As exemplified by the Haber-Bosch reaction, which sustains half the human population, and enantioselective hydrogenation, which is the foremost chemical method used to create chiral pharmaceutical and agrochemical ingredients, catalytic hydrogenation has had a greater impact on how humans live and die than any other chemical process. Prior to our work, the sole example of a ?C-C bond forming hydrogenation? was hydroformylation, which is the largest application of homogenous metal catalysis. My laboratory has pioneered a broad, new class of C-C bond formations that merge the characteristics of catalytic hydrogenation and carbonyl addition ? processes in which two or more reactants are hydrogenated to form a single, more complex product. These transformations bypass the use of stoichiometric carbanions, offering a byproduct-free alternative to a range of classical carbonyl or imine additions. This concept is extended further by ?C-C bond forming transfer hydrogenations? that directly convert lower alcohols to higher alcohols, again in the absence of stoichiometric metals. In the proposed funding period, we will develop methods for the stereo- and site-selective formation of quaternary centers, the use of ?-olefins as couplings partners, and the use of base metal (Fe, Co) catalysts. Our goal is to develop environmentally benign methods for the conversion of inexpensive chemical feedstocks to value-added building blocks for use in the manufacture of pharmaceutical and agrochemical ingredients.
C-C Bond formation is central to the endeavor of chemical synthesis. We have developed two new classes C-C bond formations: (a) reductive couplings induced via catalytic hydrogenation, and (b) H2-auto-transfer processes that directly convert lower alcohols to higher alcohols. Here, we propose to continue our investigations into the direct redox- triggered C-C coupling of alcohols with a focus on the development of stereo- and site-selective methods for construction of quaternary centers, the use of ?-olefins as couplings partners, and the use of base metal (Fe, Co) catalysts.
|Guo, Yi-An; Liang, Tao; Kim, Seung Wook et al. (2017) Nickel-Catalyzed Cross-Coupling of Vinyl Dioxanones to Form Enantiomerically Enriched Cyclopropanes. J Am Chem Soc 139:6847-6850|
|Zhang, Wandi; Chen, Weijie; Xiao, Hongde et al. (2017) Carbonyl anti-(?-Amino)allylation via Ruthenium Catalyzed Hydrogen Autotransfer: Use of an Acetylenic Pyrrole as an Allylmetal Pronucleophile. Org Lett 19:4876-4879|
|Sato, Hiroki; Fukaya, Keisuke; Poudel, Binit Sharma et al. (2017) Diols as Dienophiles: Bridged Carbocycles via Ruthenium(0)-Catalyzed Transfer Hydrogenative Cycloadditions of Cyclohexadiene or Norbornadiene. Angew Chem Int Ed Engl 56:14667-14671|
|Haydl, Alexander M; Breit, Bernhard; Liang, Tao et al. (2017) Alkynes as Electrophilic or Nucleophilic Allylmetal Precursors in Transition-Metal Catalysis. Angew Chem Int Ed Engl 56:11312-11325|
|Holmes, Michael; Nguyen, Khoa D; Schwartz, Leyah A et al. (2017) Enantioselective Formation of CF3-Bearing All-Carbon Quaternary Stereocenters via C-H Functionalization of Methanol: Iridium Catalyzed Allene Hydrohydroxymethylation. J Am Chem Soc 139:8114-8117|
|Roane, James; Wippich, Julian; Ramgren, Stephen D et al. (2017) Synthesis of the C(1)-C(13) Fragment of Leiodermatolide via Hydrogen-Mediated C-C Bond Formation. Org Lett 19:6634-6637|
|Wurm, Thomas; Turnbull, Ben W H; Ambler, Brett R et al. (2017) Thermal Hetero-Diels-Alder Reaction of Benzocyclobutenones with Isatins To Form 2-Oxindole Spirolactones. J Org Chem 82:13751-13755|
|Kim, Seung Wook; Lee, Wonchul; Krische, Michael J (2017) Asymmetric Allylation of Glycidols Mediated by Allyl Acetate via Iridium-Catalyzed Hydrogen Transfer. Org Lett 19:1252-1254|
|Luong, Tom; Chen, Shujie; Qu, Ke et al. (2017) Ruthenium(0)-Catalyzed C-C Coupling of Alkynes and 3-Hydroxy-2-oxindoles: Direct C-H Vinylation of Alcohols. Org Lett 19:966-968|
|Feng, Jiajie; Holmes, Michael; Krische, Michael J (2017) Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis. Chem Rev 117:12564-12580|
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