Collective synthesis of acetylenic pharmaceuticals via enantioselective Nickel/Lewis acid-catalyzed propargylic alkylation

Chiral acetylenic derivatives are found in many bioactive compounds and are versatile functional groups in organic chemistry. Here, we describe an enantioselective nickel/Lewis acid-catalyzed asymmetric propargylic substitution reaction from simple achiral materials under mild condition. The introduction of a Lewis acid cocatalyst is crucial to the efficiency of the transformation. Notably, we investigate this asymmetric propargylic substitution reaction for the development of a range of structurally diverse natural products. The power of this strategy is highlighted by the collective synthesis of seven biologically active compounds: (-)-Thiohexital, (+)-Thiopental, (+)-Pentobarbital, (-)-AMG 837, (+)-Phenoxanol, (+)-Citralis, and (-)-Citralis Nitrile.

Automated summary

The study introduces an enantioselective nickel/Lewis acid-catalyzed asymmetric propargylic substitution reaction for the synthesis of structurally diverse natural products from simple achiral materials under mild conditions. The addition of a Lewis acid cocatalyst is crucial for enhancing the efficiency of the transformation and the strategy is powerful for collectively synthesizing seven biologically active compounds.