TY - JOUR
T1 - Ring-Expansion Induced 1,2-Metalate Rearrangements
T2 - Highly Diastereoselective Synthesis of Cyclobutyl Boronic Esters
AU - Hari, Durga Prasad
AU - Abell, Joseph C.
AU - Fasano, Valerio
AU - Aggarwal, Varinder K.
PY - 2020/3/7
Y1 - 2020/3/7
N2 - 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.
AB - 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.
U2 - 10.1021/jacs.0c00813
DO - 10.1021/jacs.0c00813
M3 - Article (Academic Journal)
C2 - 32146807
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
ER -