Ring-Expansion Induced 1,2-Metalate Rearrangements: Highly Diastereoselective Synthesis of Cyclobutyl Boronic Esters

The
broad synthetic utility of organoboron compounds stems from
their ready ability to undergo 1,2-migrations. Normally, such shifts
are induced by α-leaving groups or by reactions of alkenyl boronates
with electrophiles. Herein, we present a new strategy to induce 1,2-metalate
rearrangements, via ring expansion of vinylcyclopropyl boronate complexes
activated by electrophiles. This leads to a cyclopropane-stabilized
carbocation, which triggers ring expansion and concomitant 1,2-metalate
rearrangement. This novel process delivers medicinally relevant 1,2-substituted
cyclobutyl boronic esters with high levels of diastereoselectivity.
A wide range of organolithiums and Grignard reagents, electrophiles,
and vinylcyclopropyl boronic esters can be used. The methodology was
applied to a short, stereoselective synthesis of (±)-grandisol.
Computational studies indicate that the reaction proceeds via a nonclassical
carbocation followed by anti-1,2-migration.