Merging the Non‐Natural Catalytic Activity of Lipase and Electrosynthesis: Asymmetric Oxidative Cross‐Coupling of Secondary Amines with Ketones

Abstract

We describe the enantioselective oxidative cross-coupling of secondary amines with ketones by combining the non-natural catalytic activity of lipase with electrosynthesis. Various 2,2-disubstituted 3-carbonyl indoles with a stereogenic quaternary carbon center were synthesized from 2-substituted indoles in yields up to 78 % with good enantioand diastereoselectivities (up to 96 : 4 e.r. and > 20 : 1 d.r.). This unprecedented protocol demonstrated that hydrolase catalysis is compatible with electrosynthesis, and the reaction can be carried out in organic solvents with a broad substrate scope and good stereoselectivity. This work provides insights into enzymatic electrosynthesis.

Direct enantioselective α-alkylation of secondary acyclic amines with ketones by combining photocatalysis and lipase catalytic promiscuity

“…Based on the performed experiments and previous literature, [25][26][27][45][46][47][48][49][50] a possible mechanistic pathway for the reaction was proposed as depicted in Fig. 3.…”

“…In the catalytic triad at this time, aspartic acid is fixed to the imidazole group of histidine through hydrogen bonding enabling histidine to accept a proton from serine. 45 This allows a proton to transfer from cyclohexanone (2a) to serine, forming an enolate anion transition state (IV). Finally, the nucleophilic attack of IV on the iminium ion II leads to the target product 3a with stereoselectivity.…”

Mechanochemical Encapsulation of Enzymes into MOFs for Photoenzymatic Enantioselective Catalysis

“…As we know, lipases from different sources have different catalytic characteristics and catalytic activities. Furthermore, upon comparing the activity of various lipases at identical loading amounts, including Aspergillus niger lipase, Candida yeast lipase, Acid lipase, and Porcine pancreatic lipase, Wheat germ lipase exhibited superior performance and has better catalytic ability against asymmetric Mannich reaction. ,, These advantages are the primary reason for selecting wheat germ lipase as the focus of our study (Figure S6)…”

“…Furthermore, upon comparing the activity of various lipases at identical loading amounts, including Aspergillus niger lipase, Candida yeast lipase, Acid lipase, and Porcine pancreatic lipase, Wheat germ lipase exhibited superior performance and has better catalytic ability against asymmetric Mannich reaction. 9,10,59 These advantages are the primary reason for selecting wheat germ lipase as the focus of our study (Figure S6) Enzyme presence, chiral preservation, the surface area and pores of MOFs, and the photonic effects of the photosensitizer collectively constitute indispensable components of the photobiological catalytic system. Fourier Transform infrared spectroscopy (FTIR) results showed that the generated catalysts contained characteristic peaks of both WGL and UiO-67-Ru/Cu, indicating the successful preparation of the composite materials (Figure S7).…”