The development of Pd(II)sulfoxide-oxazoline catalyzed allylic C—H functionalizations

Ali, Siraj Zaki

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https://hdl.handle.net/2142/114100 Copy

Description

Title

The development of Pd(II)sulfoxide-oxazoline catalyzed allylic C—H functionalizations

Author(s)

Ali, Siraj Zaki

Issue Date

2021-12-03

Director of Research (if dissertation) or Advisor (if thesis)

White, Maria C

Doctoral Committee Chair(s)

White, Maria C

Committee Member(s)

• Denmark, Scott E
• Hergenrother, Paul J
• Rauchfuss, Thomas B

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Organic Chemistry
• Catalysis

Abstract

Pd-catalyzed allylic C—H functionalization is a powerful platform to stereoselectively and regioselectively convert terminal olefins (typically considered inert under most reaction conditions) into higher value chemical commodities. At the outset of this research program, several challenges with allylic C—H functionalization included: poor to moderate enantioselectivities in stereoselective transformations, and limited scope of functionalization partners. This thesis describes effort towards the development and application of Pd(II)/sulfoxide-oxazoline (Pd(II)/SOX) catalysis towards addressing these challenges. The first chapter outlines the development and application of Pd(II)/SOX catalysis towards the difficult challenge of asymmetric allylic C—H alkylation. Critical to this strategy was investigations into the cis-SOX ligand framework—a diastereomer of the SOX ligand which was theorized to have greater enantiocontrol around the intermediate π-allyl. This chapter describes the development and application of this system to α-nitrotetralones, a versatile precursor to amino ketones and amino alcohols. The chapter also details efforts into addressing challenging β-ketoester nucleophiles, and the elucidation of a key ligand structural feature important for enantioselectivity. The second chapter outlines the development and application of Pd(II)/SOX catalysis towards allylic C—H aminations with basic secondary amines. Intermolecular C—H amination is typically limited to doubly or singly protected nitrogen species, allowing only for protected ammonia or primary amine installation. Typically, basic amines are liable to bind tightly to the electrophilic metal catalysts for C—H cleavage and can inhibit useful reactivity. An amine quaternization strategy was applied to basic secondary amines, which allowed for a slow release of the free amine. This slow release allowed for functionalization to occur with no detrimental inhibition of the electrophilic Pd(II) center. This strategy was applied to a variety of secondary amines cores, forging pharmaceutically relevant tertiary amine products. In addition, the mild selective allylic functionalization was tolerant of numerous functionalities considered traditional electrophiles for amino functionalization. Finally, several tertiary amine drugs and drug derivatives were synthesized, demonstrating the synthetic utility of this transformation.

Graduation Semester

2021-12

Type of Resource

Thesis

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http://hdl.handle.net/2142/114100

Copyright and License Information

Copyright 2021 Siraj Ali

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