UBC Theses and Dissertations
Asymmetric induction in the photochemistry of α-oxoamides and bicycle aryl ketones Wang, Keyan
Enantioselective photochemical synthesis of a β-lactam (methyl 4-[3-hydroxy-2,2- dimethyl-l-(l-methylethyl)-4-oxo-3-azetidinyl]benzoate) was investigated via the ionic chiral auxiliary method. Solid state photolysis of the chiral salts formed from optically pure amines and the achiral α-oxoamide reactant containing a carboxylic acid functional group gave variable results, but through the use of a number of auxiliaries it was possible to achieve a high degree of enantioselectivity in the β-lactam (up to 99 % ee at 99 % conversion of the starting α-oxoamide). Suspension of the prolinamide salt in hexane allowed the photoreaction to be carried out on a 500 mg scale, thus demonstrating the synthetic utility of the solid state ionic chiral auxiliary approach to asymmetric synthesis. The covalent chiral auxiliary method was also investigated for asymmetric synthesis of the β-lactam. Solid state photolysis of a chiral ester formed from an optically pure alcohol and the achiral α -oxoamide gave up to 95% de at 100 % conversion. Suspension of the chiral ester in water allowed the photoreaction to be carried out on a 200 mg scale. X-ray crystallographic data from a number of α-oxoamides provided insight on the origin of the observed enantioselectivity/diastereoselectivity. The prediction of the absolute configuration of the β-lactam based on the topochemical control principle was validated by crystal structure-reactivity correlations. Asymmetric induction in the Norrish/Yang photochemistry of a series of three bicyclic aryl ketones, bicyclo[2.2.2]octyl ketones, bicyclo[2.2.1]heptyl ketones and dimethylated bicyclo[2.2.1]heptyl ketones, was also studied by using the ionic chiral auxiliary method. Photolysis of the chiral salts in the crystalline state gave high ee's for bicyclo[2.2.2]octyl ketones, high de's for bicyclo[2.2.1]heptyl ketones, and both high ee's and de's for dimethylated bicyclo[2.2.1]heptyl ketones. Through the use of X-ray crystallography, the solid state reactivities were rationalized based on topochemical expectations with the aid of strain energy calculations on the photoproducts. Non-topochemical reactions were also found in this study. Molecular mechanics calculations were conducted to predict the solid state conformations of the substrates prior to the laboratory work. The calculations were successful in the prediction of enantioselectivity for the three bicyclic aryl ketones investigated. In this way, molecular mechanics serves as a basis for crystal engineering in asymmetric synthesis.
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