Rapid Asymmetric Access to β-Hydroxysulfinic Acids and Allylsulfonic Acids by Chemoselective Reduction of β-Sultones

Abstract

The reduction of readily available optically active β-sultones bearing a β-trichloromethyl substituent proceeds chemoselectively at three different sites via C-Cl, C-O or S-O bond cleavage and allows for the formation of highly enantioenriched β-hydroxy­sulfinic acids and allylsulfonic acids.

Key words

reduction - sulfinic acid - sulfonic acid - sultine - sultone

References and Notes

• 1a Koch FM. Peters R. Angew. Chem. Int. Ed.  2007,  46:  2685 
• 1b For β-sultams, see: Zajac M. Peters R. Org. Lett.  2007,  9:  2007 
• 2a Solladié G. Hutt J. Girardin A. Synthesis  1987,  173 
• 2b Davis FA. Reddy RE. Szewczyk JM. Reddy GV. Portonovo PS. Zhang H. Fanelli D. Reddy T. Zhou P. Carroll PJ. J. Org. Chem.  1997,  62:  2555 
• 2c Cogan DA. Liu G. Kim K. Backes BJ. Ellman JA. J. Am. Chem. Soc.  1998,  120:  8011 
• 2d Zhou P. Chen B.-C. Davis FA. Tetrahedron  2004,  60:  8003 
• 2e Evans JW. Fierman MB. Miller SJ. Ellman JA. J. Am. Chem. Soc.  2004,  126:  8134 
• 3a The Chemistry of Sulfinic Acids, Esters, and Their Derivatives   Patai S. Wiley; Chichester: 1990. 
• 3b Krauthausen E. Sulfinsäuren und ihre Derivate, In Houben-Weyl, Methoden der Organischen Chemie   4th ed., Vol. E11:  Klamann D. Thieme; Stuttgart: 1985.  p.614-664  
• 4 Fernández I. Khiar N. Chem. Rev.  2003,  103:  3651 
• 5 For example, analysis to steroid receptor binding: Doré J.-C. Gilbert J. Ojasoo T. Raynaud J.-P. J. Med. Chem.  1986,  29:  54 
• 6 Fitzpatrick K, Geiss W, Lehmann A, Sanden G, and von Unge S. inventors;  WO2002100823. 
• Previous methodologies (selected examples):
• 8a Rearrangement of thietane dioxides: Dodson RM. Hammen PD. Davis RA. J. Org. Chem.  1971,  36:  2693 
• 8b Oxidative cyclization of tert-butyl-3-hydroxyalkylsulfoxides: Sharma NK. de Reinach-Hirtzbach F. Durst T. Can. J. Chem.  1976,  54:  3012 
• 8c insertion of SO₂ into cyclopropane: Bondarenko OB. Voevodskaya TI. Saginova LG. Tafeenko VA. Shabarov YS. Zh. Org. Khim.  1987,  23:  1736 
• 8d Oxidative cyclization of sulfanyl alcohols: King JF. Rathore R. Tetrahedron Lett.  1989,  30:  2763 
• 8e Yolka S. Fellous R. Lizzani-Cuvelier L. Loiseau M. Tetrahedron Lett.  1998,  39:  991 
• 8f Radical cyclization: Coulomb J. Certal V. Fensterbank L. Lacôte E. Malacria M. Angew. Chem. Int. Ed.  2006,  45:  633 
• 9a Yolka S. Dunach E. Loiseau M. Lizzani-Cuvelier L. Fellous R. Rochard S. Schippa C. George G. Flavour Frag. J.  2002,  17:  425 
• 9b

  A biosynthesis has been proposed which proceeds via oxidation of 3-mercaptohexan-1-ol, which is mainly responsible for the flavor of the yellow passion fruit and which has also been detected to considerably contribute to the bouquet of Sauvignon blanc wines (see ref. 9a).

