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Title:Synthetic diversity in C-H activation: development of selective and efficient C-H functionalization reactions
Author(s):Strambeanu, Iulia
Director of Research:White, M. Christina
Doctoral Committee Chair(s):White, Christina M
Doctoral Committee Member(s):Katzenellenbogen, John A.; Hergenrother, Paul J.; Nuzzo, Ralph G.
Department / Program:Chemistry
Discipline:Chemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Triple Catalysis
Vanadium
Cobalt
Oxygen
Diamine
Amino alcohol
Amino acid
Sulfoxide
Palladium
Catalysis
C-H Activation
Abstract:The past century has witnessed tremendous advancements in both organic methodology and total synthesis. With the synthetic conquest of molecular giants such as amphotericin and brevetoxin A, it becomes increasingly apparent that the complexity of the target defines the time and resources needed, rather than the likelihood of success in reaching the target compound. This has, in part, nourished a general desire to develop new reactions that increase the efficiency in which molecules are made through two major strategies. First, the development of reactions that initiate powerful bond formations can reduce synthetic steps, by skipping intermediates and accessing the correct functional group(s) directly from C−H bonds. Secondly, highly selective reactions (stereo-, regio-, site-) have allowed these methods to be applied to complex molecules (having many functional groups) at late stages in a synthesis, thus eliminating traditional protecting group manipulations. Nature has already recognized the power of these strategies and routinely oxidizes C−H bonds directly for the purpose of biosynthesis or metabolism by using various tailoring enzymes. In an attempt to mimic nature, synthetic chemists have tried to change the way that molecules are made in the laboratory by establishing the C−H bond as a functional group in its own right. This work describes the development of novel C−H oxidation and amination reactions as new strategies for simplifying and diversifying synthetic sequences. First, harnessing the abundance of α-olefins as starting materials, palladium (II) catalysis is used to effect a divergent intramolecular allylic C−H activation reaction to generate two different products from a common starting material. By taking advantage of the inherent reactivity of a urea nucleophile, two medicinally important moieties are formed and further elaborated to furnish nonproteinogenic amino acids. The divergent nature of this reactivity stems from a change in mechanism as a result of switching from a Pd(II)/bis-sufloxide catalyst to a Pd(OAc)2 catalyst. Our group has previously shown that the terminal oxidant in our Pd(II)/bis-sulfoxide catalyzed systems, benzoquinone (BQ), also serves as a ligand to Pd in order to promote functionalization from a monomeric Pd-π-allyl intermediate. From this, we hypothesized that stoichiometric amounts of BQ may serve to deactivate the Pd(II)/bis-sulfoxide, requiring the use of higher catalyst loadings. In an effort to improve on the overall efficiency of the allylic C−H amination systems reported by our group, we have developed reaction conditions where the terminal oxidant, BQ, is formed in situ, in a catalytic fashion rather than being used in super stoichiometric amounts. This was accomplished via an oxidation potential relay consisting of a metal co-catalyst and catalytic amounts of dihydrobenzoquinone (DHBQ) under 1 atm of oxygen. The use of molecular O2 as the new terminal oxidant under these reaction conditions offers a low cost and non-toxic alternative to BQ. As a consequence, this new system allows for reduced palladium catalyst loadings (2.5-5 mol%) and no stoichiometric byproducts (therefore a more facile product purification), while maintaining high levels of reactivity and selectivity for the linear allylic amination reaction.
Issue Date:2015-01-08
Type:Thesis
URI:http://hdl.handle.net/2142/78701
Rights Information:Copyright 2015 Iulia Strambeanu
Date Available in IDEALS:2015-07-22
Date Deposited:May 2015


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