Daniel Lupp

The first example of cobalt-catalyzed selective hydrogenation of nitriles to secondary imines is reported. The results demonstrate the significantly different selectivity compared with the previously reported cobalt catalytic system during the nitrile hydrogenation. A variety of aromatic and aliphatic nitriles are hydrogenated to the corresponding secondary imines.

The mechanism of the molybdenum‐catalyzed deoxydehydration (DODH) of vicinal diols has been investigated using density functional theory. The proposed catalytic cycle involves condensation of the diol with an Mo^VI oxo complex, oxidative cleavage of the diol resulting in an Mo^IV complex, and extrusion of the alkene. We have compared the proposed pathway with several alternatives, and the results have been corroborated by comparison with the molybdenum‐catalyzed sulfoxide reduction recently published by Sanz et al. and with experimental observations for the DODH itself. Improved understanding of the mechanism should expedite future optimization of molybdenum‐catalyzed biomass transformations.

In this Perspective, we will focus on the use of both experimental and theoretical methods in the exploration of reaction mechanisms in homogeneous transition metal catalysis. We briefly introduce the use of Hammett studies and kinetic isotope effects (KIE). Both of these techniques can be complemented by computational chemistry – in particular in cases where interpretation of the experimental results is not straightforward. The good correspondence between experiment and theory is only possible due to recent advances within the applied theoretical framework. We therefore also highlight the innovations made in the last decades with emphasis on dispersion-corrected DFT and solvation models. The current state-of-the-art is highlighted using examples from the literature with particular focus on the synergy between experiment and theory.

The commercially available (NH₄)₆Mo₇O₂₄ and other molybdenum compounds are shown to be viable substitutes for the typically employed rhenium compounds in the catalytic deoxydehydration of aliphatic diols into the corresponding alkenes. The transformation, which represents a model system for the various hydroxyl groups found in biomass‐derived carbohydrates, can be conducted in an inert solvent (dodecane), under solvent‐free conditions, and in a solvent capable of dissolving biomass‐derived polyols (1,5‐pentanediol). The reaction is driven by the simultaneous oxidative deformylation of the diol resulting in an overall disproportionation of the substrate.

The development of a fully telescoped synthesis of a derivative of androstadiene C-17 esters made from epoxyparamethasone was demonstrated. This streamlining allowed for the elimination of isolation and solvent change after each synthetic step. Thus it not only drastically reduced the solvent waste, but also minimized the potential exposure to highly active intermediates thereby increasing the overall yield. The intuitively obvious advantage inherent to lowering the number of solvents was illustrated by applying standard green metrics.

A new technique for the ex situ generation of carbon monoxide (CO) and its efficient incorporation in palladium catalyzed carbonylation reactions was achieved using a simple sealed two-chamber system. The ex situ generation of CO was derived by a palladium catalyzed decarbonylation of tertiary acid chlorides using a catalyst originating from Pd(dba)₂ and P(tBu)₃. Preliminary studies using pivaloyl chloride as the CO-precursor provided an alternative approach for the aminocarbonylation of 2-pyridyl tosylate derivatives using only 1.5 equiv of CO. Further design of the acid chloride CO-precursor led to the development of a new solid, stable, and easy to handle source of CO for chemical transformations. The synthesis of this CO-precursor also provided an entry point for the late installment of an isotopically carbon-labeled acid chloride for the subsequent release of gaseous [¹³C]CO. In combination with studies aimed toward application of CO as the limiting reagent, this method provided highly efficient palladium catalyzed aminocarbonylations with CO-incorporations up to 96%. The ex situ generated CO and the two-chamber system were tested in the synthesis of several compounds of pharmaceutical interest and all of them were labeled as their [¹³C]carbonyl counterparts in good to excellent yields based on limiting CO. Finally, palladium catalyzed decarbonylation at room temperature also allowed for a successful double carbonylation. This new protocol provides a facile and clean source of gaseous CO, which is safely handled and stored. Furthermore, since the CO is generated ex situ, excellent functional group tolerance is secured in the carbonylation chamber. Finally, CO is only generated and released in minute amounts, hence, eliminating the need for specialized equipment such as CO-detectors and equipment for running high pressure reactions.

A protocol for the palladium(0)‐catalyzed amidation of heteroaromatic tosylates was successfully developed. The methodology proved to be effective for a variety of heteroaryl tosylates including the pyridine, pyrimidine, quinoline and quinoxaline ring systems. Successful carbonnitrogen bond formation with these heteroaryl tosylates could be performed with a wide range of primary amides, oxazolidinones, lactams, anilines and indoles, including one cyclic urea. Moreover, this CN bond forming reaction provided products with high structural diversity. The coupling reaction was also amenable to scale up applications.