Carbometallation and other catalytic palladium reactions in organic synthesis

Edward James Vawter, Purdue University

Abstract

Aryl and alkenylpalladium compounds generated by oxidative addition of a palladium(0) catalyst to the corresponding halides have been found to add in an intramolecular fashion to carbon-carbon triple bonds and undergo cyclization. The resulting alkenylpalladium species can be trapped by reaction with main group organometallic compounds in excellent yields. This allows the preparation of stereodefined tetra-substituted exocyclic alkenes, a difficult transformation using classical organic chemistry. Intramolecular catalytic carbopalladation has been developed into a method for forming bicyclic compounds containing a fused cyclopropyl ring. Various factors influence the course of the reaction. If the terminating alkene is sterically hindered or contains an electron withdrawing group then cyclopropanation occurs. The alkenylpalladium formed using an alkyne as the transfer moiety does not cyclopropanate due to conformational constraints. Finally, fused bicyclic five-five and six-five ring systems are formed without cyclopropanation occurring. In the case of fused six-six system, cyclopropanation starts to compete, giving a mixture of both six-six and six-three fused ring system. Regioselective allylation of ketones in the presence of a palladium catalyst has been developed as a method of forming bicyclic enones. The advantages of palladium catalyzed allylation of ketones over classical methods were delineated. These include selective monoalkylation, no over alkylation, and virtually complete control of regiochemistry. Wacker oxidation can be used to transform the alkene into the prerequisite 1,4-diketone, although the yields are moderate. Finally, classical adol condensation leads to the desired bicyclic $\alpha$,$\beta$-unsaturated ketone. The synthesis of the diterpene sterpurene has been attempted using organotransition metal reactions to form key intermediates. The formation of 1-(1$\sp\prime$-iodoethylidene)-2-(iodomethyl)-4,4-dimethylcyclopentane is the key step and it was synthesized by iodination of a zirconabicyclic compound using iodine in $\rm CH\sb2Cl\sb2.$ The choice of solvent for the iodinations is critical, more polar solvents yielding all possible mono and diiodides. Crosscoupling followed by alkylation and decarboxylation leads to another key intermediate, 1-(2$\sp\prime$-But-3$\sp\prime$-enylidene)-2-(3$\sp\prime$- (2$\sp\prime$-methylpropionic acid) -4,4-dimethylcyclopentane) which is correctly functionalized to undergo an intramolecular (2+2) ketene-alkene cycloaddition. However, several attempts at cycloaddition did not lead to any desired product. Further studies to overcome these difficulties are currently underway.

Degree

Ph.D.

Advisors

Negishi, Purdue University.

Subject Area

Organic chemistry

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