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Tetrahedron 68 (2012) 4242e4247

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Tetrahedron

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Convenient one-pot synthesis of thiosugars and their efficient conversion topolyoxygenated cycloalkenes

Jingjing Zhang a, Youhong Niu a,b, Xiaoping Cao b, Xin-Shan Ye a,*

a State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd No. 38, Beijing 100191, Chinab State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, China

a r t i c l e i n f o

Article history:Received 3 February 2012Received in revised form 11 March 2012Accepted 20 March 2012Available online 24 March 2012

Keywords:TetrahydrothiopyransThiepanesThiosugarsCycloalkenesRambergeBacklund reaction

* Corresponding author. Fax: þ86 10 82802724bjmu.edu.cn (X.-S. Ye).

0040-4020/$ e see front matter � 2012 Elsevier Ltd.doi:10.1016/j.tet.2012.03.086

a b s t r a c t

A convenient synthesis of polyoxygenated tetrahydrothiopyrans and thiepanes from various alditol de-rivatives with xylo, ribo, manno, gluco, galacto, and fuco configurations is described. The preparationstarted from the corresponding partially protected alditols and proceeded in a ‘one-pot’ manner to affordthe final products in 80%e95% yield. Furthermore, thiosugar compounds 2b, 2d, and 2g were convertedto the optically pure polyoxygenated cycloalkenes through RambergeBacklund reaction in moderate togood overall yield. The procedures can be used for the preparation of polyoxygenated thiosugars andcycloalkenes on a relatively large scale.

� 2012 Elsevier Ltd. All rights reserved.

1. Introduction

Thiosugars are carbohydrate analogs, in which one or moreoxygen atoms are substituted by a sulfur atom both in the pyran-oside and furanoside structures.1 In the last two decades, thesecompounds have attracted much attention from chemists andbiochemists due to their biological importance. For instance, thio-sugars and their derivatives have shown potent inhibitory activitiestoward glycosidases and some of these thiosugars have showngood specificity.2b The inhibitory activities are attributed to thestronger hydrophobic interaction between the sulfur-containingcarbohydrates and the enzymes.2 Thiosugars also can be de-veloped as potential therapeutical agents, such as antineoplastic,3

antidiabetic,4 antiviral,5 and antithrombotic6 agents. Moreover,they are important synthons for the preparation of inositol andaminocyclitol derivatives.4 Given their diverse biological activitiesand usefulness in organic synthesis, many strategies are nowavailable for the preparation of thiosugars, including chemical andbiochemical transformations.1,7

Tetrahydrothiopyrans and thiepanes are basic structures or keyintermediates of bioactive thiosugars.8 The syntheses of thesecompounds, starting from partially protected alditols or semi-protected aldoses, usually involve the activation of dihydroxylgroups to form bielectrophilic substrates, which are subsequently

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cyclized with the sulfur functionality.9 The bielectrophilic sub-strates include bis-epoxyhexitols,9c dibromoalditol derivatives,9b,9e

biscyclic sulfates,10 biscyclic thionocarbonates,11 and so on. Allthese syntheses are based on a multi-step reaction sequence.Therefore, more efficient approaches to prepare this type of com-pounds in fewer steps are still needed. As part of our continuingexploration of the syntheses and biological activities of carbohy-drate mimetics,12 we describe here a convenient ‘one-pot’ pro-cedure for the preparation of polyoxygenated tetrahydrothiopyransand thiepanes starting from alditols. Furthermore, these thiosugarcompounds can be converted to optically pure cycloalkenes, whichare also functioned as carbohydrate mimetics through Ram-bergeBlacklund reaction in two steps.

