Regioselectivity in Diels-Alder reactions and probing the use of the geminal acylation reaction for the formation of a steroid

Chinn, Tonya S. L. (2005) Regioselectivity in Diels-Alder reactions and probing the use of the geminal acylation reaction for the formation of a steroid. Masters thesis, Memorial University of Newfoundland.

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Abstract

Regioselectivity in Diels-Alder reactions is usually explained using frontier molecular orbital and/or electrostatic rationales. Steric interactions may play an important role in determining stereoselectivity. Thus, a hypothesis was suggested by the Burnell group that steric hindrance might contribute significantly to regioselectivity as well. Attempts to test this hypothesis focused on methyl-substituted para-benzoquinones. Dienes which were used had structures such that the regiochemical bias would be due to a steric factor rather than an electronic one. Previous work by the Burnell group dealt with dienes which did not show any such bias. This document deals with cyclic dienes to alleviate some prior problems. 2,6-Dimethyl-para-benzoquinone was initially used as the dienophile since many compounds found in nature have two methyl groups with a 1,3- relationship within them. Various dienes were used with this dienophile using various conditions, but unsatisfactory results required a change in the dienes to make them more stable and a change in the dienophile towards a better steric probe. Diels-Alder reactions with the new dienes and dienophiles were carried out under various conditions, still producing no satisfactory results. New dienophiles, N-phenylmaleimide and 2-methyl-Nphenylmaleimide, were used with the same dienes in an attempt to learn about the reactivity of the dienes and obtain Diels-Alder adducts. Some success was seen with these dienophiles. All of the results are summarized, along with modifications that had to be made to the Diels-Alder substrates. -- The geminal acylation reaction can be applied to many ketones and acetals. The various routes that were devised towards the synthesis of a steroid skeleton, via a double geminal acylation, as well as modifications to the original routes, are discussed. The first attempts involved the Michael addition of silyl enol ethers to α,β-unsaturated ketones to give diketones. Some success was achieved, but due to some undesired results, substrates had to be modified. These modifications led to substrates which could be used as precursors to natural products, and a route was devised for future work on this objective. The second route towards the required diketones used ozonolysis and was successful. The third and fourth routes involved alkylations, which proved to be difficult. Various conditions were tried and some showed positive results. Some new information dealing with the reactivity of alkylation substrates as well as double alkylations was discovered. Also, several substrates were more difficult to produce than anticipated. Various routes were attempted and the substrates were obtained. Some results, such as the reductive succinoylation, seen before in the Burnell group were observed with this work as well. Possible precursors to other natural molecules were obtained and routes are proposed towards such molecules.

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