clean protocolto effect oxidative cleavage of olefinic bonds involves NMO, OsO4 (cat.), 2,6-lutidine, and PhI(OAc)2 (Scheme 6).

R2 R3

R1

NMO (1.5 equivalents), OsO4 (0.02 equivalent),2,6-lutidine (2.0 equivalents), acetone:H2O (10:1)

then PhI(OAc)2 (1.5 equivalents), 25 °C

PhI(OAc)2 (2.3 equivalents), OsO4 (0.02 equivalent),2,6-lutidine (2.5 equivalents), THF, 25 °C

H R1

O

R2 R3

O+

up to 90%

H R1

O

R2 R3

O+

up to 98%

Scheme 6

The addition of a catalytic amount of AZADO (8) with PhI(OAc)2 can cleave the α-glycols to their corresponding carboxylicacids. The advantages of this reaction are that large amounts of NMO are unnecessary as compared to TPAP (reported before), anda wider scope of substrates are applicable (Scheme 7).33

N(8)

O

R1 R2

OH

OH

AZADO (10 mol%), PhI(OAc)2 (5 equivalents)

CH2Cl2, H2O, r.t. R1 OH

O

R2 OH

O+

Scheme 7

7.26.3.4 Periodate

Periodate reagents are by far the most widely used reagent for oxidative fission of vicinal diols. The reactions are usually rapid,efficient, clean, specific, and quantitative. Periodic acid was before the first choice but because of its high acidity, it is not useful forbroad synthetic applications. However, mild sodium and potassium periodate are now more popular. Shing et al. improved thesilica-gel supported metaperiodate reagent in powder form for the efficient and facile preparation of aldehydes from vicinalglycols, which is by far the most popular method. The powder is easy to prepare and stable. Nonpolar solvents such asdichloromethane can also be used.34 Later on, Dakdouki introduced the solvent-free oxidative cleavage of vicinal diols in solidphase using alumina/potassium metaperiodate. It permits preparation of the corresponding carbonyl compounds with high purityand good to excellent yields requiring only short reaction times.35 Mechanistic aspects are discussed in a previously publishedreview.5

7.26.4 Applications in Organic Syntheses

Shimada et al. also used LTA to cleave the angular trans-diol to complete the synthesis of AB-ring core of taxol (Scheme 8).36

OH

OH

LTA, C6H6

100%

O

O

O

O

KOtBu, DMSO/DMF

94% based on97% conversion

Scheme 8

Another interesting example from Deng reported that exposure of the esters to aqueous acetic acid and periodate failed to giveany of the desired γ-hydroxy-α,β- unsaturated carboxaldehydic esters (Scheme 9). Rather, shorter chain aldehydes were produced,




O (CH2)n

O

OTHP

OO

OO

C15H31 O

P OOO

NMe3

1. AcOH2. NaIO4

(CH2)n

O

OO

OO

C15H31 O

P OOO

NMe3

OI

O OH

O

(CH2)n OO

OO

C15H31 O

P OOO

NMe3

O

1. AcOH2. LTA, −80 °C, 82−85%

(CH2)n

OTHP

OO

OO

C15H31 O

P OOO

NMe3

O

Scheme 9


presumably by Michael addition of periodate to the target α,β-unsaturated aldehydes followed by oxidative fragmentation ofintermediate periodate esters. Some of the target aldehyde was obtained on hydrolytic removal of the THP and acetonide-protecting groups with aqueous acetic acid, followed by evaporation of the aqueous acetic acid and treatment of the resulting diolwith LTA in methylene chloride in the presence of a suspension of sodium carbonate at room temperature. The yield was improvedto 37% when the oxidative cleavage was conducted at 0 °C and was improved further (82–85%) by performing the oxidativecleavage at −80 °C.37

The developments of modular domino reactions are very challenging and attractive. Recently, unsaturated vicinal diols withdifferent epoxides configuration at angular position have been discovered to give different structural products by oxidative cleavageof LTA.38 It is possible to modify the regiochemical outcome of the domino process in such a way as to create a different pathway,[4+2] versus [4+3+2], and control product distribution by using the configuration bias (Scheme 10).

