Cobalt‐Catalyzed Reductive Asymmetric Dimerization of 1,3‐Enynes: Rapid Synthesis of Enantioenriched Skipped 1,3,6‐Trienes

ABSTRACT Enantioenriched skipped polyenes represent an important building block in natural products and bioactive molecules. Thus, it is of great importance for developing efficient methods for the synthesis of enantioenriched skipped polyenes yet challenging. To date, no example for direct access to skipped polyenes with controlled stereochemistry from simple and readily available starting materials has been developed. Herein, a cobalt‐catalyzed reductive asymmetric cross‐dimerization of 1,3‐enynes has been developed, affording the first rapid access to enantioenriched skipped 1,3,6‐trienes from readily available simple starting materials. Moreover, this protocol is amenable to enantioenriched skipped dienes by asymmetric reductive cross‐hydrodimerization of 1,3‐enynes with alkynes. Mechanistic investigations revealed a domino process by a chemoselective and non‐regioselective semi‐reduction of 1,3‐enynes to 1,3‐dienes followed by a chemo‐, regio‐, and enantioselective cross‐hydrodimerization of 1,3‐dienes with 1,3‐enynes. Notably, asymmetric reductive hydrodimerization of enynes represents the first example of synthesizing enantioenriched 1,3,6‐trienes, 1,3,5,8,10‐pentaenes, 1,4‐dienes from achiral starting materials.