Alkenes are exceptionally attractive functional groups for synthesis. Newly discovered and significantly improved alkene functionalization reactions can have a direct impact on the efficiency of targeted synthesis. Therefore, the development of selective, practical alkene functionalization reactions is a continuing challenge facing chemists in both academia and industry. In this proposal, we target a new collection of alkene functionalization reactions that exploit Pd(II)-catalysis and its ability to promote both alkene nucleophilic addition reactions and cross-coupling processes to form multiple new C-C, C-H, or C-X bonds across the alkene framework. This reaction method development is coupled to careful mechanistic studies, which are designed to elucidate the fundamental features governing reaction outcomes, as well as to stimulate new reaction development and catalyst design. The current proposal is directed toward the development of new Pd-catalyzed olefin functionalization reactions using both oxidative and classical methods to generate Pd-alkyl intermediates. The reaction development described herein is focused on two significant goals: A) enabling new mechanistically-derived tactics for molecule synthesis by using innovative approaches to functionalize Pd-alkyl intermediates originally derived from an alkene (Aims 1 &2), and B) exploiting our recently developed Heck reactions of electronically non-biased olefins to access important chiral building blocks, while also probing the factors that govern selective Pd-hydride insertion and ?-hydride elimination (Aim 3).

Public Health Relevance

The goal of the proposed research is to develop new palladium-catalyzed alkene functionalization reactions to enable the facile synthesis of biologically-relevant targets and novel small molecules through unique bond disconnections. Advances in the proposed methodology will directly impact the biomedical mission by providing efficient access to derivatives of biologically-active core structures.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Synthetic and Biological Chemistry B Study Section (SBCB)
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Lees, Robert G
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University of Utah
Schools of Arts and Sciences
Salt Lake City
United States
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Xu, Liping; Hilton, Margaret J; Zhang, Xinhao et al. (2014) Mechanism, reactivity, and selectivity in palladium-catalyzed redox-relay Heck arylations of alkenyl alcohols. J Am Chem Soc 136:1960-7
Stokes, Benjamin J; Bischoff, Amanda J; Sigman, Matthew S (2014) Pd(Quinox)-Catalyzed Allylic Relay Suzuki Reactions of Secondary Homostyrenyl Tosylates via Alkene-Assisted Oxidative Addition. Chem Sci 5:2336-2339
Mei, Tian-Sheng; Patel, Harshkumar H; Sigman, Matthew S (2014) Enantioselective construction of remote quaternary stereocentres. Nature 508:340-4
Stokes, Benjamin J; Liao, Longyan; de Andrade, Aline Mendes et al. (2014) A palladium-catalyzed three-component-coupling strategy for the differential vicinal diarylation of terminal 1,3-dienes. Org Lett 16:4666-9
Saini, Vaneet; Stokes, Benjamin J; Sigman, Matthew S (2013) Transition-metal-catalyzed laboratory-scale carbon-carbon bond-forming reactions of ethylene. Angew Chem Int Ed Engl 52:11206-20
DeLuca, Ryan J; Edwards, Jennifer L; Steffens, Laura D et al. (2013) Wacker-type oxidation of internal alkenes using Pd(Quinox) and TBHP. J Org Chem 78:1682-6
DeLuca, Ryan J; Sigman, Matthew S (2013) The palladium-catalyzed anti-Markovnikov hydroalkylation of allylic alcohol derivatives. Org Lett 15:92-5
McCammant, Matthew S; Liao, Longyan; Sigman, Matthew S (2013) Palladium-catalyzed 1,4-difunctionalization of butadiene to form skipped polyenes. J Am Chem Soc 135:4167-70
Saini, Vaneet; Liao, Longyan; Wang, Qiaofeng et al. (2013) Pd(0)-catalyzed 1,1-diarylation of ethylene and allylic carbonates. Org Lett 15:5008-11
Mei, Tian-Sheng; Werner, Erik W; Burckle, Alexander J et al. (2013) Enantioselective redox-relay oxidative heck arylations of acyclic alkenyl alcohols using boronic acids. J Am Chem Soc 135:6830-3

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