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Title:Oxidative Heck Reactions with Terminal Olefins
Author(s):Delcamp, Jared H.
Director of Research:White, Maria C.
Doctoral Committee Chair(s):White, Maria C.
Doctoral Committee Member(s):Denmark, Scott E.; Hergenrother, Paul J.; Rogers, John A.
Department / Program:Chemistry
Discipline:Chemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Heck reaction
oxidative
Palladium
arylation
vinylation
transition metal catalysis
Abstract:Sequential transformations in a single reaction have the potential to dramatically increase efficiency with respect to resources, time, and number of steps to access key intermediates. When sequential C-H bonds are activated a bifunctional handle arises from seemingly inert functionality. This work describes a one-pot sequential allylic C-H esterification, vinylic C-H arylation. A previously reported Pd(II)/sulfoxide system is used to generate branched allylic esters from α-olefins with only the addition of an aryl boronic acid to the reaction mixture. Styrenyl allylic esters are generated in good overall yield and excellent selectivities. The wide functional group tolerance and mild conditions of this three-component coupling reaction provide an attractive manifold for the rapid build-up of dense functionality around terminal olefins with minimal protecting group strategies or undesirable oxidation/reduction reactions.The synthetic utility of this reaction has been demonstrated through the synthesis of several intermediates to biologically active molecules. The ready availability and inertness of α-olefins relative to the oxidized precursors required for other C—C bond forming methods means that fewer steps are required for their installation and maintenance throughout a synthetic sequence. Previously, allylic esters served as non-resonance directing groups on terminal olefin for the vinylic C—H arylation (Heck reaction). This manifold is unique because previous intermolecular Heck reaction conditions require an excess of resonance activated olefin coupling partner. Further exploration of directing groups to determine the underlying directing factors led to the discovery of several terminal olefin classes with diversedirecting elements. A general and highly selective intermolecular Heck arylation of non-resonance stabilized α-olefins with aryl and stryenyl boronic reagents has been developed. The Pd(II)/sulfoxide catalyzed Heck reaction is performed under oxidative, acidic conditions and proceeds with good yields and excellent regio- and stereoselectivities to generate linear E-arylated olefins. Polyenes are prevalent motiefs in natural products and pharmaceuticals. Polyene functionality often requires mild and selective synthetic methods. The Heck vinylation uses orthogonally reactive C-H bonds and these bonds are often easy to carry through synthetic sequences. Despite this advantage, the synthetic potential of the intermolecular Heck reaction has not been realized in complex molecule formation. A method has been developed which overcomes the previous intermolecular Heck-vinylation shortcomings of excess terminal olefin and required resonance activation for regio- and stereoselectivities. The Pd(II)/sulfoxide catalyzed oxidative Heck vinylation proceeds under mild conditions to give polyene products with a variety of substitution patterns amid diverse functionality. The polyenes are formed in synthetically relevant yields with excellent stereoselectivities. Overall, the oxidative Heck vinylation compares favorably with many of the methods commonly used to synthesize polyunsaturated hydrocarbon segments. This method increases the synthetic potential of the intermolecular Heck reaction closer to that of other classic palladium cross-couplings.
Issue Date:2011-01-21
URI:http://hdl.handle.net/2142/18626
Rights Information:Copyright 2010 Jared H. Delcamp
Date Available in IDEALS:2011-01-21
2013-01-22
Date Deposited:2010-12


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