Ring expansion of cyclic ketones: The reliable determination of migration ratios for 3-keto steroids by 13C nuclear magnetic resonance and the general implications thereof

Abstract

Several ring-expansion reactions (diazomethane, diazoacetic ester, Tiffeneau–Demjanov, Baeyer–Villiger, and Schmidt) of 3-keto steroids have been reexamined to determine the true migration ratios for C-2 and C-4 in these unsymmetrical cyclohexanones. Migration ratios were measured to ±3% accuracy by integration of baseline-separated signals in the proton-decoupled 13Cmr spectra of total reaction products. This underexploited method provides for the first time a way to get accurate migration ratios without loss of components during separation and without interference from excess starting material under conditions minimizing side reactions. In contrast to numerous literature reports, all but one of the 16 reactions studied were found to give nearly the same amount of both possible A-homo products. (The single exception was the only reaction in which the A-homo product reacts markedly faster than the starting material.) This simple, consistent ∼1:1 pattern is that expected if migration is governed mainly by the electronic effect of the α- and α′-carbon atoms and not by any conformational or near-by-to-remote substituent effect.