Oxazaborolidines (CBS) have been widely utilized as organocatalysts in enantioselective organic synthesis over the past thirty years, particularly for the asymmetric reduction of ketones and enantioselective cycloaddition reactions. The history of oxazaborolidines functioning as chiral Lewis acids has demonstrated that CBS requires activation by strong protonic acids or Lewis acids to enhance the Lewis acidity of boron, such as TfOH, Tf₂NH, and AlBr₃. In our previous work, we introduced a new application of CBS in the asymmetric 1,4-addition of diarylphosphine oxides to α,β-unsaturated ketones and esters. Unlike traditional CBS-catalyzed reactions, this catalytic system does not require strong protonic acids or Lewis acids to activate CBS; instead it likely functions as a Lewis pair to cleave the O—H bond and provide a chiral phosphorous intermediate. To further expand the application of this new method, we selected α,β-unsaturated bifunctional compounds bearing both a ketone and an amide group on either side of the double bond as substrates for this study. Initially, several oxazaborolidines and reaction conditions were explored for the model reaction. The results indicated that under optimal conditions (20 mol% Me-CBS at room temperature in acetonitrile for 2 h), the reaction proceeded well with high yield (99%) and high enantiomeric excess (93% ee). Subsequently, various substrates were examined under these optimal conditions yielding products with 52%~99% yields and 63%~99% ee. The general procedure involved stirring a mixture of substrates (0.24 mmol, 1.2 equiv.), diarylphosphine oxides (0.2 mmol, 1 equiv.), and CBS (20 mol% Me-CBS) in 2 mL acetonitrile for 2 h followed by purification via flash column chromatography. Finally, the potential mechanism behind how the catalyst functions as a Lewis pair to control enantioselectivity was discussed. Additionally, the chiral products have potential applications in synthesizing valuable phosphine ligands.

Key words: oxazaborolidine, diarylphosphine oxide, α,β-unsaturated compounds, asymmetric hydrophosphination