Chemoselective Two-Directional Reaction of Bifunctionalized Substrates: Formal Ketal-Selective Mukaiyama Aldol Type Reaction

Abstract

In the presence of an acidic zwitterion bearing a highly stabilized carbanion, reactions of ω,ω-dialkoxy carbonyl compounds with ketene silyl acetals (KSA) resulted in an unusual molecular transformation; substitution reaction with the KSA at the ketal moiety and simultaneous silylative acetalization of the ketone moiety.

Key words

acid catalysis - zwitterion - carbanion - chemoselectivity - Mukaiyama aldol reaction

• References and Notes

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• 17 Typical Procedure (Table 2, Entry 1) To a solution of 5,5-dimethoxyhexan-2-one (1c, 80.1 mg, 0.501 mmol) and zwitterion 3 (2.6 mg, 5.0 μmol) in Et₂O (1.5 mL) was added a solution of tert-butyl[(1-ethoxyvinyl)oxy]dimethylsilane (5a, 121 mg, 0.598 mmol) in Et₂O (0.5 mL) at 0 °C. After being stirred for 20 min at 0 °C, the reaction was quenched by treatment with Et₃N (0.3 mL), then it was concentrated under reduced pressure. The resulting residue was dissolved in a mixed solvent of acetone, H₂O, and AcOH (1:1:1 v/v, 3.0 mL). This mixture was stirred for 30 min at r.t. After usual extractive workup, the obtained residue was purified by column chromatography on silica gel (hexane–EtOAc, 3:1) to give ethyl 3-methoxy-3-methyl-6-oxoheptanoate (9c) in 87% yield (94.1 mg, 0.436 mmol); colorless oil. IR (neat): ν = 2980, 2947, 2910, 1728, 1717, 1365, 1182, 1075, 1034 cm^–1. ¹H NMR (400 MHz, CD₃CN): δ = 1.19 (3 H, t, J = 7.2 Hz), 1.19 (3 H, s), 1.71–1.85 (2 H, m), 2.08 (3 H, s), 2.41 (1 H, d, J = 13.7 Hz), 2.46 (2 H, t, J = 8.0 Hz), 2.47 (1 H, d, J = 13.7 Hz), 3.11 (3 H, s), 4.06 (2 H, q, J = 7.2 Hz). ¹³C NMR (100 MHz, CD₃CN): δ = 13.5, 22.1, 29.1, 31.0, 37.3, 42.5, 48.6, 60.0, 74.9, 170.5, 208.2. MS (ESI-TOF): m/z = 239 [M + Na]⁺. HRMS: m/z calcd for C₁₁H₂₀O₄ [M + Na]⁺: 239.1259; found: 239.1259. Anal. Calcd for C₁₁H₂₀O₄: C, 61.09; H, 9.32. Found: C, 60.91; H, 9.29.