Development of α,α-Disubstituted Crotylboronate Reagents and Stereoselective Crotylation via Brønsted or Lewis Acid Catalysis
Shang Gao, Meng Duan, Qianzhen Shao, K. N. Houk, Ming Chen
Abstract
The development of α,α-disubstituted crotylboronate reagents is reported. Chiral Brønsted acid-catalyzed asymmetric aldehyde addition with the developed E -crotylboron reagent gave ( E )- anti -1,2-oxaborinan-3-enes with excellent enantioselectivities and E -selectivities. With BF 3 ·OEt 2 catalysis, the stereoselectivity is reversed, and ( Z )-δ-boryl- anti -homoallylic alcohols are obtained with excellent Z -selectivities from the same E -crotylboron reagent. The Z -crotylboron reagent also participates in BF 3 ·OEt 2 -catalyzed crotylation to furnish ( Z )-δ-boryl- syn -homoallylic alcohols with good Z -selectivities. DFT computations establish the origins of observed enantio- and stereoselectivities of chiral Brønsted acid-catalyzed asymmetric allylation. Stereochemical models for BF 3 ·OEt 2 -catalyzed reactions are proposed to rationalize the Z -selective allyl additions. These reactions generate highly valuable homoallylic alcohol products with a stereodefined trisubstituted alkene unit. The synthetic utility is further demonstrated by the total syntheses of salinipyrones A and B.