• 11 Inconsistency exists in literature with regard to the relative stability of γ-sultines possessing either an axial or equatorial S=O entity. While isomerization of axial S=O into equatorial S=O on storage at room temperature for several weeks has been reported (ref. 8b), isomerization to an axial S=O with I₂ has been described later: lka S. Fellous R. Lizzani-Cuvelier L. Loiseau M. Tetrahedron Lett.  1999,  40:  3159 
• See ref 1 and for example:
• 13a Corey EJ. Cimprich KA. Tetrahedron Lett.  1992,  33:  4099 
• 13b Lawrence RM. Biller SA. Dickson JK. Logan JVH. Magnin DR. Sulsky RB. DiMarco JD. Gougoutas JZ. Beyer BD. Taylor SC. Lan S. Ciosek CP. Harrity TW. Jolibois KG. Kunselman LK. Slusarchyk DA. J. Am. Chem. Soc.  1996,  118:  11668 
• 13c Enders D. Vignola N. Berner OM. Bats JW. Angew. Chem. Int. Ed.  2002,  41:  109 
• 13d Harnying W. Kitisriworaphan W. Pohmakotr M. Enders D. Synlett  2007,  2529 
• 14 The Chemistry of Sulfonic Acids, Esters and Their Derivatives   Patai S. Rappoport Z. Wiley; Chichester, New York: 1991. 

7

General Procedure for β-Hydroxysulfinic Acids 5: To a stirred solution of the corresponding β-sultone 1 in Et₂O (10 mL/mmol) a solution of LiAlH₄ (1 M in THF, 0.5 equiv) in Et₂O (2.5 mL/mmol 1) was added dropwise at r.t. After 10 min the reaction mixture was quenched with ice and HCl (1 M, 1 mL/mmol 1). Et₂O was removed in a stream of N₂ and the remaining aqueous solution was filtrated over Amberlite IR-120 (acidic form). The resin was washed with H₂O until the eluate was no longer acidic. Concentration in vacuo yielded the corresponding sulfinic acids 5. For 1d and 1e the quenched, acidified reaction mixture was not purified by ion-exchange resin, but extracted with CHCl₃ (4 ×). In the case of 1d quenching the reaction mixture with H₂O followed by extraction with CHCl₃ yielded the corresponding γ-sultine 6.
General Procedure for γ,γ-Dichloroallylsulfonic Acids 7: The corresponding β-sultone 1 was dissolved in EtOH (1 mL/5 mg 1) and Pd (10% on activated charcoal, 0.02 equiv) was added. The suspension was stirred for 21 h under a positive pressure (1 atm) of H₂. The reaction mixture was then filtrated over Celite, repeatedly washed with EtOH and the filtrate was concentrated in vacuo. H₂O (1 mL/5 mg) was added to the dark oily residue and the solids were removed by filtration. Concentration of the colorless filtrate yielded the corresponding sulfonic acids 7.
General Procedure for γ-Monochloroallylsulfonic Acids 11: To a stirred solution of the corresponding β-sultone 10 in THF (1 mL/7 mg) AcOH (5 equiv) was added, followed by Zn dust (5 equiv). The flask was subsequently closed and stirring was continued at 60 °C for 12 h. The reaction mixture was filtrated over Celite and the filter cake was washed with EtOH. The filtrate was concentrated in vacuo and the residue was dissolved in H₂O. To remove unreacted sultone the aqueous layer was washed with MTBE (2 × 25 mL). To remove Zn salts the aqueous layer was subsequently filtrated over Amberlite IR-120 (acidic form) and the resin was washed with H₂O until the eluate was no longer acidic. Concentration in vacuo yielded the corresponding monochloroallylsulfonic acids 11.

10

For a previous X-ray crystal structure analysis of a γ-sultine, see ref. 8c.

12

Each unit cell contains two independent molecules with the same configuration, but with slightly different conformations. The second conformer not depicted in Figure [1] shows a stronger distortion of the envelope resembling a half-chair conformation. Supplementary crystallographic data have been deposited with the Cambridge Crystallographic Data Centre as deposition 676601. This material is available free of charge via the In-ternet at http://www.ccdc.cam.ac.uk/products/csd/request/.