HO

HO

OH

HO

HO

O

H

O O

OAc

O

OAc

[4+2]/Oxonium

LTA

O

OH

O

AcOH

[4+2]

O O

OH

‘Oxonium’LTA AcOH

[4 + 3 + 2]

O

O

O

O

O

O

H

Scheme 10

The silica-gel supported glycol cleavage has drawn a lot of attention from synthetic chemists in recent years because of its clean,efficient, specific, and quantitative properties. It has been fully utilized in natural products syntheses, drugs syntheses, andmethods research.

The synthesis of leiodermatolide began with the synthesis of its macrocyclic core followed by cross-coupling with the δ-lactone.Paterson used the silica-gel supported glycol cleavage to generate the bis-vinyl halide (9), which was used in Stille coupling withstannane (10) to obtain diene (11) as shown in Scheme 11.39

In the total synthesis of goniodomin A, Saito et al. utilized the silica-gel supported oxidative cleavage of 1,2-diols followed byWittig reaction and Horner-reaction to synthesize the key stannane for Liebeskind–Srogl cross-coupling. The C15–C36 segment ofgoniodomin A was successfully synthesized (Scheme 12).40



HOBr

OH OTES1. NaIO4, H2O,

SiO2, CH2Cl2,r.t.

2. [Ph3PCH2I]I ,NaHMDS, THF,−78 °C76% for 2 steps

Br

(9)

(11)

(10)

I

OTES

SnMe3

HO

HO

CO2Me

Pd(PPh3)3, CuTC,Ph2PONBu4, DMF,0 °C

HO

HO

CO2Me

Br

OTES

O

HO Br

O

H2N O

O

Scheme 11

OBnO

H H

1. AD-mix �, cat. OsO4, (DHQD)2PHAL,t-BuOH/H2O, 0 °C, 25 h, 77%

2. NaIO4/SiO2, CH2Cl2, r.t.,40 min

3. Ph3P=CHCO2Et, THF, −40 °C to r.t.,14 h, 96% (2 steps), E:Z > 20:1

4. DIBALH, CH2Cl2, −78 °C, 20 min, 98%

OBnO

H H

OH

OAc OH

TBHP, (−)−DET,Ti(Oi-Pr)4, 4 Å MS

CH2Cl2, −20 °C to−15 °C, 20 h, 88%,dr > 10:1

OBnO

H HO

OHHO

H

1. NaIO4/SiO2, CH2Cl2,0 °C to r.t., 80 min

2.

K2CO3, MeOH, 0 °C,1.5 h, 95% (2 steps)

3. HgSO4, aqueous H2SO4,THF/H2O, 4 h, 94%

MeP(OMe)2

N2

OO

OBnO

H HO

COOMeH

OBnO

H HOH

SnMe3

H

H H

Scheme 12


In the synthetic studies of some dihydrotropones, a ring-expansion protocol was employed by Do (Scheme 13). The seven-membered conjugated carbonyl compounds would be synthesized by the ring-expansion strategy from the same 3-cyclohexene-1,2-diols utilizing the intramolecular aldol condensation of the immediate oxidative ring-opening products with Z-configuration.It is therefore crucial to control the Z/E-configuration in the oxidative ring opening reaction of 3-cyclohexene-1,2-diol. However,LTA was not able to give the desired Z product because acetic acid was, formed, which isomerized the Z-isomer to its E-isomer.Periodate, which is acetic acid free, produced the Z-isomer predominantly. Silica-gel supported sodium periodate could even beused to carry out one-pot cyclization from the various 3-cyclohexene-1,2-diols to form the dihydrotropones.41

In the total synthesis of guanacastepenes N and O Gampe carried out the oxidative cleavage of an olefin with osmiumtetraoxide followed by silica-gel supported glycol cleavage reaction to provide an aldehyde, which by a following intramolecularaldol reaction furnishes the key β-hydroxyketone (12) for further transformations (Scheme 14).42

In the synthetic studies of highly substituted cyclopentanes by the N-heterocyclic carbene (NHC) catalyzed addition, the mildoxidative cleavage of the α-glycol maintained the stereochemistry of the cyclopentanes and tolerated multiple functional groups(Scheme 15).43

