文摘
An enantioselective synthetic route to (+)-dynemicin A(1) is described that involves as the key andfinalstep the Diels-Alder cycloaddition of the quinone imine 6with the isobenzofuran 107 followed by anoxidativeworkup to provide (+)-1 in 40% yield. The syntheticroute begins with the condensation of (-)-menthylacetoacetateand trans-ethyl crotonate to form the crystallinecyclohexanedione 14, which is then transformed to theenantiomericallypure quinone imine 6 in 23 steps with an average yield of85% and an overall yield of 2-3%. Key features ofthissequence include the coupling of the enol triflate 11 andthe arylboronic acid 10 (90%), the thermaldeprotection/internal amidation of the coupling product 18 (84%), the useof 2-chloropyridine as an economical alternative to2,6-di-tert-butylpyridine to promote the reaction of thequinolone 9 and triflic anhydride (85%), thehighlystereoselective addition of the (Z)-enediyne 31to the quinoline 61 (89%), intramolecular acetylideaddition withinthe acetylenic ketone 66 (94%), and oxidation of the phenol76 with iodosobenzene to afford the quinoneimineprecursor 77 in 89% yield. Both the quinone imine andisobenzofuran components of the final coupling reactioncan be varied, thus providing an ideal route for the preparation of awide variety of dynemicin analogs.