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Tetrahedron 68 (2012) 2459e2464

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Tetrahedron

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A new application of BayliseHillman alcohols to a diastereoselective synthesisof 3-nitrothietanes

Ankita Rai, Lal Dhar S. Yadav *

Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211002, India

a r t i c l e i n f o

Article history:Received 14 December 2011Received in revised form 19 January 2012Accepted 23 January 2012Available online 28 January 2012

Keywords:ThietanesBayliseHillman adductsO,O-Diethyl hydrogen phosphorodithioateMichael additionIonic liquidsStereoselective synthesis

* Corresponding author. Tel.: þ91 5322500652; faaddress: ldsyadav@hotmail.com (L.D.S. Yadav).

0040-4020/$ e see front matter � 2012 Elsevier Ltd.doi:10.1016/j.tet.2012.01.062

a b s t r a c t

Three key reactions, the generation of a nucleophile, an thia-Michael addition and an intramolecularcyclisation, were used to achieve an efficient one-pot diastereoseletive synthesis of 3-nitrothietanes.Thus, BayliseHillman alcohols and their aldehydes were reacted with either O,O-diethyl hydrogenphosphorodithioate or O,O-diethyl hydrogen phosphorodithioate in combination with a task-specificionic liquid [bmim]XeY to afford the corresponding 2,3-di- or 2,3,4-trisubstituted thietanes, re-spectively. The reaction is high yielding and proceeds with complete diastereoselectivity in favour of thetrans isomers.

� 2012 Elsevier Ltd. All rights reserved.

1. Introduction

Many biological processes are directed by the compoundsbearing a heterocyclic moiety. Among these, thietanes are of con-siderable importance as reactive synthetic targets and biologicallyuseful molecules. Thietane derivatives have so far remained littleinvestigated compounds both in the sense of methods of prepara-tion and with respect to synthetic applications. However, theirsynthetic potential is extremely significant for the construction ofdifficultly obtainable heterocyclic systems.

Thietanes hold an intermediate position between the highly re-active thiiranes and more inert tetrahydrothiophenes, hence entailto be caused to react either way. They are more reactive than openchain sulfides. Thus, thietanes are widely employed for the gener-ation of sulfur ylides, which are becoming increasingly useful in-termediates in synthetic organic chemistry.1 Thietanes are also usedas mimics of unstable oxetane intermediates for the repair of mu-tagenic lesions.2 A tetramethylthietane containing dipeptide deriv-ative, Alidade, has been developed as a nutritive sweetener by Pfizerin 1983.3 3-Substituted thietanes are the most important constitu-ent of various potential antiviral and antitubercular moieties.4

3-Functionalized derivatives like 3-cyano-2,2-diphenylthietane,cis-3,4-dichloro-2,2-diphenylthietane and trans-3,4-dicyano-2,2-

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diphenylthietane are of great importance as they are starting ma-terials for insecticides and sulfur containing polymers.5 More re-cently, thietane nucleosides have been synthesised and evaluatedfor their antiviral activity against HIV-1.6 The literature recordsseveral reports on the synthesis of 3-substituted thietanes,7 but thechemistry of 3-nitrothietanes has been scarcely investigated. De-spite their synthetic and biological applications, convenientmethods for the synthesis of functionalized thietanes, especially 3-nitrothietanes, are still desired. Herein, a new method has been in-troduced for the synthesis of 3-nitrothietanes.

The presence of nitro group in the target molecules would en-able their easy conversion to various useful functionalities, such asoxime, hydroxylamine, amine and carbonyl group.8 The reportedmethods for the synthesis of thietanes (Fig. 1) involve cyclisation of1,3-dihaloalkanes with Na2S,9 cyclisation of 3-haloalkanethiols,10

conversion of 3-hydroxymercaptans with thiourea in the pres-ence of hydroiodic acid,11 interaction of 3-hydroxyalkyl halideswith thiourea,12 alkaline hydrolysis of chlorotrimethylthirane,13

thermal decomposition of carbonate esters of 1,3-diols in thepresence of KSCN,14 reduction of thietane dioxides,15 conversion ofthioesters in the presence of alkali16 and Michael additionecycli-sation employing O,O-diethyl hydrogen phosphorodithioate.17

The BayliseHillman (BH) adducts incorporate three chemo-specific groups, viz. a hydroxyl group, a double bond and an EWG.These groups could be appropriately tailored to generate an array ofcyclic compounds directly fromBHadducts.18 It has to bementionedhere that in recent years, the key constituent BH adducts 1 has been

VI

I II III

IV

V

VII

Presentwork

VIII

IX

CCX

CX

CH

HO

CH2Cl

CH2SHNa2S HSCH2CH2CH(CH2)4COOHOH

(NH2)2CS HI

HOCH2CH2CH2Cl

(NH2)2CS

SCH2Cl

OCO

O SCNSO

O

PEtOEtO

S

SHAr O

COOMe

PEtOEtO

S

SH

CH2OH(CHO)

Ar

O2N

Baylis-HillmanAdduct S

R1

R2

R3

Fig. 1. Methods for the synthesis of thietanes.

