Diastereoselective conjugate addition reactions using diverse nucleophiles on a variety of Morita-Baylis-Hillman (MBH) adducts
Date
2023-09
Authors
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Journal ISSN
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Publisher
University of the Witwatersrand, Johannesburg
Abstract
The Morita-Baylis-Hillman (MBH) reaction involves the formation of a new carbon-carbon bond, generating an MBH adduct. These MBH adducts are multi-functional molecules, which can be used as synthons for the generation of complex and diverse compounds. The first part of the work described here involved the synthesis of a series of diverse ester and nitrile MBH adducts obtained as racemic mixtures. The MBH adducts were protected using different protecting groups, which could potentially control the diastereoselectivity and the formation of alternative products in the subsequent conjugate addition reaction. Conjugate addition reactions were performed on the protected MBH adducts using different nucleophiles to obtain the product as diastereomers. These reactions were monitored to detect whether diastereomers were obtained or not. The diastereomeric ratios obtained using different substrates, protecting groups and nucleophiles were determined. The best diastereomeric ratio was 3:1, obtained for the piperidine and benzylamine addition on the TBDMS protected nitrile adducts 192a/b and 196a/b. The addition of sulfur nucleophiles gave the conjugate addition product only and the addition of nitrogen nucleophiles gave both conjugate addition and allylic substitution products. It was found that the protecting groups did not have an effect on the diastereomeric ratio obtained, nor on the formation of alternative products. The last step performed in the sequence was the deprotection of the conjugate addition products. The configuration of the major and the minor diastereomers were determined, the major product was assigned as the syn diastereomer. The major:minor diastereomeric ratio for compound 208a/b was 3:1 and for compound 209a/b, a ratio of 2:1 was obtained. The next part of the work involved the synthesis of MBH adducts with amide as the electron withdrawing group. The originally proposed route involved the synthesis of MBH esters and their conversion into amides. The conjugate addition reactions were attempted on these amide adducts, but were unsuccessful. A number of alternative routes were attempted for the synthesis of amide adducts and conjugate addition products resulting from these adducts. From all the alternative routes, the best route was the originally proposed route.
Description
A dissertation submitted in fulfilment of the requirements for the degree of Master of Science, to the Faculty of Science, School of Chemistry, University of the Witwatersrand, Johannesburg , 2023.
Keywords
Morita-Baylis-Hillman (MBH), Sulfur nucleophiles, Diastereomers, Piperidine, Benzylamine, Ester, Nitrile, UCTD
Citation
Bhom, Nafisa. (2023). Diastereoselective conjugate addition reactions using diverse nucleophiles on a variety of Morita-Baylis-Hillman (MBH) adducts. [Master's dissertation, University of the Witwatersrand, Johannesburg]. https://hdl.handle.net/10539/42297