Nickel-Catalyzed Enantioselective Synthesis of 2,3,4-Trisubstituted 3-Pyrrolines

The development of synthetic methods to produce highly functionalized chiral 3-pyrrolines is of indisputable importance because of their prevalence in natural and synthetic bioactive molecules. Unfortunately, previous general cycloaddition approaches using allenoates, could not synthesize 3,4-disubstituted 3-pyrrolines. Herein, an original approach to yield 2,3,4-trisubstituted 3-pyrrolines with chirality at the 2-position is presented. A Ni-II/Fc-i-PrPHOX catalytic system facilitated a redox-neutral highly stereoselective process that exhibited an enantioselectivity of up to 99 %. Enantioenriched 3-pyrrolines can be converted to other valuable classes of N-heterocycles.

Automated summary

The synthesis of highly functionalized chiral 3-pyrrolines is important for the production of natural and synthetic bioactive molecules. Previous methods using allenoates could not synthesize 3,4-disubstituted 3-pyrrolines. This study presents a novel approach to produce 2,3,4-trisubstituted chiral 3-pyrrolines through a highly stereoselective process using a Ni-II/Fc-i-PrPHOX catalytic system.