Table 1Synthesis of 2,3-disubstituted thietanes 4a

(i) NaHTHF, 60 oC, 30 min

(ii) 1, THF, rt, 3-5 hPEtO

EtO

S

SH

2H

H Ar

HO2N

S

4

Entry Ar Product Time (h)b Yieldc,d (%)

1 Ph 4a 3.5 862 4-ClC6H4 4b 4 933 4-CH3OC6H4 4c 4 904 4-CH3C6H4 4d 4.5 915 2-CH3OC6H4 4e 5 846 2-ClC6H4 4f 3 907 2-CH3C6H4 4g 4.5 898 3-Furyl 4h 3 87

a Reaction conditions: 1 (5 mmol), 2 (5 mmol) and NaH (10 mmol) were used indry THF (4 mL).

b Time required for completion of step (ii).c Yield of isolated and purified product.

A. Rai, L.D.S. Yadav / Tetrahedron 68 (2012) 2459e24642460

used in a variety of applications.18 The present study will widen thescope of synthetic applications of BH adducts 1.

d All compounds gave C, H and N analyses within�0.36% and satisfactory spectral(IR, 1H NMR, 13C NMR and EIMS) data.

2. Results and discussion

Prompted by the above considerations and in continuation ofour work on heterocyclisations,19 especially using sulfur basedleaving groups,17,20 we herein report the first synthesis of 3-nitrothietanes 4 and 6 as depicted in Scheme 1. The protocol in-volves a thia-Michael addition of O,O-diethyl hydrogen phosphor-odithioate to nitroalkene-derived BH adducts18a 1 or theiraldehydes 3 followed by anion induced cyclisation to afford 3-nitrothietanes 4 or 6, respectively, in excellent yields with com-plete diastereoselectivity. This divergent route can be used toproduce skeletally diverse thietane scaffolds from the same pre-cursor. Especially, this work is concentrated to obtain new tri- andtetrasubstituted 3-nitrothietanes from BH alcohols.

2,3-Disubstitutedthietanes

2,3,4-Trisubstitutedthietanes

OH

Ar

NO2

O

Ar

NO22. [bmim][X−Y]

1

3

IBX1 h, rt

3-5 h, rt

4-5 h, rt

Baylis-Hillman Alcohol

PEtOEtO

S

SH

PEtOEtO

S

SH1.

5

2

2

HH

H Ar

HO2N

S

4

HH

Y-X Ar

HO2N

S

6

NaH;

NaH;

Scheme 1. Synthesis of 3-nitrothietanes 4 and 6.

At the outset, we synthesised 2,3-disubstituted thietanes 4 bya novel one-pot procedure. Thus, O,O-diethyl hydrogen phosphor-odithioate 2 was treated with sodium hydride in dry THF to thegenerate anion 7, which in situ underwent thia-Michael addition toBH adducts 1 followed by cyclisation to afford thietanes 4 in84e93% yields (Table 1). The formation of thietanes 4 is best

explained through anionic domino process as outlined in Scheme 2.The exclusive formation of trans isomer 4 is understandable in viewof the fact thatMichael additions usually give anti/trans products. Inorder to enhance the generality of the method and introduce fur-ther functionalities into the thietane ring, we undertook for the firsttime the oxidation of BH alcohols 1 of nitroalkenes to their alde-hydes employing IBX21 as it is a mild oxidant, and a variety offunctional groups are compatible with its use. The aldehydes 3underwent thia-Michael addition with O,O-diethyl hydrogenphosphorodithioate 2 followed by anion induced cyclisation witha task-specific ionic liquid (TSIL) [bmim]XeY to afford thietanes 6 in83e94% yields (Table 2) as depicted in Scheme 3.

With the above results in hand, the possible mechanism of thiscyclisation reaction can be best explained through the attack ofa nucleophile (�XeY) on the carbonyl carbon of 11 followed by theintramolecular attack of the alkoxide ion 12 on the phosphorusatom. Then, the lone pair of X forms a bond with carbon, and car-boneoxygen bond breaks leading to the formation of products 6through 13 and 14 (Scheme 3). Furthermore, during the formationof products 6 a sulfenium ion probably comes into play, which setsequilibrium to furnish the thermodynamically more favourabletransetrans product as depicted in Scheme 3.

A comparison of TSIL with KSCN or PhSNa for the synthesis of 6was carried out under similar conditions by stirring BayliseHillmanadduct18a 1 with in situ generated O,O-diethyl hydrogen phos-phorodithioate anion 7 and 1.5 equiv of KSCN or PhSNa for 3e5 h atrt. In this case, the anion induced cyclisation afforded the corre-sponding 6 in relatively lower yields (40e54%). This indicates thatthe nucleophilicty of SCN or PhS anion is considerably higher in[bmim]SCN or [bmim]SPh compared to that from KSCN or PhSNa.The high affinity of phosphorus for oxygen is the main driving forcefor both of the present cyclisation reactions depicted in Schemes 2and 3.

