Diastereo- and Enantioselective Cross-Couplings of Secondary Alkylcopper Reagents with 3-Halogeno-Unsaturated Carbonyl Derivatives

Abstract

Chiral secondary alkylcopper reagents were prepared from the corresponding alkyl iodides with retention of configuration by an I/Li-exchange using tBuLi (−100 °C, 1 min) followed by a transmetalation with CuBr⋅P(OEt)3 (−100 °C, 20 s). These stereodefined secondary alkylcoppers underwent stereoretentive cross-couplings with several 3-iodo or 3-bromo unsaturated carbonyl derivatives leading to the corresponding γ-methylated Michael acceptors in good yields and with high diastereoselectivities (dr up to 96:4). The method was extended to enantiomerically enriched alkylcoppers, providing optically enriched advanced natural product intermediates with up to 90 % ee.