15

Analytical data for sulfinic acids 5: 5a: ¹H NMR (300 MHz, D₂O): δ = 4.66 (d, J = 1.6 Hz, 1 H, CHOH), 3.19 (dq, J = 1.6, 7.2 Hz, 1 H, CHS), 1.36 (dd, J = 7.2 Hz, 3 H, Me). ¹³C NMR (75 MHz, D₂O): δ = 101.8 (CCl₃), 76.9 (CHCCl₃), 61.6 (CSO₂H), 6.3 (Me). IR (ATR): 2970, 2497, 1454, 1365, 1216 cm^-1. [α]_D ^23.6 +37.68 ± 0.12 (c = 1.25, H₂O; sample with ee = 87%). 5b: ¹H NMR (300 MHz, D₂O): δ = 4.57 (d, J = 1.3 Hz, 1 H, CHOH), 2.91 (ddd, J = 1.3, 4.4, 9.3 Hz, 1 H, CHS), 2.00 (tdd, J = 3.4, 7.8, 15.6 Hz, 1 H, CHHCHS), 1.60 (tdd, J = 7.5, 9.3, 15.6 Hz, 1 H, CHHCHS), 0.96 (dd, J = 7.5, 7.8 Hz, 3 H, Me). ¹³C NMR (75 MHz, D₂O): δ = 102.2 (CCl₃), 75.8 (CHCCl₃), 67.1 (CSO₂H), 16.6 (CH₂CH₃), 11.9 (Me). IR (ATR): 3356, 2970, 1365, 1228 cm^-1. [α]_D ^27.9 +53.18 ± 0.12 (c = 0.6, H₂O; sample with ee >99%). 5c: ¹H NMR (300 MHz, D₂O): δ = 4.72 (m, 1 H, CHOH), 2.94-3.06 (m, 1 H, CHS), 1.94-2.14 (m, 1 H, CHHCHS), 1.41-1.81 (m, 3 H, CHHCHS, CH ₂CH₃), 0.83-1.01 (m, 3 H, Me). ¹³C NMR (75 MHz, D₂O): δ = 102.4 (CCl₃), 76.1 (CHCCl₃), 65.5 (CSO₂H), 25.1 (CH₂Et), 20.8 (CH₂ CH₂CH₃), 13.4 (Me). IR (ATR): 3402, 1352, 1139 cm^-1. [α]_D ^24.0 +30.32 ± 0.93 (c = 0.55, H₂O; sample with ee = 85%). 5d: ¹H NMR (300 MHz, CDCl₃): δ = 5.02 (m, 1 H, CHOH), 2.74-3.82 (m, 2 H, CHHCl, CHS), 2.54-3.61 (m, 1 H, CHHCl), 2.74-2.86 (m, 1 H, CHHCHS), 2.28-2.41 (m, 1 H, CHHCHS). ¹³C NMR (75 MHz, CDCl₃): δ = 101.5 (CCl₃), 77.2 (CHCCl₃), 61.7 (CSO₂H), 42.2 (CH₂Cl), 26.0 (CH₂CHS). IR (ATR): 3386, 2923, 1111 cm^-1. [α]_D ^22.0 +31.93 ± 0.49 (c = 1.00, CHCl₃; sample with ee = 96%). 5e: ¹H NMR (300 MHz, CDCl₃): δ = 7.25-7.35 (m, 5 H, CH_Ph), 5.23 (br, 2 H, OH, SO₂H), 5.15 (m, 1 H, CHOH), 2.60-3.78 (m, 2 H, CHHPh, CHS), 3.12 (dd, J = 11.5, 15.3 Hz, 1 H, CHHPh). ¹³C NMR (75 MHz, CDCl₃): δ = 129.2 (2 × C_Ph), 128.8 (2 × C_Ph), 128.7 (C_Ph,q), 127.2 (C_Ph), 101.8 (CCl₃), 76.0 (CHCCl₃), 65.5 (CSO₂H), 29.7 (CH₂Ph). IR (ATR): 3383, 1496, 1454, 1106 cm^-1. [α]_D ^21.5 +41.51 ± 0.44 (c = 1.15, CHCl₃; sample with ee = 99%). γ-Sultine 6: HRMS (EI): m/z [M]⁺ calcd for C₅H₇O₃SCl₃: 251.9176; found: 251.9175. Anal. Calcd for C₅H₇Cl₃O₃S: C, 23.69; H, 2.78. Found: C, 23.90; H, 2.88. (2S)-6: R _f 0.39 (EtOAc-cyclohexane, 1:1); mp 123.5-124.4 °C. ¹H NMR (300 MHz, CDCl₃): δ = 4.88 (ddd, J = 4.0, 8.7, 12.8 Hz, 1 H, CHHO), 4.70 (m, 1 H, CHOH), 4.48-4.57 (m, 1 H, CHHO), 3.76 (d, J = 4.4 Hz, 1 H, OH), 3.72 (ddd, J = 4.4, 8.4, 10.6 Hz, 1 H, CHS), 2.76-2.90 (m, 1 H, CH₂CHHCH), 2.39-2.49 (m, 1 H, CH₂CHHCH). ¹³C NMR (75 MHz, CDCl₃): δ = 101.4 (CCl₃), 78.6 (Cl₃CCHO), 76.0 (CH₂ CH₂O), 68.5 (CHS), 24.1 (CH₂ CH₂CH). IR (ATR): 3292, 1082, 1075 cm^-1. [α]_D ^23.9 -92.33 ± 0.21 (c = 1.05, CHCl₃; sample with ee = 96%). (2R)-6: R _f : 0.50 (EtOAc-cyclohexane, 1:1); mp 108.1-110.0 °C. ¹H NMR (300 MHz, CDCl₃): δ = 4.89 (dt, J = 7.2, 8.4 Hz, 1 H, CHHO), 4.70-4.78 (m, 1 H, CHHO), 4.58 (m, 1 H, CHOH), 3.78-3.85 (m, 1 H, CHS), 3.38 (br, 1 H, OH), 2.52-2.73 (m, 2 H, CH₂CH ₂CH). ¹³C NMR (75 MHz, CDCl₃): δ = 102.0 (CCl₃), 78.1 (Cl₃CCHO), 77.2 (CHS), 75.7 (CH₂ CH₂O), 24.6 (CH₂ CH₂CH). IR (ATR): 3289, 1088, 1051 cm^-1. [α]_D ^23.6 +4.24 ± 1.1 (c = 0.20, CHCl₃; sample with ee = 96%).

