Taxoid synthesis: Ketene cycloadditions as a radical cyclization approach.

Abstract

Studies directed towards the synthesis of the taxane skeleton is described. The synthesis and cyclopropanation of 170 was attempted, and the preparation and base induced cyclization of gamma,delta-epoxyketone 187 and gamma,delta-epoxyester 198 examined. An unusual cycloaddition of ethyl vinyl ether to ketene carbonyls to form oxetanes was uncovered. The ketenes were generated from the cyclic diazoketones 210, 211 and 213 and the acyclic system 215. In all cases, with either Rh2(OAc)4, Pd(OAc) 2 or CuCl as catalyst, the oxetanes were the major products. Irradiation afforded the cyclobutanones 236, 237, 238 and 239, while triplet sensitized photolysis afforded both oxetane and cyclobutanone. Less electron rich olefins followed literature precedent for metal catalyzed decomposition to yield cyclopropanes. These features are consistent with a zwitterionic intermediate such as 247 (Scheme i illustrates these general features). The preparation of the key radical cyclization precursor 282 and related compounds, 289 and 305 containing the taxol A and C ring models from enone 202 and subsequent radical cyclization to the taxane skeleton 284a are also described.* *Please refer to dissertation for diagrams.