A general synthesis of alkylpyridines Beatriz Iglesias, Rosana Alvarez and Angel R. de Lera p Departamento de Quõ Âmica Orga Ânica, Universidade de Vigo, 36200 Vigo, Spain Received 11 December 2000; revised 26 January 2001; accepted 6 February 2001 Abstract ÐThe hydroboration of alkenes, followed by the coupling of the B-alkyl-9-borabicyclo[3.3.1]nonane derivatives with bromo- pyridines constitutes an ef®cient procedure for the attachment offunctionalized alkyl chains to the pyridine nucleus. q 2001 Elsevier Science Ltd. All rights reserved. 1. Introduction Besides its presence as partial structures of many pharma- ceuticals, alkylpyridines constitute a structural motif commonly found in biologically active natural products. 1a Notably among the latter are 3-alkylpyridines produced by sponges of the Niphatidae family 1b which have been proposed as biosynthetic precursors of the more complex manzamine and related alkaloids. 2 Given the ready avail- ability of halogenated pyridines, their cross-coupling to alkynylcopper species catalyzed by palladium Sonogashira coupling reaction) 3 followed by hydrogenation of the alkynyl moiety 3a has been the most frequently used method for attachment of the side chain to the pyridine nucleus. However, a most straightforward approach could be envis- aged if direct attachment of the alkyl chain using the trans- metalation to palladium of the corresponding alkyl organometallic derivative was feasible. The formation of the Csp 3 ±Csp 2 bond has proven to be a dif®cult endeavour. The discovery by Suzuki that the 9-alkyl-9-BBN derivatives ef®ciently transmetalate to palladium was an important breakthrough in this ®eld. Since alkylboranes are easily prepared by hydroboration of alkenes, and the Suzuki reac- tion shows excellent compatibility with an array of func- tional groups in both reactants, being the by-products rather inocuous, the preparative scope of this coupling process is remarkable. 4,5 In connection with a synthetic project aimed at the prepara- tion of some metabolites with alarm pheromone activity found in Mediterranean cephalaspideans, 6 we directed our efforts to implement the Suzuki reaction for attachment of alkyl side chains to the pyridine ring found on these metabolites. Gratifyingly, the palladium-catalyzed cross- coupling reaction of the alkylborane generated in situ by hydroboration of the corresponding alkene 1c, and 3-bromo- pyridine 2b was very ef®cient, providing in high yield the alkanol 3c on route to haminol-C 4 Scheme 1). As an extension of this work, we have found that the Suzuki cross-coupling of 9-alkyl-9-BBN derivatives is equally Tetrahedron 57 2001) 3125±3130 Pergamon TETRAHEDRON 0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved. PII: S0040-402001)00170-3 Keywords: pyridines; Suzuki reactions; heterocycles. p Corresponding author. Tel.: 134-86-812316; fax: 134-86-812382; e-mail: qolera@uvigo.es Scheme 1.