Iron- and Cobalt-Catalyzed Alkene Hydrogenation: Catalysis with Both Redox-Active and Strong Field Ligands

Abstract

The hydrogenation of alkenes is one of the most impactful reactions catalyzed by homogeneous transition metal complexes finding application in the pharmaceutical, agrochemical, and commodity chemical industries. For decades, catalyst technology has relied on precious metal catalysts supported by strong field ligands to enable highly predictable two-electron redox chemistry that constitutes key bond breaking and forming steps during turnover. Alternative catalysts based on earth abundant transition metals such as iron and cobalt not only offer potential environmental and economic advantages but also provide an opportunity to explore catalysis in a new chemical space. The kinetically and thermodynamically accessible oxidation and spin states may enable new mechanistic pathways, unique substrate scope, or altogether new reactivity. This Account describes my group's efforts over the past decade to develop iron and cobalt catalysts for alkene hydrogenation. Particular emphasis is devoted to the interplay of the electronic structure of the base metal compounds and their catalytic performance. First generation, aryl-substituted pyridine(diimine) iron dinitrogen catalysts exhibited high turnover frequencies at low catalyst loadings and hydrogen pressures for the hydrogenation of unactivated terminal and disubstituted alkenes. Exploration of structure-reactivity relationships established smaller aryl substituents and more electron donating ligands resulted in improved performance. Second generation iron and cobalt catalysts where the imine donors were replaced by N-heterocyclic carbenes resulted in dramatically improved activity and enabled hydrogenation of more challenging unactivated, tri- and tetrasubstituted alkenes. Optimized cobalt catalysts have been discovered that are among the most active homogeneous hydrogenation catalysts known. Synthesis of enantiopure, C1 symmetric pyridine(diimine) cobalt complexes have enabled rare examples of highly enantioselective hydrogenation of a family of substituted styrene derivatives. Because improved hydrogenation performance was observed with more electron rich supporting ligands, phosphine cobalt(II) dialkyl complexes were synthesized and found to be active for the diastereoselective hydrogenation of various substituted alkenes. Notably, this class of catalysts was activated by hydroxyl functionality, representing a significant advance in the functional group tolerance of base metal hydrogenation catalysts. Through collaboration with Merck, enantioselective variants of these catalysts were discovered by high throughput experimentation. Catalysts for the hydrogenation of functionalized and essentially unfunctionalized alkenes have been discovered using this approach. Development of reliable, readily accessible cobalt precursors facilitated catalyst discovery and may, along with lessons learned from electronic structure studies, provide fundamental design principles for catalysis with earth abundant transition metals beyond alkene hydrogenation.

Mechanistic interpretation of selective catalytic hydrogenation and isomerization of alkenes and dienes by ligand deactivated Pd nanoparticles

“…Comparatively, the t -butyl group in 4 does not contribute to, but hinders di-σ-bond formation, preventing hydrogenation to take place. The effect of substitution pattern around nonaromatic sp 2 carbons was also studied using isomers of stilbene. Under the same reaction conditions, both trans -stilbene ( 8 ) and cis -stilbene ( 10 ) were hydrogenated to 1,2-diphenylethane ( 9 ) with 4% and 9% conversion, respectively.…”

“…1,2 Diene transformations represent an especially interesting problem due to the similar reactivity of both alkenes. 3,4 To overcome this problem, synthetic methods utilizing alkene masking and modification of the other alkene followed by demasking have been demonstrated.…”

“…Palladium based catalytic materials circumvent some of these challenges and have been adopted by many industries. 1,2 One of the most challenging problems associated with palladium, however, has been the poisoning and deactivation of these materials. 18–21 …”

Reactivity and Properties of Metal Complexes Enabled by Flexible and Redox-Active Ligands with a Ferrocene Backbone

“…[13][14][15][16][17][18][19][20][21] In addition, Chirik and coworkers exploited the potential of base metals in catalytic transformations by using flexible and redox non-innocent ligands to overcome the limitation of first row transition metals that usually undergo single electron processes (Chart 1d). [22][23][24][25] Besides traditional phosphine and nitrogen donors, an arene is suitable for metal-ligand cooperation as well: first, the coordination mode of the arene can vary from  6 to  2 according to the degree of delocalization. 26,27 Second, while the HOMO of an arene can act as a  or  donor, its LUMO has the appropriate symmetry and energy to engage in back-donation with electron-rich metals.…”

Highly Active and Selective Manganese C=O Bond Hydrogenation Catalysts: The Importance of the Multidentate Ligand, the Ancillary Ligands, and the Oxidation State

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The replacement of expensive noble metals by earthabundant transition metals is a central topic in catalysis. [2] The application of homogeneous hydrogenation catalysts is especially promising for the reduction of C = O bonds since a bifunctional mechanism involving the ligand can operate for efficient H 2 activation. Our catalyst has a broad substrate scope, it is able to hydrogenate aryl-alkyl, diaryl, dialkyl, and cycloalkyl ketones as well as aldehydes.

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