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Synergistic Peptide and Gold Catalysis: Enantioselective Addition of Branched Aldehydes to Allenamides
Author(s) -
Nicholls Leo D. M.,
Wennemers Helma
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202103197
Subject(s) - stereocenter , enantioselective synthesis , chemistry , catalysis , alkoxy group , combinatorial chemistry , aldehyde , peptide , alkyl , organic chemistry , biochemistry
The combination of a peptide catalyst and a gold catalyst is presented for enantioselective addition reactions between branched aldehydes and allenamides. The two catalysts act in concert to provide γ,δ‐enamide aldehydes bearing a fully substituted, benzylic stereogenic center – a structural motif common in many natural products and therapeutically active compounds – with good yields and enantioselectivities. The reaction tolerates a variety of alkyl and alkoxy substituted aldehydes and the products can be elaborated into several chiral building blocks bearing either 1,4‐ or 1,5‐ functional group relationships. Mechanistic studies showed that the conformational features of the peptide are important for both the catalytic efficiency and stereochemistry, while a balance of acid/base additives is key for ensuring formation of the desired product over undesired side reactions.