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

Abstract

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 2arylpent-3-yn-2-ols and a subsequent stereoselective enzyme-catalysed transamination of the resulting α,βunsaturated 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 Nheterocyclic carbene complex [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]-[bis(trifluoromethanesulfonyl)-imide]gold(I) ([Au(IPr)(NTf 2 )] (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).

Combination of gold and redox enzyme catalysis to access valuable enantioenriched aliphatic β-chlorohydrins

“…Recently, bulky NHC–gold( i ) complexes have demonstrated to stabilize the metal center under aqueous conditions, therefore allowing possible combinations with different biological catalysts in a cascade manner. 14,28 Herein, we have implemented this methodology to provide a general and simple synthetic chemoenzymatic approach to enantioenriched aliphatic β-chlorohydrins, building-blocks of important derivatives, which otherwise are not easily accessible using traditional methods.…”

Expanding the Synthetic Toolbox through Metal–Enzyme Cascade Reactions

“…However, the combination of both worlds must be employed in a reasonable way, taking advantage of both catalysis but also being aware of existing limitations to advance, and therefore considering solutions in the reaction setups. − There is no more powerful technique than organometallic chemistry for C–C or C–X bond formation, while enzymes can provide unique possibilities for chiral induction, so their cooperative work in one-pot multistep transformations undoubtedly constitutes one of the most straightforward manners to design controlled complexity. Gladly, this is an area in continuous evolution, and remarkable examples have recently appeared in the literature including valuable chemoenzymatic cascades. − …”

Chemoenzymatic Cascades Combining Biocatalysis and Transition Metal Catalysis for Asymmetric Synthesis

“…This methodology has been expanded to the synthesis of β,β‐disubstituted allylic amines by merging a similar Au I ‐catalyzed rearrangement with a biotransamination step with commercial ATAs. A concurrent cascade protocol using less nucleophilic alanine as amine donor was tried, but a sequential approach worked better by addition of 2‐PrNH 2 after the metal‐catalyzed step, providing both enantiomers of eight allylic amines in moderate to high isolated yields (53–84 %) [51] …”

“…A concurrent cascade protocol using less nucleophilic alanine as amine donor was tried, but a sequential approach worked better by addition of 2-PrNH 2 after the metal-catalyzed step, providing both enantiomers of eight allylic amines in moderate to high isolated yields (53-84 %). [51] In 2009, Asikainen and Krause obtained different chiral 2,5-dihydrofurans by combining a lipase-catalyzed kinetic resolution via ester hydrolysis with a subsequent Aumediated cycloisomerization in a concurrent manner. [52] The first stage was the selective formation of an allenol catalyzed by immobilized PSL in an aqueous phosphate-buffered solution, followed by the activation of the allenol with an Au III catalyst, which promoted a ring closure, providing the oxygenated cyclic compounds in moderate yields (28-50 %) and high stereoselectivities (88-98 % ee, Scheme 10B).…”