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Synthesis 2006(21): 3679-3705  
DOI: 10.1055/s-2006-950313
PAPER
© Georg Thieme Verlag Stuttgart · New York

Studies on the Synthesis of Richardianidin-1 via the Tautomer-Arrested Annulation of Fischer Carbene Complexes

Mary Ellen Bos, Catherine Loncaric, Chunrui Wu, William D. Wulff*
Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA
e-Mail: wulffw@msu.edu;
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Publication History

Received 6 July 2006
Publication Date:
12 October 2006 (online)

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Abstract

A strategy for the synthesis of richardianidin-1 is evaluated which has as its key step the tautomer-arrested annulation of chromium-carbene complexes. Both inter- and intramolecular variations of the strategy are examined. The intramolecular reaction involves the tethering of the alkyne to the oxygen stabilizing substituent of the carbene carbon. The outcome of the intramolecular tautomer-arrested annulation was found to be highly dependent on the nature of the tether and the on the type of substituent on the alkyne. The product distribution from these reactions included the desired hydrindenone resulting from tautomer-arrested annulation, a naphthalenedione, and a spirocyclohexadienone. The latter two products result from CO insertion prior to cyclization. The optimal tether length for the tautomer-arrested product is four atoms between the alkyne and the carbene carbon. The yields for the intramolecular reaction dropped significantly for a substituent on the alkyne terminus that was larger than a methyl group and this was not suitable for a synthesis of richardianidin-1. Initial studies on the intermolecular tautomer-arrested annulation focused on the regioselectivity of alkyne incorporation. The reaction with isopropyl(methyl)acetylene gives a single regioisomer and reveals that the tautomer-arrested annulation is more regioselective than the normal benzannulation. Furthermore, the intermolecular reaction is more tolerant of larger substituents on the terminus of the alkyne. As a result of the studies on the intermolecular tautomer-arrested annulation a suitable alkyne was found that introduces all of the carbons present in the six-membered lactone of richardianidin-1.

Key words

richardianidin-1 - chromium-carbene complexes - annulation - carbon monoxide insertion - cyclization