Investigation of a Stereoselective Co-Mediated Rearrangement Reaction

Abstract

A stereocontrolled approach to alpha-alkyl beta-alkynyl cyclohexanones is reported through a Lewis acid mediated rearrangement reaction of enol ethers bearing an Co-alkyne moiety. The reaction proceeds with high levels of stereoselectivity in the presence of Ti- and B-Lewis acids to provide a range of alpha,beta-disubstituted cyclohexanones in high yield although the products are prone to epimerization at the alpha-position in the presence of the B-promoter system. The potential for an enantioselective variant of this process is outlined, and a rationale for the observed stereochemical trends and detailed structural analyses of the ketone products are described.

Palladium-Catalyzed [1,3]-O-to-C Rearrangement of Pyrans toward Functionalized Cyclohexanones

“…The chemical shift of the enol ether protons of compounds 10-17 were used as a basis to assign the E/Z stereochemistry, and is based on increment calculations performed on related enol ethers. 4 Specifically, the E-isomers are shifted 0.3-0.7 ppm to a lower field than the corresponding Z-isomers, and the general trends are followed for a large range of 6-membered ring based analogs, including work by Lieberknecht and Bravo (assignments based on NMR and X-ray), 5 Taylor (NMR) 6 and us (nOe) 7 . Moreover, we confirmed this assignment in the case of compound 15 by nOe spectroscopic analysis.…”

Substituent effects in the Nicholas epimerization of glycosides

“…Hence, the α:β ratio of a Nicholas epimerization is controlled by the size of the substituents on a thp ring and their positions relative to each other . Luckily, the racemization of the carbocation, and hence the stereochemistry of the Nicholas reaction, can be controlled via the experimental setup, which made the Nicholas reaction a fixture in the synthesis of natural products …”