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Synlett 2002(10): 1727-1729
DOI: 10.1055/s-2002-34229
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Practical Approach Towards the Asymmetric Synthesis of α,γ-Substituted γ-Sultones

Dieter Enders*, Wacharee Harnying, Nicola Vignola
Institut für Organische Chemie, Rheinisch-Westfälische Technische Hochschule, Professor-Pirlet-Straße 1, 52074 Aachen, Germany
Fax: +49(241)8092127; e-Mail: enders@rwth-aachen.de;
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Publication History

Received 22 July 2002
Publication Date:
23 September 2002 (online)

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Abstract

The first auxiliary controlled synthesis of enantiopure α,γ-substituted γ-sultones via α-allylated chiral sulfonates is described. The high asymmetric inductions of the α-allylations were reached with our previously described auxiliary 1,2:5,6-di-O-isopropylidene-α-d-allofuranose (de≥98%). Cleavage of the auxiliary and successive diastereoselective ring closure of the sulfonic acid intermediates led to the title compounds in high selectivities (de, ee≥98%) and good to excellent yields (52-90%). Enantiopure α,γ-substituted γ-sultones are interesting intermediates in the reaction with various nucleophiles.

Key words

asymmetric synthesis - sugar auxiliary - α-allylation - sulfonates - sultones

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General Procedure for the α-Allylation of Chiral Sulfonates 1: To a solution of enantiopure sulfonate 1 (5.0 mmol) in dry THF (50 mL), n-butyllithium (1.0 equiv) was added dropwise at -(90-95) °C under an argon atmosphere. After stirring at -(90-95) °C for 1 h, the allylic halide (1.5 equiv) was added dropwise. The reaction mixture was stirred for additional 2 h and then stirring was continued at -78 °C over night. The mixture was quenched with water. After separation of the organic layer the aq phase was extracted with CH2Cl2 (3 × 20 mL). The combined organic layers were washed with water, brine and dried over MgSO4. The solvent was evaporated under reduced pressure and the crude product was purified by flash column chromatography (SiO2, n-pentane/diethyl ether 5:1) to afford (R)-2.

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General Procedure for the Removal of the Chiral Auxiliary: The sulfonates (R)-2 (1.0 mmol) were dissolved in a 2% TFA/EtOH solution (40 mL). The solution was refluxed for 24 h after which the solvent was removed under reduced pressure and the crude sulfonic acid was used in the next reaction step without further purification. General Procedure for the Cyclization: The crude product 3 was dissolved in a TFA/CH2Cl2 solution (20 mL). The reaction mixture was refluxed for 24 h. After separation of the organic layer the aq phase was extracted with CH2Cl2 (3 × 20 mL). The combined organic layers were washed with sat. aq NaHCO3-solution and brine. After drying over MgSO4 the solvent was evaporated and the crude product was purified by flash column chromatography (SiO2, n-pentane/diethyl ether 4:1) to afford 4.
(R,R)-4c: IR (KBr): 3035, 2995, 2973, 1498, 1459, 1387, 1331 (s), 1252, 1194, 1165 (s), 1130, 1113, 1026 (s), 942, 910, 858, 820 (s), 795 (s), 770, 698 (s), 598 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.56 (d, J = 6.0 Hz, 3 H, CH 3), 2.56 (ddd, J = 10.4, 13.2, 13.2 Hz, 1 H, CHH), 2.79 (ddd, J = 5.5, 6.9, 13.2 Hz, 1 H, CHH), 4.54 (dd, J = 6.9, 13.2 Hz, 1 H, CHPh), 4.78 (m, 1 H, CHO), 7.36-7.45 (m, 5 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ = 20.8 (CH3), 37.6 (CH2), 63.25 (CHPh), 77.4 (CHO), 128.6, 128.8, 129.25 (PhCH), 129.3(PhC) ppm. MS (EI, 70eV): m/z = 212 (10)[M+], 148 (14), 104 (100), 91 (5), 78 (10).

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All new compounds showed suitable spectroscopic data (NMR, MS, IR) and correct elemental analyses.