Various BH alcohols and aldehydes were chosen to examine thescope of this reaction and found that, generally, these reactedsmoothly with aldehydes with either O,O-diethyl hydrogen phos-phorodithioate or O,O-diethyl hydrogen phosphorodithioate incombination with [bmim]XeY to furnish a range of 3-nitrothietanes 4 and 6. The reaction was monitored by TLC andthe results are shown in Tables 1 and 2. The annulation of BH al-cohols 1 and their aldehydes 3 to functionalized thietanes wasentirely diastereoselective and afforded exclusively the trans iso-mers. The configurational assignment of thietanes 4 and 6 was

HH

H Ar

HO2N

S

4

NaH

OH

Ar

NO2

1

NaH

O

Ar

NO2

SPS

EtOEtO

O

Ar

NO2

SPEtO

EtO

SO

Ar

NO2

SPEtO

EtO

S

8

72

9

10

(EtO)2P

S

SH (EtO)2P SNa

S

-(EtO)2PO

S

Scheme 2. A plausible mechanism for the formation of 3-nitrothietanes 4.

Table 2Synthesis of 2,3,4-trisubstituted thietanes 6a

PEtOEtO

S

SH5

2

(i) NaHTHF, 60 oC, 30 min

(ii) 3, [bmim][X-Y]THF, rt, 4-5 h HH

Y-X Ar

HO2N

S

6

Entry Ar XeY Product Time [h]b Yieldc,d [%]

1 Ph SCN 6a 4.5 842 4-ClC6H4 SCN 6b 4.5 943 2-ClC6H4 SCN 6c 5 874 4-CH3OC6H4 SCN 6d 5 935 Ph SPh 6e 5 856 4-ClC6H4 SPh 6f 4.5 917 2-ClC6H4 SPh 6g 4 908 4-CH3OC6H4 SPh 6h 4.5 929 Ph NO3 6i 4 8310 Ph TfO 6j 4 9011 3-Furyl SCN 6k 5 8912 3-Furyl SPh 6l 4.5 93

a Reaction conditions: 2 (5 mmol), 3 (5 mmol), NaH (10 mmol) and [bmim]XeY(5 mmol) were used in dry THF (4 mL).

b Time required for completion of step (ii).c Yield of isolated and purified product.d All compounds gave C, H and N analyses within�0.36% and satisfactory spectral

(IR, 1H NMR, 13C NMR and EIMS) data.

A. Rai, L.D.S. Yadav / Tetrahedron 68 (2012) 2459e2464 2461

made on the basis of 1H NMR coupling constants JtransH/H of 2-H, 3-H and 3-H, 4-H of the heterocycle, which are in the range of7.4e8.9 Hz as already reported for substituted thietanes.17,22,23

The relative configuration was further confirmed by NOE ex-periments as shown in Fig. 2. Strong NOE was observed between 3-H and the ortho proton of the aromatic ring at position C-4, whichshows that the aromatic ring and NO2 group are trans to each otherin both 4a and 6a (Fig. 2). Furthermore, the presence of measurableNOE between 2-H and 4-H, and the absence of anymeasurable NOEbetween aromatic protons and 4-H indicates that 6a has thetransetrans stereochemistry.

3. Conclusion

In summary, we have developed a one-pot procedure fora highly diastereoselective synthesis of 2,3- and 2,3,4-trisubstitutedthietanes from BH alcohols and their aldehydes, respectively. Thesynthetic protocol presents the first application of nitroalkene de-rived BH alcohols and their aldehydes to the synthesis of nitro-thietanes via an anionic domino process. Thus, the presentmethodology widens the scope of synthetic utility of BH adducts.

4. Experimental

4.1. General

Reagents were obtained from commercial supplier, and usedwithout further purification unless otherwise specified by a refer-ence. All reactions were performed using oven-dried glasswareunder a nitrogen atmosphere. Organic solutions were concentratedusing a Buchi rotary evaporator. Column chromatography wascarried out over silica gel (Merck 100e200 mesh) and TLC wasperformed using silica gel GF254 (Merck) plates. Melting pointswere determined by open glass capillary method and are un-corrected. IR spectra in KBr were recorded on a PerkineElmer 993IR spectrophotometer, 1H NMR spectra were recorded on a BrukerAVII 400 spectrometer in CDCl3 using TMS as internal referencewith chemical shift value being reported in parts per million. Allcoupling constants (J) are reported in hertz (Hz). 13C NMR spectrawere recorded on the same instrument at 100 MHz in CDCl3 andTMS was used as internal reference. Mass (EI) spectra were recor-ded on a JEOL D-300 mass spectrometer. Elemental analyses werecarried out in a Coleman automatic carbon, hydrogen and nitrogenanalyzer.

4.2. Synthesis of aldehydes 3: general procedure

These were prepared following the procedure reported in theliterature.21 Thus, to a solution of BayliseHillman alcohol 1(1 equiv) in DMSO/THF (1:2, 6 mL) was added IBX (1.1 equiv) andstirred at rt for 45 min. After the reaction was complete as checkedby TLC, water (15 mL) was added, the mixture was extracted withether (3�10 mL), the combined organic layers were dried overanhydrous sodium sulfate, filtered and evaporated under reducedpressure. The crude product thus obtained was purified by silica gelcolumn chromatography (hexane/EtOAc, 90:10) to afford an ana-lytically pure sample of 3.

