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

Abstract

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 SN 2 substitutions with allylic bromides (up to >99 % SN 2 regioselectivity). The addition of ZnCl2 and the use of chiral allylic phosphates allowed to switch the regioselectivity towards SN 2' substitution (up to >99 % SN 2' regioselectivity) and to perform highly selective anti-SN 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).