We describe herein the asymmetric synthesis of α-allyl carboxylic acids containing an α-quaternary stereocenter by a chiral hybrid catalyst system comprising palladium and boron complexes. The reaction proceeded through palladium-catalyzed ionization of α,α-disubstituted O-allyl esters for the generation of chiral π-allyl palladium complex as an electrophile, boron-catalyzed enolization of the carboxylate part for the generation of chiral α,α-disubstituted carboxylic acid-derived enolates as a nucleophile, and enantioselective coupling between the thus-generated nucleophile and electrophile. Proper combinations of chiral ligands for the boron and palladium catalysts were crucial. The reaction proceeded chemoselectively at the α-position of the carboxylic acid group.

The catalytic asymmetric aldol reaction is among the most useful reactions in organic synthesis.Despite the existence of many prominent reports,h owever,t he late-stage,c hemoselective,c atalytic, asymmetric aldol reaction of multifunctional substrates is still difficult to achieve.H erein, we identified that in situ pre-conversion of carboxylic acids to siloxy esters facilitated the boron-catalyzed direct aldol reaction, leading to the development of carboxylic acidselective,c atalytic, asymmetric aldol reaction applicable to multifunctional substrates.Combining experimental and computational studies rationalized the reaction mechanismand led to the proposal of Si/B enediolates as the active species.T he silyl ester formation facilitated both enolization and catalyst turnover by acidifying the a-proton of substrates and attenuating poisonous Lewis bases to the boron catalyst.

The catalytic asymmetric aldol reaction of carboxylic acids is among the most useful reactions for the synthesis of biologically active compounds and pharmaceuticals. Despite the existence of many prominent reports, no general method is available to incorporate the aldol motif into complex carboxylic acids and their derivatives at late stages. Chemoselective catalytic asymmetric aldol reaction of multifunctional carboxylic acids is difficult to achieve, due to the high basicity required for enolization and the poisonous chelation of β-hydroxy acid products to Lewis acid catalysts. Herein, we identified that preconversion of carboxylic acids to siloxy esters facilitated the boron-catalyzed direct aldol reaction, leading to the development of carboxylic acid-selective, catalytic asymmetric aldol reaction applicable to multifunctional substrates. The asymmetric boron catalyst stereodivergently controlled the products’ stereochemistry depending on the catalyst’s chirality, not on the stereochemical bias of substrates. Computational studies rationalized the mechanism of the catalytic cycle and the stereoselectivity, and proposed Si/B enediolates as the active species for the asymmetric aldol reaction. The silyl ester formation facilitated both enolization and catalyst turnover through acidifying the α-proton of substrates and attenuating poisonous Lewis bases to the boron catalyst.

The catalytic asymmetric aldol reaction is among the most useful reactions in organic synthesis.Despite the existence of many prominent reports,h owever,t he late-stage,c hemoselective,c atalytic, asymmetric aldol reaction of multifunctional substrates is still difficult to achieve.H erein, we identified that in situ pre-conversion of carboxylic acids to siloxy esters facilitated the boron-catalyzed direct aldol reaction, leading to the development of carboxylic acidselective,c atalytic, asymmetric aldol reaction applicable to multifunctional substrates.Combining experimental and computational studies rationalized the reaction mechanismand led to the proposal of Si/B enediolates as the active species.T he silyl ester formation facilitated both enolization and catalyst turnover by acidifying the a-proton of substrates and attenuating poisonous Lewis bases to the boron catalyst.

The catalytic asymmetric aldol reaction of carboxylic acids is among the most useful reactions for the synthesis of biologically active compounds and pharmaceuticals. Despite the existence of many prominent reports, no general method is available to incorporate the aldol motif into complex carboxylic acids and their derivatives at late stages. Chemoselective catalytic asymmetric aldol reaction of multifunctional carboxylic acids is difficult to achieve, due to the high basicity required for enolization and the poisonous chelation of β-hydroxy acid products to Lewis acid catalysts. Herein, we identified that preconversion of carboxylic acids to siloxy esters facilitated the boron-catalyzed direct aldol reaction, leading to the development of carboxylic acid-selective, catalytic asymmetric aldol reaction applicable to multifunctional substrates. The asymmetric boron catalyst stereodivergently controlled the products’ stereochemistry depending on the catalyst’s chirality, not on the stereochemical bias of substrates. Computational studies rationalized the mechanism of the catalytic cycle and the stereoselectivity, and proposed Si/B enediolates as the active species for the asymmetric aldol reaction. The silyl ester formation facilitated both enolization and catalyst turnover through acidifying the α-proton of substrates and attenuating poisonous Lewis bases to the boron catalyst.