Enzyme-Catalyzed Asymmetric Primary Amination of Benzylic and Allylic C(sp³)–H Bonds

Key words

amines - directed evolution - cytochrome P411 hydroxylamines - amination - C–H bond activation

Significance

The Arnold group reports the directed evolution of P411-B2 to give efficient benzylic (P411_BPA) and allylic (P411_APA) C–H aminases. By using hydroxylamine derivatives as nitrogen sources under anaerobic conditions, the authors converted a variety of benzylic and allylic C(sp³)–H bonds into primary amines in good yields with high chemo- and enantioselectivities and promising regioselectivities­.

Comment

This work represents a milestone in the development of a general C–H amination reaction. Mechanistic investigations are highly desirable in further developing this method to overcome the limitation toward alkyl-substituted allyl systems. In addition, this work encourages and challenges other groups to develop small-molecule catalysts to enable this reaction.