Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Chemistry

Supervisor

Brian L. Pagenkopf

Abstract

A variety of methodologies developed in our research group have inspired the three separate projects reported. First, the total synthesis of (±)-quebrachamine was performed in 13 steps and 17.8% overall yield. Highlights of the synthesis include an efficient preparation of a functionalized indole core via a [3+2] annulation cycloaddition reaction between a functionalized nitrile and donor-acceptor cyclopropane and a photo induced 9-membered ring closure.

Secondly, we have reported the most efficent and highest yielding route to several tetrahydroisoquinocarbazoles, where the core was prepared in six steps from tryptophol in 51% overall yield. This work highlights for the first time the synthetic utility of the dipolar C-2 alkylation of 3-substituted indoles with 2-alkoxycyclopropanoate esters. The synthesis also features a selective SmBr2-HMPA promoted ring closure of an aldehyde onto a sterically congested trisubstituted alkene.

Lastly, we have developed efficient syntheses towards several fragments of biselide A, which could be used to explore both ring closing metathesis and relay ring closing metathesis to construct the 14-membered macrolactone. The trans-THF ring was furnished by using our second generation Co(nmp)2 catalyst in a Mukaiyama oxidative cyclization, while the chloroalkene moiety was introduced with a chloropalladation reaction. Key steps in the synthesis of the southern fragment included a Sharpless asymmetric kinetic resolution, or a diastereoselective aldol reaction. Significant synthetic efforts toward biselide E have also been reported. We have designed an efficient method to access the western fragment, which also employed our second generation Co(nmp)2 catalyst in a Mukaiyama oxidative cyclization to furnish the trans-THF ring. A proficient method towards the eastern fragment was also designed, using a Suzuki coupling reaction as the key step.

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