16

Analytical data for sulfonic acids 7 and 11: 7a: ¹H NMR (300 MHz, D₂O): δ = 5.83 (d, J = 10.1 Hz, 1 H, CH=CCl₂), 3.78-3.88 (m, 1 H, CHS), 1.26 (d, J = 6.9 Hz, 3 H, Me). ¹³C NMR (75 MHz, D₂O): δ = 126.0 (C=C), 123.8 (C=C), 56.6 (CSO₃H), 14.8 (Me). IR (ATR): 2941, 1621, 1141, 1007 cm^-1. HRMS (ESI): m/z [M - H]^- calcd for C₄H₆O₃SCl₂: 202.9332; found: 202.9343. [α]_D ^22.9 -75.46 ± 0.42 (c = 1.30, H₂O; sample with ee = 85%). 7b: ¹H NMR (300 MHz, D₂O): δ = 5.77 (d, J = 10.4 Hz, 1 H, CH=CCl₂), 3.57-3.67 (m, 1 H, CHS), 1.79-1.95 (m, 1 H, CHHCHS), 1.41-1.57 (m, 1 H, CHHCHS), 0.79 (t, J = 7.3 Hz, 3 H, Me). ¹³C NMR (75 MHz, D₂O): δ = 125.1 (C=C), 124.9 (C=C), 63.1 (CSO₃H), 23.1 (CH₂CHS), 10.2 (Me). IR (ATR): 3412, 1663, 1621, 1178, 1039 cm^-1. HRMS (ESI): m/z [M - H]^- calcd for C₅H₈O₃SCl₂: 216.9498; found: 216.9495. [α]_D ^28.0 -87.32 ± 0.10 (c = 0.95, H₂O; sample with ee >99%). 7c: ¹H NMR (300 MHz, D₂O): δ = 5.77 (d, J = 10.4 Hz, 1 H, CH=CCl₂), 3.66-3.77 (m, 1 H, CHS), 1.70-1.85 (m, 1 H, CHHCHS), 1.42-1.59 (m, 1 H, CHHCHS), 1.07-1.36 (m, 2 H, CH ₂CH₃), 0.75 (t, J = 7.3 Hz, 3 H, Me). ¹³C NMR (75 MHz, D₂O): δ = 125.4 (C=C), 124.7 (C=C), 61.3 (CSO₃H), 31.5 (CH₂CHS), 19.1 (CH₂CH₃), 12.8 (Me). IR (ATR): 2958, 1622, 1198, 1080 cm^-1. HRMS (ESI): m/z [M - H]^- calcd for C₆H₁₀O₃SCl₂: 230.9655; found: 230.9654. [α]_D ^26.4 -79.53 ± 0.14 (c = 1.20, H₂O; sample with ee = 86%). 7d: ¹H NMR (300 MHz, D₂O): δ = 5.83 (d, J = 10.4 Hz, 1 H, CH=CCl₂), 3.99 (td, J = 3.7, 10.4 Hz, 1 H, CHS), 3.64 (td, J = 5.4, 10.9 Hz, 1 H, CHHCl), 3.37-3.38 (m, 1 H, CHHCl), 2.23-2.36 (m, 1 H, CHHCHS), 1.96-2.28 (m, 1 H, CHHCHS). ¹³C NMR (75 MHz, D₂O): δ = 126.0 (C=C), 124.0 (C=C), 59.0 (CSO₃H), 41.7 (CH₂Cl), 32.5 (CH₂CHS). IR (ATR): 2539, 1621, 1193, 1060 cm^-1. HRMS (ESI): m/z [M - H]^- calcd for C₅H₇O₃SCl₃: 250.9109; found: 250.9109. [α]_D ^28.5 -134.18 ± 0.07 (c = 1.37, MeOH; sample with ee = 94%). 