Champagne, P. J.2009-04-172009-04-1719781978Source: Dissertation Abstracts International, Volume: 68-07, Section: B, page: 4480.http://hdl.handle.net/10393/10936http://dx.doi.org/10.20381/ruor-8527The stereoselectivity of isotopic exchange by the diastereotopic methylene protons was examined for two ketones: (a) the conformationally rigid biarylcycloheptadienone, 16; (b) the conformationally rigid tricycloketone, Twistan-4-one, 17. (a) The diastereotopic alpha-keto methylene protons in 16 were found to undergo H/D exchange with a rate ratio of 63:1 in methanol-0-d with sodium methoxide as base, the proton whose C-H bond is perpendicular to the direction of the C=0 bond exchanging fastest. The ratio decreased to 34:1 with sodium phenoxide base and 7:1 with sodium 2,6-dimethylphenoxide as base (both in methanol-0-d), showing that the more labile proton is in the more sterically hindered position. The effect of internal return was evaluated qualitatively by measuring the rate ratio for H/D exchange in the presence of crown ether. No change in stereoselectivity was observed. Also, the rate ratio for the back exchange (D/H) was measured as 12:1, a change consistent with the absence of internal return. Attempts to quantitatively evaluate the effect of internal return by measurement of the primary isotope effects (kH/kT and kD/kT) gave unacceptable results, probably due to the large effect of experimental errors on the calculated internal return vales. The absence of internal return was therefore assumed. However, these primary isotope effects along with the D/H exchange ratio of 12:1 were used to estimate the kH/kD values and solvent isotope effects at the two diastereotopic positions. It was found that the two protons exhibit different primary isotope effects (kH/k D) and different solvent isotope effects. F or the fast position, kH/kD = 3.8, kMeOD/kMeOH = 2.6. For the slow positions, kH/kD = 2.3, kMeOD/kMeOH = 1.2. These results are consistent with the two protons having different exchange mechanisms and therefore with the stereoselectivity of H/D exchange being due to the stereoelectronic control effect. The secondary isotope effect for the fast exchanging position was measured as i = 1.18. (b) The diasteriotopic alpha-keto methylene protons in 17 were found to undergo H/D exchange with a rate ratio of 300:1in methanol-0-d with sodium methoxide as base and 340:1 with sodium phenoxide as base. It was therefore concluded that the diastereotopic protons were in sterically similar environments. Assuming no internal return and the same secondary and solvent isotope effects which had been measured directly for 16, the measured rate ratio for back exchange (D/H) for 17 of 52:1 was used to estimate KH/kD = 5.8 for the fast position and kH/kD = 2.9 for the slow position. These results are again consistent with differing mechanisms for exchange at the two diastereotopic positions and therfore with stereoelectronic control as the factor responsible for the high exchange ratio for these protons.102 p.Chemistry, Organic.Thesis