Cyclopropylmethyl- and cyclobutylmethyllithium by an arene-catalyzed lithiation. Stability and reactivity Itziar Pen ˜afiel, Isidro M. Pastor * , Miguel Yus * Departamento de Quı ´mica Orga ´nica, Facultad de Ciencias and Instituto de Sı ´ntesis Orga ´nica (ISO), Universidad de Alicante, Apdo. 99, 03080 Alicante, Spain article info Article history: Received 2 February 2010 Received in revised form 23 February 2010 Accepted 24 February 2010 Available online 1 March 2010 Keywords: Cyclopropylmethyllithium Cyclobutylmethyllithium Homoallyllithium Bishomoallyllithium DTBB and naphthalene catalyzed lithiation S E reaction Lithium abstract The reaction of (chloromethyl)cyclopropane 5 and (bromomethyl)cyclobutane 8 with lithium and a substoichiometric amount of DTBB, in the presence of different carbonyl compounds as electrophiles, in THF at 78  C leads, after hydrolysis, to the corresponding cycloalkyl alcohols 6 and 9, respectively. However, when the same starting materials are lithiated using naphthalene as catalyst in diethyl ether and at higher temperature (0 or 25  C), and then react with the same electrophiles, the final hydrolysis yields the corresponding unsaturated alcohols 7 and 10, respectively. Ó 2010 Elsevier Ltd. All rights reserved. 1. Introduction The formation of carbon–carbon bonds constitutes a key step during the synthesis of many organic products, and organometallic reagents are versatile reagents for carrying out this trans- formation. 1 Among organometallic compounds, functionalized organolithium compounds constitute a unique class due to their characteristic reactivity. 1c,2 Regarding the lithiation agent employed for the preparation of organolithium intermediates, two different methodologies can be considered. 3 The first one consists in the use of another organolithium reagent, and the second is the reductive lithiation using lithium metal. For the latter, the use of a substoichiometric amount of an arene to facilitate the electron transfer from the lithium to the substrate has shown to be very useful under different reaction conditions and for several types of starting materials. 4 The intramolecular carbolithiation of carbon–carbon double bonds is an interesting procedure to prepare functionalized carbocyclic and heterocyclic compounds. 5 Thus, the carbanionic cy- clization reaction of different alk-5-enyllithium intermediates has been extensively studied. 6–8 Bailey et al. reported a very interesting methodology employing a catalytic amount of phenyllithium that allowed the cycloisomerization of different alkenyl primary, secon- dary, tertiary, and aryl iodides to the corresponding cyclic isomer iodides, and the mechanism of this procedure being substrate dependent. 6 Our laboratory reported the intramolecular cyclization of different hex-5-enyllithium derivatives prepared by chlorine/lithium exchange employing lithium metal. 8a,b On the other hand, organo- lithium intermediates having in a-position a small cycloalkane (three- or four-membered rings) undergo rapidly a transformation to the more stable homoallyl- or bishomoallyllithium intermediates. Thus, cyclopropylmethyllithium 1 is an unstable intermediate even at low temperature, giving the corresponding homoallyllithium 2 with less than 1 h half-life time (Scheme 1). 9 Intermediates of type 1 and 2 have been prepared employing: (a) an organolithium reagent by iodine–lithium exchange, 9,10 selenium–lithium exchange, 11 or sili- con–lithium exchange (involving a Brook-type process), 12 and (b) lithium metal in a mercury–lithium transmetallation process. 13 Regarding the stability of the cyclobutylmethyllithium intermediate Scheme 1. * Corresponding authors. Fax: þ34 965 903549; e-mail addresses: ipastor@ua.es (I.M. Pastor), yus@ua.es (M. Yus). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2010.02.090 Tetrahedron 66 (2010) 2928–2935