2. Results and discussion

Our ‘one-pot’ synthesis started from different diols, which wereprepared from natural sugars or alditols according to literatureprocedures.13 After the activation of two hydroxyl groups by mesy-lation, the cyclization was subsequently achieved by the treatmentwith Na2S$9H2O in DMF. The two reactions were performed in oneflask without the purification of the intermediates, and the finalproducts were obtained in high isolated yields. For example, when2,3,4-tris(benzyloxy)pentane-1,5-diols 1a and 1b were mesylatedwith methylsulfonyl chloride followed by the treatment with so-dium sulfide, the corresponding tetrahydrothiopyrans 2a and 2bwere furnished in 90%and85%yields, respectively, (Table 1, entries 1

Table 1Synthesis of tetrahydrothiopyrans and thiepanes from diols

Entry Diol Cyclic thioether Yield (%)

1

OH OH

OBn

OBnBnO1a

S

OBn

OBnBnO2a

90%

2

OH OH

OBn

OBnBnO1b

S

OBn

OBnBnO2b

85%

3

OH

OBn

OH

OBn

OBnBnO1c

S

OBn

OBn

OBnBnO2c

80%

4

OH

OBn

OH

OBn

OBnBnO1d

S

OBn

OBn

OBnBnO2d

95%

5

OH

OBn

OH

OBn

OBnBnO1e

S

OBn

OBn

OBnBnO2e

91%

6

OH

OBn

OBnBnO

OH

1f

S

OBn

OBnBnO2f

83%

7 BnO

BnO OBn

OBn

HO OH

1g

S

BnO

BnO OBn

OBn

2g

90%

8 BnO

BnO OBn

OBn

HO OH

1h

S

BnO

BnO OBn

OBn

2h

91%

9 BnO

BnO OBn

OBn

HO OH

1i

S

BnO

BnO OBn

OBn

2i

89%

J. Zhang et al. / Tetrahedron 68 (2012) 4242e4247 4243

and 2). The same one-pot reaction was also applied to diols 1ce1f,each of them possessed both a secondary and a primary hydroxylgroups. As expected, the products 2ce2fwere obtained smoothly in80%e95%yieldswith the inversionof C5 chiral centers of diols1ce1f

(Table 1, entries 3e6). Thus, polyoxygenated tetrahydrothiopyranswere efficiently achieved in this way.

Moreover, this one-pot approach was perfectly extended to thesynthesis of the seven-membered polyoxygenated thiepanes as

J. Zhang et al. / Tetrahedron 68 (2012) 4242e42474244

well. Polyoxygenated thiepanes are potential inhibitors towardglycosidases14 and HIV proteases.15 The existing methods for thesynthesis of thiepanes suffer from low yield and poor regiose-lectivity due to the formation of rearranged products.9e Startingfrom various 2,3,4,5-tetrakis-benzyloxy-hexane-1,6-diols, the pol-yoxygenated thiepanes with different configurations were pre-pared in a one-pot fashion. As shown in Table 1, the correspondingthiepanes 2g, 2h, 2i were provided in 90%, 91%, and 89% yield, re-spectively, and no rearrangement products were isolated (entries7e9). In addition, all these reactions were able to be performed ona relatively large scale (30e40mmol) with practically no changes inyields or the reaction time.

On the other hand, polyoxygenated cycloalkenes are the im-portant structural units of many naturally occurring compounds,such as prostaglandins,16 mannostatins,17 trehazolin,18 and pente-nomycins.19 This type of compounds are also used as carbohydratemimetics. Currently, there are many methods for the synthesis ofpolyoxygenated cycloalkenes including McMurry coupling,20 olefinmetathesis,21 free radical reaction, RambergeBacklund rearrange-ment,22 and so on. It is known that thiosugars can be used as thestarting materials for the RambergeBacklund rearrangement.Therefore the RambergeBacklund rearrangement reactions by us-ing the synthetic tetrahydrothiopyrans and thiepanes to generatepolyoxygenated cycloalkenes were examined.

Tetrahydrothiopyran 2b was chosen for this purpose. Aftertreatment with N-chlorosuccinimide, compound 2bwas convertedto the anomeric chloride, which was followed by in situ oxidizationto yield chlorosulfone 3b. Compound 3bwas treatedwith t-BuOK inTHF at �15 �C, affording optically pure polyoxygenated cyclo-pentene 4b in 72% isolated yield. Likewise, using the same reactionsequence, tetrahydrothiopyran 2d and thiepane 2g with four sub-stituents were also transformed to the corresponding cyclopentene4d and cyclohexene 4g in 40% and 51% overall yield, respectively,(Scheme 1). The transformation from thiosugars to cycloalkenes ona relatively large scale was also performed. Starting from 30 mmolof 2d and 2g, the respective products 4d and 4g were obtained in48% and 55% yield, which are even higher than the yields of smallscale reactions. Therefore, this is an efficient and practical strategyfor the preparation of polyoxygenated cycloalkenes from the thio-sugar derivatives made by our one-pot procedure.

