TETRAHEDRON LETTERS Tetrahedron Letters 42 (2001) 6069–6072 Pergamon Regioselective ring-closing metathesis on terpenoid acrylates and acrylamides Yanming Du and David F. Wiemer* Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA Received 21 May 2001; revised 26 June 2001; accepted 27 June 2001 Abstract—A series of acrylate esters was prepared by treatment of representative terpenoid aldehydes with allyl or vinyl magnesium bromide followed by reaction with acryloyl chloride. In all cases, ring-closing metathesis (RCM) resulted in regioselective formation of unsaturated lactones through metathesis of the acrylate and terminal olefins. After condensation of farnesal with a primary amine, a parallel series of reactions led to formation of the corresponding lactam. © 2001 Elsevier Science Ltd. All rights reserved. Ring-closing metathesis has become a well-established strategy for construction of a wide range of cyclic structures. 1 Various studies have shown that the most popular metathesis reagent, the Grubbs catalyst 1, can tolerate a number of polar functional groups. 2 Its reac- tivity with any specific substrate is influenced by a combination of the steric and electronic effects of sub- stituents on the reacting olefins as well as entropic factors, 3 but most ring-closing metathesis reactions have been reported on diene substrates that contain no other alkenes. Some recent studies 3a,4 have reported reaction of the two less-substituted olefins in trienes, but information on metathesis in systems containing multiple double bonds with varied substitution patterns is still limited. In connection with our studies of farnesol derivatives, 5 a convenient method to append ,-unsaturated lac- tones on a terpenoid skeleton was needed. The ring- closing metathesis of acrylates derived from allylic and homoallylic alcohols has been used to form unsaturated five- and six-membered ring lactones. 4c,6 However, at this time there is no literature precedent for such reac- tions in the presence of the other double bonds typical of common terpenoids. In this communication, we describe the construction of conjugated lactones on terpenoid templates via the regioselective ring-closing metathesis of acrylate esters. As shown in Scheme 1, the general approach involved addition of allyl or vinyl magnesium bromide to a terpenoid aldehyde. The initial Grignard adduct could be quenched by addition of acryloyl chloride (Method A) or isolated as the alcohol and then esterified by treatment with acryloyl chloride (2 equiv.) and triethyl- amine (3 equiv.) (Method B). 7 In acrylates of the general structure 3 or 5 without additional olefins in the R group, treatment with Grubbs catalyst would be expected to afford an unsaturated lactone. But to test whether metathesis would be successful in the presence Scheme 1. * Corresponding author. Fax: 319-335-1270; e-mail: david-wiemer@uiowa.edu 0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII:S0040-4039(01)01179-0