Part I: Asymmetric synthesis of alpha-allyl-alpha-aryl alpha-amino acids. Part II: Asymmetric spirocyclization of allenyl ketones. Part III: Chemoselective activation of C(sp3)--H bond over C(sp 2)--H bond with Pd(II).

Format:

Book

Thesis/Dissertation

Author/Creator:

Curto, John M, author.

Contributor:

Kozlowski, Marisa C., 1967- degree supervisor.

University of Pennsylvania. Chemistry.

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 (412 pages)

Contained In:

Dissertation Abstracts International 76-05B(E).

Place of Publication:

[Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor, MI : ProQuest, 2014.

System Details:

Mode of access: World Wide Web.

text file

Summary:

Part I. The first asymmetric synthesis of alpha-allyl-alpha-aryl alpha-amino acids by means of a three component coupling of a-iminoesters, Grignard reagents, and cinnamyl acetate is reported. Notably, the enolate from the tandem process provides a much higher level of reactivity and selectivity than the same enolate generated via direct deprotonation, presumably due to differences in the solvation/aggregation state.

A novel method for removal of a homoallylic amine protecting group delivers the free amine congeners. The alpha-allyl moiety offers a means to generate further valuable alpha-amino acid structures. Cross-metathesis of the tandem product provided allylic diversity not afforded in the parent reaction. Cyclic alpha-amino acid derivatives could be accessed by ring closing metathesis presenting a viable strategy to higher ring homologues of enantioenriched a-substituted proline. The 8-member proline analog was successfully converted to the pyrrolizidine natural product backbone.

Part II. The asymmetric spirocyclization of allenyl ketones is reported. High-throughput experimentation by means of a chiral Lewis acid library enabled the determination of a suitable catalyst system. Protecting group manipulation provides an orthogonal route to enantioenriched para-quinone and ortho-quinone spirocycles. This novel technology provides access to the spirocyclic core that is prevalent in many natural products.

Part III. Palladium has been identified as a suitable catalyst for the chemoselective activation of C(sp3)--H bond over C(sp2)--H bond of toluene and tolyl analogs. This technology has been combined with the C(sp3)--H activation of acidic C--H bonds to form new C--C bonds. High-throughput experimentation was used for identifying conditions that reduced toluene loading and engendered catalyst turnover via a suitable oxidant.

The parent reaction has been extended to include the Pd catalyzed alkylation of phenylglycine azlactones with ethylbenzene, 2-ethylnaphthalene, propylbenzene and butylbenzene. Mechanistic studies were initiated to determine whether the process occurs via free radicals or via Pd mediated C(sp3)--H activation. Our studies support a Pd mediated process in which the C(sp 3)--H activation of the tolyl analog is the rate determining step. This finding represents a paradigm shift in our understanding of Pd and its selectivity for arene activation vs benzylic activation.

Notes:

Source: Dissertation Abstracts International, Volume: 76-05(E), Section: B.

Adviser: Marisa C. Kozlowski.

Department: Chemistry.

Thesis Ph.D. University of Pennsylvania 2014.

Local Notes:

School code: 0175.

ISBN:

9781321479348

Access Restriction:

Restricted for use by site license.