Asymmetric Enzymatic Synthesis of Allylic Amines: A Sigmatropic Rearrangement Strategy

Sigmatropic rearrangements, while rare in biology, offer opportunities for the efficient and selective synthesis of complex chemical motifs. A “P411” serine‐ligated variant of cytochrome P450_BM3 has been engineered to initiate a sulfimidation/[2,3]‐sigmatropic rearrangement sequence in whole E. coli cells, a non‐natural function for any enzyme, providing access to enantioenriched, protected allylic amines. Five mutations in the enzyme substantially enhance its activity toward this new function, demonstrating the evolvability of the catalyst toward challenging nitrene transfer reactions. The evolved catalyst additionally performs the highly enantioselective imidation of non‐allylic sulfides.