S

OBn

OBnBnO

S

O

BnO

O

S

OBn

OBnBnO

OBn

BnO

BnO O

OBnBnO

S

OBnBnO

BnO

BnO

O

NCS, CCl4

NCS, CCl4

2b

2d

2g

NCS, CCl4

m-CPBA,CH2Cl273%

m-CPBA,CH2Cl276%

m-CPBA,CH2Cl278%

Scheme 1. Synthesis of polyo

3. Conclusions

In summary, a convenient one-pot protocol was developed forthe synthesis of polyoxygenated tetrahydrothiopyrans and thie-panes with xylo, ribo, gluco,manno, fuco, and galacto configurationsin good yields starting from various diols. And the conversion ofpolyoxygenated tetrahydrothiopyrans and thiepanes to opticallypure polyoxygenated cycloalkenes also proceeded very well. Theprocedures can be applied to the preparation of polyoxygenatedthiosugars and cycloalkenes on a relatively large scale. Due to thesemerits, the disclosed strategy may find wide applications in thesynthesis of biologically important carbohydrate mimetics, such asthiosugars and polyoxygenated cycloalkenes.

4. Experimental section

4.1. General

Reagents were purchased and used without further purification.Tetrahydrofuran (THF) was distilled over sodium/benzophenone,and dichloromethane (CH2Cl2) was dried over calcium hydride. Allreactions were carried out under argon atmosphere with dry,freshly distilled solvents under anhydrous conditions, unless oth-erwise noted. Reactions were monitored with analytical TLC onsilica gel 60-F254 precoated aluminum plates and visualized underUV (254 nm) and/or by staining with acidic ceric ammonium mo-lybdate. Column chromatography was performed on silica gel(35e75 mm). 1H NMR spectra were recorded on a Varian VXR-300Mspectrometer at 20 �C. 13C NMR spectra were obtained by using thesame Varian NMR spectrometers. Mass spectra were recorded us-ing a PE SCLEX QSTAR spectrometer. Elemental analysis data wererecorded on PE-2400C elemental analyzer.

4.2. General procedure for the synthesis of polyoxygenatedtetrahydrothiopyrans and thiepanes

To a stirred solution of diol (1.0 mmol) in CH2Cl2 (30 mL) andEt3N (3.0 mmol) cooled with an iceeacetone bath under argon,MeSO2Cl (2.4 mmol) was added dropwise. The solution was stirredfor 2 h followed by the addition of saturated NaHCO3 (30 mL). The

Bn

OBn

ClO

OBn

OBnBnO

S

OBn

OBnOBn

OBnBnO

OOBn

OBn

S

OBn

OCl

BnO

BnO OBn

OBn

3b 4b

3d 4d

3g 4g

Cl

t-BuOK

THF, 72%

t-BuOK

THF, 52%

THF, 65%

t-BuOK

xygenated cycloalkenes.

J. Zhang et al. / Tetrahedron 68 (2012) 4242e4247 4245

mixture was extracted with CH2Cl2 (3�30 mL), and the combinedorganic phase was washed with brine (60 mL), dried over Na2SO4and evaporated to give crude product. The crude product was dis-solved in DMF (20 mL), to this solution excessive Na2S$9H2O(1.5 mmol) was added, and the mixture was heated at 85 �C untilthe starting material disappeared. The solvent was removed underreduced pressure, and the residue was purified by column chro-matography on silica gel (petroleum ether:ethyl acetate¼40:1e20:1) to afford the product.

