Efficient Synthesis of α‑Haloboronic Esters via Cu-Catalyzed Atom Transfer Radical Addition

The synthesis of α-haloboronic esters via atom
transfer radical
addition (ATRA) is constrained due to its limited range of compatible
substrates or the need to manipulate the olefin coupling partners.
Herein, we present a novel approach for their synthesis via Cu-catalyzed
ATRA to vinyl boronic esters. The catalyst is proposed to mediate
a traditionally inefficient halogen atom transfer of the α-boryl
radical intermediate, thus significantly expanding the range of participating
substrates relative to established methods. The forty-eight examples
illustrate that a wide range of radical precursors, including primary,
secondary, and tertiary alkyl halides, readily add across both unsubstituted
and α-substituted vinyl pinacol boronic esters. Further, a one-pot,
two-step protocol is presented for direct access to an array of α-functionalized
products. Finally, the synthetic utility of this methodology is demonstrated
in the synthesis of an ixazomib analogue.