Enzymatic Nitrene Transfer/Sigmatropic Rearrangement to Access Allylic Amines
Asymmetric Enzymatic Synthesis of Allylic Amines: A Sigmatropic Rearrangement Strategy.
Angew. Chem. Int. Ed. 2016;
17 May 2016 (online)
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.
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.