4.2.1. (3S,4R,5R)-3,4,5-Tris(benzyloxy)etetrahydro-2H-thiopyran(2a). This compound was prepared from 1a13a (60.0 mg,0.14 mmol) according to the general procedure to give product 2a(54.2 mg, 90%) as an oil. 1H NMR (300 MHz, CDCl3): d 7.41e7.25 (m,15H), 4.87 (s, 2H), 4.60 (d, J¼12.0 Hz, 2H), 4.52 (d, J¼12.0 Hz, 2H),4.14 (s, 1H), 3.57 (d, J¼11.4 Hz, 2H), 3.04 (t, J¼11.4 Hz, 2H), 2.44 (m,2H). 13C NMR (75 MHz, CDCl3): d 139.30, 138.32, 128.42, 128.09,127.79, 127.63, 127.37, 80.22, 74.12, 70.73, 25.45. HRMS calcd forC26H28NaO3S (MþNaþ): 443.1651, found: 443.1649. Anal. calcd forC26H28O3S: C, 74.25; H, 6.71; found C, 74.37; H, 6.80.

4.2.2. (3S,4S,5R)-3,4,5-Tris(benzyloxy)etetrahydro-2H-thiopyran(2b). This compound was prepared from 1b13b (600.0 mg,1.42 mmol) according to the general procedure to give product 2b(507.0 mg, 85%) as a white solid. 1H NMR (300 MHz, CDCl3):d 7.34e7.25 (m, 15H), 4.86 (s, 2H), 4.72 (d, J¼11.7 Hz, 2H), 4.65 (d,J¼11.4 Hz, 2H), 3.67 (dd, J¼4.5, 12.0 Hz, 1H), 3.64 (dd, J¼1.8, 6.6 Hz,1H), 3.34 (t, J¼8.7 Hz, 1H), 2.75 (dd, J¼2.4, 13.2 Hz, 2H), 2.51 (t,J¼11.1 Hz, 2H). 13C NMR (75 MHz, CDCl3): d 138.81, 138.29, 128.42,128.30, 128.07, 127.82, 127.73, 127.53, 86.71, 82.19, 76.35, 73.01,31.45. HRMS calcd for C26H32NO3S (MþNH4

þ): 438.2097, found:438.2089. The spectroscopic data coincide with the previousreport.23

4.2.3. (2S,3S,4R,5R)-3,4,5-Tris(benzyloxy)-2-(benzyloxymethyl)etet-rahydro-2H-thiopyran (2c). This compound was prepared from1c13c (80.0 mg, 0.15 mmol) according to the general procedure toafford product 2c (64.4 mg, 80%) as an oil. 1H NMR (300 MHz,CDCl3): d 7.36e7.28 (m, 20H), 4.76e4.60 (m, 8H), 3.87e3.80 (m, 3H),3.66 (m,1H), 3.54 (t, J¼9.0 Hz, 1H), 3.08 (br s, 1H), 2.82 (t, J¼13.2 Hz,1H), 2.61 (dd, J¼2.1, 13.2 Hz, 1H). 13C NMR (75 MHz, CDCl3):d 138.76, 138.32, 138.19, 138.15, 128.38, 128.24, 128.05, 127.76,127.65, 127.50, 82.65, 82.42, 81.95, 75.98, 73.15, 72.91, 72.82, 67.31,41.89, 27.32. HRMS calcd for C34H40NO4S (MþNH4

þ): 558.2673,found: 558.2671. Anal. calcd for C34H36O4S: C, 75.52; H, 6.71; foundC, 75.33; H, 6.76. The spectroscopic data coincide with the previousreport.23

4.2.4. (2S,3R,4R,5R)-3,4,5-Tris(benzyloxy)-2-(benzyloxymethyl)etet-rahydro-2H-thiopyran (2d). This compound was prepared from1d13c (4.5 g, 8.4 mmol) according to the general procedure to affordproduct 2d (4.3 g, 95%) as an oil. 1H NMR (300 MHz, CDCl3):d 7.33e7.25 (m, 20H), 4.67 (d, J¼12.0 Hz, 1H), 4.59e4.49 (m, 6H),4.43 (d, J¼12.0 Hz, 1H), 4.04 (dd, J¼2.4, 9.3 Hz, 1H), 3.86e3.84 (m,1H), 3.74 (dd, J¼4.2, 9.6 Hz, 1H), 3.69e3.63 (m, 2H), 3.55e3.49 (m,1H), 3.05 (dd, J¼2.1, 14.1 Hz, 1H), 2.51 (dd, J¼4.5, 13.8 Hz, 1H). 13CNMR (75 MHz, CDCl3): d 138.47, 138.25, 138.21, 138.09, 128.30,128.02, 127.65, 77.21, 77.17, 75.49, 74.96, 73.09, 72.14, 71.10, 69.53,40.82, 27.35. HRMS calcd for C34H40NO4S (MþNH4

