Development of base metal-catalyzed C—H functionalization reactions

Griffin, Jennifer Rae

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https://hdl.handle.net/2142/99185 Copy

Description

Title

Development of base metal-catalyzed C—H functionalization reactions

Author(s)

Griffin, Jennifer Rae

Issue Date

2017-10-10

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

White, Christina

Doctoral Committee Chair(s)

White, Christina

Committee Member(s)

• Denmark, Scott E.
• Hull, Kami
• Katzenellenbogen, John

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Catalysis
• C—H functionalization

Abstract

For decades, synthetic organic chemists have constructed organic molecules by manipulating functionality already existing on the scaffold. Simple chemical feedstocks, typically derived from petroleum, are pre-installed with oxidized moieties, which can then undergo a series of transformations known as functional group manipulations to build up molecular complexity. Recently, a different approach has emerged wherein inert and ubiquitous C—H bonds in organic molecules can be specifically targeted for chemical transformations, obviating the need for preexisting functional groups. However, this approach confronts organic chemists with an inherent and paradoxical challenge of developing reagents and catalysts that are reactive enough to cleave these strong and inert C—H bonds, while still being able to functionalize in a selective and predictable manner. Nature has evolved powerful metalloenzymes based on earth abundant base metals like iron that are capable of selectively cleaving and functionalizing C—H bonds. Cytochrome P450 enzymes contain an iron-heme center that reacts with oxygen and water to form high-valent iron-oxo intermediates. These species can directly and selectively convert C—H bonds into C—O bonds, even in complex molecule settings. However, the analogous transformation of C—H bonds to C—N and C—C bonds via metallonitrenes and metallocarbenes is not known in nature. The majority of synthetic, small molecule catalysts thus far developed for these C—H functionalization processes have been comprised of precious or noble metals like palladium, rhodium, ruthenium, and iridium. This work describes the discovery and development of two novel base metal catalysts for C—H amination and alkylation that proceed through high-valent metallonitrene and carbene intermediates. First, a C—H amination catalyst, manganese tert-butylphthalocyanine [Mn(tBuPc)], is described. This catalyst is an outlier to the reactivity-selectivity paradigm, i.e. is capable of oxidizing strong aliphatic C(sp3)—H bonds while displaying chemoselectivity (i.e. tolerance of more oxidizable functionality). It is unique in its capacity to functionalize all types of C(sp3)—H bonds intramolecularly, while displaying excellent chemoselectivity in the presence of π-functionality. Mechanistic studies indicate that [Mn(tBuPc)] transfers bound nitrenes to C(sp3)—H bonds via a pathway that lies between concerted C—H insertion, observed with reactive noble metals (e.g. rhodium), and stepwise radical C—H abstraction/rebound, observed with chemoselective base metals (e.g. iron). Rather than achieving a blending of effects, [Mn(tBuPc)] aminates even 1° aliphatic and propargylic C—H bonds, reactivity and selectivity unusual for previously known catalysts. Second, a C—H alkylation catalyst, iron phthalocyanine [FePc], is described that is capable of alkylating allylic, benzylic and ethereal C(sp3)—H bonds via a metallocarbene intermediate. The catalytic transformation of a C(sp3)—H bond to a C(sp3)—C bond via an iron carbene intermediate represents a long-standing challenge. Despite the success of enzymatic and small molecule iron catalysts to mediate challenging C(sp3)—H oxidations and aminations via high-valent iron oxos and nitrenes, C(sp3)—H alkylations via isoelectronic iron carbene intermediates have thus far been unsuccessful. Iron carbenes have been inert, or shown to favor olefin cyclopropanation and heteroatom-hydrogen insertion. Mechanistic investigations support that an electrophilic iron carbene mediates homolytic C—H cleavage and rebounds from the resulting organoiron intermediate to form the new C—C bond; both of these steps are tunable via catalyst modifications. These studies suggest that for iron carbenes, distinct from other late metal carbenes, C—H cleavage is partially rate-determining and must be promoted to effect reactivity.

Graduation Semester

2017-12

Type of Resource

text

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Copyright and License Information

Copyright 2017 Jennifer R. Griffin

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