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The precise mechanism of the chiral phosphoric acid-catalyzed aldol-type reaction of azlactones with vinyl ethers was investigated. DFT calculations suggested that the reaction proceeds through a Conia-ene-type transition state consisting of the vinyl ether and the enol tautomer of the azlactone, in which the catalyst protonates the nitrogen atom of the azlactone to promote enol tautomerization. In addition, the phosphoryl oxygen of the catalyst interacts with the vinyl proton of the vinyl ether. The favorable transition structure features dicoordinating hydrogen bonds. However, these hydrogen bonds are not involved in the bond recombination sequence and hence the catalyst functions as a template for binding substrates. From the results of theoretical studies and experimental supports, the high enantioselectivity is induced by the steric repulsion between the azlactone substituent and the binaphthyl backbone of the catalyst under the catalyst template effect.

Natural lipases typically recognize enantiomers of alcohols based on size differences of substituents near the carbinol moiety and selectively react with ( R )-enantiomers of secondary alcohols. Therefore, lipase-catalyzed dynamic kinetic resolution (DKR) of racemic secondary alcohols produces only ( R )-enantiomers. We report herein a method for obtaining ( S )-enantiomers by DKR of secondary 3-(trialkylsilyl)propargyl alcohols using a well-known ( R )-selective Pseudomonas fluorescens lipase in combination with a racemization catalyst VMPS4, in which the silyl group reverses the size relationship of substituents near the carbinol moiety. Since we have already reported ( R )-selective DKR of the corresponding propargyl alcohols without substituents on the ethynyl terminal carbon, the presence of an easily removable silyl group has enabled us to produce both enantiomers of propargyl alcohols in high chemical yields and with high enantiomeric excess. In addition, the immobilization of the lipase on Celite was found to be important for achieving the high efficiency of the DKR. © 2022 Wiley-VCH GmbH.

Highly enantioselective Michael-type addition (MTA) reactions between N-protected alkenyl benzimidazoles and either pyrazoles or indazoles as nitrogen nucleophiles are accomplished for the first time using chiral phosphoric acid catalyst. Theoretical studies elucidated the reaction pathway and the origin of the stereochemical outcomes, where the catalyst substituent and the N-protecting group of benzimidazole contributed to the resulting high enantioselectivity.

Sterically hindered aryl substituents (e.g., o-bromophenyl) induce axial chirality thus affording diastereomeric mixtures of products.

A chiral BINAP-derived phosphoric acid is demonstrated to be an efficient catalyst for the formation of title compounds with adjacent quaternary and tertiary stereogenic centers after alkaline methanolysis.