| The development of radical-based methodology for efficient generation of acyclic N-acylimines is described in Chapter 1. This process involves cuprous ion promoted decomposition of an o-diazobenzamide 7 to give N-acyliminium ion 10 via a 1,5 hydrogen shift, followed by subsequent metal catalyzed oxidation. The objective of this work was to extend the radical oxidation of cyclic systems accomplished in previous work to acyclic systems, leading to potential applications in alkaloid synthesis. The purpose was to generate N-acylimines equivalent to those derived from secondary amides which proven to be unsuitable substrates for the radical oxidation process The key to this variation was to promote an amide conformation favorable for 1,5 hydrogen translocation. In the study, it was found that the presence of N-t -butyl or N-cumyl groups, which can be removed in subsequent reactions, effectively suppresses the undesired amide conformation, giving the desired oxidation products in excellent yields. These oxidation products were demonstrated to be useful intermediates for regenerating N-acyliminium ions for further transformations, such as C-allylation and hetero Diels-Alder cyclizations.; A novel intramolecular hetero Diels-Alder cyclization has been developed to construct quaternary carbon centers a to an amine, a structural feather found in a number of marine alkaloids. This process involves the initial generation of an N-acyliminium ion from a ketone-derived enamide bearing a PMB group on the nitrogen and subsequent intramolecular hetero Diels-Alder reaction, leading to formation of 3,6-dihydro-1,3-oxazines such as 86 (Chapter 2) in good yields. It has been found that the stereochemical outcome of this type of reaction is critically dependent on the substrates employed. For example, enamide 84a or 84b containing an E-olefin gave 6,6 cis-fused dihydrooxazine 85 or 87, respectively, as a single isomer, while enamide 96 having a Z-olefin produced a mixture of 6,6 trans-fused and cis-fused oxazines 97a and 97b.; We have also used the intramolecular hetero Diels-Alder reaction as a key step in a synthesis of the marine alkaloid cylindricine B (Chapter 3). The synthetic plan was first to construct core structure 86 as a pivotal intermediate to access cylindricine B. The synthesis of the bicycle 86 includes an intramolecular hetero Diels-Alder reaction to build A ring and to establish the quaternary carbon center, subsequent Michael reaction is planned to close the C ring and ring-closing metathesis of a vinyl chloride will be used to form the B ring.; The discovery of the ring-closing metathesis of vinyl chlorides during the course of the synthesis of the cylindricines has been further studied, leading to a development of general and efficient methodology for formation of five- to seven-membered cyclic vinyl chlorides (Chapter 4). The possibility of further transformations with the metathesis products has also been demonstrated by a Negishi coupling and a hypochlorite oxidation. However, analogous ring-closing metathesis with vinyl bromides was not effective under the reaction conditions used for the vinyl chlorides. |
