Biotransformation of 3-azidomethyl-4-phenyl-3-buten-2-one and analogs by Saccharomyces cerevisiae: New evidence for an SN2' mechanism

Abstract ( Z )-3-XCH 2 -4-(C 6 H 5 )-3-buten-2-one enones (X = SCN, N 3 , SO 2 Me, OC 6 H 5 ) were synthesized and submitted to biotransformations using whole Saccharomyces cerevisiae cells. The enone (X = SCN) produced ( R )-4-(phenyl)-3-methylbutan-2-one ( R )- 6 with 93% ee and enones (X = N 3 , SO 2 Me, OC 6 H 5 ) yielded a mixture of ( R )- 6 and the corresponding C C bond reduction products. Biotransformation with enone (X = N 3 ) mediated by Saccharomyces cerevisiae resulted in two products via two different routes: (i) the ketone ( R )-4-azido-3-benzylbutan-2-one in 28% yield and with >99% ee by C C bond reduction; (ii) ketone ( R )- 6 in 51% yield and with 95% ee via cascade reactions beginning with azido group displacement by the formal hydride from flavin mononucleotide in an S N 2′ type reaction followed by reduction of the newly formed C C bond.