Synfacts 2016; 12(06): 0635
DOI: 10.1055/s-0035-1562137
Organo- and Biocatalysis
© Georg Thieme Verlag Stuttgart · New York

Enzymatic Nitrene Transfer/Sigmatropic Rearrangement to Access Allylic Amines

Benjamin List
Lucas Schreyer
Prier CK, Hyster TK, Farwell CC, Huang A, Arnold FH * California Institute of Technology, Pasadena, USA
Asymmetric Enzymatic Synthesis of Allylic Amines: A Sigmatropic Rearrangement Strategy.

Angew. Chem. Int. Ed. 2016;
55: 4711-4715
Further Information

Publication History

Publication Date:
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.