Generation and Tandem Reactions of 1-Alkenyl-1,1-Heterobimetallics: Practical and Versatile Reagents for Organic Synthesis

A practical and straightforward method for generation of versatile 1-alkenyl-1,1-heterobimetallic
intermediates and their application to construction of functionalized building blocks are disclosed. Beginning
with readily available air-stable 1-alkynyl-1-boronate esters, hydroboration with dicyclohexylborane generates
1-alkenyl-1,1-diboro species. In situ transmetallation with dialkylzinc reagents furnishes 1-alkenyl-1,1-heterobimetallic intermediates. Direct treatment with aldehydes followed by workup allows isolation of B(pin)-substituted allylic alcohols in 70−95% yield. The B(pin)-substituted allylic alcohols react with NBS to afford
(E)-α,β-unsaturated aldehydes in 51−77% yield via a semipinacol-type rearrangement. In situ treatment
of 1-alkenyl-1,1-heterobimetallic intermediates with aldehydes followed by TBHP oxidation enables the
preparation of α-hydroxy ketones. Under optimized conditions, addition of 1-alkenyl-1,1-heterobimetallic
intermediates to a variety of protected α- and β-hydroxy aldehydes proceeds with good to excellent control
over diastereoselectivity to furnish differentially protected dihydroxy ketones. The 1-alkenyl-1,1-heterobimetallic intermediates have also been employed in tandem aldehyde addition/Suzuki cross-coupling reactions
to provide densely functionalized allylic alcohols in good to excellent yields.