Jonas Wuyts

Nature, Published online: 05 December 2022; doi:10.1038/d41586-022-04364-2

Dual catalysis is one of the most powerful strategies for the development of chemical reactions in organic synthesis. This Perspective aims to introduce the different categories of dual catalytic systems and demonstrate their benefits in constructing new chemical bonds and enhanced stereoselectivity.

Abstract

Dual catalysis is one of the most powerful strategies for the development of chemical reactions in organic synthesis. This strategy can be divided into cooperative catalysis, relay catalysis, and sequential catalysis according to the actual mode of operation and the communication between the catalysts. In recent years, such strategy has been applied in a large number of studies since it has the advantages of: 1) increasing reactivity and enabling challenging transformations; 2) offering a powerful way of controlling the stereoselectivity of asymmetric reactions, which is challenging for traditional catalytic systems; 3) catalyze the stereodivergent synthesis of molecules bearing one or more stereocenters from the same starting materials. This Perspective, which intends to introduce the reader to EurJOC special collection on Dual Catalysis , aims to summarize and introduce the different categories of dual catalysis and demonstrate their benefits in constructing new chemical bonds in a selective manner. Finally, current challenges and new trends in dual catalysis will be also presented.

Thioester represents a distinctive synthetic intermediate, engaged in biosynthesis as well as chemical synthesis. In this Review, the recent progress of advanced methods towards the synthesis of thioesters have concisely been portrayed, relying on strategic metal-catalyzed/mediated carbonylative thiolation of unsaturated hydrocarbons, organohalides/phenol derivatives, among others, and radical-based C−H thiolation of aldehydes.

Abstract

Thioester constitutes a fundamentally unique intermediate, engaged in various biosynthesis processes in living systems as well as a versatile synthon in modern organic synthesis. Transition metal catalysis and radical reaction manifolds have enabled to enrich the repertoire of synthetic methods for thioesters. In this review, we have accommodated the recent reports on modern strategies towards thioester synthesis from a plethora of readily available feedstocks, such as alkenes, alkynes, alcohols, phenols or commodity chemicals/synthetic building blocks like organic aldehydes, halides or organoboron reagents under various catalysis domains. Furthermore, the momentous advancements of employing progenitors of odorous thiols as well as CO-surrogates have contextually been emphasized, alongside the utilization of native free thiols and CO gas.

Synlett
DOI: 10.1055/a-1934-1056

Herein, we report a nickel-catalyzed sustainable, environment­-friendly, and economically affordable borrowing hydrogen approach (BHA) for synthesizing various α-alkylated ketones via dehydro­genative coupling of primary and secondary alcohols. Using a well-­defined, air-stable, inexpensive, and easy-to-prepare four-coordinate macrocyclic Ni(II)-catalyst [Ni(MeTAA)] of a tetra-aza macrocyclic ligand (tetramethyltetraaza[14]annulene (H2MeTAA)), a series of α-alkylated ketones were prepared in good yields. A few control reactions, including deuterium-labelling experiments, were performed to unveil the reaction mechanism.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Hg^II interacting with a naturally Zn^II-containing Rad50 protein interface yields HgS₄ species, the strongest metal–protein interaction known to date. It also introduces the novel manifestation of Hg^II mechanism of prokaryotic and eukaryotic cells. Furthermore, the substitution of naturally occurring Zn^II possibly has an impact on the quaternary structure and the protein assembly process, thus disrupting the DNA-repair mechanisms that engage the Mre11–Rad50 complex. More information can be found in the Research Article by A. Krężel and co-workers. (DOI: 10.1002/chem.202202738).

Nature, Published online: 10 November 2022; doi:10.1038/d41586-022-03668-7

Isolated metal centers in single-atom catalysts (SACs) hold significant potential to attain high substrate specificities and reaction selectivities. This makes them an excellent platform in tandem catalysis. This Concept article showcases the foundation of this emerging research area and discusses opportunities but also challenges for the development as well as the verification of innovative tandem catalysis processes based on solid SACs.

Abstract

Tandem catalysis stands out as a major instrument towards the intensification of existing and future chemical processes. Initially formulated in the field of homogeneous catalysis, the concept relies on the single-pot integration of two (or more) catalysts showing high specificity for mechanistically decoupled reactions, while being operational and compatible under a single set of operation conditions. Isolated metal atoms stabilized on solid carriers in single-atom catalysts (SACs) hold the potential to reconcile the high reaction specificities of mononuclear sites in molecular catalysts with an intrinsic catalyst compartmentalization on inorganic matrices. Understandably, SACs have started to be considered as platforms in tandem catalysis. Tandem (electro)catalytic processes based on SACs have been showcased recently. While this sets excellent prospects for the expansion of this research subarea, challenges are faced, particularly as to the verification of the tandem nature of the processes.