þ): 558.2673,found: 558.2684. Anal. calcd for C34H36O4S: C, 75.52; H, 6.71; foundC, 75.33; H, 6.81.

4.2.5. (2S,3S,4R,5S)-3,4,5-Tris(benzyloxy)-2-(benzyloxymethyl)etet-rahydro-2H-thiopyran (2e). This compound was prepared from1e13c (160.0 mg, 0.29 mmol) according to the general procedure toafford product 2e (143.0 mg, 91%) as an oil. 1H NMR (300 MHz,

CDCl3): d 7.36e7.25 (m, 18H), 7.14 (dd, J¼7.2, 2.4 Hz, 2H), 4.72 (d,J¼2.0 Hz, 1H), 4.57 (t, J¼12.3 Hz, 1H), 4.49e4.36 (m, 6H), 4.01e3.95(ddd, J¼3.9, 6.0, 9.3 Hz, 1H), 3.87 (dd, J¼1.8, 4.8 Hz, 1H), 3.68e3.64(m, 1H), 3.56 (td, J¼1.8, 8.4 Hz, 1H), 3.52e3.41 (m, 2H), 3.15 (t,J¼12.6 Hz, 1H), 2.50 (dd, J¼3.6, 12.6 Hz, 1H). 13C NMR (75 MHz,CDCl3): d 138.60, 138.47, 138.06, 137.98, 128.36, 128.27, 128.20,127.86, 127.73, 127.61, 127.52, 75.99, 75.73, 74.26, 73.22, 72.98,72.85, 70.92, 68.76, 39.76, 25.44. HRMS calcd for C34H40NO4S(MþNH4

þ): 558.2673, found: 558.2666. Anal. calcd for C34H36O4S: C,75.52; H, 6.71; found C, 75.29; H, 6.87.

4.2.6. (2R,3S,4R,5S)-3,4,5-Tris(benzyloxy)-2-methyletetrahydro-2H-thiopyran (2f). This compound was prepared from 1f13d (35.0 mg,0.08 mmol) according to the general procedure to afford product 2f(29.5 mg, 83%) as an oil. 1H NMR (300 MHz, CDCl3): d 7.37e7.25 (m,15H), 4.69 (d, J¼12.0 Hz, 1H), 4.55 (d, J¼12.0 Hz, 2H), 4.50 (d,J¼6.0 Hz, 2H), 4.40 (d, J¼12.6 Hz, 1H), 3.85e3.82 (m, 1H), 3.71e3.68(m, 2H), 3.37e3.32 (m, 1H), 3.13 (dd, J¼2.1, 14.1 Hz, 1H), 2.41 (dd,J¼3.9, 14.1 Hz, 1H), 1.27 (d, J¼6.9 Hz, 3H). 13C NMR (75 MHz, CDCl3):d 138.52, 138.32, 138.15, 128.35, 128.27, 128.05, 127.66, 127.56, 81.57,75.10, 74.65, 73.13, 72.38, 70.96. 34.59, 27.59, 16.97. HRMS calcd forC27H34NO3S (MþNH4

þ): 452.2254, found: 452.2252.

