Regio‐ and Stereoselective Allylic Substitutions of Chiral Secondary Alkylcopper Reagents: Total Synthesis of (+)‐Lasiol, (+)‐13‐Norfaranal, and (+)‐Faranal

Chiral secondary alkylcopper reagents were prepared from chiral secondary alkyl iodides by a retentive I/Li exchange followed by a retentive transmetalation with CuBr⋅P(OEt) 3 . Switching the solvent to THF significantly increased their configurational stability and made these copper reagents suitable for regioselective allylic substitutions. The optically enriched copper species underwent S N 2 substitutions with allylic bromides (up to >99 % S N 2 regioselectivity). The addition of ZnCl 2 and the use of chiral allylic phosphates allowed to switch the regioselectivity towards S N 2′ substitution (up to >99 % S N 2′ regioselectivity) and to perform highly selective anti ‐S N 2′ substitutions with absolute control over two adjacent stereocenters. This method was applied in the total synthesis of the three ant pheromones (+)‐lasiol, (+)‐13‐norfaranal, and (+)‐faranal (up to 98:2 dr, 99 % ee ).