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The Brønsted Acid Catalyzed, Enantioselective Vinylogous Mannich Reaction
Author(s) -
Sickert Marcel,
Abels Falko,
Lang Matthias,
Sieler Joachim,
Birkemeyer Claudia,
Schneider Christoph
Publication year - 2010
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.200902537
Subject(s) - enantioselective synthesis , chemistry , stereocenter , mannich reaction , cationic polymerization , protonation , silylation , nucleophile , brønsted–lowry acid–base theory , imine , catalysis , organic chemistry , silanol , oxonium ion , tetracoordinate , phosphoric acid , medicinal chemistry , ion , computer graphics (images) , computer science , planar
Abstract The first catalytic, enantioselective vinylogous Mannich reaction of acyclic silyl dienolates is reported. A second‐generation 2,2′‐dihydroxy‐1,1′‐binaphthyl (BINOL)‐based phosphoric acid has been developed and further optimized as an enantioselective organocatalyst. Upon protonation of the imines, chiral contact ion pairs are generated in situ and attacked highly diastereoselectively by the nucleophile. γ‐Substituted silyl dienolates that lead to more highly substituted Mannich products with a second stereogenic center in good diastereoselectivity have been employed in these reactions. The reaction path has been elucidated with NMR spectroscopy and mass spectrometry, which suggest that the protic reaction medium found to be optimal in these reactions serves to trap the cationic silicon species as silanol. A crystal structure of a phosphoric acid bound imine was obtained that provides insight into the binding mode and a rationale for the stereochemical course of the reaction.