In the improved synthesis of the key intermediate of (+)-biotin from D-mannose, Chen used the silica-gel supported oxidativecleavage to obtain the intermediate aldehyde (13) quantitatively, which was followed by Horner–Emmons olefination. Furthermodification led to the formation of the key intermediate (Scheme 16).44

In the total synthesis of (+)-rishirilide, the clean and reliable character of silica-gel supported glycol cleavage gave the desiredintermediate (14). Excess periodate would lead to lactone (15) and reverted back to the starting material (Scheme 17).45



O

HOHO

R

NaIO4

OO

R

SiO2

OR

O

O

OEtO

OCH3

H

H

CNH

OO

R

LTA

O R

O

X

50−96%

3 Steps

69%3 Steps41%

Scheme 13

Me

O1. OsO4, NMO, THF(aqueous)2. NaIO4-SiO2, CH2Cl2

Me

(12)

O

O

Me

Guanacastepenes N

Guanacastepenes O

O OH

AcO

O

Me

O

Me

O OHAcO

O

Me

3. KOH, MeOH

4. (CH2O)2, (EtO)3CH,

p-TsOH5. DMSO, (COCl)2, NEt3,

CH2Cl2, −78 °C to r.t.

53% over 4 steps

OO

0.4%16 Steps

16 Steps0.8%

Scheme 14

H

OH

OH

OH

H OH

O

NaIO4-SiO2

CH2Cl2, r.t., 69%

H

OH

CO2i-Pr

OH O

1. NaIO4-SiO2,CH2Cl2, r.t.

2. DMSO/H2O,130 °C, 71%

Scheme 15


The effective silica-gel supported periodate oxidative cleavage and further reduction successfully provided the key intermediatediol quantitatively in the synthesis of the mixed acetal segment of S-glyceroplasmalopsychosine. The diol could be used directlywithout purification (Scheme 18).46 More examples of silica-gel supported periodate oxidative cleavage in natural productssyntheses are illustrated from Schemes 19–23.47–51

In the development of the synthesis of chiral aminoalcohol from carbohydrates and amino acids, Dunlap et al. utilized thesilica-gel supported glycol cleavage on various kinds of carbohydrates so as to obtain the key aldehydic intermediate, which wasfurther converted into the corresponding amide in one step. The amide was fully converted into the desired chiral amino alcohol(Scheme 24).52

Shibuya et al. further extended the use of silica-gel supported periodate with TEMPO for rearrangement of tertiary allylicalcohols to β-substituted and α,β-unsaturated ketones (Scheme 25).53 The reaction is mild, efficient and gives high yields. Thereaction proceeds well with all acyclic, medium-size, and macrocyclic tertiary alcohols.




O

O O

BnO OH

OH

NaIO4-SiO2

CH2Cl2, 0 °C, 1.5 h,100%

O

O O

(13)

BnOO

HO

O O

HOCOOMe

Scheme 16

O

OOH

Me

OBn

Et2NCOCl

DIPEA

O

OOH

Me

OBn

NEt2

O Li

EtO

O

OH

Me

OBn

1.

2. Brinework-up

3. DMDO,1MHCl OH

OOH

O

O

Me

OBn

OOH

O

(15)

(14)

