Synthesis and Reactions of Novel Heteroarylzirconocene Reagents

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Caleb F. Harris (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Advisor

Shouquan Huo

Abstract: The cross-coupling of metallated heteroaromatic species with aryl and heteroaryl halides is a powerful and highly desirable transformation in both the synthesis of pharmaceutical compounds as well as materials development. However current methodology in this area has some limitations particularly with organometallic reagents derived from 2-halopyridines 2-haloquinolines and other similar heteroaromatic compounds. Suzuki cross-coupling reactions of 2-pyridyl boronic acids or esters is often reported to be low yielding due to protodeborylation. In particular the preparation of the corresponding heteroaromatic boronic reagents is often associated with low yields. Although Negishi cross-coupling reactions are often reported to be high yielding the generation of heteroaromatic Negishi reagents require the use of expensive and user unfriendly Rieke® Zinc. The Stille reaction is the least desirable because of the highly toxic tin waste streams generated. Zirconium is a non-toxic inexpensive and abundant metal that exists primarily in the Zr(IV) oxidation state and its application in organic synthesis has been extensively studied. However the preparation of heteroaromatic zirconocene reagents and their application in organic synthesis have not been reported. In 1986 Negishi reported the generation of a Zr(II) species in situ by reacting Cp₂Zr(IV)Cl₂ with 2 equivalents of n-BuLi followed by a [beta]-H abstraction process. We anticipated that the oxidative addition of a heteroaromatic halide to the Negishi reagent "Cp₂Zr(II)" would generate the desired heteroaromatic zirconocene reagents. These novel reagents were successfully generated and used in palladium-catalyzed cross-coupling reactions.

Additional Information

Publication

Thesis

Date: 2012

Keywords

Chemistry, Cross-coupling, Heteroaromatic, Organometallic, Palladium-catalyzed, Zirconocene

Subjects

Zirconium

Chemical tests and reagents

Organic compounds--Synthesis

Halides

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