Stereochemical aspects of keto-enol tautomerism

The stereochemistry of enolisation has been mostly examined in cyclic systems where the relative positions of the enolisable hydrogen atoms are fixed. Over the last decade, these studies have benefited from important improvements in the experimental methods, namely mass spectrometry and nmr spectroscopy. Of great interest is the comparison of the relative mobilities of diastereoisomeric axial and equatorial protons from ketones in the cyclohexane series. Indeed, since axial a(C—H) bonds of rigid cyclohexanones are closer than equatorial a(C—H) bonds to the desirable conformation in which the breaking C—H bond is perpendicular to the direction of the C=0 bond, it can be expected that the axial a(C—H) bond-breaking is easier than that of the equatorial one. 

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). 

4-t-butylcyclohexanone [21] in basic and acidic media (Trimitsis and Van Dam, 1974 Lamaty and Roques, 1976). All these studies have led to the 

These results on hydrogen-deuterium exchange are also in agreement with the data obtained by House et al. (1968). When the lithium enolate of 4-t-butylcyclohexanone [22] was added to a solution of deuterioacetic acid in 

70 and 30% respectively of the axial [23] and equatorial [24] deuteriated ketone were formed. If it is assumed that protonation of the enolate oxygen atom is faster than that of C(c), this result corresponds to the stereoselectivity of axial and equatorial attachment of D+ to the enol (27). The higher selectivity between axial and equatorial deuteriated ketones observed for hydrolysis of the corresponding ethyl enol ether (90 10) and pyrrolidine enamine ( 90 10) means that the stereoselectivity is probably smaller for the enol than for the related compounds. 

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