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Synthesis 2007(5): 779-790  
DOI: 10.1055/s-2007-965917
FEATUREARTICLE
© Georg Thieme Verlag Stuttgart · New York

Generally Applicable Organocatalytic Tetrahydropyranylation of Hydroxy Functionalities with Very Low Catalyst Loading

Mike Kotke, Peter R. Schreiner*
Institute of Organic Chemistry, Justus-Liebig University Gießen, Heinrich-Buff-Ring 58, 35392 Gießen, Germany
Fax: +49(641)9934309; e-Mail: prs@org.chemie.uni-giessen.de;
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Publication History

Received 14 December 2006
Publication Date:
08 February 2007 (online)

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Abstract

This paper presents the first acid-free, organocatalytic tetrahydropyran and 2-methoxypropene protection of alcohols, phenols, and other ROH derivatives utilizing privileged N,N′-bis[3,5-bis(trifluoromethyl)phenyl]thiourea and a polystyrene-bound analogue. The reactions are broadly applicably (also on preparative scale), in particular, to acid-sensitive substrates such as aldol products, hydroxy esters, acetals, silyl-protected alcohols, and cyanohydrins. The catalytic efficiency is truly remarkably with turnover numbers of 100,000 and turnover frequencies of up to 5700 h-1 at catalyst loadings down to 0.001 mol%. The computationally supported mechanistic interpretation emphasizes the hydrogen bond assisted heterolysis of the alcohol and concomitant preferential stabilization of the oxyanion hole in the transition state.

Key words

acetals - alcohols - catalysis - protecting groups - supported catalysis