4.2.7. (3S,4S,5S,6S)-3,4,5,6-Tetrakis(benzyloxy) thiepane (2g). Thiscompound was prepared from 1g13e (70.0 mg, 0.13 mmol)according to the general procedure to afford product 2g (51.3 mg,90%) as an oil. 1H NMR (300 MHz, CDCl3): d 7.35e7.22 (m, 20H),4.73 (d, J¼12.0 Hz, 2H), 4.59 (d, J¼11.4 Hz, 4H), 4.49 (d, J¼12.0 Hz,2H), 4.03 (dd, J¼2.4, 9.6 Hz, 2H), 3.89 (s, 2H), 3.13 (dd, J¼9.6,13.5 Hz, 2H), 2.66 (dd, J¼2.7, 13.5 Hz, 2H). 13C NMR (75 MHz,CDCl3): d 138.58, 138.33, 128.30, 128.24, 127.62, 127.52, 78.87,78.10, 73.42, 71.41, 26.98. HRMS calcd for C34H40NO4S (MþNH4

þ):558.2673, found: 558.2679. Anal. calcd for C34H36O4S: C, 75.52; H,6.71; found C, 75.31; H, 6.68.

4.2.8. (3S,4R,5S,6R)-3,4,5,6-Tetrakis(benzyloxy) thiepane (2h). Thiscompound was prepared from 1h13f (70.0 mg, 0.13 mmol) accord-ing to the general procedure to afford product 2h (51.5 mg, 91%) asan oil. 1H NMR (300 MHz, CDCl3): d 7.30e7.25 (m, 20H), 4.72e4.57(m, 8H), 4.30 (br s, 2H), 3.89 (br s, 2H), 2.97e2.83 (m, 4H). 13C NMR(75 MHz, CDCl3): d 138.66, 138.49, 128.27, 127.66, 127.55, 127.46,81.80, 73.37, 71.46, 35.17. HRMS calcd for C34H40NO4S (MþNH4

þ):558.2673, found: 558.2675. Anal. calcd for C34H36O4S: C, 75.52; H,6.71; found C, 75.31; H, 6.77.

4.2.9. (3S,4S,5S,6R)-3,4,5,6-Tetrakis(benzyloxy) thiepane (2i). Thiscompound was prepared from 1i13g (93.0 mg, 0.26 mmol)according to the general procedure to afford product 2i (83.0 mg,89%) as an oil. 1H NMR (300 MHz, CDCl3): d 7.32e7.19 (m, 20H),4.71 (d, J¼12.0 Hz, 1H), 4.65e4.45 (m, 7H), 4.58 (t, J¼6.9 Hz, 1H),4.54e4.45 (m, 5H), 3.97 (br s, 1H), 3.89 (dd, J¼3.0, 10.5 Hz, 1H),3.78e3.74 (m, 2H), 3.30 (dd, J¼10.8, 13.2 Hz, 1H), 3.20 (dd, J¼9.9,14.4 Hz, 1H), 2.55e2.50 (m, 2H). 13C NMR (75 MHz, CDCl3):d 138.31, 138.24, 138.23, 138.18, 128.35, 128.27, 127.82, 127.74,127.66, 127.55, 127.46, 88.04, 82.05, 80.93, 79.89, 72.81, 71.78,71.31, 29.60, 29.08. HRMS calcd for C34H40NO4S (MþNH4

þ):558.2673, found: 558.2674. Anal. calcd for C34H36O4S: C, 75.52; H,6.71; found C, 75.51; H, 6.60.

4.3. Synthesis of a-chlorosulfones

4.3.1. (2R,3R,4S,5S)-2-Chloro-3,4,5-tris(O-benzyloxy)etetrahy-drothiopyran 1,1-dioxide (3b). Tetrahydrothiopyran 2b (410.0 mg,1.86 mmol) was dissolved in anhydrous CCl4 (20 mL), and the so-lution were heated to 90 �C. Then N-chlorosuccinimide (279.0 mg,2.05mmol) was added in one portion, and the reactionmixturewas

