Taxane synthesis via (2+2) photoaddition fragmentation chemistry with a novel beta-ketoester equivalent

This dissertation describes the preparation of the tricyclic skeleton 3.64 of taxol (1.1) from readily available Wieland-Miescher ketone 2.42. This route features the use of a newly developed $\beta$-ketoester equivalent, oxazinone heterocycle 3.60, as a substrate for (2+2) photoaddition fragmentation chemistry.* In the taxane systems described, it was found that the oxazinone heterocycle can be formed in higher yields and under milder conditions than the previously employed dioxenone. Conditions for oxazinone formation and fragmentation were tested and optimized on several simple models systems, and were then applied to the synthesis of taxanes.* Due to the milder conditions required for oxazinone formation, efforts were undertaken to further functionalize the photosubstrate prior to tricycle formation. To this end, the preparation of compound 3.147, which contains the oxetane D ring as well as the C-2 and C-4 oxygenation of taxol, is described. Further elaboration of this compound to the oxazinone photosubstrate is currently under investigation.* ftn*Please refer to the dissertation for diagrams