Steric effects in bicyclic systems. IV. Base-catalyzed enolization of bicyclo[2.2.2]octan-2-one, bicyclo[2.2.1]heptan-2-one, and bicyclo[2.1.1]hexan-2-one

Abstract

Deuterium exchange of bicyclic ketones in 2:1 (v/v) dioxane-D20 catalyzed by NaOD was measured by a mass spectrometric technique developed for this purpose. Second-order rate constants (M-1 sec-1) at 25.0°a nd activation parameters AH* (kcal mol-1) and AS* (eu) were determined as follows: bicyclo[2.2.2]octan-2-one (1) 3.03 X 10-2, 13.1, and -21; bicyclo[2.2.1]heptan-2-one (2) 5.58 X 10-2, 14.0, and -17 (exo); 8.26 X 10-6, 17.1, and -20 (endo); and bicyclo[2.1.1]hexan-2-one (3) 6.04 X 10-6, 17.8 and -23. The rate of base-catalyzed bromination of cyclohexanone was found to exceed that of 1 by a factor of 3.1 in water at 10.0°. The secondary isotope effect £d/&h for deuteration of 1 was 0.94 ± 0.04 at 25.0°. These results are interpreted as showing that the rates reflect the relative facility of proton abstraction from the different sites, and that the principal factors governing the rates of attack are the angle strain generated in the resulting enolates, which favors reactivity in the series 1 > 2 > 3, and the greater steric blocking of access of the base to the reaction site by a two-carbon bridge as opposed to a one-carbon bridge, which favors reactivity in the series exo-2 > endo-2, and 3 > 1. Bicyclic ring systems have been widely used as substrates for the examination of organic reactions, particularly the steric requirements of those reac-(1) Address correspondence concerning this work to the University of Toronto. For part III, see ref 2a. Portions of this work were reported in preliminary communications, ref 2b,c.

Towards a complete account of the exchange chemistry of a diastereotopic proton pair. I. Base-catalyzed enolization–exchange of 2-norbornanones; on the rate controlling factors

“…That the rate is depressed in the medium containing more water is consistent with 'For a preliminary account, see Ref. Tidwell's findings (4). Figures In and b illustrate, for 3, the pseudo-first-order plots for exo and endo exchange, respectively.…”

On the Mechanism of Base-catalyzed Hydrogen Isotope Exchange in Cyclic Ketones

“…Stereoselectivity in the base-catalyzed deuteration at the 3-position of norcamphor (1) has been noted by several workers (1)(2)(3). Kinetic measurements have shown that in dioxane-D20 kHe:f/ k!, ' , : is approximately 650 (2, 3).2 As a part of our studies on the isotope exchange of bicyclic mono-and diketones (3), we have measured the dedeuteration of norcamphor-3,3-d2 (6) in protic media, and have found kDe;;/ k:, ' , H to be 72.…”

“…Rates of H + D exchange in 1 and D -+ H exchange in 6 were measured in 60% dioxane-H 2 0 (D20) at 30.0 "C by monitoring the decrease in substrate by mass spectrometry (2,3). The observed rate data are listed in Table 1, and second-order rate constants derived from these are collected in Table 2.…”

“…The observed rate data are listed in Table 1, and second-order rate constants derived from these are collected in Table 2. Since exo exchange is faster than endo exchange, the deuteration of 1 proceeds with predominant retention (5) to give 3 (2). If secondary isotope effects are 'To whom enquiries should be addressed.…”

Towards a complete account of the mechanism of hydrogen isotope exchange of diastereotopic protons of carbon acids. II. Acid- and base-catalyzed enolization of bicyclo[2.2.1]heptan-2-ones. Evidence for exchange by inversion

“…Ilheptan-Zones. Of particular interest to us was the possibility of exchange of diastereotopic protons by an inversion mechanism, which had been recognized, but not quantified (8). A research program was initiated at that time to detail the mechanistic intricacies of hydrogen isotope exchange (enolization) of bicyclic ketones and determine the effect of groups located remote (P or y) from an a enolizable site.…”