Engineering novel tandem reactions using organometallic catalysts and metalloenzymes

Denard, Carl

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https://hdl.handle.net/2142/44107 Copy

Description

Title

Engineering novel tandem reactions using organometallic catalysts and metalloenzymes

Author(s)

Denard, Carl

Issue Date

2013-05-24T21:50:55Z

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

Zhao, Huimin

Department of Study

Chemical & Biomolecular Engr

Discipline

Chemical Engineering

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

M.S.

Degree Level

Thesis

Keyword(s)

• Tandem catalysis
• metalloenzymes
• epoxidation
• ruthenium olefin metathesis
• isomerization
• cytochrom P450
• biocatalysis

Abstract

Organometallic chemistry and bioinorganic chemistry are two prominent sub-disciplines of chemistry. Complexes of the transition metals are prominent components of both disciplines. On the one hand, considerable efforts in transition-metal catalysis have culminated in practical and efficient transformations such as isomerization, olefin metathesis, hydroxylation, epoxidation and others. On the other hand, metalloenzymes and enzymes with bound metal centers have been investigated and engineered to catalyze reactions with organic compounds that are synthetically and industrially important. While these two fields of transition metal catalysis have grown and matured, they have often learned from each other, but not worked cooperatively. Enzymes work mostly in buffer, at mild conditions, and in air. Organometallic catalysts often require very different conditions, such as organic solvents, inert atmosphere, and high temperatures. Research interests over the last several years have grown in attempting to combine these two sub-disciplines for asymmetric synthesis to achieve atom-economical transformations, a process called aptly tandem catalysis. However, until now, in no case has a metalloenzyme and an organometallic complex been shown to react cooperatively. Our project aims at combining organometallic catalysts and metalloenzymes for cooperative reactions to access products and selectivities that would not occur with either catalyst alone and would occur in lower yield if conducted as two sequential reactions. In particular we present our work on tandem reactions between ruthenium catalysts and P450s for enantioselective and regioselective enzymatic asymmetric epoxidations, a reaction which still poses a few issues for organic chemists with respect to scope and enantioselecitivty. In Chapter 2, we combined a ruthenium isomerization catalyst and P450 BM3 mutants for the oxidation of olefins from an equilibrium established by the ruthenium-catalyzed isomerization. We found that the two catalysts can effectively work together in a biphasic system, for a successive isomerization and epoxidation of alkenes and short olefinic acids. However, we observed that under the reaction conditions, the trans- to cis- isomerization rate of olefins is too slow. Lastly, we also found that the enzymatic reaction is not selective enough, and that yields are mass transfer limited. Therefore, the enzymatic epoxidation cannot exert a driving force powerful enough to drive the reaction towards the epoxidation of one alkene of interest. In Chapter 3, we engineered a cross-metathesis-epoxidation reaction using a ruthenium olefin metathesis catalyst and the wild type P450 from Bacillus megaterium. We show that 90% yield of a single epoxide can be obtained selectively from the cross metathesis of two alkenes, a reaction that would yield a maximum 64% yield if ran sequentially. This study suggests that these two classes of catalyst can be combined in new ways as the metal catalysts become more tolerant of functional groups and the enzymes become more tolerant of organic media.

Graduation Semester

2013-05

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http://hdl.handle.net/2142/44107

Copyright and License Information

Copyright 2013 Carl Denard

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