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.
|Cabrera, James M; Tauber, Johannes; Zhang, Wandi et al. (2018) Selection between Diastereomeric Kinetic vs Thermodynamic Carbonyl Binding Modes Enables Enantioselective Iridium-Catalyzed anti-(?-Aryl)allylation of Aqueous Fluoral Hydrate and Difluoroacetaldehyde Ethyl Hemiacetal. J Am Chem Soc 140:9392-9395|
|Meza, Arismel Tena; Wurm, Thomas; Smith, Lewis et al. (2018) Amphiphilic ?-Allyliridium C,O-Benzoates Enable Regio- and Enantioselective Amination of Branched Allylic Acetates Bearing Linear Alkyl Groups. J Am Chem Soc 140:1275-1279|
|Kim, Seung Wook; Wurm, Thomas; Brito, Gilmar A et al. (2018) Hydroamination versus Allylic Amination in Iridium-Catalyzed Reactions of Allylic Acetates with Amines: 1,3-Aminoalcohols via Ester-Directed Regioselectivity. J Am Chem Soc 140:9087-9090|
|Holmes, Michael; Schwartz, Leyah A; Krische, Michael J (2018) Intermolecular Metal-Catalyzed Reductive Coupling of Dienes, Allenes, and Enynes with Carbonyl Compounds and Imines. Chem Rev 118:6026-6052|
|Cabrera, James M; Tauber, Johannes; Krische, Michael J (2018) Enantioselective Iridium-Catalyzed Phthalide Formation through Internal Redox Allylation of Phthalaldehydes. Angew Chem Int Ed Engl 57:1390-1393|
|Brito, Gilmar A; Della-Felice, Franco; Luo, Guoshun et al. (2018) Catalytic Enantioselective Allylations of Acetylenic Aldehydes via 2-Propanol-Mediated Reductive Coupling. Org Lett 20:4144-4147|
|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|
|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|
|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|
|Roane, James; Holmes, Michael; Krische, Michael J (2017) Reductive C-C Coupling via Hydrogenation and Transfer Hydrogenation: Departure from Stoichiometric Metals in Carbonyl Addition. Curr Opin Green Sustain Chem 7:1-5|
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