Minisci-Type Alkylation of Heterocycles with Organoboron Derivatives Assisted by Catechol

Key words

alkylation - metal-free - boron

Significance

A metal-free alkylation strategy of heterocycles using organoboron derivatives is described. It may be useful for late-stage alkylation of heterocycle-containing drug candidates for SAR studies where metal-contamination is a concern. The alkylation provides 4-substituted products, complimentary to C–H activation, which provides 2-substitution.

Comment

The substrate scope suggests preference for alkylation at the 4-position (para to the heteroatom), but will alkylate at the ortho position if para is blocked. Double alkylation will occur if multiple ortho positions are present. Isolation of intermediates and radical trapping experiments support the proposed mechanism.

Publication History

Article published online:
25 July 2024