Strategies Towards the Hydrogenation of CO2 and Carboxylic Acid Derivatives

Increasing energy demands have been met with added combustion of fossil fuels. The massive quantities of carbon dioxide (CO2) given off as a byproduct of these processes have led to environmental and economical ramifications. Consequently, great emphasis has been placed in remediating CO2 emissions through Carbon Capture and Sequestration (CSS) technologies. A limitation of CSS is that it fails to productively use CO2. A complementary approach is to utilize CO2 as a C-1 source. This dissertation discusses several strategies for the valorization of CO2 to methanol (CH3OH) stemming from fundamental hydrogenation studies. Chapter 2 outlines a facile approach for the in situ generation of ester hydrogenation catalysts. Unlike traditional methods, this simple approach circumvents the use of sub-stoichiometric alkoxide base. Systematic studies of ligand and base effects on the hydrogenation of the esters, are disclosed. Generally, diphenylphosphinoethylamine, was found to form the most active catalyst for the hydrogenation of alkyl and aryl esters with >80% yield for select substrates. Mechanistic studies elucidated the unproductive, base-catalyzed decarbonylation of the formate ester with traditional alkoxide bases. Consequently, alternatives were investigated and K3PO4 was found to be a viable and compatible substitute. The improved insight from formate ester hydrogenation guided our studies for the one-pot hydrogenation of CO2 to CH3OH. Application of these catalysts and conditions to the cascade hydrogenation of CO2 identified incompatibility with Lewis acids. Chapter 3 focuses on this limitation and discloses a new class of ester hydrogenation catalysts that are compatible with Lewis acids. Application of these half-sandwich ester hydrogenation catalysts to the Lewis acidic cascade system led up to 8 turnovers of CH3OH in a single-pot batch reactor. Further studies implicate labile ligands as a source of inhibition. In Chapter 4, a conceptually novel approach is disclosed, wherein CO2 is captured using an amine scrubbing agent (NHMe2) and subsequently hydrogenated in a single pot to >500 turnovers of CH3OH. Up to 96% of CO2 was converted to a mixture of CH3OH and N,N-dimethylformamide (DMF). Mechanistic studies of the pathway identify DMF as a key intermediate. This strategy of carbon capture and hydrogenation provides a complementary approach to many industrial carbon capture methods. In an effort to develop an earth-abundant process for the hydrogenation of CO2 to CH3OH, iron catalysts were investigated as surrogates to the ruthenium catalysts used in Chapter 4. These iron-catalysts demonstrated high activity for the hydrogenation of amides yielding C–N bond scission products with high selectivity. DMF, a key intermediate in the CO2 to CH3OH pathway developed in Chapter 4, was hydrogenated to yield >1000 turnovers of CH3OH and HNMe2. Kinetic studies were performed to compare the activity of the earth abundant iron catalyst to ruthenium. Remarkably, under otherwise identical conditions, the iron and ruthenium catalysts displayed rates within a factor of 2. Application of these catalysts to the CO2-capture and hydrogenation pathway is also discussed. Finally, with the development of hydrogenation methodologies for C–N bond scission of formamides to yield CH3OH, complementary methods have been disclosed to yield the methylated amine through deoxy-hydrogenation. Fundamental studies were undertaken in Chapter 6 to explore the origin of selectivity for the hydrogenation of amides (C–N vs. C–O bond cleavage). Through these fundamental studies, a proton responsive catalyst was identified that enabled selective access to each product (C–N or C–O bond cleavage).PHDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/140933/1/nomaanr_1.pd

Prevalence of Diarylprolinol Silyl Ethers as Catalysts in Total Synthesis and Patents

Diarylprolinol silyl ethers are among the most utilized stereoselective organocatalysts for the construction of complex molecules. With their debut in 2005, these catalysts have been applied in numerous method developments primarily leveraging enamine and iminium-ion catalysis. These strategies have extended into the preparation of complex molecules in both academic and industrial settings. This Review intends to give an overview of the application of the diarylprolinol silyl ether catalysts in total synthesis. Furthermore, integration of these catalysts in patent literature is also disclosed highlighting the versatility of the catalytic system

Iron-Catalyzed Hydrogenation of Amides to Alcohols and Amines

This article describes the iron-catalyzed hydrogenation of unactivated amides. Under the optimal conditions, a PNP-ligated Fe catalyst affords 25–300 turnovers of products derived from C–N bond cleavage. This reaction displays a broad substrate scope, including a variety of 2° and 3° amide substrates. The reaction progress of <i>N,N</i>-dimethylformamide hydrogenation has been monitored in situ using Raman spectroscopy. This technique enables direct comparison of the relative activity of the Fe-PNP catalyst to that of its Ru analogue. Under otherwise identical conditions, the Fe and Ru catalysts exhibit rates within a factor of 2

Tandem Amine and Ruthenium-Catalyzed Hydrogenation of CO₂ to Methanol

This Communication describes the hydrogenation of carbon dioxide to methanol via tandem catalysis with dimethylamine and a homogeneous ruthenium complex. Unlike previous examples with homogeneous catalysts, this CO₂-to-CH₃OH process proceeds under basic reaction conditions. The dimethylamine is proposed to play a dual role in this system. It reacts directly with CO₂ to produce dimethylammonium dimethylcarbamate, and it also intercepts the intermediate formic acid to generate dimethylformamide. With the appropriate selection of catalyst and reaction conditions, >95% conversion of CO₂ was achieved to form a mixture of CH₃OH and dimethylformamide

Base-Free Iridium-Catalyzed Hydrogenation of Esters and Lactones

Half-sandwich iridium bipyridine complexes catalyze the hydrogenation of esters and lactones under base-free conditions. The reactions proceed with a variety of ester and lactone substrates. Mechanistic studies implicate a pathway involving rate-limiting hydride transfer to the substrate at high pressures of H₂ (≥50 bar)

An Asymmetric SN2 Dynamic Kinetic Resolution

The SN2 reaction exhibits the classic Walden inversion, indicative of the stereospecific backside attack of the nucleophile on the stereogenic center. Observation of the inversion of the stereocenter provides evidence for an SN2-type displacement. However, this maxim is contingent on substitution proceeding on a discrete stereocenter. Here we report an SN2 reaction that leads to enantioenrichment of product despite starting from a racemic mixture of starting material. The enantioconvergent reaction proceeds through a dynamic Walden cycle, involving an equilibrating mixture of enantiomers, initiated by a chiral aminocatalyst and terminated by a stereoselective SN2 reaction at a tertiary carbon to provide a quaternary carbon stereocenter. A combination of computational, kinetic, and empirical studies elucidates the multifaceted role of the chiral organocatalyst to provide a model example of the Curtin–Hammett principle. These examples challenge the notion of enantioenriched products exclusively arising from predefined stereocenters when operating through an SN2 mechanism. Based on these principles, examples are included to highlight the generality of the mechanism. We anticipate the asymmetric SN2 dynamic kinetic resolution to be used for a variety of future reactions