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Harnessing the Silicon Effect for Copper-Catalyzed Linear-E-Selective Reductive Coupling of Ketones with
Qingbin Lu1, Weixiang Ye1, Yixiao Li1
1State Key Laboratory of Natural Medicines (SKLNM) and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing210009, P. R. China.
Abstract:
We report a copper-catalyzed reductive coupling of ketones with allenylsilanes that delivers γ-silyl homoallylic alcohols with exceptional linear E-selectivities. Mechanistic investigations indicate that the silyl substituent functions as a directing element for regioselectivity control. DFT calculations further reveal that the allyl addition is the regio-determining step, where the branched allylcopper species shows a markedly lower activation barrier. The vinylsilane products serve as versatile platforms for downstream functionalization, enabling efficient carbon-chain elongation.
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