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Diversity‐Oriented Syntheses by Combining CuAAC and Stereoselective INCIC Reactions with Peptides
Author(s) -
Wang Yuanyuan,
Madsen Anders Ø.,
Diness Frederik,
Meldal Morten
Publication year - 2017
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.201702900
Subject(s) - iminium , stereoselectivity , chemistry , combinatorial chemistry , aminal , stereochemistry , ion , organic chemistry , catalysis
Cascade reactions proceeding through peptide‐derived N ‐carbamoyl iminium ions are reported. Two new reactions of N ‐carbamoyl iminium ions are described, including a stereoselective double cyclization generating N , N′ ‐aminals and an acid‐promoted auto‐oxidation. Mechanistic investigations revealed that the N , N′ ‐aminal formation is reversible under strongly acidic conditions. Both of these new reactions proved to be completely orthogonal to subsequent CuAAC chemistry. The reactions were performed in solution and on solid support. The robustness and high stereoselectivity of the methodology holds great promise for applications in parallel diversity‐oriented synthesis and in combinatorial synthesis for drug screening.