STEROIDS .80. EFFECT OF C-12 SUBSTITUTION ON REACTIVITY OF DELTA16-20-KETO STEROIDS TOWARD 1,4-NUCLEOPHILIC ADDITION

The presence of a ketone function at C-12 has a marked rate accelerating effect on 1,4 additions to Δ16-20-keto steroids. The rates of the base-catalyzed 1,4 addition of methanol to a wide variety of 12-substituted Δ16-20-keto steroids have been measured. On the basis of nmr and ultraviolet spectral data it is concluded that the rapid rate of reaction exhibited by the 12-keto steroids is anomalous. A mechanism is proposed to explain the unexpected rate of 1,4 addition displayed by Δ16-12,20-diketo steroids. This effect is shown to be applicable to a number of nucleophiles, some of which undergo further reaction to produce polycyclic derivatives. © 1969, American Chemical Society. All rights reserved.