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Highly Stereoselective Peptide Modifications through Pd‐Catalyzed Allylic Alkylations of Chelated Peptide Enolates
Author(s) -
Deska Jan,
Kazmaier Uli
Publication year - 2007
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.200700084
Subject(s) - chemistry , deprotonation , nucleophile , allylic rearrangement , electrophile , peptide , palladium , combinatorial chemistry , chelation , catalysis , tsuji–trost reaction , alkylation , medicinal chemistry , stereoselectivity , amino acid , stereochemistry , organic chemistry , ion , biochemistry
Deprotonation of peptides in the presence of zinc chloride gives rise to highly reactive nucleophiles that can be subjected to palladium‐catalyzed allylic alkylation reactions. Excellent diastereoselectivities are obtained that are nearly independent of the allylic substrate used. By using this protocol, highly functionalized side chains can also be incorporated in excellent yields and selectivities. The stereochemical outcome of the reaction is exclusively controlled by the peptide chain as long as terminal π‐allyl–palladium complexes are involved. Probably, there is a threefold coordination, at least, of the deprotonated peptide chain to the chelating zinc ion. In such metal peptide complexes, one face of the generated enolate is shielded by the side chain of the adjacent amino acid, thus directing the electrophilic attack onto the opposite face. This behavior explains why an S amino acid always generates an R amino acid (and the other way round).