Synthesis of Tri¯uoromethylnaphthalenes John M. Mellor, a, * Afaf H. El-Sagheer, a El-Sayed H. El-Tamany b and Reda N. Metwally c a Department of Chemistry, University of Southampton, Southampton SO17 1BJ, UK b Department of Chemistry, Faculty of Science, Suez Canal University, Ismailia, Egypt c Department of Science and Maths., Faculty of Petroleum and Mining Engineering, Suez Canal University, Suez, Egypt Received 18 July 2000; revised 14 September 2000; accepted 12 October 2000 Abstract ÐReaction of 1-(3,4-dihydro-2H-5-pyranyl)-2,2,2-tri¯uoro-1-ethanone with benzylic Grignard reagents affords by 1,2-addition unsaturated allylic alcohols. These alcohols readily undergo dehydration and cyclisation to give tri¯uoromethylnaphthalenes. The generality of this procedure was established by reaction with diverse benzyl and allyl Grignard reagents and by reaction of a number of unsaturated ketones. The resulting tri¯uoromethylnaphthalenes were oxidised to give substituted acetic- and propionic acids. q 2000 Elsevier Science Ltd. All rights reserved. Introduction Acyclic ¯uorinated building blocks 1 have been used widely in the synthesis of ¯uorinated heterocyclic compounds. Routes to ¯uorinated carbocyclic aromatic compounds have relied more on either direct ¯uorination 2 or the intro- duction of tri¯uoromethyl groups from tri¯uorobromo- methane, 3 tri¯uoroiodomethane, 4 tri¯uoromethyltrimethyl- silane 5 and other silanes, 6 silver tri¯uoroacetate, 7 sodium tri¯uoroacetate, 8 N-tri¯uoromethyl-N-nitrosotri¯uoromethane- sulfonamide, 9 or bistri¯uoromethylmercury. 10 Introduction of tri¯uoromethyl side chain substituents into aromatic carbocycles via a building block approach permitting construction of the ring with incorporation of the tri¯uoro- methyl substituent is little developed. The possibility that the [313] benzannulation procedures, recently developed by Junjappa et al. 11 and reviewed by Katritzky et al., 12 might be used to give ¯uorinated naphthalenes, is attractive. In this methodology an unsaturated ketone is reacted with a benzyl organometallic reagent to afford a 1,2-adduct, which on dehydration affords aromatic products. In order that this procedure might be applied to tri¯uoromethylketones, thus giving tri¯uoromethyl substituted aromatic compounds (Scheme 1), it is essential that the benzyl organometallic reagent should undergo 1,2-addition with, for example, a b-alkoxy-a,b-unsaturated ketone, rather than the possible 1,4-addition. Earlier 13,14 we have shown that benzyl mag- nesium bromide reacts with the ketone (1) by 1,2-addition in high yield. There are a number of protocols using organo- metallic reagents to favour 1,2-addition and minimise 1,4- addition. In the favourable case of allyl derivatives, not only do allyl Grignard reagents preferentially add 15 by 1,2- addition, but direct reaction of an allyl halide with indium metal leads to in situ formation of an indium allyl 16 and hence to selective 1,2-addition. We ®nd that either this protocol, or the related Barbier conditions 17 whereby an allyl Grignard reagent is generated in situ, are effective. In the case of 1,2-addition of benzyl groups, although the Tetrahedron 56 (2000) 10067±10074 Pergamon TETRAHEDRON 0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved. PII: S0040-4020(00)00977-7 Keywords: Grignard reagents; naphthalenes; tri¯uoromethylketones. * Corresponding author. Tel.: 1238059-2392; fax: 1238059-6805; e-mail: jmm4@soton.ac.uk Scheme 1.