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.