Preparation of o-bromobenzophenone derivatives from lithium diarylcuprate(I) reagents Selhan Karago È z, Demet K. Astley and Stephen T. Astley* Ege Universitesi, Fen Fakultesi, Kimya Bolumu, Bornova-Izmir, 35100 Turkey The reaction of lithium diarylcuprate(I) re- agents with o-bromobenzoyl chloride has been investigated. In general, the reaction proceeds well to give synthetically useful o-bromobenzo- phenone derivatives as the major product. It is suggested that a minor substituent effect, where- by diarylcuprate reagents containing an ortho or meta substituent react more favourably, may be attributed to small changes in the structure of the organometallic reagent. Copyright # 2000 John Wiley & Sons, Ltd. Keywords: synthesis; organo-cuprate Received 11 September 1999; accepted 20 January 2000 INTRODUCTION As part of an ongoing study into the transition- metal-mediated preparation of novel heterocyclic compounds, it has became desirable for us to prepare a series of 2-bromobenzophenone deriva- tives. 1 A currently popular method for the synthesis of such unsymmetrical ketones, which avoids the formation of isomers, is the reaction of organo- metallic reagents with acid chlorides. 2 Recently Palladium(0) catalysts 3 and some elaborately pre- pared organocopper 4 or copper–zinc 5 reagents have been employed for this purpose. However, due to their familiarity and relative ease of preparation, we initially considered the reaction of lithium diaryl- cuprate(I) reagents with ortho bromo-substituted aromatic acid chlorides as a possible means of synthesis of these derivatives. (Eqn [1]). In contrast to the extensive use which has been made of organocuprates for coupling reactions with R—X 6,7 and for conjugate addition to (a,b)- unsaturated carbonyl compounds, 7,8 relatively little attention has been paid to their application in the reaction with acid chlorides; 9 in those studies that have been carried out, concentration has generally focused on the reaction of methyl or n-alkyl cuprates with unsubstituted acid chlorides. 10 How- ever, there has been one example reported con- cerning the reaction of a cuprate (lithium dimethylcuprate) with a substituted aromatic acid chloride (p-iodobenzoyl chloride). 11 This reaction occurs cleanly at the low temperature of À78 °C. However, above this temperature side reactions are expected to occur, as are seen in the reaction of (nBu) 2 CuLi with iodobenzene at 0 °C, which affords both metal–halogen exchange and alkyla- tion products. 12 These types of competing side reactions may also be expected to occur at the bromide position of 2- bromoaroyl chlorides. 13 Indeed, in reactions closely related to this work, alkylation is the major process in the copper-assisted reaction of active methylene carbanions with ortho-substituted bromobenzenes such as o-bromobenzoic acid 14 and o-bromophe- nol. 15 In comparison, metal–halogen exchange occurs at the alkyl bromide site in a-bromoketones to afford enolates. 16 For these reasons, we decided it would be beneficial to carry out an investigation into the reactivity of lithium diarylcuprate(I) reagents with o-bromobenzoyl chloride. We report here our results that in this reaction C–C bond formation proceeds readily at convenient tempera- tures to afford the desired diaryl ketones, and that other expected side reactions do not occur to more than a small extent. APPLIED ORGANOMETALLIC CHEMISTRY Appl. Organometal. Chem. 14, 341–344 (2000) Copyright # 2000 John Wiley & Sons, Ltd. * Correspondence to: Stephen T. Astley, Ege Universitesi, Fen Fakultesi, Kimya Bolumu, Bornova-Izmir, 35100 Turkey. E-mail: astley@sci.ege.edu.tr Contract/grant sponsor: Faculty of Science, Ege University, Turkey.