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DOI: 10.1055/s-2007-968756
Organocatalytic Reaction Cascade
Contributor(s):Benjamin List, Sebastian HoffmannMax-Planck-Institut für Kohlenforschung, Mülheim an der Ruhr, Germany
Organocatalytic Asymmetric Reaction Cascade to Substituted Cyclohexylamines
J. Am. Chem. Soc. 2007, 129: 7498-7499
Publication History
Publication Date:
24 July 2007 (online)
Key words
cascade reaction - diones - cyclohexylamines - Brønsted acid catalysis - enamine catalysis - iminium catalysis
Significance
An organocatalytic asymmetric reaction cascade towards 3-substituted cyclohexylamines 4 is described. Self-sacrificing achiral amines 2 in combination with a chiral phosphoric acid catalyst have proven to promote the transformation of 2,6-diones 1 to cis-3-substituted cyclohexylamines 4 in moderate to excellent diastereo- and enantioselectivities. Overall, the triple cascade is believed to proceed via (1) an initial aldol reaction via an enamine intermediate, (2) a conjugate reduction of an iminium ion, and (3) a Brønsted acid catalyzed reductive amination. Hantzsch ester 3 serves as a hydride donor for the conjugate reduction and the reductive amination.
Comment
Chiral secondary amines are important organocatalysts, which are known to catalyze reactions via enamine or iminium intermediates. Previous interest in organocatalytic domino reactions has led to various multicomponent two- and three-step reactions using these activation strategies. However, the combination of amine catalysis with Brønsted acid catalysis is less explored. After having established related asymmetric organocatalytic single-step processes, Zhou and List could now show the compatibility of enamine and iminium catalysis with chiral Brønsted acid catalysis.