Stereoselective Sulfonate Aldol Reactions: Asymmetric Synthesis of α,β-Substituted β-Hydroxy Sulfonates

Wacharee Harnying; Wipaporn Kitisriworaphan; Manat Pohmakotr; Dieter Enders

doi:10.1055/s-2007-986642

LETTER

Stereoselective Sulfonate Aldol Reactions: Asymmetric Synthesis of α,β-Substituted β-Hydroxy Sulfonates

Wacharee Harnying*^a, Wipaporn Kitisriworaphan^a, Manat Pohmakotr^b, Dieter Enders^c
^a Department of Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand
Fax: +66(43)202373; e-Mail: hwacha@kku.ac.th;
^b Department of Chemistry, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand
^c Institut für Organische Chemie, Rheinisch-Westfälische Technische Hochschule, Landoltweg 1, 52074 Aachen, Germany

Abstract

Alle Artikel dieser Rubrik

Abstract

An efficient asymmetric synthesis of β-hydroxy sulfonates is described via stereocontrolled aldol reactions of sulfonates using 1,2:5,6-di-O-isopropylidene-α-d-allofuranose as the chiral auxiliary. The aldol reactions with aromatic aldehydes yielded predominantly syn adducts in very good yields and excellent diastereo- and enantiomeric excesses (de, ee ≥98%).

Key words

asymmetric synthesis - sulfonates - aldol reaction - sugar auxiliary - hydroxy sulfonates

Volltext

Referenzen

References and Notes

1 Kalir A. Kalir HH. In The Chemistry of Sulfonic Acids, Esters and their Derivatives Patai S. Rappoport Z. Wiley; Chichester / New York: 1991. p.767

2 Traynor SG. Kane BJ. Betkouski MF. Hirschy LM. J. Org. Chem. 1979, 44: 1557

3 Prager RH. Schafer K. Hamon DPG. Massy-Westropp RA. Tetrahedron 1995, 51: 11465

4 Kitamura M. Yoshimura M. Kanda N. Noyori R. Tetrahedron 1999, 55: 8785

5 Nkunya MHH. Zwanenburg B. Recl. Trav. Chim. Pays-Bas 1983, 102: 461

6 Carretero JC. Davies J. Marchand-Brynaert J. Ghosez L. Bull. Soc. Chim. Fr. 1990, 127: 835

7a Enders D. Vignola N. Berner OM. Angew. Chem. Int. Ed. 2002, 41: 109 ; Angew. Chem. 2002, 114, 116

