Synthesis of Arylethyl (E)-Styrylsulfones and Arylsulfones by One-Pot DIBAL-H/NaH-Mediated Reaction of β-Ketosulfones

Abstract

A facile one-pot synthetic route for preparing a series of arylethyl (E)-styrylsulfones or arylethyl arylsulfones is developed. The efficient one-pot DIBAL-H/NaH-mediated route includes reduction of α-benzyl-β-arylketosulfones and retroaldol/aldol or retro­aldol reaction of the resulting intermediate. The DIBAL-H/NaH-mediated reaction mechanism has been discussed.

Key words

aldol reaction - aluminum - condensation - sulfones - tandem reaction

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• 11 CCDC 979312 (5a), 982010 (5r), and 979313 (6k) contain the supplementary crystallographic data for this paper. This data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: [phone]; e-mail: [e-mail]].
• 12 Representative Procedure for the Synthesis of Skeleton 5DIBAL-H (1.0 M in hexane, 0.5 mL, 0.5 mmol) was added to a solution of substituted β-ketosulfones 3 (0.5 mmol) in THF (10 mL) at r.t. The reaction mixture was stirred at r.t. for 10 min. NaH (60% in oil, 60 mg, 1.5 mmol) was added to the stirred solution at r.t. The reaction mixture was stirred at r.t. for 8 h. NH₄Cl aq (15%, 1 mL) was added to the reaction mixture, and the solvent was concentrated. The residue was diluted with H₂O (10 mL), and the mixture was extracted with CH₂Cl₂ (3 × 20 mL). The combined organic layers were washed with brine, dried, filtered, and evaporated to afford the crude product. Purification on silica gel (hexanes–EtOAc = 10:1 to 6:1) afforded skeleton 5.Compound 5a: yield 84% (114 mg); colorless solid; mp 63–65 °C (recrystallized from hexanes and EtOAc). ESI-HRMS: m/z calcd for C₁₆H₁₇O₂S [M⁺ + 1]: 273.0949; found: 273.0952. ¹H NMR (400 MHz, CDCl₃): δ = 7.60 (d, J = 15.6 Hz, 1 H), 7.48–7.39 (m, 5 H), 7.33–7.21 (m, 5 H), 6.72 (d, J = 15.2 Hz, 1 H), 3.39–3.35 (m, 2 H), 3.18–3.14 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 144.97, 137.52, 132.12, 131.36, 129.08 (2×), 128.85 (2×), 128.55 (2×), 128.40 (2×), 126.95, 124.68, 56.50, 28.78. Anal. Calcd for C₁₆H₁₆O₂S: C, 70.56; H, 5.92. Found: C, 70.75; H, 6.30. Single-crystal X-ray crystallography: crystal of compound 5a was grown by slow diffusion of EtOAc into a solution of compound 5a in CH₂Cl₂ to yield colorless prisms. The compound crystallizes in the orthorhombic crystal system, space group Pna21, a = 26.9302(15) Å, b = 9.6456(5) Å, c = 5.2760(5) Å, V = 1372.01(17) ų, Z = 4, δ _calcd = 1.318 g cm^–3, F(000) = 576, 2θ range 1.511–25.057°, R indices (all data) R1 = 0.0419, wR2 = 0.1113.