Merging gold(I) catalysis with amine transaminases in cascade catalysis : chemoenzymatic transformation of propargylic alcohols into enantioenriched allylic amines

The compatibility between gold(I) catalysts and amine transaminases has been explored to transform racemic propargylic alcohols into enantioenriched allylic amines in a straightforward and selective manner. The synthetic approach consists of a gold(I)-catalysed Meyer-Schuster rearrangement of a series of 2-arylpent-3-yn-2-ols and a subsequent stereoselective enzyme-catalysed transamination of the resulting alpha,beta-unsaturated prochiral ketones. The design of cascade processes involving sequential or concurrent approaches has been studied in our search for ideal reaction conditions to produce the desired amines. Thus, the N-heterocyclic carbene complex [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]-[bis(trifluoromethanesulfonyl)-imide]gold(I) ([Au(IPr)(NTf2)] (A) in aqueous medium was found to be an ideal catalyst, while selective, made-in-house and commercial amine transaminases permitted the asymmetric synthesis of both (E)-4-arylpent-3-en-2-amine enantiomers in good isolated yields (53-84%) and excellent stereoselectivities (97 to >99% enantiomeric excess).The compatibility between gold(I) catalysts and amine transaminases has been explored to transform racemic propargylic alcohols into enantioenriched allylic amines in a straightforward and selective manner. The synthetic approach consists of a gold(I)-catalysed Meyer-Schuster rearrangement of a series of 2-arylpent-3-yn-2-ols and a subsequent stereoselective enzyme-catalysed transamination of the resulting alpha,beta-unsaturated prochiral ketones. The design of cascade processes involving sequential or concurrent approaches has been studied in our search for ideal reaction conditions to produce the desired amines. Thus, the N-heterocyclic carbene complex [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]-[bis(trifluoromethanesulfonyl)-imide]gold(I) ([Au(IPr)(NTf2)] (A) in aqueous medium was found to be an ideal catalyst, while selective, made-in-house and commercial amine transaminases permitted the asymmetric synthesis of both (E)-4-arylpent-3-en-2-amine enantiomers in good isolated yields (53-84%) and excellent stereoselectivities (97 to >99% enantiomeric excess).A