4.3. General procedure for the synthesis of 2,3-disubstitutedthietanes 4

To a solution of O,O-diethyl hydrogen phosphorodithioate 2(5 mmol) in dry THF (4 mL) was added dropwise a suspension ofNaH (10 mmol) in dry THF (20 mL) with stirring at rt. After theaddition was complete and evolution of hydrogen gas (efferves-cence) had ceased, the reaction mixture was stirred at 60 �C for30 min and then cooled to rt. Next, a solution of BayliseHillmanalcohol 1 (5 mmol) in dry THF (5 mL) was added, and the reactionmixture was stirred at rt for 3e5 h. Water (30 mL) was added, themixture was extractedwith ether (3�30mL), the combined organic

HH

Y-X Ar

HO2N

S

6

-(EtO)2PO

(EtO)2P SNa

S

S

NaH

O

Ar

NO2

2

O

Ar

NO2

SPS

EtOEtO

S ArO2N

O

Ar

NO2

SPS

EtOEtO

[bmim][XY]

[bmim]

X

X

3

711

5

12 1314

X = S, O, N

O

Ar

NO2

SPS

EtOEtO

XY Y

Ar

NO2

S

X Y

YS Ar

O2N

XY

S ArO2N

Y = CN, Ph, O3, Tf

XY

(EtO)2P SH

S

H

H H H

H H

Scheme 3. A plausible mechanism for the formation of 3-nitrothietanes 6.

HH

Y-X

HO2N

S

6a

18.9 %

HH

H

HO2N

S

16.2 %

HH

4a

Fig. 2. NOE for 3-nitrothietanes.

A. Rai, L.D.S. Yadav / Tetrahedron 68 (2012) 2459e24642462

layers were dried over anhydrous sodium sulfate, filtered andevaporated under reduced pressure. The crude product thus ob-tained was purified by silica gel column chromatography (hexane/EtOAc, 95:5) to afford an analytically pure sample of 4.

4.3.1. 3-Nitro-2-phenylthietane (trans-4a). Yield (0.84 g, 86%) asa white solid; mp 169e171 �C; [Found: C, 55.07; H, 4.38; N, 7.49C9H9NO2S requires C, 55.37; H, 4.65; N, 7.17%]; Rf (5% EtOAc/hexane)0.58; IR (KBr) nmax 3052, 2992, 1605, 1585, 1455, 745, 700 cm�1. 1HNMR(400MHz;CDCl3) 7.35e7.72 (5H,m,Ph), 4.55 (1H,d, J¼8.8Hz,2-H), 4.10 (1H,ddd, J¼8.8, 7.9, 2.9Hz,3-H), 3.61 (1H,dd, J¼11.4, 7.9Hz,4-Hb), 3.24 (1H, dd, J¼11.4, 2.9 Hz, 4-Ha). 13C NMR (100 MHz, CDCl3)139.4, 128.9, 127.8, 125.9, 91.7, 45.9, 27.6. EIMS (m/z)¼195 (Mþ).

4.3.2. 2-(4-Chlorophenyl)-3-nitrothietane (trans-4b). Yield (1.06 g,93%) as a white solid; mp 162e164 �C; [Found: C, 47.31; H, 3.32; N,6.46 C9H8ClNO2S requires C, 47.06; H, 3.51; N, 6.10%]; Rf (5% EtOAc/hexane) 0.51; IR (KBr) nmax 3057, 2989, 1601, 1589, 1454, 747,702 cm�1. 1H NMR (400 MHz; CDCl3) 8.10e8.17 (2H, m, 4-ClPh),8.09e8.13 (2H, m, 4-ClPh), 4.52 (1H, d, J¼8.7 Hz, 2-H), 4.14 (1H, ddd,J¼8.7, 7.8, 2.7 Hz, 3-H), 3.56 (1H, dd, J¼11.5, 7.8 Hz, 4-Hb), 3.27 (1H,dd, J¼11.5, 2.7 Hz, 4-Ha); 13C NMR (100 MHz, CDCl3) 137.2, 131.8,130.1, 128.7, 91.4, 45.7, 27.4; EIMS (m/z) 229, 231 (Mþ, Mþþ2).

4.3.3. 2-(4-Methoxyphenyl)-3-nitrothietane (trans-4c). Yield(1.01 g, 90%) as a white solid; mp 156e159 �C; [Found: C, 53.63; H,5.17; N, 5.96 C10H11NO3S requires C, 53.32; H, 4.92; N, 6.22%]; Rf (5%EtOAc/hexane) 0.53; IR (KBr) nmax 3059, 2991, 1604, 1582, 1451, 749,708 cm�1. 1H NMR (400 MHz; CDCl3) 8.01e8.04 (2H, m, 4-OCH3Ph),7.66e7.69 (2H, m, 4-OCH3Ph), 4.50 (1H, d, J¼8.9 Hz, 2-H), 4.18 (1H,ddd, J¼8.9, 7.6, 3.1 Hz, 3-H), 3.85 (3H, s, OCH3), 3.59 (1H, dd, J¼11.1,

7.6 Hz, 4-Hb), 3.21 (1H, dd, J¼11.1, 3.2 Hz, 4-Ha); 13C NMR (100 MHz,CDCl3) 158.4, 130.9, 129.1, 114.9, 91.7, 55.8, 45.2, 27.9; EIMS (m/z)¼225 (Mþ).

