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

Skotnitzki, Juri; Spessert, Lukas und Knochel, Paul (2019): Regio- and Stereoselective Allylic Substitutions of Chiral Secondary Alkylcopper Reagents: Total Synthesis of (+)-Lasiol, (+)-13-Norfaranal, and (+)-Faranal. In: Angewandte Chemie-International Edition, Vol. 58, No. 5: pp. 1509-1514

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 center dot 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 ZnCl2 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).

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy > Department of Chemistry
• Subjects: 500 Science > 540 Chemistry
• ISSN: 1433-7851
• Language: English