Photoredox/Cr/Co-Cocatalyzed Regio- and Diastereoselective Propargylation of Carbonyls via Radical Umpolung

Catalytic regio- and diastereoselective carbonyl propargylation has been established as one of the most important strategies in the realm of carbon-carbon bond-forming reactions. The 1,3-enyne moiety has been recognized as a more desirable propargyl precursor in the synthesis of homopropargyl alcohols due to its multiple reaction sites and easy availability. However, only a few protocols have been explored using photoredox catalysis. Herein, a photoredox/Cr/Co-cocatalyzed regio- and diastereoselective propargyl addition to aldehydes via radical umpolung is presented, enabling the construction of a library of valuable homopropargyl alcohols from 1,3-enynes. However, the reaction failed to proceed with aromatic aldehydes and ketones, likely due to steric hindrance or low electrophilicity. Mechanistic studies and DFT calculations demonstrated that the selective MHAT of 1,3-enynes to generate the propargylic radicals proved to be the key step, and the diastereoselectivity is determined by Zimmerman-Traxler-type transition states.