4.3.4. 3-Nitro-2-p-tolylthietane (trans-4d). Yield (0.95 g, 91%) asa white solid; mp 162e165 �C; [Found: C, 57.04; H, 5.02; N, 6.89C10H11NO2S requires C, 57.39; H, 5.30; N, 6.69%]; Rf (5% EtOAc/hexane) 0.57; IR (KBr) nmax 3052, 2994, 1604, 1583, 1455, 745,704 cm�1; 1H NMR (400 MHz; CDCl3) 7.71e7.75 (2H, m, 4-CH3Ph),7.32e7.39 (2H, m, 4-CH3Ph), 4.54 (1H, d, J¼8.5 Hz, 2-H), 4.17 (1H,ddd, J¼8.5, 7.5, 2.9 Hz, 3-H), 3.58 (1H, dd, J¼11.3, 7.5 Hz, 4-Hb), 3.25(1H, dd, J¼11.3, 2.9 Hz, 4-Ha), 2.41 (3H, s, CH3); 13C NMR (100 MHz,CDCl3) 136.5, 135.1, 129.4, 127.9, 91.5, 45.8, 27.5, 24.1. EIMS (m/z)¼209 (Mþ).

4.3.5. 2-(2-Methoxyphenyl)-3-nitrothietane (trans-4e). Yield(0.94 g, 84%) as a white solid; mp 170e173 �C; [Found: C, 53.53; H,4.62; N, 5.97 C10H11NO3S requires C, 53.32; H, 4.92; N, 6.22%]; Rf (5%EtOAc/hexane) 0.54; IR (KBr) nmax 3055, 2990,1601,1586,1458, 744,706 cm�1. 1H NMR (400MHz; CDCl3) 8.03e8.08 (2H, m, 4-OCH3Ph),7.61e7.67 (2H, m, 4-OCH3Ph), 4.56 (1H, d, J¼8.7 Hz, 2-H), 4.20 (1H,ddd, J¼8.7, 7.9, 2.6 Hz, 3-H), 3.81 (3H, s, OCH3), 3.58 (1H, dd, J¼11.1,7.9 Hz, 4-Hb), 3.29 (1H, dd, J¼11.1, 2.6 Hz, 4-Ha); 13C NMR (100 MHz,CDCl3) 157.6, 128.8, 127.3, 121.4, 118.9, 114.2, 91.1, 56.5, 35.9, 27.5;EIMS (m/z)¼225 (Mþ).

4.3.6. 2-(2-Chlorophenyl)-3-nitrothietane (trans-4f). Yield (1.03 g,90%) as a white solid; mp 169e171 �C; [Found: C, 46.80; H, 3.82; N,5.88 C9H8ClNO2S requires C, 47.06; H, 3.51; N, 6.10%]; Rf (5% EtOAc/hexane) 0.53; IR (KBr) nmax 3058, 2994, 1608, 1585, 1451, 749,705 cm�1. 1H NMR (400 MHz; CDCl3) 8.11e8.16 (2H, m, 2-ClPh),7.67e7.70 (2H, m, 2-ClPh), 4.57 (1H, d, J¼8.3 Hz, 2-H), 4.12 (1H, ddd,J¼8.3, 7.4, 2.9 Hz, 3-H), 3.61 (1H, dd, J¼11.7, 7.4 Hz, 4-Hb), 3.24 (1H,dd, J¼11.7, 2.9 Hz, 4-Ha); 13C NMR (100 MHz, CDCl3) 138.0, 132.9,130.7, 129.5, 127.8, 126.9, 91.2, 36.1, 27.2; EIMS (m/z)¼229, 231 (Mþ,Mþþ2).

4.3.7. 3-Nitro-2-(o-tolyl)thietane (trans-4g). Yield (1.01 g, 89%) asa white solid; mp 165e168 �C; [Found: C, 57.08; H, 5.06; N, 7.00C10H11NO2S requires C, 57.39; H, 5.30; N, 6.69%]; Rf (5% EtOAc/

A. Rai, L.D.S. Yadav / Tetrahedron 68 (2012) 2459e2464 2463

hexane) 0.58; IR (KBr) nmax 3057, 2992, 1606, 1581, 1452, 748,707 cm�1. 1H NMR (400 MHz; CDCl3) 7.67e7.70 (2H, m, 2-CH3Ph),7.41e7.43 (2H, m, 2-CH3Ph), 4.55 (1H, d, J¼8.3 Hz, 2-H), 4.17 (1H,ddd, J¼8.3, 7.6, 2.5 Hz, 3-H), 3.59 (1H, dd, J¼11.9, 7.6 Hz, 4-Hb), 3.27(1H, dd, J¼11.9, 2.5 Hz, 4-Ha), 2.37 (3H, s, CH3); 13C NMR (100 MHz,CDCl3): d 137.4, 135.8, 129.5, 128.2, 126.7, 125.1, 91.3, 39.7, 27.5, 17.2;EIMS (m/z)¼229 (Mþ).