O

O

Me

OBn

OOH

OH

OH

NaIO4excessNaIO4

O

OH

Me

OBn H

OOH

OH

MeOH

HO

HOHO

O

1. NaOCl

1. NaBH3CN

2. NaIO4, SiO276% overall yield

2. H2, Pd/C

(+)-Rishirilide

Scheme 17

O

O

OOBn

OBnBnO

BnO

HOPMBO

HOH 1. NaIO4-SiO2,

CH2Cl2, 2 h

2. NaBH4, MeOH100% (2 steps)

O

O

OOBn

OBnBnO

BnOHO

PMBOHO

H

O

O

HOOH

OH

C15H31

OH

HO

HO

OH

Scheme 18

OTBS

H OMe

1. OsO4, NMO,acetone-H2O

2. NaIO4, silica-gel,CH2Cl2, 20 min

60% overall yield

O

OTBS

H OMe

OHH

MeOH

O

OOH

Scheme 19






O

O

OOHH

H

O

1. HCl, MeCN,

2. NaIO4/SiO2,O

O

H

H

O O

O

H

O

H

HO

5 min

CH2Cl2, r.t.,15 min

PMBO

3 Steps

41%

(+)-Aspergillide

Scheme 20

HO I

MeOMe

OH

NaIO4/SiO2

CH2Cl2, r.t.,15 min, 98%

I

MeOMe

O

OO

Me

Me

OTBDPS

MPMO

NaHMDS

THF, −78 °C,15 min, 51%

OO

Me

Me

OTBDPS

MPMO

I

MeHO

H

,O

OMeHO

AcO

HO

H

(−)-Pestalotiopsin A

Scheme 21

O

H

H

H

HO

HOCH2Cl2, r.t.,3h, 93%

NaIO4-SiO2

O

H

H

H

O

O

H

H

H

Antheliolide A

O

O

H

H

O

Scheme 22

OHO

OH

HO OH O O

OBnTBSO

OH1. TBAF, THF,

95%

2. NaIO4-SiO2,CH2Cl2, 30 min,95%

O O

OBnO

O

HO

OH

Goniothalesdiol A

OMeO

Scheme 23


In the synthesis of novel [3.3.1]bicyclic sulfonamide-pyrazoles, which serve as potent γ-secretase inhibitors, oxidative cleavageof intermediate (16) gives the key intermediate dialdehyde, which was then subjected to Mannich reaction to obtain the core of[3.3.1]bicyclic sulfonamide-pyrazole (Scheme 26). Further modification gave a series of novel drugs. The series is not only potent,metabolically stable, and exhibits 4190-fold selectivity for inhibition of APP versus Notch processing by γ-secretase, but is alsoefficacious in reducing the cortical Abx-40 levels in wild-type FVB mice via a single pharmaceutically relevant oral dose.54

In the synthesis of ezetimibe, a powerful cholesterol inhibitor, silica-gel supported NaIO4 oxidative cleavage allows thecleavage of 1,2-diols (17). When the Schering–Plow method is employed, decomposition products always accompany the desiredaldehyde during isolation. It is suspected that the formation of the hydrate by the aldehydic product lead to the difficulties of theisolation. Such problems can be avoided by using Shing's method (Scheme 27).55





OOO OH

OHHO

4,6-O-benzylidene-D-glucopyranoside

1,2,5,6-diisopropylidene-D-mannitol

Ph NaIO4-SiO2 OO

H

Ph OHO

1. I2, NH4OH

2. H2O2O

O

H2N

Ph OHO

76% for 3 steps

O O O O

OHHO

NaIO4-SiO2 1. I2, NH4OH

2. H2O2

70% for 3 steps

OO

H

O

OO

NH2

O

O

O

OHO

1,2-isopropylidene-D-glucofuranose

OHHO

NaIO4-SiO2 1. I2, NH4OH

2. H2O2

65% for 3 steps

O

O

OHO

O

H

O

O

OHO

O

NH2

Scheme 24

n-Bu

OH

TEMPO, NaIO4, SiO2

CH2Cl2, r.t., 15 h, 84%O

n-Bu

Ph

OH TEMPO, NaIO4,SiO2

CH2Cl2, r.t., 14 h, 92% Ph

O

OH

Ph

TEMPO, NaIO4, SiO2

CH2Cl2, r.t., 24 h, 89%Ph

O

Scheme 25

OMe

HO OH

OMe

CHO

NaIO4

OMe

O O

+

OH

OH

O

O

O

NPh

HN

O

OMe

N

OMe

S

HN N

O

O

R

21%for

2 steps

(16)

Scheme 26


In the synthesis of pipecolic acid-based spiro bicyclic lactam scaffolds as β-turn mimics, Shing's method does improve theoxidative cleavage of the olefin (18). If OsO4 and NaIO4 were used, the yield of the desired product was only 33%. However, amodified procedure involving first the dihydroxylation followed by silica adsorbed with NaIO4 gave a superior yield (490% overtwo steps) of the desired aldehyde without the need for column chromatography (Scheme 28).56




N

HOHO

O

F

OBn

HH

NO

F

OBn

HHO

NO

FEzetimibe

OBn

HHF

OHNaIO4-SiO2CH2Cl2, 2 h,0 °C

1.

