Bio-Inspired Primary Amine α-C–H Functionalization

<div>The selective manipulation of complex amine architectures has received great attention in recent years with widespread applications including inter alia drug discovery. Inspired by an enzymatic copper amine oxidase process, a synthetic quinone co-factor mediated general platform for the construction of α-fully substituted primary amines from abundant α-branched primary amine starting materials is described. This procedure pivots on the efficient generation of reactive ketimine intermediates in situ which are primed to react with carbon-centered nucleophiles such as organomagnesium and organolithium reagents, and TMSCN. Extension to reverse polarity photoredox catalysis enables reactivity with electrophiles. Subsequent oxidative hydrolysis releases the unprotected α-fully substituted primary amine product. This efficient, broadly applicable and scaleable amine-to-amine synthetic platform was successfully applied to library and API synthesis and in the late stage functionalization of drug molecules.</div>