Peptide-based catalysts offer a unique platform to perform bifunctional catalysis. However, they are somewhat limited in scope as most rely on amino acids to catalyze reactions. We envision the development of a general catalytic platform that can be used with a wide variety of catalysts. Herein we describe a proof-of-concept study involving the conjugate addition of cyclohexanone to nitroolefin electrophiles. A 14mer α-helical peptide was used as a scaffold and functionalized with a proline and thiourea catalyst. The peptide-bound catalyst resulted in significant increases in reactivity and selectivity compared to the unbound catalysts. Further engineering of the peptide structure by the rational placement of phenylalanine residues yielded further increases in selectivity, with % ee as high as 95% being obtained. These results were consistent over various substrates. This study serves as a proof-of-principle for the use of helical peptide scaffolds to enable enantioselective bifunctional catalysis.

Rational design of a bifunctional helical peptide catalyst demonstrated in the conjugate addition of nitroolefins to cyclohexanone

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.