COBALT-MEDIATED SYNTHESIS OF A VERSATILE PSEUDOGUAIANOLIDE INTERMEDIATE

An efficient stereocontrolled synthesis of hydroxy ketone 24a, a versatile precursor of various pseudoguaianolides, is described starting from bicyclic ketoacetylene 7. Synthesis of the latter compound using as a key step alkylation of a suitable silylenol ether by (ethoxypropynylium)Co2(CO)6BF4 was described earlier. Annulation of 7 was accomplished by hydration followed by aldol cyclization to ketol 9. The latter was converted to the key intermediate hydroxy ether 15a by two different schemes. In one sequence removal of the keto group from 9, regioselective dehydration, Me2BBr-induced regioselective cyclic ether cleavage, and stereoselective hydrogenation afforded 15a efficiently. Alternatively, 9 was first dehydrated regioselectively followed by dithioketalization/desulfurization, which also induced oxacycle cleavage to 22, which, in turn, underwent stereoselective hydrogenation giving 15a in good overall yield. Oxidation of 15a and ethyl ether cleavage afforded the known damsin precursor 24a. © 1990, American Chemical Society. All rights reserved.