On the Stereochemistry of Diaryl-Substituted Cyclohexanones Formed by Michael Reactions. Trans to Cis Isomerization of Their Ketals under Basic Conditions

• Published in: Journal of organic chemistry 1998-06, Vol.63 (13), p.4359-4365
• Main Authors: Rowland, Alex T, Filla, Sandra A, Coutlangus, Marilyn L, Winemiller, Mark D, Chamberlin, Mark J, Czulada, Gary, Johnson, Steven D, Sabat, Michal
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo9801059

The stereochemistry of C-1-substituted 2,6-diphenylcyclohexan-4-ones 1−3 prepared by Michael reactions has been investigated. While preparations of these compounds have been reported over the past 70 years, in many instances the correct stereochemistry at C-2 (6) and, in some instances at C-1, was uncertain. We show here that in one case in which two identical substituents (CN) are present at C-1, it is possible to isomerize the initially formed trans isomer 1d to the cis isomer 3f. When a cyano group and a dissimilar substituent are present at C-1, the initially formed trans isomer may be isomerized to the cis compound. The stereochemistry is vertified by NMR spectroscopy and by X-ray analysis. Reaction of the ethylene ketals (4 and 5) of these ketones with KOH in DMSO at elevated temperatures gives rise to cis products, and deuterium-labeling studies demonstrated the acidity of the benzylic hydrogen at C-2 (6). Isomerization was evident since the trans ketal 4a and the cis ketal 4b gave the same amide 6a. 1H and 13C NMR spectra provided conclusive evidence for the cis → trans rearrangement.