Enzymatic Nitrene Transfer/Sigmatropic Rearrangement to Access Allylic Amines

Key words

sigmatropic rearrangement - nitrene - directed evolution - allylic amines - enzymes

Significance

Arnold and co-workers report an enzymatic synthesis of allylic amines through a sulfimidation/[2,3]-sigmatropic rearrangement of phenyl allyl sulfides with tosyl azide. A mutant variant of cytochrome P411 from Bacillus megaterium efficiently catalyzes a highly enantioselective ­nitrene transfer to the sulfides, and permits a subsequent rearrangement with partial retention of the stereochemical information. In a scale-up experiment with reduced catalyst loading, 0.1 mmol of substrate was converted into the corresponding allylic amine in 71% yield and a remarkable total turnover number of 6100.

Comment

The authors have successfully employed directed evolution to achieve a chemo­selective nitrene transfer over the competing ­reduction. Furthermore, they achieved a sigmatropic rearrangement of the intermediate allylic sulfimides, a process unknown in wild-type biological systems.