A radical approach for the selective C-H borylation of azines.

Abstract

Boron functional groups are often introduced in place of aromatic carbon-hydrogen bonds to expedite small-molecule diversification through coupling of molecular fragments1-3. Current approaches based on transition metal-catalysed C-H activation are effective for the borylation of many (hetero)aromatic derivatives4,5 but show narrow applicability to azines, N-containing aromatic heterocycles and key components of many pharmaceutical and agrochemical products.6 Here, we report an azine borylation strategy using stable and inexpensive amine-borane7 reagents. Photocatalysis converts these low molecular weight materials into highly reactive boryl radicals8 that undergo efficient addition to azine building blocks. This reactivity provides a mechanistically alternative tactic for sp2 carbon-boron bond assembly where the elementary steps of transition-metal mediated C-H activation and reductive elimination from azine-organometallic intermediates are replaced with a direct, Minisci9-style, radical addition. The strong nucleophilic character of the amine-boryl radicals is the key feature enabling predictable and site-selective carbon-boron bond formation by targeting the azine s most activated position, including the challenging sites adjacent to the basic N-atom. This approach enables access to aromatic sites currently elusive to C-H activation strategies and has led to borylated materials that would otherwise be difficult to prepare. The process has been applied to the introduction of amine-borane functionalities onto complex and industrially-relevant products. The diversification of the borylated azine products by mainstream cross-coupling technologies establishes aromatic amino-boranes as a powerful class of building blocks for chemical synthesis.