2. 20 equivalentsNaHCO3, CH2Cl2,0 °C, 3 h 82–86%for 2 steps

(17)

Scheme 27

NCO2Me CO2Me

CO2Me

BocN

O

Boc

OsO4, NaIO4

THF/H2O, 33%

N

Boc

HOOH

(18)

OsO4, NMO,THF/H2O, 93%

NaIO4-SiO2,CH2Cl2, 100%

Scheme 28


The milder silica-gel supported periodate gave a better yield of the desired lactone for the oxidative cleavage of the corre-sponding diols comparing with LTA. The overall yield was 26% higher if Shing's method was chosen for cleavage (Scheme 29).57

MeOO KMnO4, AcOH

O O OMeHO

HOH

HO

O

O O OMeH

HO

O

O

Pb(OAc)4,29% (2 steps)

NaIO4-SiO2,55% (2 steps)

Scheme 29

The oxidative cleavage of vicinal diols by DMP is illustrated in Scheme 30. The oxidative cleavage of the glycol carbon–carbonbond leads to the intramolecular cycloaddition to form the tricyclic enol.58

HO

HO

O

DMP

OO

O

O O

O

[4+2]

Scheme 30

Periodic acid is now one of the most useful tools to cleave vicinal acetals. Such a transformation is very crucial in syntheticchemistry. The traditional way to cleave an acetal is to hydrolyze the acetal by acid followed by cleavage of the vicinal diols. However,this sequence is not entirely chemoselective and usually suffers from tedious workup, providing the product in moderate yield.Especially, the application of this strategy has limited value in some cases, such as in the presence of acid-sensitive groups(e.g., TBDMS) or of a protecting group (Ac) susceptible of migrations. Ethereal periodic acid can cleave a vic-glycol or epoxide smoothly,especially in the case of water-insoluble compounds or where a cleavage product is sensitive to aqueous acid. A hydrated form ofperiodic acid can affect the selective hydrolytic cleavage of terminal isopropylidene acetals in one pot as shown in Scheme 31.59

In the total synthesis of (−)-gabosine O and (+)-4-epi-gabosine O, Shing used periodic acid to cleave the vicinal acetal,which was then converted into an oxime bearing free hydroxyl groups and perform an INOC to generate the key hydro-xylated cycloadduct. The cycloadduct was further functionalized to synthesize the (−)-gabosine O and (+)-4-epi-gabosine O(Scheme 32).60





O O

O

O

OHHO

H5IO6

H5IO6

Et2O, r.t., 92%

Et2O, r.t., 98%

O

O OEtEt

HO

O

O O

O

O OBz O

O O

OBzH

O

Scheme 31

O O

OHO

O OH1. H5IO6, Et2O,

r.t., 18 h, 79%

2. NH2OH, MeOH r.t., 2 days, 100%

O O

OHHON Chloramine-T,

silica gel

EtOH, r.t., 15 min,79%(�:� 4.6:1)

ON

OO

OH

O

HO OH

OH

O

HO OH

(−)-gabosine O

(+)-4-epi-gabosine O

OH


In the total synthesis of (−)-cleistenolide, periodic acid was employed to cleave one terminal vicinial acetal selectively, followedby Wittig olefination to afford a key alkene intermediate (Scheme 33).61

Scheme 32

OO

O

+ –OOBz

OBz1. H5IO6, Et2O, r.t.

OO

OBz

OBz

2. Ph3PCH3Br, KOtBu, THF71% overall yield

O

O

(−)-Cleistenolide

BzO

OAc OAc

Scheme 33

In the total synthesis of laulimalide and its nonnatural analogs, all LTA, silica-gel supported glycol cleavage and periodic acidwere employed to synthesize the key intermediate aldehyde (19), which was highly volatile. The low boiling solvent employed inall methods facilitated the isolation of the aldehyde (Scheme 34).62

HO OH

O O

LTA, Na2CO3

CH2Cl2, 0 °C, 15 min

CH2Cl2, 0 °C to r.t., 2 h

H5IO6

Et2O, 0 °C to r.t., 2 hNaIO4-SiO2

OO

H OH

O

O

Laulimalide

OH

OH

H

O

H

O

H

(19)

