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Michael addition is an important reaction to form C–C bonds. Different hydrolases (e.g., lipases, proteases, and D-aminoacylase) have been reported to catalyze C–C forming reactions, but the reaction mechanism is not entirely clear. This study examined several model Michael reactions catalyzed by lipases and amino acids in various solvents, and found that “‘water-like”’ functionalized ionic liquids (ILs) increased the reaction yield to 35-55% from 30% in triglyme and 17% in [BMIM][Tf2N]. Interestingly, tertiary amides as solvents remarkably increased the reaction yield (to up to 65–85%) and enantioselectivity (up to 71–84% ee) when catalyzed by porcine pancreatic lipase (PPL). Our experimental, spectroscopic, and computational studies discovered that the lipase catalysis can be attributed to basic amino acid residues as the catalysts to promote Michael addition, especially when tertiary amide solvents partially unfold the protein and expose its basic amino acid residues.
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Methodology to Control the Regioselective Installation of a Carboxylic Acid for the Synthesis of 2,3‐Diarylpropionic Acids
A stepwise copper‐catalyzed boracarboxylation then palladium‐catalyzed Suzuki‐Miyaura cross‐coupling methodology was developed to access 2,3‐diarylpropionic acid derivatives regioselectively by pre‐setting the position of the carboxylic acid in the boracarboxylation reaction. This method provides access to a wide range of aryl and heteroaryl products in up to 80% isolated yield. Pharmaceutical potential was demonstrated by synthesizing a glucagon receptor antagonist drug in three steps (31% overall yield) from commercially available 4‐tert‐butylstyrene.
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- PAR ID:
- 10572974
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- Advanced Synthesis & Catalysis
- ISSN:
- 1615-4150
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1002/adsc.202400952
