ceverelst

An amine–carboxylic acid C−C coupling would be a valuable addition to the synthetic toolbox of carbon–carbon bond-forming reactions. Using miniaturized high-throughput experimentation, we have developed the first amine–acid cross-coupling to form C(sp³)−C(sp³) bonds based on preactivation of the building blocks and nickel catalysis.

Abstract

We have developed a deaminative–decarboxylative protocol to form new carbon(sp³)–carbon(sp³) bonds from activated amines and carboxylic acids. Amines and carboxylic acids are ubiquitous building blocks, available in broad chemical diversity and at lower cost than typical C−C coupling partners. To leverage amines and acids for C−C coupling, we developed a reductive nickel-catalyzed cross-coupling utilizing building block activation as pyridinium salts and redox-active esters, respectively. Miniaturized high-throughput experimentation studies were critical to our reaction optimization, with subtle experimental changes such as order of reagent addition, composition of a binary solvent system, and ligand identity having a significant impact on reaction performance. The developed protocol is used in the late-stage diversification of pharmaceuticals while more than one thousand systematically captured and machine-readable reaction datapoints are reposited.

Nature, Published online: 21 October 2021; doi:10.1038/d41586-021-02867-y

Nature, Published online: 01 October 2021; doi:10.1038/d41586-021-02575-7

Suitable heterogeneous sulfonic acid derivatives ensure the smooth dearomatization of phenols and bare naphthalenes under mild conditions. The method uses hydrogen peroxide which is a clean oxidant, offering a convenient metal-free tool to access families of quinones derivatives in good yields and with low catalyst loadings.

Abstract

We report herein a method for the oxidative dearomatization of phenols and bare polycyclic arenes into the corresponding quinoid derivatives using hydrogen peroxide. The reaction is catalyzed by sulfonic acids and best results were achieved using heterogenized species. The best results using phenols were achieved using a hybrid material, namely a perfluorinated polymer functionalized with sulfonic acid groups supported on silica. The dearomatization of polycyclic aromatic hydrocarbons performed better using the polymeric acid catalyst. These methods operate under mild conditions, using mild and benign oxidants and thus minimizing the formation of waste.

Aryl sulfonyl fluorides, typically inert to transition metal catalysis, undergo a Pd-catalyzed desulfonative Suzuki–Miyaura coupling. The reaction can occur without added base and turns the −SO₂F group into a divergent handle for C−C or S−Nu coupling.

Abstract

Sulfonyl fluorides have emerged as powerful “click” electrophiles to access sulfonylated derivatives. Yet, they are relatively inert towards C−C bond forming transformations, notably under transition-metal catalysis. Here, we describe conditions under which aryl sulfonyl fluorides act as electrophiles for the Pd-catalyzed Suzuki–Miyaura cross-coupling. This desulfonative cross-coupling occurs selectively in the absence of base and, unusually, even in the presence of strong acids. Divergent one-step syntheses of two analogues of bioactive compounds showcase the expanded reactivity of sulfonyl fluorides to encompass both S−Nu and C−C bond formation. Mechanistic experiments and DFT calculations suggest oxidative addition occurs at the C−S bond followed by desulfonation to form a Pd-F intermediate that facilitates transmetalation.

Abstract

Lignin valorization allows the generation of a number of value-added products such as cis,cis-muconic acid (ccMA), which is widely used for the synthesis of chemicals for the production of biodegradable plastic materials. In the present work, we reported the first multi-enzymatic, one-pot bioconversion process of vanillin into ccMA. In details, we used four sequential reactions catalyzed by xanthine oxidase, O-demethylase LigM (and the tetrahydrofolate-regeneration enzyme methyl transferase MetE), decarboxylase AroY (based on the use of E. coli transformed cells) and catechol 1,2-dioxygenase CatA. The optimized lab-scale procedure allowed to reach, for the first time, the conversion of 5 mM vanillin into ccMA in ∼30 h with a 90% yield: this achievement represents an improvement in terms of yields and time when compared to the use of a whole-cell system. This multi-enzymatic system represents a sustainable alternative for the production of a high value added product from a renewable resource.