Development of α,α-Disubstituted Crotylboronate Reagents and Stereoselective Crotylation via Bronsted or Lewis Acid Catalysis

The development of alpha,alpha-disubstituted crotylboronate reagents is reported. Chiral Bronsted 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 BF3 center dot OEt2 catalysis, the stereoselectivity is reversed, and (Z)-delta-boryl-anti-homoallylic alcohols are obtained with excellent Z-selectivities from the same E-crotylboron reagent. The Z-crotylboron reagent also participates in BF3 center dot OEt2-catalyzed crotylation to furnish (Z)-delta-boryl-syn-homoallylic alcohols with good Z-selectivities. DFT computations establish the origins of observed enantio- and stereoselectivities of chiral Bronsted acid-catalyzed asymmetric allylation. Stereochemical models for BF3 center dot OEt2-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.