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Synthesis 2011(12): 1853-1858  
DOI: 10.1055/s-0030-1260526
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Origins of Enantioselectivity in Proline-Catalyzed Friedländer Condensations of 4-Substituted Cyclohexanones

Le Li, Daniel Seidel*
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
Fax: +1(732)4455312; e-Mail: seidel@rutchem.rutgers.edu;
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Publikationsverlauf

Received 16 April 2011
Publikationsdatum:
27. Mai 2011 (online)

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Abstract

Computational studies reveal the origin of the enantioselectivity in proline-catalyzed Friedländer condensations of 4-substituted cyclohexanones with aminobenzaldehydes. Both the catalyst structure and the nature of the substituent on cyclohexanone play important roles in this desymmetrization process. The model presented herein provides a satisfying explanation for the vastly different selectivities that are observed for 4-phenylcyclohexanone versus 4-(tert-butyldimethylsilyloxy)cyclohexanone.

Key words

Friedländer synthesis - quinolines - amino aldehydes - organocatalysis - proline

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The predicted enantiomeric excesses were determined by converting the differences in the calculated gas-phase free energies of activation, ΔΔG 298, into % ee using absolute rate theory: ln(k 1/k 2) = -eΔΔ G / RT .

21

Li, L.; Seidel, D. unpublished results.