Synthesis of cis‐Hedione ® and Methyl Jasmonate via Cascade Baylis–Hillman Reaction and Claisen 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.