Cyclohexanone deuterium exchange

The relative mobilities of the axial and equatorial hydrogen atoms from C(2) and C(6) positions of rigid cyclohexanones have been determined by several authors from the relative rate constants of hydrogen-deuterium exchange. Indeed, according to the principle of microscopic reversibility, the elementary rate constants for axial and equatorial proton detachment correspond to those of proton addition on the two faces of the enol or enolate (26). 

Deuterium exchange at the /2-carbon yields, for a given secondary amine, the following reactivity for the ketone substrate120 cyclopentanone (47) > cycloheptanone (49) > cyclohexanone (48). 

The Baeyer-Villiger reaction occurs with retention of stereochemistry at die migrating center. This stereoselectivity has been utilized in a practical method for the preparation of isotopically chiral metiiyl acetic acid (5) ftom [2- H]cyclohexanone (4) prepared by enzyme-catalyzed stereoselective exchange of the pro-R a -proton and enantioconvergent exchange of the a-proton with deuterium (Scheme 2). As a cautionary note, prior epimerization of an acyl group prior to oxidation has been observed. ... 

Also, all the -situated hydrogen atoms of ketones are readily replaceable by deuterium in an aqueous alkaline medium, since these atoms take part one after the other in the reversible keto-enol tautomerism. This applies, for instance, to the four -positions of cyclohexanone and to the one of 2,2,6-tri-methylcyclohexanone, whereas no exchange occurs in camphor or camphor-quinone which cannot enolize owing to the particular stereochemistry of the molecules.90 Open-chain ketones and also steroidal ketones91 that are not subject to this limitation are often used for exchange reactions. The following description of the preparation of [D6]acetone illustrates the point 29... 

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