Scheme 34






Compared to nonmetal reagents, metallic reagents are less frequently applied in synthetic chemistry, whereas vanadium(V) andruthenium species are relatively more popular. Kirihara et al. used VOCl3 with molecular oxygen to cleave the cyclic ditertiaryglycols and interestingly, both the cis- and trans-glycols reacted similarly (Scheme 35).24 In the study of oxidative cleavage ofpinacol by vanadium(V) dipicolinate complex, Hanson discovered that the vanadium(V) was reduced to vanadium(III) after thereaction. The complex is easily oxidized back to vanadium(V) by air.63

Me OH

OH

Me

Me OH

Me

OH

2.4 mol% VOCl3, O2 (Balloon)

2.4 mol% VOCl3, O2 (Balloon)

EtOAc, r.t., 8 h, 40%

EtOAc, r.t., 8 h, 60%

O

O

Scheme 35

Sharpless used catalytic amounts of RuCl3 in the presence of periodate as the cooxidant to successfully cleave vicinal diols totheir corresponding aldehydes. It is interesting to note that the stereochemistry of the chiral center can be retained (Scheme 36).64

Such a method is also employed by Ivanova to synthesize cyclopentane derivatives, which can be further functionalized for naturalproducts syntheses (Scheme 37).65

Ph OH

Me

OH2.2 mol% RuCl3, NaIO4

CCl4/CH3CN/H2O, r.t., 92%Ph

H

Me

O

96% ee 94% ee

Scheme 36

O

O

MsO H

H

CCl4/CH3CN/H2O, r.t., 85% O

O

MsO H

H

HO

ORuCl3.H2O, NaIO4

Scheme 37

Anaya et al. used the triphenylbismuthcarbonate to cleave a glycol to yield the corresponding aldehyde. The aldehyde wasfurther transformed to the methyl ester carbapenam, which can act as an antibiotic precursor (Scheme 38).66

NO

S

MeO

Et3SiO

Et3SiOOSiEt3

OSiEt3

1. TBAF, THF, 0 °C

2. Ph3BiCO3, CH3CN reflux

NO

S

MeO

CHO

NO

MeO

COOMe2 steps 40%

Scheme 38

Outram has compared the reactivity of MnO2 and silica-gel supported NaIO4 in the in situ oxidative diol cleavage-Wittigreaction. In most cases, the silica-gel supported periodate gave a better yield than manganese dioxide except for the hydro-xybenzoin synthesis (Scheme 39).67





OH

OH NaIO4-SiO

2, CH2Cl2, Ph3P=CHCO2Et, r.t., 37%

CO2Et

CO2Et

E:Z 15:1

E:Z 14:1

MnO2, CH2Cl2, P

h3P=CHCO2Et, r.t., 97%

Scheme 39


References

1. Perlin, A. S. Adv. Carbohydr. Chem. Biochem. 2006, 60, 183–250.2. Constantieux, T.; Rodriguez, J. Sci. Synth. 2005, 26, 413–462.3. Drewry, D. H.; Coe, D. M.; Poon, S. Med. Res. Rev. 1999, 19, 97–148.4. Postel, M.; Dunach, E. Coord. Chem. Rev. 1996, 155, 127–144.5. Shing, T. K. M. Glycol Cleavage. In Comprehensive Organic Synthesis; Ley, S. V. Ed.; Pergamon Press: Oxford, 1991, Vol. 7, Chapter 5.13; pp 703–715.6. Perlin, A. S. The Carbohydrates − Glycol-Cleavage Oxidation. In The Carbohydrates, Chemistry and Biochemistry, 2nd ed.; Pigman, W. W., Horton, D., Wander, J. D.,

