Three-Step One-Pot Photocatalytic Oxidation of Feedstocks and Organocatalytic Sequential Cascade to Access Enantioenriched α-Aminonitriles.

Abstract

A three-step, one-pot, sequential cascade starting from simple feedstocks to increase complexity toward value-added chiral synthetic building blocks is reported. This is achieved by precisely integrating organic photocatalysis and noncovalent organocatalysis, often operating at dissimilar conditions and reaction media. In particular, this strategy is used to enable the direct transformation of readily available benzylic substrates, such as methylbenzenes, benzyl alcohols, or amines, into enantioenriched α-aminonitriles by benzylic CH photooxidation to their corresponding aldehydes, followed by in situ imine formation and final asymmetric organocatalytic Strecker reaction. The enantioenriched α-aminonitrile products are built in moderate to good yields and moderate to high enantiomeric ratios (up to 96:4 e.r.), highlighting the effectiveness of the overall cascade process. This methodology simplifies complex synthetic pathways, enhances atom economy, and broadens the applicability of metal-free photocatalytic methodologies, offering a robust platform for constructing chiral building blocks from abundant starting materials and feedstocks.