Download PDF
Synlett 2007(16): 2529-2532  
DOI: 10.1055/s-2007-986642
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Wacharee Harnying*a, Wipaporn Kitisriworaphana, Manat Pohmakotrb, Dieter Endersc
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
Further Information

Publication History

Received 18 July 2007
Publication Date:
12 September 2007 (online)

    Permissions and Reprints All articles of this category

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

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).