A New General Synthetic Approach to Diterpenes: Application to Syntheses of (+ -)-Taxodione and (+ -)-Royleanone.

Article abstract of DOI:10.1021/jo00285a018

High-pressure Diels - Alder reactions of 1,3,3-trimethyl-2-vinyl-1-cyclohexenes 3a,b,i with substituted 1,4-benzoquinones afford, in good yield, highly functionalized tricyclic ring systems which are found in many classes of naturally occuring terpenes.Notably, the reactions of 3a are highly regio- and stereoselective.Efficient, formal syntheses of antitumor diterpenes (+ -)-taxodione and (+ -)-royleanone are reported, which demonstrate the practical application of this new strategy for the preparation of varied terpene systems.Of particular interest is that the high-pressure reactions are accelerated by mild Lewis acids and the regio- and stereoselectivity of these reactions is also improved under the combined high-pressure / Lewis acid conditions in comparison to the high-pressure conditions alone.Indeed, in the reaction of 3a with 2-methoxy-5-methyl-1,4-benzoquinone, ZnBr2 is required to effect the Diels-Alder reaction even at 12 kbar, and endo adduct 12c is formed stereoselectively in<*> 90percent yield.In contrast, low-temperature Ti(IV)-catalyzed reactions of diene 3a with methoxy-substituted 1,4-benzoquinones at atmospheric pressure regioselectively produce dihydrobenzofurans 19 and 20, apparently via alkylation of the quinone Ti(IV) complex by the diene followed by the ring closure.