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Synthesis 2011(6): 895-900  
DOI: 10.1055/s-0030-1258419
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Enantioselective Synthesis of Hexahydroisobenzofuran and Hexahydro­isoindole Derivatives with Quaternary Stereocenters

Jens Christoffers*, Jonas Sluiter, Jan Schmidt
Institut für Reine und Angewandte Chemie, Carl von Ossietzky-Universität Oldenburg, 26111 Oldenburg, Germany
Fax: +49(441)7983873; e-Mail: jens.christoffers@uni-oldenburg.de;
Further Information

Publication History

Received 3 November 2010
Publication Date:
01 March 2011 (online)

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Abstract

Oxo esters with pyrrolidine and tetrahydrofuran rings were converted into optically active isobenzofuran and isoindole derivatives. The key step of the sequence was a copper-catalyzed asymmetric Michael reaction with methyl vinyl ketone and en­amines prepared from the oxo esters and l-valine diethylamide. The chiral auxiliary was cleaved from the products during workup and 1,5-diketones with a quaternary stereocenter are obtained with 97-99% ee. Subsequent annulation reactions were achieved in two steps via the intermediate aldol products.

Key words

tetrahydrofurans - pyrrolidines - isoindoles - isobenzofurans - chirality - Michael addition - quaternary stereocenters

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CCDC 785562 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033.