7e: ¹H NMR (300 MHz, D₂O): δ = 7.20-7.35 (m, 5 H, CH_Ph), 5.94 (d, J = 10.3 Hz, 1 H, CH=CCl₂), 4.09 (m, 1 H, CHS), 3.37 (dd, J = 3.1, 13.7 Hz, 1 H, CHHPh), 2.82 (m, 1 H, CHHPh). ¹³C NMR (75 MHz, D₂O): δ = 139.7 (C_Ph,q), 131.7 (2 × C_Ph), 131.1 (2 × C_Ph), 129.3, 127.9, 127.2 (C=C), 65.5 (CSO₃H), 38.5 (CH₂Ph). IR (ATR): 3029, 1621, 1216, 1154, 1038 cm^-1. HRMS (ESI): m/z [M - H]^- calcd for C₁₀H₁₀O₃SCl₂: 278.9655; found: 278.9654. [α]_D ^23.8 -75.97 ± 0.13 (c = 0.95, MeOH; sample with ee = 99%). 7f: ¹H NMR (300 MHz, D₂O): δ = 6.75-6.85 (m, 4 H, CH_Ph), 5.84 (d, J = 10.6 Hz, 1 H, CH=CCl₂), 3.90-4.05 (m, 2 H, CHS, CH₂OAr), 3.75-3.87 (m, 1 H, CH₂C_ring), 3.63 (s, 3 H, OMe), 2.23-2.39 (m, 1 H, CH ₂CHS), 1.81-1.97 (m, 1 H, CH ₂CHS). ¹³C NMR (75 MHz, D₂O): δ = 153.2 (C_Ph), 151.9 (C_Ph), 125.2 (C=C), 124.4 (C=C), 116.4 (2 × CH_Ph), 114.8 (2 × CH_Ph), 65.9 (CH₂O), 58.9 (CSO₃H), 55.7 (OMe), 29.5 (CH₂CHS). IR (ATR): 3422, 1621, 1509, 1216, 1167, 1032 cm^-1. HRMS (ESI): m/z [M - H]^- calcd for C₁₂H₁₄O₅SCl₂: 338.9866; found: 338.9866. [α]_D ^20.3 -80.63 ± 0.26 (c = 0.55, MeOH; sample with ee >99%). 11b: ¹H NMR (300 MHz, D₂O; E-isomer): δ = 6.34 (d, J = 13.4 Hz, 1 H, CH=CHCl), 5.81 (dd, J = 10.3, 13.4 Hz, 1 H, CH=CHCl), 3.38 (dt, J = 3.7, 10.3 Hz, 1 H, CHS), 1.88-2.04 (m, 1 H, CHHCHS), 1.50-1.66 (m, 1 H, CHHCHS), 0.86 (t, J = 7.5 Hz, 3 H, Me). ¹H NMR (300 MHz, D₂O; Z-isomer): δ = 6.45 (d, J = 7.2 Hz, 1 H, CH=CHCl), 5.74 (dd, J = 7.2, 10.3 Hz, 1 H, CH=CHCl), 3.95 (dt, J = 3.2, 10.3 Hz, 1 H, CHS), 1.88-2.04 (m, 1 H, CHHCHS), 1.50-1.66 (m, 1 H, CHHCHS), 0.87 (t, J = 7.5 Hz, 3 H, Me). ¹³C NMR (75 MHz, D₂O; E-isomer): δ = 127.9 (C=C), 123.0 (C=C), 64.1 (CSO₃H), 22.7 (CH₂CHS), 10.6 (Me). ¹³C NMR (75 MHz, D₂O; Z-isomer): δ = 126.3 (C=C), 123.6 (C=C), 60.5 (CSO₃H), 23.2 (CH₂CHS), 10.4 (Me). IR (ATR): 2973, 1694, 1115 cm^-1. HRMS (ESI): m/z [M - H]^- calcd for C₅H₉O₃SCl: 182.9888; found: 182.9889.