Cytochrome P450-catalyzed insertion of carbenoids into N–H bonds

Expanding nature's catalytic repertoire to include reactions important in synthetic chemistry will open new opportunities for 'green' chemistry and biosynthesis. We demonstrate enzyme-catalyzed insertion of carbenoids into N-H bonds. This type of bond disconnection, which has no counterpart in nature, can be mediated by variants of the cytochrome P450 from Bacillus megaterium. The N-H insertion reaction takes place in water, provides the desired products in 26-83% yield, forms the single addition product exclusively, and does not require slow addition of the diazo component.