Robby Vroemans

Nature Sustainability, Published online: 28 August 2023; doi:10.1038/s41893-023-01201-w

Abstract

Nitrogen radicals are one of the most useful reactive intermediates for selective transposition via intramolecular hydrogen atom transfer (HAT). The Hofmann-Löffler-Freytag (HLF) reaction is a distinctive radical-based approach in which nitrogen radicals are used for remote C−H bond functionalization via intramolecular HAT. Due to its excellent regioselectivity and atomic economy, the HLF reaction represents a new approach for the preparation of valuable functional molecules. In this review, we provide a brief overview of recent research advances in remote C−H bond functionalization via nitrogen radicals mediated HLF-type reactions involving intermolecular cyclization, intramolecular cyclization, and remote δ-site functionalization.

Nature, Published online: 25 August 2023; doi:10.1038/d41586-023-02646-x

Manganese(I) complexes bearing simple, non-bifunctional bis(NHC) ligands were investigated as hydrogenation catalysts. Applying these complexes with KHBEt₃ as additive, various carboxylic acid esters and, additionally, ketones, nitriles, N-heteroarenes and alkenes were successfully hydrogenated. Mechanistic investigations by control experiments and DFT calculations indicate an inner-sphere mechanism and reveal the role of BEt₃ as cocatalyst.

Abstract

The use of bis(NHC) manganese(I) complexes 3 as catalysts for the hydrogenation of esters was investigated. For that purpose, a series of complexes has been synthesized via an improved two step procedure utilizing bis(NHC)-BEt₃ adducts. By applying complexes 3 with KHBEt₃ as additive, various aromatic and aliphatic esters were hydrogenated successfully at mild temperatures and low catalyst loadings, highlighting the efficiency of the novel catalytic system. The versatility of the developed catalytic system was further demonstrated by the hydrogenation of other substrate classes like ketones, nitriles, N-heteroarenes and alkenes. Mechanistic experiments and DFT calculations indicate an inner sphere mechanism with the loss of one CO ligand and reveal the role of BEt₃ as cocatalyst.

Publication date: October 2023

Source: Molecular Catalysis, Volume 549

Author(s): Xiaoqing Gao, Shanhui Zhu, Hongyan Zheng, Feng Wang, Wanjun Li, Huifang Wang, Yulan Niu

The atroposelective formation of isoquinoline heterocycles by a P^III/P^V=O redox organocatalyzed Staudinger–aza-Wittig reaction is described. With N₂ release and aromatization as ideal driving forces, the method permits the synthesis of a broad range of atropisomeric isoquinolines under mild conditions with enantioselectivities of up to 98 : 2 e.r. and 93 % yield.

Abstract

Herein, we describe the feasibility of atroposelective P^III/P^V=O redox organocatalysis by the Staudinger–aza-Wittig reaction. The formation of isoquinoline heterocycles thereby enables the synthesis of a broad range of valuable atropisomers under mild conditions with enantioselectivities of up to 98 : 2 e.r. Readily prepared azido cinnamate substrates convert in high yield with stereocontrol by a chiral phosphine catalyst, which is regenerated using a silane reductant under Brønsted acid co-catalysis. The reaction provides access to diversified aryl isoquinolines, as well as benzoisoquinoline and naphthyridine atropisomers. The products are expeditiously transformed into N-oxides, naphthol and triaryl phosphine variants of prevalent catalysts and ligands. With dinitrogen release and aromatization as ideal driving forces, it is anticipated that atroposelective redox organocatalysis provides access to a multitude of aromatic heterocycles with precise control over their configuration.

Halogen-atom-transfer (XAT) processes have revolutionized the use of ubiquitous halide reagents in organic chemistry. This mini-review focuses on recent C−C bond forming reactions that have exploited α-aminoalkyl radicals as metal-free XAT procedures.

Abstract

The merging of photocatalysis with halogen-atom transfer (XAT) processes has proven to be a versatile tool for the generation of carbon-centered radicals in organic synthesis. XAT processes are unique in that they generate radicals without requiring the use of strong reductants necessary for the traditional single electron transfer (SET) activation of halides. Pathways to achieve XAT in synthetic applications can be categorized into three major sections: i) heteroatom-based activators, ii) metal-based activators, and iii) carbon-based activators among which α-aminoalkyl radicals have taken the center stage. Access to these α-aminoalkyl radicals as XAT reagents has gained significant attention in the past few years due to the robustness of the reactions, the simplicity of the reagents required, and the broadness of their applications. Generation of these α-aminoalkyl radicals is simply achieved through the single electron oxidation of tertiary amines, which after deprotonation at the α-position generates the α-aminoalkyl radicals. Due to the wide scope of tertiary amines available and the tunable nucleophilicity of α-aminoalkyl radical formed, this strategy has become an attractive alternative to heteroatom/metal-based radicals for XAT. In this minireview, we focus our attention on recent (2020–2023) developments and uses of this robust technology to mediate XAT processes.

