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Titanocene Catalyzed 4-exo Cyclizations:  Mechanism, Experiment, Catalyst Design

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Institut für Theoretische Chemie der Universität zu Köln, Greinstr. 4, 50939 Köln, Germany, and Kekulé-Institut für Organische Chemie und Biochemie der Universität Bonn, Gerhard Domagk Str. 1, 53121 Bonn, Germany
Cite this: J. Am. Chem. Soc. 2008, 130, 5, 1788–1796
Publication Date (Web):January 12, 2008
https://doi.org/10.1021/ja077596b
Copyright © 2008 American Chemical Society
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Abstract

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A method for the preparation of a variety of cyclobutanes via 4-exo cyclization of radicals is presented. Radical generation is carried out by electron transfer from titanocene(III) chlorides to epoxides. The reaction relies on the acceleration of the cyclization through the use of α,β-unsaturated carbonyl compounds as radical traps and the thermodynamic stabilization of the cyclobutylcarbinyl radicals through conjugation. The mechanism of the transformation was investigated by a combined theoretical and experimental study. The computational results provide the crucial energetic and structural features of pertinent intermediates and transition structures. Moreover, the origins of the diastereoselectivity of the 4-exo cyclization are outlined for the first time. Catalysts for those cases where “Cp2TiCl” did not perform in a satisfactory manner have been devised. Through the introduction of tert-butyl or cyclo-hexyl substituted cyclopentadienyl ligands the longevity of the pivotal β-titanoxy radicals is increased sufficiently enough to enable the slow but often surprisingly diastereoselective formation of the cyclobutylcarbinyl radical. The resulting transformation constitutes the first general approach to cyclobutanes using radical chemistry.

*

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

†

 Universität zu Köln.

‡

 Universität Bonn.

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