CN Bond Formation Through Hydrogen Borrowing

<jats:p> Hydrogen‐borrowing amination is a metal‐ or enzyme‐catalyzed <jats:italic>N</jats:italic> ‐alkylation process that uses alcohols as alkyl transfer agents. In this reaction, alcohol dehydrogenation affords a carbonyl compound, which then undergoes condensation with an amine nucleophile. The imine or iminium salt product is subsequently reduced by a metal hydride generated during the preceding dehydrogenation step. This methodology is a green alternative to classical CN bond‐forming reactions such as nucleophilic substitution and reductive amination. Hydrogen‐borrowing <jats:italic>N</jats:italic> ‐alkylation is an atom economical, cost‐efficient, and environmentally benign method, making it an attractive approach for the preparation of amines and nitrogen‐containing groups. Continued development of these reactions has enabled the preparation of challenging substrates, and facilitated tandem and multistep reaction sequences, mainly promoted by ruthenium‐ and iridium‐based catalytic systems. This chapter describes the history, mechanism, stereochemistry, scope and limitations, and synthetic applications of hydrogen‐borrowing amination reactions. The tabular survey includes extensive coverage of coupling reactions that use a variety of nitrogen nucleophiles (i.e., ammonia, higher amines, heterocycles, acyl hydrazides, amides, iminophosphoranes, nitriles) and alcohol electrophiles. </jats:p>