Synthesis ofcis-Hedione® and Methyl Jasmonatevia CascadeBaylis-Hillman Reaction andClaisen Ortho Ester Rearrangement

The exocyclically unsaturated conjugated keto esters 10, obtained via a Claisen ortho ester rearrangement of the allylic hydroxy ketones 9, were either directly hydrogenated or partially isomerized into the endocyclically unsaturated tetrasubstituted didehydrojasmonoid intermediates 14, prior to a more selective hydrogenation with Pd/C in cyclohexane to the disubstituted oxocyclopentaneacetates 15 (Scheme 2). The key intermediates 9 were obtained either by a four-step sequence, including acetal protection/deprotection from enone 1, in the specific case of hydroxy ketone 9a (Scheme 1), or more directly and generally by a Baylis–Hillman reaction from cyclopent-2-en-1-one (16) and the appropriate aldehydes 17 (Scheme 2). The judicious choice of these aldehydes opens versatile modifications for the stereoselective introduction of the partially cis- or epimerized trans-C(2) jasmonoid side chain, while the Baylis–Hillman reaction, catalyzed by chiral [1,1′-binaphthalene]-2,2′-diols (BINOLs) 19 (Scheme 3), may be efficiently conducted in a one-pot cascade fashion including the ortho ester Claisen rearrangement.