Chan–Lam Cross‐Coupling With Alkylboron Reagents: From Transmetallation to Radical Pathways

The Chan–Lam coupling offers a mild and versatile method for the arylation of heteronucleophiles and has found applications in diverse field of organic chemistry. However, the development of an alkylative variant of this transformation remains a major challenge. The main barrier is the transmetallation of boronic acid derivatives to a copper complex, which is facile with arylboronic acid derivatives but problematic for their alkyl counterpart. While some boronic acid derivatives, such as cyclopropyl derivatives, can undergo coupling under standard conditions, others require either forcing conditions or/and formation of a radical intermediate. Such radical‐based approaches have blossomed over recent years and now provide alternative and attractive strategies for heteroatom alkylation. Moreover, since alkyl residues—and particularly alkyl amines—are often unstable under strong oxidative conditions, adopting a milder radical process is appealing. This review focuses on the development of an alkylative variant of the Chan–Lam coupling, from early examples with cyclopropylboronic acid, to radical transfer‐based strategies. Mechanistic aspects are discussed, highlighting how the discovery that alkylative Chan–Lam coupling can proceed via a radical intermediate has transformed the approach, sparking further research in the field.