A Spiro Phosphamide Catalyzed Enantioselective Proton Transfer of Ylides in a Free Carbene Insertion into N-H Bonds

Free carbene readily causes multiple side reactions due to its high energy, thus its asymmetric transformation is very difficult. We present here our findings of high-pK(a) Bronsted acid catalysts that enable free carbene insertion into N-H bonds of amines to prepare chiral alpha-amino acid derivatives with high enantioselectivity. Under irradiation with visible light, diazo compounds produce high-energy free carbenes that are captured by amines to form free ylide intermediates, and then the newly designed high-pK(a) Bronsted acids, chiral spiro phosphamides, promote the proton transfer of ylides to afford the products. Computational and kinetic studies uncover the principle for the rational design of proton-transfer catalysts and explain how the catalysts accelerate this transformation and provide stereocontrol.