STUDIES ON THE SYNTHESIS OF CHLOROTHRICOLIDE - DIASTEREOSELECTIVE ANDENANTIOSELECTIVE 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, ar e described. Key steps in these syntheses are the Diels-Alder reaction s of trienes 11 and 12 with the chiral dienophile (R)-6 that provide c ycloadducts 18 and 38 with remarkably high stereoselectivity. These re actions exhibit exquisite regioselectivity for addition across the tri substituted 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 indica ting 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)-1 1 and (E,E,E)-12 can be used as the starting material for the Diels-Al der reactions, and the desired exo-cycloadducts 18 and 38 are still ob tained in good yield, without products of competitive Diels-Alder reac tions of the disubstituted C(16)-C(19) dienes being observed.