An Expeditious Synthesis of Methyl Jasmonate

Abstract

We present an efficient three-step, two-pot synthesis of methyl jasmonate (trans-1) based on DielsAlder cycloaddition of cyclopent-2-enone (2) and chloroprene (= 2-chlorobuta-1,3-diene; 3d) in either CHCl 3 or CH 2 Cl 2 , catalyzed by SnCl 4 (0.2 mol-equiv.) at 208 (75% yield). Subsequent ozonolysis of a cis/trans 55 : 45 mixture of the cycloadduct 4d in either CH 2 Cl 2 or AcOEt at À 788, followed by addition of Me 2 A C H T U N G T R E N N U N G S and MeOH in the presence of NaHCO 3 , afforded, in 64% yield, a cis/trans 40 : 60 mixture of the known aldehyde 5c. The latter was reacted at À 508 under salt-free conditions with the propyl Wittig reactant to furnish 1 as a cis/trans 20 : 80 mixture ((E/Z) 3 : 97). Alternatively, a cis/trans 7 : 93 mixture ((E/Z) 4 : 96) was obtained in 88% yield from epimerized 5c (AcOH, H 2 O, 408; 99%) under usual Wittig conditions at À 208.Introduction. -We recently presented a new synthesis of methyl jasmonate (trans-1) based on a cascade Baylis-Hillman reaction in combination with an ortho-ester Claisen rearrangement [1]. During our initial literature search, previous approaches were studied in detail, and we were attracted by the Diels-Alder methodology reported by Tanaka and Torii [2]. Indeed, their strategy based on cycloaddition of commercially available cyclopent-2-enone (2) 2 ) to buta-1,3-diene (3a) had been earlier reported to afford, under thermal conditions (autoclave, 1108, 12 d; or 2108, 1 d [4]), an epimerized mixture of cis/trans-4a in 22 -29% yield (for structures, see the Scheme below). This strategy necessitates, after a 75-cm spinning-band distillation (48% yield), eleven further synthetic steps towards methyl epijasmonate (cis-1). Alternatively, Fringuelli and Wenkert and co-workers reported that [4 + 2] cycloaddition to either butadiene (3a) or isoprene (3b) may be conducted in the presence of 0.9 to 0.2 mol-equiv. of AlCl 3 in toluene at 70 -508 to afford a cis/trans-epimeric mixture of 4a,b in ca. 74 -85% isolated yield, respectively [5] 3 ). This latter intermediate, also obtained in 74% yield after column-chromatographic purification by Hailes et al.[6] via a cationic Diels-Alder reaction of cyclopent-2-enone acetal [7], followed by deprotection, necessitates, after reduction, protection, ozonolysis, and Wittig reaction, a haloform degradation prior to the last three steps, to transform the methyl ketone into a methyl carbox-

Reflexion on Bio-Sourced Mosquito Repellents: Nature, Activity, and Preparation

“…Given its importance, many efforts have been made to synthetize methyl jasmonates (epi, ent-epi, cis/trans, racemic, enantiopur) and analogs such as dihydrojasmonates (Scheme 3). A great variety of strategies have been studied for the construction of the cyclic moiety: preparation of a functionalized bicycle (Sisido et al, 1969), preparation of a chloroindenone by cycloaddition (Chapuis et al, 2006), functionalization of a cyclopentanone into 2 then 1 position (Buchi and Egger, 1971;Näf and Decorzant, 1978;Kataoka et al, 1987), functionalization of a cyclopentanone into 1 then SCHEME 3 | (A) Key steps of the octadecanoid pathway of cis-and trans-methyl jasmonates in plants; (B) retrosynthesis based on industrial syntheses of methyl jasmonate.…”