7b Enders D. Vignola N. Berner OM. Harnying W. Tetrahedron 2005, 61: 3231

8a Enders D. Berner OM. Vignola N. Chem. Commun. 2001, 2498

8b Enders D. Berner OM. Vignola N. Harnying W. Synthesis 2002, 1945

9a Enders D. Harnying W. Vignola N. Synlett 2002, 1727

9b Enders D. Harnying W. Vignola N. Eur. J. Org. Chem. 2003, 20: 3939

10 Enders D. Harnying W. ARKIVOC 2004, (ii): 181

11 Enders D. Harnying W. Raabe G. Synthesis 2004, 590

12 Enders D. Harnying W. Synthesis 2004, 2910

13 Enders D. Adelbrecht J.-C. Harnying W. Synthesis 2005, 2962

14

General Procedure for Aldol Reactions of the Sulfonate 1: To a cooled (-78 °C) solution of freshly generated lithium diisopropylamide [prepared by treatment of diisopropyl-amine (1.1 mmol) in anhyd THF (3 mL) with n-BuLi (1 mmol) at -78 °C for 30 min] was added dropwise a solution of the sulfonate 1 (1 mmol) in THF (2 mL) under N₂. After stirring for 1 h, a mixture of aldehyde (2 mmol) and 1 M ZnCl₂ in THF (1.2 mmol) was added dropwise. The reaction mixture was stirred at -78 °C for 1 h and then quenched with sat. NH₄Cl. The mixture was poured into an ice-cooled 1 N HCl solution (10 mL) and extracted with EtOAc. The combined organic layers were washed with H₂O, brine and dried over Na₂SO₄. The solvent was removed under reduced pressure to give the crude product. The diastereomeric ratio was determined at this stage by ¹H NMR (400 MHz). The crude product was purified by flash column chromatography (SiO₂, EtOAc-hexane) to give the aldol product 2.
(1S,2R)-2a: colorless solid; de ≥ 98%; mp 103-104 °C; [α]_D ²⁹ +93.1 (c = 0.105, EtOH). IR (KBr): 3446 (s), 2986, 1630, 1375, 1344 (s), 1217, 1150 (s), 1059 (s), 1017 (s), 886, 705 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 1.29, 1.30, 1.37, 1.57 (4 × s, 12 H, 4 × Me), 3.65 (br s, 1 H, OH), 3.75 (dd, J = 6.6, 8.7 Hz, 1 H, CHH), 3.95 (dd, J = 6.7, 8.7 Hz, 1 H, CHH), 4.09 [dd, J = 4.1, 8.6 Hz, 1 H, CH₂CHCHO), 4.25 (dt, J = 4.1, 6.6 Hz, 1 H, CH₂CHCHO), 4.46 [t, J = 4.4 Hz, 1 H, OCHCH(OC)₂], 4.47 (d, J = 2.2 Hz, 1 H, CHSO₃), 4.81 (dd, J = 4.7, 8.6 Hz, 1 H, CHOSO₂), 5.71 [d, J = 3.7 Hz, 1 H, CH(OC)₂], 5.80 (br d, J = 1.8 Hz, 1 H, CHOH), 7.01-7.30 (m, 10 H, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 25.2, 26.1, 26.6, 26.7 (4 × Me), 65.4 (CH₂), 72.1 (CHOH), 74.0 (CHSO₃), 74.6, 76.4, 76.9, 77.6 (4 × CHO), 103.8 (OCHO), 110.3, 113.8 [2 × C(CH₃)₂], 126.0 (ArCH), 127.76 (ArC), 127.83, 128.1, 128.2, 129.1, 131.3 (ArCH), 139.2 (ArC). MS (EI, 70 eV): m/z (%) = 520 (0.2)[M⁺], 505 (22), 399 (16), 341 (23), 292 (17), 197 (31), 167 (31), 127 (51), 91 (100), 77 (33), 55 (17). Anal. Calcd for C₂₆H₃₂O₉S (520.59): C, 59.99; H, 6.20. Found: C, 60.13; H, 6.19.

15

(1S,2R)-4: colorless solid; de, ee ≥ 98%; mp 169-170 °C; [α]_D ²⁹ +122.0 (c = 0.115, EtOH). IR (KBr): 3467 (s), 1220, 1163 (s), 1049 (s), 795, 713, 651, 572 cm^-1. ¹H NMR (400 MHz, CDCl₃-CD₃OD): δ = 3.87 (br s, 1 H, OH), 4.02 (d, J = 1.8 Hz, 1 H, CHSO₃), 5.71 (d, J = 1.8 Hz, 1 H, CHOH), 6.93-6.97 (m, 2 H, ArH), 7.02-7.11 (m, 6 H, ArH), 7.17-7.21 (m, 2 H, ArH). ¹³C NMR (100 MHz, CDCl₃-CD₃OD): δ = 71.7, 73.1 (2 × CH), 126.0, 127.0, 127.19, 127.22, 127.6, 130.7 (ArCH), 132.5, 140.7 (2 × ArC). MS (EI, 70 eV): m/z (%) = 179 (100)[PhCH=C(Ph)⁺], 165 (55), 152 (20).

16

epi-4 obtained from the cleavage of the anti isomer 3a under the same conditions exhibits a different ¹H NMR spectrum. ¹H NMR (400 MHz, CDCl₃-CD₃OD): δ = 3.67 (br s, 1 H, OH), 4.16 (d, J = 10.1 Hz, 1 H, CHSO₃), 5.29 (d, J = 10.1 Hz, 1 H, CHOH), 7.00-7.30 (m, 10 H, ArH).