Synthesis 2010(9): 1531-1535  
DOI: 10.1055/s-0029-1218737
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Metalation of 2-Heterosubstituted Naphthalenes at the 1- or 3- Position: Factors That May Determine the Regiochemistry

Renzo Ruzziconi*a, Sara Spizzichinoa, Mirosav Giurgb, Eva Castagnettib, Manfred Schlosser*b
a Chemistry Department, University, Via Elce di Sotto 10, 06100 Perugia, Italy
Fax: +39(075)5855262; e-Mail: ruzzchor@unipg.it;
b Institute of Chemical Sciences and Engineering Ecole Polytechnique Fédérale (EPFL-BCh), 1015 Lausanne, Switzerland
Fax: +41(21)6939365; e-Mail: manfred.schlosser@epfl.ch;
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Publikationsverlauf

Received 21 October 2009
Publikationsdatum:
15. April 2010 (online)

Abstract

Upon metalation and subsequent electrophilic trapping, 2-fluoronaphthalene inevitably gives rise to regioisomeric mixtures in varying proportions, whereas 2-(trifluoromethyl)naphthalene undergoes deprotonation either at the 1- or the 3-position, depending on the choice of the reagent. On the other hand, 2-(trifluoromethoxy)naphthalene and 2-methoxynaphthalene react exclusively at the 3-position when, respectively, sec-butyllithium and superbasic reagents are employed. Steric repulsion by the peri hydrogen in combination with crowding due to coordination of the lithium atom with the methoxy group disfavors attack at the 1-position.

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Desponds, O.; Schlosser, M. 1995, unpublished results.