An autonomous continuous flow platform for the rapid development of multistep synthetic pathways is reported. New multipoint sampling and Bayesian optimization techniques were combined, enabling simultaneous identification of optimum reaction conditions within a pharmaceutical process. The short optimization times achieved are promising for development of telescoped reactions in the future.

Abstract

The optimization of multistep chemical syntheses is critical for the rapid development of new pharmaceuticals. However, concatenating individually optimized reactions can lead to inefficient multistep syntheses, owing to chemical interdependencies between the steps. Herein, we develop an automated continuous flow platform for the simultaneous optimization of telescoped reactions. Our approach is applied to a Heck cyclization-deprotection reaction sequence, used in the synthesis of a precursor for 1-methyltetrahydroisoquinoline C5 functionalization. A simple method for multipoint sampling with a single online HPLC instrument was designed, enabling accurate quantification of each reaction, and an in-depth understanding of the reaction pathways. Notably, integration of Bayesian optimization techniques identified an 81 % overall yield in just 14 h, and revealed a favorable competing pathway for formation of the desired product.

An efficient and convenient rhodium-catalyzed formylation of alkyl chlorides to synthesize aldehydes has been developed. Depending on the conditions both linear and branched aldehydes can be obtained in a selective manner from readily available substrates.

Abstract

The first rhodium-catalyzed formylation of non-activated alkyl chlorides with syn gas (H₂/CO) allows to produce aldehydes in high yields (25 examples). A catalyst optimization study revealed Rh(acac)(CO)₂ in the presence of 1,3-bisdiphenylphosphinopropane (DPPP) as the most active catalyst system for this transformation. Key for the success of the reaction is the addition of sodium iodide (NaI) to the reaction system, which leads to the formation of activated alkyl iodides as intermediates. Depending on the reaction conditions, either the linear or branched aldehydes can be preferentially obtained, which is explained by a different mechanism.

Nature, Published online: 03 November 2022; doi:10.1038/d41586-022-03534-6

Synthesis
DOI: 10.1055/a-1950-5110

A decarboxylative Claisen condensation involving substituted malonic acid half oxyesters (SMAHOs) as pronucleophiles has been developed. The addition of their magnesium enolates to various acyl donors allows the synthesis of functionalized α-substituted β-keto esters in moderate to excellent yields (13–96%). In addition to acyl chlorides and acid anhydrides, these conditions proved efficient for the use of carboxylic acids as acylating agents, thus allowing to greatly extend the scope of this transformation (32 examples overall).
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Synthesis
DOI: 10.1055/s-0042-1753053

The dehydrogenation of saturated substrates is fundamentally essential for producing value-added unsaturated organic molecules both in academia and industry. In recent years, homogeneously catalyzed acceptorless C–C, C–N, and C–O bond desaturations have attracted increasing attention due to high atom economy, environmentally benign nature, and wide availability of the starting materials. This short review discusses the acceptorless dehydrogenation of aliphatics, alcohols, and amines by homogeneous catalytic systems based on two categories of reaction mechanisms: thermal transition-metal-catalyzed two-electron pathway and photoredox catalyzed or electrochemically driven one-electron pathway.1 Introduction2 Catalytic Acceptorless Dehydrogenation of Aliphatics3 Catalytic Acceptorless Dehydrogenation of Amines4 Catalytic Acceptorless Dehydrogenation of Alcohols5 Conclusion
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Nature, Published online: 02 November 2022; doi:10.1038/d41586-022-01886-7

Frustrated Lewis H⁺−H⁻ pairs, generated in situ by hydrogen spillover on partially oxidized MAX phases, act as the hydrogenation sites for C=O hydrogenation and provide acid sites for ring opening. The close intimate hydrogenation and acid sites demonstrate unprecedented bifunctional catalytic performance for the conversion of furfurals.

Abstract

Currently, less favorable C=O hydrogenation and weak concerted acid catalysis cause unsatisfactory catalytic performance in the upgrading of biomass-derived furfurals (i.e., furfural, 5-methyl furfural, and 5-hydroxymethyl furfural) to ketones (i.e., cyclopentanone, 2,5-hexanedione, and 1-hydroxyl-2,5-hexanedione). A series of partially oxidized MAX phase (i.e., Ti₃AlC₂, Ti₂AlC, Ti₃SiC₂) supporting Pd catalysts were fabricated, which showed high catalytic activity; Pd/Ti₃AlC₂ in particular displayed high performance for conversion of furfurals into targeted ketones. Detailed studies of the catalytic mechanism confirm that in situ hydrogen spillover generates Frustrated Lewis H⁺−H⁻ pairs, which not only act as the hydrogenation sites for selective C=O hydrogenation but also provide acid sites for ring opening. The close intimate hydrogenation and acid sites promote bifunctional catalytic reactions, substantially reducing the reported minimum reaction temperature of various furfurals by at least 30–60 °C.