Computational Studies on the Mechanisms for Deaminative Amide Hydrogenation by Homogeneous Bifunctional Catalysts

Abstract

The deaminative hydrogenation of amides is one of the most convenient pathways for the synthesis of amines and alcohols. The ideal source of reducing equivalents for this reaction is molecular hydrogen, though, in practice, this approach requires high pressures and temperatures, with many catalysts achieving only small turnover numbers and frequencies. Nonetheless, during the last ten years, this field has made major advances towards larger turnovers under milder conditions thanks to the development of bifunctional catalysts. These systems promote the heterolytic cleavage of hydrogen into proton and hydride by combining a basic ligand with an acidic metal centre. The present review focuses on the computational study of the reaction mechanism underlying bifunctional catalysis. This review is structured around the fundamental steps of this mechanism, namely the C=O and C–N hydrogenation of the amide, the C–N protonolysis of the hemiaminal, the C=O hydrogenation of the aldehyde, and the competition between hydrogen activation and catalyst deactivation. In line with the complexity of the mechanism, we also provide a perspective on the use of microkinetic models. Both Noyori- and Milstein-type catalysts are discussed and compared.

Enhanced Enzymatic Synthesis of Puerarin Palmitate with Different Acyl Donors for Lipid Solubility Improvement

“…These carboxylic acid derivatives act as acyl donors, providing an acyl group through nucleophilic acyl substitution reactions. The reactivity of nucleophilic acyl substitution reactions depends on the acyl group, with the reactivity order as follows: acid halide > acid anhydride > ester ≈ carboxylic acid > amide [10,43]. In this investigation, various compounds, including carboxylic acid, ester, and acid anhydride, were utilized as sources of acyl groups, with acid anhydride exhibiting the highest level of reactivity.…”

From Data to Chemistry: Revealing Causality and Reaction Coordinates through Interpretable Machine Learning in Supramolecular Transition Metal Catalysis

“…7,8 Complimentary to experimental advances, computational chemistry has played a key role in the design and understanding of catalytic systems, by elucidating reaction mechanisms. [9][10][11][12] Despite considerable efforts, quantum chemistry is limited in its predictive abilities. 13 As these systems grow in complexity, there is a need to improve not only on the underlying electronic structure theory used to study them, but also the chemical model that describes the catalytic system in its environment.…”

Reactivity of Heterobimetallic Ion Pairs in Formic Acid Dehydrogenation

“…Bifunctional catalysts bearing the basic and acidic sites on the same molecule or on different ones demonstrate good efficiencies in a great variety of catalytic processes. , Braunstein and Mankad have developed cooperative bimetallic systems featuring polar metal–metal bonds or frustrated transition-metal Lewis acid/base pairs that catalyze versatile transformations from C–C and C–B coupling reactions to hydrogenation. , Related bimetallic complexes (η 5 -C 5 R 5 )­Ru­(CO)­(μ-dppm)­M­(CO) 2 (η 5 -C 5 H 5 ) (R = H, CH 3 ; M = Mo, W) with the metal–metal bond reported by Lau’s group showed catalytic activities in the formic acid dehydrogenation. , However, they are not very efficient, even under harsh conditions (10 mol % catalyst, THF, 80 °C), due to the formation of a stable cationic complex featuring a bridging hydride (Ru–(μ-H)–Mo). An unusual concept of bifunctional formic acid dehydrogenation catalyst has been described recently by Esteruelas’ group.…”