4.3.8. 3-(3-Nitrothietan-2-yl)furan (trans-4h). Yield (0.84 g, 87%) asa white solid; mp 168e171 �C; [Found: C, 45.61; H, 4.17; N, 7.24C7H7NO3S C, 45.40; H, 3.81; N, 7.56%]; Rf (5% EtOAc/hexane) 0.55; IR(KBr) nmax 3051, 2999, 1603, 1585, 1454, 745, 701 cm�1. 1H NMR(400 MHz; CDCl3) 7.70 (1H, dd, J¼1.8 Hz, 3-furyl), 6.96 (1H, d,J¼3.5 Hz, 3-furyl), 6.61(1H, dd, J¼3.5 Hz,1.8 Hz, 3-furyl), 4.52 (1H, d,J¼8.5 Hz, 2-H), 4.19 (1H, ddd, J¼8.5, 7.8, 2.9 Hz, 3-H), 3.66 (1H, dd,J¼11.2, 7.8 Hz, 4-Hb), 3.22 (1H, dd, J¼11.2, 2.9 Hz, 4-Ha); 13C NMR(100 MHz, CDCl3): d 27.2, 37.9, 91.4, 110.7, 118.4, 139.6, 142.9. EIMS(m/z)¼195 (Mþ).

4.4. General procedure for the synthesis of 2,3,4-trisubs-tituted thietanes 6

To a solution of BayliseHillman adduct 1 (5 mmol) in dry THF(4 mL) was added IBX (5 mmol) and stirred at rt for 5 h to get a,b-unsaturated aldehyde 3. Then, to a solution of O,O-diethyl hydrogenphosphorodithioate 2 (5 mmol) in dry THF (5 mL) was addeddropwise a suspension of NaH (10 mmol) in dry THF (20 mL) withstirring to rt. After the addition was complete and evolution ofhydrogen gas (effervescence) had ceased, the reaction mixture wasstirred at 60 �C for 30min and then cooled to rt. In this solutionwasadded a,b-unsaturated aldehyde 3 followed by [bmim]XeY(5 mmol) and the reaction mixture was stirred at rt for 2e4 h.Water (30 mL) was added, the mixture was extracted with ether(3�30mL), the combined organic layers were dried over anhydroussodium sulfate, filtered and evaporated under reduced pressure.The crude product thus obtained was purified by silica gel columnchromatography (hexane/EtOAc, 95:5) to afford an analyticallypure sample of 6.

4.4.1. 3-Nitro-2-phenyl-4-thiocyanatothietane (trans-6a). Yield(1.05 g, 84%) as a white solid; mp 178e180 �C; [Found: C, 47.87; H,3.41; N, 10.91 C10H8N2O2S2 requires C, 47.60; H, 3.20; N, 11.10%]; Rf(5% EtOAc/hexane) 0.56; IR (KBr) nmax 3052, 2992, 2195,2070,1605, 1585, 1455, 750, 705 cm�1; 1H NMR (400 MHz; CDCl3)7.38e7.77 (5H, m, Ph), 4.50 (1H, d, J¼8.9 Hz, 4-H), 4.15 (1H, dd,J¼8.9, 7.7 Hz, 3-H), 3.45 (1H, d, J¼7.7 Hz, 2-H); 13C NMR (100 MHz,CDCl3) 139.4, 129.9, 128.4, 126.5, 112.1, 97.1, 43.9, 42.5; EIMS (m/z)¼252 (Mþ).

4.4.2. 2-(4-Chlorophenyl)-3-nitro-4-thiocyanatothietane (trans-6b). Yield (1.34 g, 94%) as a white solid; mp 174e179 �C; [Found: C,41.58; H, 2.20; N, 9.48 C10H7ClN2O2S2 requires C, 41.88; H, 2.46; N,9.77%]; Rf (5% EtOAc/hexane) 0.49; IR (KBr) nmax 3051, 2995, 2194,2071, 1601, 1585, 1457, 751, 702 cm�1; 1H NMR (400 MHz; CDCl3)8.10e8.17 (2H, m, 4-ClPh), 8.09e8.13 (2H, m, 4-ClPh), 4.54 (1H, d,J¼8.7 Hz, 4-H), 4.17 (1H, dd, J¼8.7, 7.8 Hz, 3-H), 3.41 (1H, d, J¼7.8 Hz,2-H); 13C NMR (100 MHz, CDCl3) 137.9, 131.8, 129.0, 128.7, 111.4,97.5, 43.1, 42.9; EIMS (m/z)¼286, 288 (Mþ, Mþþ2).

4.4.3. 2-(2-Chlorophenyl)-3-nitro-4-thiocyanatothietane (trans-6c). Yield (1.24 g, 87%) as a white solid; mp 171e173 �C; [Found: C,42.13; H, 2.27; N, 9.98 C10H7ClN2O2S2 C, 41.88; H, 2.46; N, 9.77%]; Rf(5% EtOAc/hexane) 0.52; IR (KBr) nmax 3054, 2991, 2197, 2070, 1606,1581, 1454, 754, 701 cm�1; 1H NMR (400 MHz; CDCl3) 3.43 (1H, d,J¼7.6 Hz, 2-H), 4.12 (1H, dd, J¼8.9, 7.6 Hz, 3-H), 4.56 (1H, d,J¼8.9 Hz, 4-H), 8.09e8.13 (2H, m, 2-ClPh), 8.10e8.17 (2H, m, 2-

ClPh); 13C NMR (100 MHz, CDCl3) 137.5, 133.9, 129.6, 128.7, 127.6,126.5, 112.3, 97.1, 43.7, 33.2; EIMS (m/z)¼286, 288 (Mþ, Mþþ2).