Eds.; Academic Press: New York, 1980, Vol. 1B, Chapter 4; pp 1167–1215.7. Fatiadi, A. J. Synthesis 1974, 229–272.8. Tandon, P. K.; Khanam, S. Z.; Singh, S. B. Open Catal. J. 2012, 5, 1–7.9. Maki, S.; Ishihara, J.; Nakanishi, K. J. Indian. Chem. Soc. 2000, 77, 651–655.10. Bieser, A.; Borsotti, G.; Digioia, F.; Ferrari, A.; Pirocco, A. Continuous Process of Oxidative Cleavage of Vegetable Oils. PCT Int. Appl. WO 2011080296 A1, Jul 7, 2011.11. Criegee, R. Chem. Ber. 1931, 64, 260–266.12. Ohloff, G.; Giersch, W. Angew. Chem., Int. Ed. Engl. 1973, 12, 401–402.13. Barroso, S.; Blay, G.; Fernández, I.; et al. J. Mol. Catal. A Chem. 2006, 243, 214–220.14. Fernández, D.; Riaño, S.; Fadini, L. Open Catalysis Journal 2009, 2, 101–109.15. Ferreira, J. T.; Sabino, A. A. J. Braz. Chem. Soc. 1994, 5, 67–68.16. Felthouse, T. J. Am. Chem. Soc. 1987, 109, 7566−7568.17. Wolfe, S.; Hassan, S. K.; Campbell, J. R. J. Chem. Soc. D. 1970, 1420–1421.18. Emons, C. H. H.; Kuster, B. F. M.; Vekemans, J. A. J. M.; Sheldon, R. A. Tetrahedron Asymmetry 1991, 2, 359–362.19. Takezawa, E.; Sakaguchi, S.; Ishii, Y. Org. Lett. 1999, 1, 713–715.20. Schmidt, A.-K. C.; Stark, C. B. W. Org. Lett. 2011, 3, 5788–5791.21. Cheng, H.; Stark, C. B. W. Angew. Chem. 2010, 122, 1632–1635; Cheng, H.; Stark, C. B. W. Angew. Chem., Int. Ed. 2010, 45, 1587–1590.22. Schmidt, A.-K. C.; Stark, C. B. W. Org. Lett. 2011, 3, 4164–4167.23. Du, G.-D.; Ellern, A.; Woo, L. K. Inorg. Chem. 2004, 43, 2379–2386.24. Kirihara, M.; Yoshida, K.; Noguchi, T.; et al. Tetrahedron Lett. 2010, 51, 3619–3622.25. Gosain, J.; Sharma, P. K. Proc. Indian Acad. Sci. (Chem. Sci.) 2003, 115, 135–145.26. Singh, K. N.; Kumar, R.; Shukla, A. K. Indian J. Chem., Sec. B 2007, 46B, 1347–1351.27. Klein-Koerkamp, C.; Granet, R.; Zerrouki, R.; et al. Carbohydr. Polym. 2009, 78, 938–944.28. Beebe, T. R.; Hii, P.; Reinking, P. J. Org. Chem. 1981, 46, 1927–1929.29. McDonald, C. E.; Holcomb, H.; Leathers, T.; Ampadu-Nyarko, F.; Frommer, J., Jr. Tetrahedron Lett. 1990, 31, 6283–6286.30. Moorthy, J. N.; Singhal, N.; Senapati, K. Org. Bimol. Chem. 2007, 5, 767–771.31. Criegee, R.; Beucker, H. Ann. Chem. 1931, 541, 218–238.32. Nicolaou, K. C.; Adsool, V. A.; Hale, C. R. H. Org. Lett. 2010, 12, 1552–1555.33. Shibuya, M.; Shibuta, T.; Fukuda, H.; Iwabuchi, Y. Org. Lett. 2012, 14, 5006–5009.34. Zhong, Y.-L.; Shing, T. K. M. J. Org. Chem. 1997, 62, 2622–2624.35. Dakdouki, S. C.; Villemin, D.; Bar, N. Eur. J. Org. Chem. 2011, 76, 4448–4457.36. Shimada, Y.; Nakamura, M.; Suzuka, T.; et al. Tetrahedron Lett. 2003, 44, 1401–1403.37. Deng, Y.-J.; Salomon, R. G. J. Org. Chem. 1998, 63, 7789–7794.38. Aquino, M.; Safir, I.; Elkhayat, Z.; et al. Org. Lett. 2009, 11, 3610–3613.39. Paterson, I.; Paquet, T.; Dalby, S. M. Org. Lett. 2011, 13, 4398–4401.40. Saito, T.; Fuwa, H.; Sasaki, S. Org. Lett. 2009, 11, 5274–5277.41. Do, Y.-S.; Sun, R.-Y.; Kim, H. J.; et al. J. Org. Chem. 2009, 74, 917–920.42. Gampe, C. E.; Carreira, E. M. Angew. Chem. Int. Ed. 2011, 50, 2962–2965.43. Cohen, D. T.; Cardinal-David, B.; Scheidt, K. A. Angew. Chem. Int. Ed. 2011, 50, 1678–1682.44. Chen, F.-E.; Zhao, J.-F.; Xiong, F.-J.; Xie, B.; Zhang, P. Carbohydr. Res. 2007, 342, 2461–2464.45. Mejorado, L. H.; Pettus, T. R. R. J. Am. Chem. Soc. 2006, 128, 15625–15631.46. Parhi, A. K.; Mootoo, D. R.; Franck, R. W. Tetrahedron 2008, 64, 9821–9827.47. Xue, H.-R.; Gopal, P.; Yang, J. J. Org. Chem. 2012, 77, 8933–8945.48. Panarese, J. D.; Waters, S. P. Org. Lett. 2009, 11, 5086–5088.49. Takao, K.-I.; Hayakawa, N.; Yamada, R.; et al. Angew. Chem. Int. Ed. 2008, 47, 3426–3429.50. Mushti, C. S.; Kim, J.-H.; Corey, E. J. J. Am. Chem. Soc. 2006, 128, 14050–14052.51. Yadav, J. S.; Rao, R. N.; Harikrishna, R. S. V.; Reddy, B. V. S. Helv. Chim. Acta. 2010, 93, 1362–1368.52. Dunlap, N. K.; Drake, J.; Ward, A.; Salyard, T. L. J.; Martin, L. J. Org. Chem. 2008, 73, 2928–2930.

