Palladium-catalyzed intramolecular 5-endo–trig oxidative Heck cyclization: a facile pathway for the synthesis of some sesquiterpene precursors Devalina Ray, Sunanda Paul, Sulagna Brahma and Jayanta. K. Ray * Department of Chemistry, Indian Institute of Technology, Kharagpur 721 302, India Received 19 June 2007; revised 30 August 2007; accepted 7 September 2007 Available online 12 September 2007 Abstract—An efficient and convenient method for the construction of substituted cyclopentenones via palladium-catalyzed intra- molecular 5-endo–trig oxidative cyclization has been introduced as a powerful new strategy for the synthesis of sesquiterpenes. Ó 2007 Elsevier Ltd. All rights reserved. 1. Introduction Transition metal-catalyzed intramolecular reactions of alkenes are representative reactions in the organic chem- istry of palladium 1 which can continuously stimulate research due to their immense synthetic potential. Recently substituted cyclopentenones have been evalu- ated as useful synthons for the synthesis of natural 2 and unnatural 3 products. As an extension of the palla- dium-catalyzed intramolecular Heck cyclization for the synthesis of substituted cyclopentenones, we have already reported synthetic approaches starting from allylated, 4a propargylated, 4b and methallylated 4c deriva- tives of a number of b-bromovinylaldehydes following different pathways. Intermolecular Heck reactions of ha- lides with allylic alcohols 5 are widely known while the intramolecular version 6 is somewhat rare. The palla- dium-catalyzed alkylation of thiopene at the 3-position is accomplished by adopting the intermolecular coupling of 3-bromothiopene with substituted allyl alcohols. 7 As part of our ongoing effort to expand the synthetic utility of substituted cyclopentenones, we have been investigat- ing palladium-catalyzed Heck reactions on substrates possessing allylic alcohols. In this context, we describe the intramolecular palladium-catalyzed 5-endo–trig Heck cyclization of 1-bromopenta-1,4-dien-3-ols resulting in substituted cyclopentenones. Based on the successful use of vinyl halides or vinyl triflates as vinyl donors in palladium- catalyzed reactions with olefinic systems 8 and the known behavior of allylic alcohols in palladium-catalyzed reac- tions with organic halides, we thought that our method would be a viable route toward the synthesis of cyclo- pentenones related to natural product precursors. endo-Cyclizations are relatively rare in comparison to the exo mode of cyclization. 9 Vinylated derivatives of the b-bromovinylaldehydes were chosen as our substrate because their reactions with aromatic analogues are very sluggish and result in the formation of low yields of products. The reactions are of preparative value for the synthesis of sesquiterpene precursors. The structural skeleton 6b is the core structure of (±)-a-cuparenone (6d) and lau- rene (6e). 10 Both sesquiterpenes can be obtained from 6b, which in turn can be prepared by our methodology (Scheme 1). The starting materials were synthesized by the addition of vinylmagnesium bromide (1 mmol) to b-bro- movinylaldehydes (1 mmol) in tetrahydrofuran (THF) at 0 °C to afford the bromo alcohols (1a–9a)(Table 1) in good yield (Scheme 2). Treatment of the substrates (1a–9a) (1 mmol) with Pd(OAc) 2 (5 mol %), PPh 3 (0.5 equiv) and triethylamine (1.2 equiv) in acetonitrile (8 mL) at 80 °C yielded the cyclized keto compounds (1b–9b)(Table 2) in moderate 0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2007.09.052 Keywords: Intramolecular Heck cyclization; Sesquiterpenes; Vinylated derivatives. * Corresponding author. Tel.: +91 3222 283326; fax: +91 3222 282252; e-mail: jkray@chem.iitkgp.ernet.in Tetrahedron Letters 48 (2007) 8005–8008