UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Conformationally controlled reactions of 14-membered lactones Yu, Hongping


Hydrolysis reactions were performed on two comformationally biased 14-membered lactones 11 and 12 to investigate the effect of the ring conformations of these lactones on the hydrolysis reaction rates. Hydroboration reactions were carried out at the double bond of compound 14 for the purpose of achieving regioselectivity under the control of ring conformations. The two products of the hydroboration reaction, 37 and 38, were subjected to methylation at the a- positions of the ester carbonyl groups to probe the possibility of achieving diastereoselectivity. The face selectivity at the double bond in macrolide 43 was also investigated using hydroboration and epoxidation reactions. 1. Hydrolysis of conformationally biased 14-membered lactones The reaction rates of the hydrolysis of lactones 11 and 12, under both acidic and basic conditions, were predicted to be different based on the understanding of their lowest energy conformations. The reactions between the lactones and sodium methanethiolate were expected to have relatively similar reaction rates due to the reaction mechanisms. To support these predictions, the two lactones were synthesized by multistep syntheses. The X-ray structures of both lactones were obtained, which were the same as the expected lowest energy conformations. Molecular mechanics calculations and DNMR studies indicated that the majority of the molecular populations of both lactones existed under these lowest energy conformations. The results of the hydrolysis of these two lactones proved the validity of our predictions. The results were further rationalized by molecular mechanics calculations performed on 11 and 12 as well as the transition state analogues for the hydrolysis of 11 and 12, structures A and B . 2. Hydroboration of the double bond in lactone 14 Hydroboration of the double bond in lactone 14 produced two regioisomers, 3 7 and 38, with low regioselectivity. The regiochemistry of these two products was determined chemically, through the cleavage of the epoxide in 5 4 which was found to be highly regioselective. These results were rationalized using molecular mechanics calculations. 3. Methylation reactions at the a- position of the carbonyl groups in 3 7 and 3 8 Methylation of the silyl ether of 3 8 was achieved with 10 : 1 (41 : 4 2 ) diastereoselectivity, while only 1.4 : 1 (39 : 40) selectivity was achieved from methylation of the silyl ether of 37. The relative stereochemistries in these products were determined by correlating their conformational behavior with their !H NMR spectra and with molecular mechanics calculations. 4. Hydroboration and epoxidation of the double bond in macrolide 4 3 Face selectivity in 4 3 was found to be low upon both hydroboration ((42+40) : (39+41) = 1.6 : 1) and epoxidation (45 : 4 4 = 1.7 : 1 @ 25°C; 2.3 : 1 @ 0°C) of the double bond. The reaction results were rationalized using molecular mechanics calculations.

Item Media

Item Citations and Data


For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.