http://refhub.elsevier.com/B978-0-08-097742-3.00731-X/sbref1










http://refhub.elsevier.com/B978-0-08-097742-3.00731-X/bib10














































53. Shibuya, M.; Tomizawa, M.; Iwabuchi, Y. Org. Lett. 2008, 10, 4715–4718.54. Sun, M.-H.; Garofalo, A. W.; Konradi, A. W.; et al. Bioorg. Med. Chem. Lett. 2011, 21, 5791–5794.55. Michalak, M.; Stodulski, M.; Stecko, S.; et al. J. Org. Chem. 2011, 76, 6931–6936.56. Somu, R. V.; Johnson, R. L. J. Org. Chem. 2005, 70, 5954–5970.57. Brown, R. C. D.; Bataille, C. J.; Hughes, R. M.; Kenney, A.; Luker, T. J. J. Org. Chem. 2002, 67, 8079–8085.58. Candela Lena, J. I.; Martin Hernando, J. I.; Rico Ferreira, M. d. R.; Altinel, E.; Arseniyadis, S. Synlett 2001, 597–600.59. Wu, W.-L.; Wu, Y.-L. J. Org. Chem. 1993, 58, 3586–3588.60. Shing, T. K. M.; So, K. H.; Kwok, W. S. Org. Lett. 2009, 11, 5070–5073.61. Chanti Babua, D.; Ashalathaa, K.; Bhujanga Raoa, C.; Selvam Jondossa, J. P.; Venkateswarlu, Y. Helv. Chim. Acta. 2011, 94, 2215–2220.62. Ahmed, A.; Hoegenauer, E. K.; Enev, V. S.; et al. J. Org. Chem. 2003, 68, 3026–3042.63. Hanson, S. K.; Baker, R. T.; Gordon, J. C.; et al. J. Am. Chem. Soc. 2009, 131, 428–429.64. Carlsen, P. H. J.; Katsuki, T.; Martin, V. S.; Sharpless, K. B. J. Org. Chem. 1981, 46, 3936–3938.65. Ivanova, N. A.; Akhmetdinova, N. P.; Valiullina, Z. R.; Miftakhov, M. S. Russ. J. Org. Chem. 2009, 45, 1718–1720.66. Anaya, J.; Barton, D. H. R.; Géro, S. D.; et al. Angew. Chem., lnt. Ed. Engl. 1993, 32, 867–869.67. Outram, H. S.; Raw, S. A.; Taylor, R. J. K. Tetrahedron Lett. 2002, 43, 6185–6187.
















comprehensive organic synthesis ii || 7.26 glycol cleavage reactions

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