Synthesis 2014; 46(03): 387-393
DOI: 10.1055/s-0033-1338573
paper
© Georg Thieme Verlag Stuttgart · New York

Overcoming the Inherent Alkylation Selectivity of 2,3-trans-3,4-cis-Trisubstituted Cyclopentanones

Michael B. Reardon
Clark University, Carlson School of Chemistry & Biochemistry, 950 Main Street, Worcester, MA 01610, USA   Fax: +1(508)7937117   Email: cjakobsche@clarku.edu
,
George W. Carlson
Clark University, Carlson School of Chemistry & Biochemistry, 950 Main Street, Worcester, MA 01610, USA   Fax: +1(508)7937117   Email: cjakobsche@clarku.edu
,
Charles E. Jakobsche*
Clark University, Carlson School of Chemistry & Biochemistry, 950 Main Street, Worcester, MA 01610, USA   Fax: +1(508)7937117   Email: cjakobsche@clarku.edu
› Author Affiliations
Further Information

Publication History

Received: 23 September 2013

Accepted after revision: 18 November 2013

Publication Date:
10 December 2013 (online)


Abstract

Some ketones, especially 2,3-trans-3,4-cis-trisubstituted cyclopentanones, have strong inherent preferences to react through their less-substituted enolates, with neither kinetic nor thermodynamic conditions being able to selectively functionalize their more-substituted enolate isomers. Herein we report a synthetic strategy to overcome this limitation and selectively access the more-substituted alkylation products of these ketones. The strategy’s key feature is to utilize a MeOCH2O group to temporarily block the more-reactive α position and to direct the ketone to react through its inherently less-reactive enolate isomer. The products formed by this strategy are useful synthetic intermediates on the path to multiple families of natural products.

Supporting Information

 
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