Cycloaddition of phenyl vinyl sulphone to 3-methoxy-16-methylestra-1,3,5(10),14,16-pentaen-17-yl acetate: synthesis of 14-functional ised 19-norpregnane derivatives

Abstract

Diets–Alder reaction of 3-methoxy-16-methylestra-1,3,5(10),14,16-pentaen-17-y1 acetate 3 with phenyl vinyl sulphone affords three 14,17-cycloadducts; the two major products (ca. 37% each) are the regioisomers derived from endo addition on the β-face, whereas the minor product (ca. 14%) is the endo isomer of meta-directed attack on the α-face. Sequential reductive desulphonylation, hydroxylation, and oxidative cleavage of the major products is described, and the derived 14-hydroxymethyl-3-methoxy-19-norpregna-1,3,5(10)-trien-20-one 16 is converted into 14α-hydroxymethyl and 14α-formyl analogues of 19-norprogesterone. A route to 3-methoxy-1.4-methyl-19-norpregna-1,3,5(10)-trien-20-one 27 is described.