4.4.4. 2-(4-Methoxyphenyl)-3-nitro-4-thiocyanatothietane (trans-6d). Yield (1.31 g, 93%) as a white solid; mp 174e177 �C; [Found: C,46.48; H, 3.81; N, 9.58 C11H10N2O3S2 requires C, 46.79; H, 3.57; N,9.92%]; Rf (5% EtOAc/hexane) 0.50; IR (KBr) nmax 3054, 2998, 2194,2069, 1602, 1581, 1452, 754, 708 cm�1; 1H NMR (400 MHz; CDCl3)8.01e8.04 (2H, m, 4-OCH3Ph), 7.66e7.69 (2H, m, 4-OCH3Ph), 4.52(1H, d, J¼8.6 Hz, 4-H), 4.13 (1H, dd, J¼8.6, 7.9 Hz, 3-H), 3.81 (3H, s,OCH3), 3.47 (1H, d, J¼7.9 Hz, 2-H); 13C NMR (100MHz, CDCl3) 158.3,132.1,129.4,114.7,111.5, 97.6, 55.4, 43.9, 42.1; EIMS (m/z)¼282 (Mþ).

4.4.5. 3-Nitro-2-phenyl-4-thiocyanatothietane (trans-6e). Yield(1.28 g, 85%) as a white solid; mp 179e182 �C; [Found: C, 59.74; H,4.11; N, 4.35 C15H13NO2S2 requires C, 59.38; H, 4.32; N, 4.62%]; Rf(5% EtOAc/hexane) 0.57; IR (KBr) nmax 3050, 2996, 2195, 2072, 1602,1583, 1456, 755, 705 cm�1; 1H NMR (400 MHz; CDCl3) 3.46 (1H, d,J¼7.9 Hz, 2-H), 4.17 (1H, dd, J¼8.8, 7.9 Hz, 3-H), 4.50 (1H, d,J¼8.8 Hz, 4-H), 7.32e7.79 (10H, m, Ph); 13C NMR (100 MHz, CDCl3)139.7, 136.4, 130.6, 129.5, 128.6, 127.8, 126.8, 125.4, 96.8, 44.1, 42.4;EIMS (m/z)¼303 (Mþ).

4.4.6. 2-(4-Chlorophenyl)-3-nitro-4-(phenylthio)thietane (trans6f). Yield (1.54 g, 91%) as a white solid; mp 167e170 �C; [Found: C,53.01; H, 3.30; N, 4.41 C15H12ClNO2S2 C, 53.33; H, 3.58; N, 4.15%]; Rf(5% EtOAc/hexane) 0.53; IR (KBr) nmax 3057, 2995, 2192, 1608, 1587,1454, 751, 706 cm�1; 1H NMR (400 MHz; CDCl3) 8.12e8.18 (2H, m,4-ClPh), 8.05e8.10 (2H, m, 4-ClPh), 7.37e7.78 (5H, m, Ph), 4.55 (1H,d, J¼8.9 Hz, 4-H), 4.19 (1H, dd, J¼8.9, 7.6 Hz, 3-H), 3.49 (1H, d,J¼7.6 Hz, 2-H); 13C NMR (100 MHz, CDCl3) 137.8, 130.7, 129.8, 128.5,126.4, 125.5, 97.3, 44.5, 42.7; EIMS (m/z)¼337, 339 (Mþ, Mþþ2).

4.4.7. 2-(2-Chlorophenyl)-3-nitro-4-(phenylthio)thietane (trans6g). Yield (1.52 g, 90%) as a white solid; mp 174e177 �C; [Found: C,53.52; H, 3.91; N, 4.42 C15H12ClNO2S2 requires C, 53.33; H, 3.58; N,4.15%]; Rf (5% EtOAc/hexane) 0.55; IR (KBr) nmax 3054, 2998, 2194,1602, 1581, 1452, 754, 708 cm�1; 1H NMR (400 MHz; CDCl3) 3.47(1H, d, J¼7.9 Hz, 2-H), 4.13 (1H, dd, J¼8.6, 7.9 Hz, 3-H), 4.52 (1H, d,J¼8.6 Hz, 4-H), 7.35e7.71 (5H, m, Ph), 8.07e8.11 (2H, m, 2-ClPh),8.12e8.17 (2H, m, 2-ClPh); 13C NMR (100 MHz, CDCl3) 137.4, 136.1,132.9, 131.8, 130.6, 129.8, 128.9, 128.0, 126.9, 125.7, 96.2, 44.7, 32.9;EIMS (m/z)¼337, 339 (Mþ, Mþþ2).

4.4.8. 2-(4-Methoxyphenyl)-3-nitro-4-(phenylthio)thietanes (trans6h). Yield (1.53 g, 92%) as a white solid; mp 178e179 �C; [Found: C,57.96; H, 4.83; N, 4.01 C16H15NO3S2 requires C, 57.64; H, 4.53; N,4.20%]; Rf (5% EtOAc/hexane) 0.56; IR (KBr) nmax 3054, 2998, 2194,1602, 1581, 1452, 754, 708 cm�1; 1H NMR (400 MHz; CDCl3)8.01e8.04 (m, 2H, 4-OCH3Ph), 7.66e7.69 (m, 2H, 4-OCH3Ph), 4.52(1H, d, J¼8.6 Hz, 4-H), 4.13 (1H, dd, J¼8.6, 7.9 Hz, 3-H), 2.32 (3H, s,CH3); 13C NMR (100 MHz, CDCl3) 158.5, 136.7, 131.8, 130.4. 129.1,127.2, 125.8, 114.9, 97.6, 55.1, 44.5, 42.4; EIMS (m/z)¼333 (Mþ).

