The 500 MHz 1H spectra of the 3‐methyl ethers of estrone, estradiol and their 14α‐methyl analogues were assigned by proton decoupling and analysed by second‐order calculations for chemical shifts and coupling constants. Introduction of a 14α‐Me group effects consistent deshielding of 1,3 diaxially disposed protons. Coupling constant values show characteristic changes for ring D protons, and suggest that some minor perturbation in the H‐9α, ‐11α, ‐11β region is caused by the additional methyl group.
Methylation of 3-methoxy-I 4P-estra-1,3,5(10),8-tetraen-l5-one (5) in the presence of base affords a ca. 5 : l mixture of the corresponding 1 4~-and 14P-methyl compounds (6) and ( 7 ) respectively, whereas similar treatment of 20,20-ethylenedioxy-3-methoxy-l9-norpregna-1,3,5( 10) -trien-I 5-one (15) results in exclusive formation of the 14~-methyl product (18). The latter compound (18) has been converted into 1 4~-m e t h y l -l 9-norprogesterone (23). The stereoselectivity of 14-methylation of 15ketones is correlated with the propensity of ring D to adopt a quasi-trans or quasi-cis conformation in the derived enolate, leading to preferred 1 &-or 1 4P-methylation respectively.The sterically directing role of unsaturation in rings B or c, and of 17-functionality, upon the course of base-mediated alkylation of steroidal 15-ketones is implied in earlier reports in the l i t e r a t~r e . '~~ We have shown * that highly stereoselective 140-methylation takes place in simple 15-0x0-19-norsteroids, and that this reaction course is retained in 17,17-ethylenedioxyand I7P-acetoxy-1 Sketones, both of which proceed through A16-intermediates. However, it has been reported that only 14%alkylation occurs in cholest-8( 14)-en-15-ones and in pregnan-15-0nes.~ The former result was authenticated through eventual correlation of the derived products with the synthetic target, l a n~s t e r o l ,~ and has, more recently been successfully adapted for a synthesis of methyl 14~-methyl-l5-oxo-5~-chol-8-en-24oate from cholic acid.5It is tempting to conclude that the stereochemical course of the reaction is dictated by the conformation imposed upon ring D by the 14(15)-en-15-olate anion or a derived transition state,
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