J. Zhang et al. / Tetrahedron 68 (2012) 4242e42474246

stirred at this temperature until TLC showed that the starting ma-terial disappeared. After cooled to room temperature, the mixturewas filtered with exclusion of moisture. The filtrate was dilutedwith CH2Cl2 (20 mL) and cooled at 0 �C, then treated with m-chloroperbenzoic acid (1.3 g, 5.58 mmol). After stirred for 18.5 h atroom temperature under argon, the thick slurry was partitionedbetween dichloromethane (40 mL�3) and saturated Na2S2O3(20 mL). The combined organic layer was washed with brine, driedover MgSO4, filtered, and concentrated under reduced pressure.The residue was purified by column chromatography (petroleumether:ethyl acetate¼8:1) to afford 3b as white solids (345.3 mg,73%). 1H NMR (300 MHz, CDCl3): d 7.34e7.25 (m, 15H), 4.93e4.82(m, 4H), 4.72 (d, J¼11.4 Hz, 1H), 4.67 (d, J¼10.8 Hz, 1H), 4.64 (d,J¼12.0 Hz, 1H), 3.98 (ddd, J¼4.5, 9.0, 13.5 Hz, 1H), 3.82 (t, J¼9.9 Hz,1H), 3.66 (t, J¼9.3 Hz, 1H), 3.54 (dd, J¼4.2, 14.4 Hz, 1H), 3.04 (dd,J¼11.4, 14.4 Hz, 1H). 13C NMR (75 MHz, CDCl3): d 137.67, 137.00,136.80, 128.70, 128.49, 128.37, 128.21, 127.97, 127.74, 85.37, 80.70,74.78, 73.81, 72.05, 51.57. HRMS calcd for C26H31ClNO5S (MþNH4

þ):504.1592, found: 504. 1595.

4.3.2. (2R,3R,4S,5R,6R)-2-Chloro-3,4,5-tris(O-benzyloxy)-6-benzyloxymethyltetrahydrothiopyran 1,1-dioxide (3d). Compound3dwas prepared from tetrahydrothiopyran 2d (260mg, 0.48 mmol)following the same procedure as described in the preparation ofcompound 3b, yielding 3d (221 mg, 76%) as white solids. 1H NMR(300 MHz, CDCl3): d 7.40e7.13 (m, 20H), 4.99 (d, J¼3.3 Hz, 1H),4.71e4.58 (m, 4H), 4.49e4.21 (m, 5H), 4.19 (dd, J¼2.7, 11.1 Hz, 1H),4.12 (dd, J¼5.7, 11.1 Hz, 1H), 3.87e3.84 (m, 2H), 3.67e3.69 (m, 1H).13C NMR (75 MHz, CDCl3): d 137.57, 137.16, 137.02, 136.90, 128.59,128.37, 128.24, 128.19, 127.98, 127.79, 127.66, 74.67, 74.32, 73.96,73.73, 73.53, 73.29, 69.32, 62.56, 61.98. HRMS calcd for C34H36ClO6S(MþHþ): 624.2181, found: 624.2176. Anal. calcd for C34H35ClO6S: C,67.26; H, 5.81; found C, 66.98; H, 5.89.

4.3.3. (2R,3S,4S,5R,6S)-2-Chloro-3,4,5,6-Tetrakis(O-benzyloxy)thie-pane 1,1-dioxide (3g). This compound was prepared from com-pound 2g (350 mg, 0.65 mmol) following the same procedure asdescribed in the preparation of compound 3b, yielding 3g(306 mg, 78%) as white solids. 1H NMR (300 MHz, CDCl3):d 7.31e7.15 (m, 20H), 5.29 (d, J¼8.7H, 1H), 4.77 (d, J¼11.7 Hz, 1H),4.65 (d, J¼12.6 Hz, 1H), 4.62 (d, J¼11.7 Hz, 1H), 4.60 (d, J¼12.9 Hz,1H), 4.49 (d, J¼12.0 Hz, 1H), 4.46 (d, J¼12.3 Hz, 1H), 4.46e4.40(m, 2H), 4.22 (d, J¼9.9 Hz, 1H), 4.02e3.90 (m, 3H), 3.80 (d,J¼5.7 Hz, 1H), 3.36 (d, J¼15 Hz, 1H). 13C NMR (75 MHz, CDCl3):d 137.53, 137.09, 136.89, 136.69, 128.50, 128.17, 128.06, 127.95,127.86, 78.21, 77.19, 75.34, 74.50, 74.13, 73.85, 73.60, 71.77, 71.54,52.01. HRMS calcd for C34H39ClNO6S (MþNH4

þ): 624.2181, found:624.2171.