4.4.9. 3-Nitro-4-phenylthietan-2-yl-nitrate (trans-6i). Yield (1.06 g,83%) as a white solid; mp 178e182 �C; [Found: C, 42.39; H 3.57; N,9.57 C9H8N2O4S requires C, 42.19; H, 3.15; N, 10.93%]; Rf (5% EtOAc/hexane) 0.55; IR (KBr) nmax 3056, 2997, 2192, 1602, 1584, 1454, 754,702 cm�1; 1H NMR (400 MHz; CDCl3) 7.35e7.77 (5H, m, Ph), 4.56(1H, d, J¼8.5 Hz, 4-H), 4.14 (1H, dd, J¼8.5, 7.4 Hz, 3-H), 3.44 (1H, d,J¼7.4 Hz, 2-H); 13C NMR (100 MHz, CDCl3) 139.7, 130.2, 128.9, 126.4,92.1, 85.7, 42.4; EIMS (m/z)¼256 (Mþ).

4.4.10. 3-Nitro-4-phenylthietan-2-yl-trifluoromethanesulfonate(trans-6j). Yield (1.54 g, 90%) as a white solid; mp 176e179 �C;[Found: C, 34.63; H, 2.65; N, 3.87 C10H8F3NO5S2 requires C, 34.99; H,

A. Rai, L.D.S. Yadav / Tetrahedron 68 (2012) 2459e24642464

2.35; N, 4.08%.]; Rf (5% EtOAc/hexane) 0.58; IR (KBr) nmax 3054,2993, 2194, 1609, 1581, 1450, 751, 708 cm�1; 1H NMR (400 MHz;CDCl3) 7.32e7.74 (m, 5H, Ph), 4.55 (d, J¼8.6 Hz, 1H, 4-H), 4.19 (dd,J¼8.6, 7.6 Hz, 1H, 3-H), 3.47 (1H, d, J¼7.6 Hz, 2-H); 13C NMR(100 MHz, CDCl3) 138.7, 130.4, 128.6, 125.8, 117.5 (q, CF3), 94.1, 68.6,39.6; EIMS (m/z)¼343 (Mþ).

4.4.11. 3-(3-Nitro-4-thiocyanatothietan-2-yl)furan (trans-6k). Yield(1.07 g, 89%) as a white solid; mp 172e176 �C; [Found: C, 39.41; H,2.78; N,11.76 C8H6N2O3S2 requires C, 39.66; H, 2.50; N,11.56%]; Rf (5%EtOAc/hexane) 0.54; IR (KBr) nmax 3052, 2991, 2194, 2070,1601,1585,1458,759,703cm�1; 1HNMR(400MHz;CDCl3)7.69 (1H,dd, J¼1.9Hz,3-furyl), 6.98 (1Hd, J¼3.5Hz, 3-furyl), 6.64 (1H, dd, J¼3.5Hz,1.9Hz, 3-furyl), 4.51 (1H, d, J¼8.3Hz, 4-H), 4.15 (1H, dd, J¼8.3, 7.9 Hz, 3-H), 3.42(1H, d, J¼7.9 Hz, 2-H); 13C NMR (100 MHz, CDCl3) 154.8, 142.1, 112.5,110.8, 105.6, 96.7, 42.2, 40.5; EIMS (m/z)¼242 (Mþ).

4.4.12. 3-(3-Nitro-4-(phenylthio)thietan-2-yl)furan (trans-6l). Yield(1.36 g, 93%) as a white solid; mp 179e183 �C; [Found: C, 53.46; H,3.47; N, 5.04 C13H11NO3S2: C, 53.22; H, 3.78; N, 4.77%]; Rf (5% EtOAc/hexane) 0.58; IR (KBr) nmax 3054, 2995, 2196, 1605, 1581, 1455, 752,706 cm�1. 1H NMR (400 MHz; CDCl3) 7.30e7.75 (m, 5H, Ph), 7.70(1H, dd, J¼1.7 Hz, 3-furyl), 6.96 (1H, d, J¼3.5 Hz 3-furyl), 6.61(1H,dd, J¼3.5 Hz, 1.7 Hz, 3-furyl), 4.52 (1H, d, J¼8.6 Hz, 4-H), 4.13 (1H,dd, J¼8.6, 7.9 Hz, 3-H), 3.47 (1H, d, J¼7.9 Hz, 2-H); 13C NMR(100MHz, CDCl3) 152.4, 141.5, 136.9, 129.4, 127.2, 125.6, 110.4, 104.6,95.9, 42.1, 39.5; EIMS (m/z)¼293 (Mþ).

Acknowledgements

We sincerely thank SAIF, Punjab University, Chandigarh, forproviding microanalyses and spectra. A.R. is grateful to the CSIR,New Delhi, for a Research Associateship (CSIR File No. 09/001/(0327)/2010/EMR-I).

References and notes

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