Convergent Synthesis of α‐Branched Amines by Transition‐Metal‐Catalyzed C−H Bond Additions to Imines

Abstract

α-Branched amines are ubiquitous in drugs and natural products, and consequently, synthetic methods that provide convergent and efficient entry to these structures are of considerable value. Transition-metal-catalyzed C–H bond additions to imines have the potential to be highly practical and atom-economic approaches for the synthesis of a diverse and complex array of α-branched amine products. These strategies typically employ readily available starting inputs, display high functional group compatibility, and often avoid the production of stoichiometric waste byproducts. A number of C–H functionalization methods have also been developed that incorporate cascade cyclization pathways to give amine-substituted carbocycles, and in many cases, proceed with the formation of multiple stereogenic centers. Advances in the area of asymmetric C–H bond additions to imines have also been achieved through the use of chiral imine N-substituents as well as by enantioselective catalysis.

New Strategies for the Transition-Metal Catalyzed Synthesis of Aliphatic Amines

“…), Chang, and Yu (J.-Q) using Pd and Ir catalysts, these processes are predominantly limited to the activation of methyl and benzylic C­( sp 3 )–H bonds. Pioneering work by Bergman and Ellman, Shi, − Huang, Cramer , and Miura, among others, have seen the development of transition metal catalyzed C–H bond addition to imines. In contrast to the traditional addition of organometallic reagents to imine derivatives, the activation of C–H bonds and their addition to imines is both more atom-economical and displays greater functional group tolerance.…”

α-Branched amines through radical coupling with 2-azaallyl anions, redox active esters and alkenes

“…A more atom economical method employs transition-metal-catalyzed C-H bond activation followed by addition of the resulting organometallic nucleophile to imines (Scheme 1b). [11][12][13] The a-functionalization of amines toward the formation of a-branched derivatives has also been developed. Here, both transition-metal-catalyzed processes 14 and photoredox catalyzed radical coupling approaches to form C-C bonds have been successfully introduced (Scheme 1c).…”

Multicomponent Synthesis of α-Branched Tertiary and Secondary Amines by Photocatalytic Hydrogen Atom Transfer Strategy

“…In particular, these integral benefits make MCRs highly attractive for natural product and pharmaceuticals synthesis, heterocyclic chemistry, as well as bioconjugation . Considering the fact that branched amines are privileged structural motifs present in bioactive molecules and drug candidates, the synthesis of α-branched tertiary and secondary amines by MCRs would be of considerable interest.…”