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

• Published in: Journal of the American Chemical Society Vol. 142; no. 12; pp. 5515 - 5520
• Main Authors: Hari, Durga Prasad, Abell, Joseph C, Fasano, Valerio, Aggarwal, Varinder K
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 25.03.2020; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; ALKYLATION; COMPLEXES
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.0c00813

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.