A 1,3-Dipolar Cycloaddition Approach to the Synthesis of Resiniferatoxin
The Rh(I)-catalyzed allenic cyclocarbonylation reaction is a formal [2 + 2 + 1] cycloaddition process that has been used to gain access to 4-alkylidenecyclopentenones. Incorporation of a six-membered ring on the tether between the allene and the alkyne components allows access to a variety of [6-7-5] ring structures featured in the skeletons of various natural products, including resiniferatoxin. This thesis describes the development of two systems, each with a future synthesis of resiniferatoxin in mind. First, a model system was designed to demonstrate the compatibility of the isoxazoline moiety with the Rh(I)-catalyzed cyclocarbonylation reaction. The second investigation involved the synthesis of an asymmetrically functionalized 2-cyclohexenone in order to attempt a stereoselective 1,3-dipolar cycloaddition. The first model system successfully led to the synthesis of the unfunctionalized [6-7-5] core of resiniferatoxin via cyclocarbonylation of an isoxazoline-containing allene-yne. Unfortunately, under numerous conditions, the functionalized cyclohexenone synthesized for the second study failed to undergo [2 + 3] cycloaddition with a nitrile oxide.
Advisor:Kay M. Brummond; Tara Y. Meyer; Dennis P. Curran
School:University of Pittsburgh
School Location:USA - Pennsylvania
Source Type:Master's Thesis
Date of Publication:09/28/2008