Carbon–heteroatom (C–X) bonds are prevalent in organic compounds. Transition metal-catalyzed insertion of carbenes into heteroatom–hydrogen bonds (X–H, X = O, N, S, etc.) provides one of the most efficient approaches to the formation of C–X bonds. However, only limited successes have been achieved for asymmetric carbene insertions into heteroatom–hydrogen bonds. By developing transition metal catalysts with chiral spiro bisoxazoline ligands SpiroBOXs and diimine ligands SIDIMs, chiral proton transfer catalysts such as chiral spiro phosphoric acids and chiral amino thioureas, a series of highly enantioselective carbene insertion reactions of B‒H, N–H, O–H, S–H and Si–H bonds have been realized.

n Cu(I)-SpiroBOX complexes catalyzed asymmetric carbene insertion of aromatic amines N‒H bond

n Cu(I)/chiral amino-thiourea cooperatively catalyzed asymmetric carbene insertion of aliphatic amine N‒H bond

n Rh(II)/SPA cooperatively catalyzed asymmetric carbene insertion of amide N‒H bond

n Fe(II)-SpiroBOX complexes catalyzed asymmetric carbene insertion of O‒H bonds of alcohols and water

n Pd(II)-SpiroBOX complexes catalyzed asymmetric carbene insertion of O‒H bond of phenols

n Cu(I)-SpiroBOX complexes catalyzed asymmetric carbene insertion of B‒H bond

n Cu(II)-SIDIM complexes catalyzed asymmetric carbene insertion of Si‒H bonds

n Rh₂(SPA)₄ complexes catalyzed asymmetric carbene insertion of Si‒H bond

n Rh(II)/SPA cooperatively catalyzed asymmetric carbene insertion of S‒H bond