I. Biomimetic oxidations using non-heme iron catalysis. II. Palladium- and hypervalent iodine-catalyzed tandem wacker-dehydrogenation of terminal olefins

ABSTRACT I. BIOMIMETIC OXIDATIONS USING NON-HEME IRON CATALYSIS Nature’s oxidation catalysts promote a remarkable variety of highly selective oxidation reactions of alkanes, olefins, and arenes. Inspired by this diversity of reactivity, the chemical community has long sought to replicate enzymatic reactivity within the synthetic laboratory, both for the purposes of better understanding enzymatic reaction mechanisms and to advance the frontier of chemical synthesis. In the first part of this thesis, a series of projects exploring novel oxidation reactivity and mechanism, as well as several unique synthetic applications, will be described. First, a comprehensive study of the use of carboxylic acids as directing groups for non-heme iron catalyzed C—H hydroxylation will be described. Examination of substrates for C—H hydroxylation that featured unfavorable electronic, steric, or stereoelectronic effects demonstrated that carboxylic acids were capable of overcoming these substrate biases during hydroxylation. The developed methodology was utilized to install the C2 oxidation on a taxane derivative, demonstrating the first example of such an oxidation using a small molecule catalyst or reagent. Second, the unexpected discovery of ‘double oxidation’ products resulting from non-heme iron catalyzed C—H hydroxylation of carboxylic acid-containing substrates will be described. The mechanism accounting for their formation was studied in detail and suggested operation of mixed desaturase/oxygenase reactivity, only previously observed within natural systems. These studies suggested that, in analogy to nature, a short-lived substrate-derived carbon-centered radical either underoges hydroxyl rebound to provide for C—H hydroxylation or further oxidation to an olefin intermediate en route to ‘double oxidation’. Third, oxidation of the characteristic furan ring of a cafestol derivative using a non-heme iron catalyst allowed the rapid synthesis of tricalysiolide B, a natural product isolated in 2006 from Japanese tree bark. This result suggested that non-heme iron oxygenases were responsible for metabolizing cafestol to tricalysiolide B within tricalysia dubia, and demonstrated how non-heme iron catalysis can be used to rapidly test biosynthetic proposals. II. PALLADIUM AND HYPERVALENT IODINE-CATALYZED TANDEM WACKER- DEHYDROGENATION OF TERMINAL OLEFINS Catalytic C—H functionalization reactions promise to increase synthetic efficiency by enabling the direct installation of useful functionality onto traditionally unreactive hydrocarbon frameworks. The White group has pioneered a toolbox of synthetically useful palladium-catalyzed allylic C—H functionalization reactions of terminal olefins, including C—O, C—N, and C—C bond forming reactions. This section will describe the discovery and development of a palladium/hypervalent iodine-catalyzed tandem Wacker-dehydrogenation reaction, allowing direct access to linear α,β-unsaturated ketones from readily available terminal olefins.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2013

Author dc:creator

• Bigi, Marinus

Contributors dc:contributor

• White, Maria C.
• Katzenellenbogen, John A.
• Nuzzo, Ralph G.
• Hull, Kami L.

• Non-heme
• Iron Catalysis
• oxidation
• catalysis
• biomimetic

Statement dc:rights

• Copyright 2013 Marinus Bigi

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/44446

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/44446