ChemInform Abstract: Catalytic Enantioselective Transformations of Borylated Substrates: Preparation and Synthetic Applications of Chiral Alkylboronates

Abstract

Organoboronic acid derivatives are well-established intermediates for the prepara- tion of alcohols and amines, and in the formation of C-C bonds via different reactions, including homologations, carbonyl allylboration, or transition-metal-catalyzed cross-cou- pling chemistry. In the past decade, there has been great interest in the development of cat- alytic enantioselective methods for the preparation of chiral, optically enriched organoboronates as precursors of enantioenriched compounds. While the mainstream strat- egy remains the late-stage borylation of organic functional groups, our group has focused on an alternate strategy focused on modification of boron-containing substrates. In this way, acyclic and cyclic secondary alkyl - and allyl-boronates were prepared through catalytic enantio selective processes such as (4 + 2) cycloadditions, isomerizations, allylic substitu- tions, and conjugate additions. The resulting optically enriched boronates have been suc- cessfully utilized in the syntheses of complex natural products and drugs. One remaining challenge in the chemistry of secondary alkylboronate derivatives is their cross-coupling, especially with control of stereoselectivity. In this regard, our recent approach featured the conjugate asymmetric borylation of β-boronyl acrylates, providing the first enantioselective preparation of highly optically enriched 1,1-diboronyl derivatives. The chirality of these geminal diboron compounds is conferred through the use of two distinct boronate adducts, which can be coupled chemo- and stereoselectively with a variety of aryl and alkenyl halides under palladium catalysis.