4.4. Synthesis of cycloalkenes from a-chlorosulfones

4.4.1. (3R,4R,5S)-3,4,5-Tris(benzyloxy)cyclopent-1-ene (4b). To a so-lution of a-chlorosulfone 3b (49.0 mg, 0.1 mmol) in dry THF (3 mL)cooled at e15 �C, t-BuOK (31.3 mg, 0.28 mmol) was added in oneportion. The reaction mixture was stirred at this temperature for20 min, and the saturated NH4Cl aqueous solution (3 mL) wasadded. Then THF was removed under reduced pressure, and theresidue was partitioned between CH2Cl2 (20 mL�3) and water(20mL). The combined organic layer was rinsedwith brine (20mL),dried over Na2SO4, filtered, and concentrated. The residue waspurified by column chromatography (petroleum ether:ethylacetate¼30:1e20:1) to afford product 4b as an oil (28.6 mg, 72%).1H NMR (300 MHz, CDCl3): d 7.35e7.25 (m, 15H), 5.91 (s, 2H), 4.68(s, 2H), 4.60 (s, 4H), 4.48 (d, J¼3.9 Hz, 2H), 4.22 (t, J¼3.9 Hz, 1H). 13CNMR (75 MHz, CDCl3): d 138.29, 138.13, 132.15, 128.37, 127.91,

127.83,127.65, 91.42, 86.28, 72.05, 71.03. HRMS calcd for C26H30NO3(MþNH4

þ): 404.2220, found: 404.2210.

4.4.2. 1-((((3S,4R,5S)-3,4,5-Tris(benzyloxy)cyclopent-1-enyl)me-thoxy)methyl)benzene (4d). This compound was prepared fromcompound 3d (112 mg, 0.18 mmol) following the same procedureas described in the preparation of compound 4b, yielding 4d(48.6 mg, 52%) as an oil. 1H NMR (300 MHz, CDCl3): d 7.39e7.26 (m,20H), 5.99 (d, J¼1.5 Hz, 1H), 4.80e4.78 (m, 1H), 4.74 (d, J¼11.7 Hz,1H), 4.66e4.61 (m, 5H), 4.53 (d, J¼11.7 Hz, 2H), 4.48 (d, J¼12.0 Hz,1H), 4.08 (s, 2H), 4.01 (dd, J¼5.1, 6.0 Hz, 1H). 13C NMR (75 MHz,CDCl3): d 142.22, 138.55, 138.32, 138.21, 138.01, 130.19, 128.38,128.27, 128.08, 127.90, 127.79, 127.69, 127.55, 86.33, 84.29, 78.76,72.62, 72.21, 71.82, 71.40, 67.18. HRMS calcd for C34H38NO4(MþNH4

þ): 524.2838, found: 524.2827. The spectroscopic data co-incide with the previous report.24

4.4.3. (3R,4R,5R,6R)-3,4,5,6-Tetrakis(benzyloxy)ecyclohex-1-ene(4g). This compound was prepared from compound 3g (221 mg,0.36 mmol) following the same procedure as described in thepreparation of compound 4b, yielding 4g (120mg, 65%) as an oil. 1HNMR (300 MHz, CDCl3): d 7.34e7.25 (m, 20H), 5.83 (s, 2H), 4.70 (d,J¼12.0 Hz, 2H), 4.64 (d, J¼12.3 Hz, 2H), 4.62 (d, J¼11.1 Hz, 2H), 4.58(d, J¼12.3 Hz, 2H), 4.25 (s, 2H), 3.99 (s, 2H). 13C NMR (75 MHz,CDCl3): d 138.64,128.30,128.12,128.07,127.87,127.68,127.55, 76.02,73.32, 73.28, 71.63. HRMS calcd for C34H38NO4 (MþNH4

þ): 524.2838,found: 524.2825. The spectroscopic data coincide with the previousreport.13d

Acknowledgements

This work was financially supported by the National NaturalScience Foundation of China (21072014) and ‘973’ grant from theMinistry of Science and Technology of China (2012CB822100).

Supplementary data

Supplementary data related to this article can be found online atdoi:10.1016/j.tet.2012.03.086.

References and notes

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