Studies on the Synthesis of Chlorothricolide: Diastereo- and Enantioselective Syntheses of Model Top-Half Spirotetronate Units

Highly enantio- and diastereoselective syntheses of spirotetronates 9 and 10, corresponding to the top-half fragment of chlorothricolide, are described. Key steps in these syntheses are the Diels−Alder reactions of trienes 11 and 12 with the chiral dienophile ( R )- 6 that provide cycloadducts 18 and 38 with remarkably high stereoselectivity. These reactions exhibit exquisite regioselectivity for addition across the trisubstituted C(18)−C(21) diene unit; they also proceed with remarkable orientational control of the dienophile with respect to the C(18)−C(21) diene, as well as with excellent exo diastereofacial selectivity on the part of the chiral dienophile, ( R )- 6 . Results are presented indicating that it is not necessary to control the stereochemistry of the C(20)−C(21) trisubstituted olefin of the triene precursors, as this unit readily isomerizes under the conditions of the Diels−Alder reaction. Remarkably, the seemingly unreactive ( E, E, E )-triene isomers ( E, E, E )- 11 and ( E, E, E )- 12 can be used as the starting material for the Diels−Alder reactions, and the desired exo-cycloadducts 18 and 38 are still obtained in good yield, without products of competitive Diels−Alder reactions of the disubstituted C(16)−C(19) dienes being observed.