Merging Gold(I) Catalysis with Amine Transaminases in Cascade Catalysis: Chemoenzymatic Transformation of Propargylic Alcohols into Enantioenriched Allylic Amines

• Published in: Advanced synthesis & catalysis 2022-11, Vol.364 (22), p.3856-3866
• Main Authors: González‐Granda, Sergio, Tzouras, Nikolaos V., Nolan, Steven P., Lavandera, Iván, Gotor‐Fernández, Vicente
• Format: Article
• Language: English
• Subjects: Alcohols; Amines; Aqueous solutions; Catalysis; Catalysts; Chiral amines; Enantiomers; Gold; Gold catalysis; Ketones; Meyer-Schuster rearrangement; N-Heterocyclic carbene; Stereoselectivity; Transaminases
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.202200777

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 α,β‐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).