Palladium-mediated carbon-carbon bond formation: Methodology and mechanism. Part I: Palladium-catalyzed alpha-arylation of aryl nitromethanes, phosphonoacetates, and phosphine oxides. Part II: Mechanistic study of the palladium-mediated chemoselective activation of C(sp3)-H bonds / VanGelder, Kelsey Faith.

Format:

Book

Thesis/Dissertation

Author/Creator:

VanGelder, Kelsey Faith, author.

Contributor:

Kozlowski, Marisa C., 1967- degree supervisor.

Winkler, Jeffrey D., degree committee member.

Smith, Amos B., degree committee member.

Joullié, Madeleine M., degree committee member.

University of Pennsylvania. Chemistry, degree granting institution.

Language:

English

Subjects (All):

Organic chemistry.

Chemistry--Penn dissertations.

Penn dissertations--Chemistry.

Local Subjects:

Organic chemistry.

Chemistry--Penn dissertations.

Penn dissertations--Chemistry.

Genre:

Academic theses.

Physical Description:

1 online resource (317 pages)

Contained In:

Dissertation Abstracts International 78-04B(E).

Place of Publication:

[Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2016.

Language Note:

English

System Details:

Mode of access: World Wide Web.

text file

Summary:

Part I: The catalytic alpha-arylation of aryl nitromethanes has been a longstanding challenge, due to the reported lack of reactivity of these compounds under cross-coupling conditions. Conditions for this transformation have been developed using mechanistically-driven high-throughput experimentation. The method efficiently provides access to a variety of isolable diaryl nitromethanes, which are useful synthetic intermediates, as well as diaryl ketones and diaryl methyl amines in sequential transformations. Additionally, a one-pot process has been developed for the differential di-arylation of nitromethane.

The catalytic alpha-arylation of phosphonoacetates has also been achieved using mechanistically-driven high-throughput experimentation. alpha-Arylated phosphonoacetates are biologically active structural motifs, and are synthetically useful in the Horner-Wadsworth-Emmons olefination. The conditions developed provide a significant improvement to the range of accessible phosphonoacetates, as previously reported methods were limited in scope and/or required harsh reaction conditions. The method is useful for both aryl bromide and aryl chloride starting materials at low catalyst loadings, and has been shown to be robust on large scale.

The challenging racemic quaternary alpha-arylation of phosphine oxides has been achieved as well, in 50% yield. Reaction conditions were thoroughly investigated using high-throughput experimentation. Improvements to the yield of the quaternary product were limited by decomposition of both the starting material and the product. More mild conditions with palladium catalysts were investigated, and a preliminary investigation of alternative catalysts was undertaken. The asymmetric quaternary alpha-arylation reaction was also studied.

Part II: A unique C(sp3)--H bond activation of toluene by Pd(OAc)2 was recently discovered. The mechanism of this reaction was studied. The initially proposed mechanism was ruled out, and another mechanism, more consistent with experimental evidence, is proposed. Evidence for a rate-limiting C--H activation event is presented, as is as evidence for radical character in both the oxazolone starting material and toluene coupling partner. Kinetics studies were undertaken, which revealed a completely zero-order reaction, perhaps implicating an intramolecular rate-determining step.

Notes:

Source: Dissertation Abstracts International, Volume: 78-04(E), Section: B.

Advisors: Marisa C. Kozlowski; Committee members: Madeleine M. Joullie; Amos B. Smith; Jeffrey D. Winkler.

Department: Chemistry.

Ph.D. University of Pennsylvania 2016.

Local Notes:

School code: 0175

ISBN:

9781369339833

Access Restriction:

Restricted for use by site license.