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

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Abstract

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.
Original languageEnglish
JournalJournal of the American Chemical Society
Early online date7 Mar 2020
DOIs
Publication statusE-pub ahead of print - 7 Mar 2020

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