Browsing by Subject "Catalysis"
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Item Development of Metal-Catalyzed and Photochemical Approaches to Carbon-Carbon Bond Forming Reactions(2022-05) Nair, Vaishnavi Narayanan; Ready, Joseph M.; De Brabander, Jef K.; Chen, Chuo; Tambar, UttamThe development of methods to construct carbon-carbon bonds is fundamental to synthetic organic chemistry. This transformation provides access to a variety of organic compounds including medicinal and pharmaceutical agents, agrochemicals, and polymers. There is a growing interest in practical and efficient catalytic approaches to construct carbon-carbon bonds allowing access to valuable organic molecules. This manuscript describes a review of catalytic methods for onium ylide rearrangements in aromatic systems, our studies on catalyst-controlled rearrangements of onium ylides in indole systems, and our approaches toward photocatalytic asymmetric coupling of imines and alkylarenes. In the first chapter, an overview of the known synthetic approaches for metal-catalyzed onium ylide rearrangements in aromatic systems is discussed. Various catalytic examples from the recent literature show onium ylides undergoing dearomative [2,3]-rearrangement to give alkylated aromatic compounds as final products. The influence of substrate and solvent effects in the selectivity of rearrangements has been demonstrated through several examples. The second chapter describes our studies in the development of catalytic rearrangements of indole-based onium ylides. Our approach allows regiodivergent rearrangements of oxonium ylides in a catalyst-controlled manner to access substituted indole compounds. This method shows the impact of transition-metal catalysis in governing the selectivity of chemical transformations. We also present various experimental and theoretical studies to analyze the mechanistic pathways involved in the methodology. The development of the methodology has also allowed further functionalization of the products resulting in the total synthesis and structural revision of an indole alkaloid. In the third chapter, we describe our approaches in exploiting photocatalysis to perform the functionalization of feedstock chemicals to access enantioenriched chiral amines. Our synthetic strategy leverages the known photophysical properties of compounds to rationally design and develop a catalytic transformation in an enantioselective fashion. The challenges associated with realizing this transformation and our approaches to solving them are discussed.Item [Southwestern News](1997-04-18) Steeves, Susan A.Item Synthetic Studies in the Selective Functionalization of Unsaturated Compounds: From Initial Applications in Medicinal Chemistry to General Applications in Unactivated Systems(2016-09-16) Bayeh, Liela Antoinette; Ready, Joseph M.; Tambar, Uttam; De Brabander, Jef K.; Chen, ChuoMedicinal chemistry and reaction development have influenced one another in the field of organic chemistry. The synthesis of therapeutic small molecules often requires the use of practical synthetic methodologies, while reaction development is frequently inspired by the demands of medicinal chemistry. First the development of small molecule inhibitors of hypoxia inducible factors, which are heterodimeric transcription factors that have been implicated in a number of cancer environments, will be discussed. Two scaffolds have been designed and evaluated for their ability to selectively bind within the binding domain of the hypoxia inducible factor-2α isoform and inhibit heterodimerization, with the most potent agonist exhibiting a half maximal inhibitory concentration value of 23 nanomolar. Inspired by the stereospecific mode of action exhibited by the diaryl-tetrazolo-tetrahydropyrimidine-based scaffold of hypoxia inducible factor-2 antagonists, a potential co-catalyst system for the asymmetric synthesis of these derivatives has been identified, utilizing a synergistic combination of a cinchona alkaloid-based primary amine and acid catalysts. While the enantioselectivity of this reaction as it currently stands remains modest, these products can be isolated in up to 96:4 enantiomeric ratio through recrystallization efforts. Secondly, the development of a series of general and efficient methods for the synthesis of functionalized olefin products from simple unsaturated systems will be described. Unfunctionalized olefins and dienes are ideal substrates for chemical synthesis due to their low cost and ease of availability. However they present a variety of challenges when attempting to selectively differentiate between sterically and electronically similar carbon-hydrogen bonds. The processes described herein exploit the ability of sulfurimide and sulfurdiimide reagents to undergo hetero-ene reactions with terminal and internal olefins as well as [4+2] couplings with dienes. These reactions result in reactive intermediates that are utilized in a host of chemical transformations, including [2,3]-rearrangements to generate allylic amines and alcohols, Grignard coupling to generate linear and branched alkylated products, and aminoarylation chemistry. Most notably, a regio- diastereo- and enantioselective synthesis of multifunctional allylic sulfinimides from internal olefins is discussed.Item Titanium-Mediated Carbometallation of Homoallylic Alcohols(2012-07-20) Peng, Bo; Ready, Joseph M.Addition of zinc dichloride as an additive allows for the titanium-mediated carbometalation of homoallylic alcohols with Grignard reagents. The zinc dichloride additive successfully inhibits the B-hydride elimination of the titanium intermediate. The unsaturated products are obtained in up to 90 percent yield and up to >20 to 1 ratio of the carbometallation to oxidative arylation products. Subsequent electrophilic trapping is possible with elemental halides to yield the respective halohydrin products or oxidation to yield the diol products. The reaction is tolerant of both alkyl and aryl substituents on the homoallylic alcohol. This reaction allows ready access to unsaturated secondary alcohols or further functionalized products from an initial homoallylic alcohol.