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DOI: 10.1055/s-0028-1083573
Desymmetrizing Aldol Cyclodehydration
Contributor(s):Benjamin List, Corinna ReisingerMax-Planck-Institut für Kohlenforschung, Mülheim/Ruhr, Germany and Givaudan Schweiz AG, Dübendorf, Switzerland
Primary-Amine-Catalyzed Enantioselective Intramolecular Aldolizations
Angew. Chem. Int. Ed. 2008, 47: 7656-7658
Publication History
Publication Date:
20 November 2008 (online)
Key words
4-substituted 2,6-heptanediones - aldol cyclodehydra-tion - desymmetrization - 9-amino-9-deoxyepiquinine
Significance
A highly enantioselective desymmetrizing intramolecular aldol condensation reaction of 4-substituted 2,6-heptanediones 1 has been established to furnish 5-substituted 3-methyl-2-cyclohexene-1-ones 3. Quinine-derived primary amine 2a in combination with acetic acid proved to be the ideal catalytic system for the desired transformation. The use of its pseudoenantiomeric analogue 2b derived from quinidine gives access to the opposite product enantiomer in equally high enantioselectivity.
Comment
The present work solves the longstanding problem of enantiogroup-selective aldolizations of 4-substituted 2,6-heptandiones. The synthetic utility of the described method was demonstrated by means of the first asymmetric synthesis of both enantiomers of the synthetic fragrance material celery ketone 5, which strikingly differ in their olfactory properties. Moreover, the synthesis of chiral nonracemic 3-methyl cyclohexenone 4, a valuable synthetic intermediate, was achieved in two steps from 2,4,6-lutidine. This study alongside others reveals the high potential of cinchona alkaloid-derived primary amine catalysts, for example, 2a and 2b, in both asymmetric enamine and iminium catalysis (see Review).
Review: F. Peng, Z. Shao J. Mol. Catal.: A 2008, 285, 1-13.