Nature, Published online: 15 August 2023; doi:10.1038/d41586-023-02558-w

Publication date: 25 September 2023

Source: Tetrahedron, Volume 145

Author(s): Jeffrey I. Seeman

Mechanochemistry makes the next move in advancing organometallic synthesis. In their Research Article (e202305775), Riina Aav, Dzmitry G. Kananovich et al. report a mechanochemical adaptation of the Mg-mediated Barbier reaction, which overcomes the limitations of the classic solvent-based approach. Mechanochemical activation enables the rapid generation of Grignard reagents in situ, making the process resistant to air and allowing solid Brønsted acids to be used as additives to improve yields.

Julia-Kocienski olefination has been lately often used in the preparation of trisubstituted alkenes which serve as precursors of natural products and their analogs as well of pharmaceutically interesting/biologically important compounds. Significant observations regarding the stereoselectivity of those reactions are described in this reviewing work covering comprehensively the period 2016–2022.

Abstract

Julia-Kocienski olefination, a coupling reaction between a carbonyl component and a sulfone partner, has emerged as a powerful synthetic tool in the preparation of several organic compounds. A number of interesting examples involving particularly the preparation of trisubstituted alkenes along with important observations regarding the stereoselectivity of those reactions have been recently reported. This reviewing work covers the literature for the period 2016–2022 and describes in a comprehensive way the progress and developments of Julia-Kocienski olefination application in the synthesis of trisubstituted alkenes which serve as precursors of natural products and their analogs as well of pharmaceutically interesting/biologically important compounds. Moreover, key methodology results dealing with the investigation of the optimum conditions and stereoselectivities and new modifications and approaches are discussed.

Photocatalytic synthesis is at the center of this Special Collection which displays the recent developments of a fast-developing field. Herein, a diverse range of topics including catalyst development, mechanistic investigations, method development and the use of enabling technologies are showcased in the form of original research articles and emerging topics are surveyed in reviews and a concept article.

Abstract

This Special Collection is dedicated to the field of photocatalytic synthesis and contains a diverse selection of original research contributions. It includes studies on catalyst development, mechanistic investigations, method development and the use of enabling technologies, illustrating the many facets of state-of-the-art research in photocatalytic synthesis. Further, emerging topics are surveyed and discussed in three reviews and a concept article.

Pd-Catalyzed switchable access to imines and amines from secondary alcohols. Pd(OAc)₂ catalyzes the challenging synthesis of imines through acceptorless alcohol dehydrogenation using secondary alcohols and amines. Interestingly, when the catalytic reaction is performed in a closed system, in the presence of base, the reaction selectively yields the corresponding amine.

Abstract

The use of Pd(OAc)₂ as catalyst for the challenging synthesis of imines through acceptorless alcohol dehydrogenation using secondary alcohols and amines is reported. The reaction requires low catalyst loading, shows high selectivity for the formation of the imine without the need of adding any base or additive, and can be scaled up. Interestingly, when the catalytic reaction is performed in a closed system, in the presence of base, the reaction selectively yields the corresponding amine. To highlight the practical utility of the synthesis of imines, a family of structurally important scaffold, an indole, were synthesized.

Herein, an oxygen atom deletion strategy via sequential Pd-catalyzed decarboxylative carbonylation of carbonates and carbamates to afford esters and amides is reported. Operating under low pressures (near stoichiometric or substoichiometric), either ¹³C labeled products are accessed or a proof-of-concept that CO₂ formed upon decarboxylation can be reduced in situ and reincorporated as CO is shown.

Abstract

Herein, we report a methodology to access isotopically labeled esters and amides from carbonates and carbamates employing an oxygen deletion strategy. This methodology utilizes a decarboxylative carbonylation approach for isotope labeling with near stoichiometric, ex situ generated ¹²C, or ¹³C carbon monoxide. This reaction is characterized by its broad scope, functional group tolerance, and high yields, which is showcased with the synthesis of structurally complex molecules. A complementary method that operates by the catalytic in situ generation of CO via the reduction of CO₂ liberated during decarboxylation has also been developed as a proof-of-concept approach that CO₂-derived compounds can be converted to CO-containing frameworks. Mechanistic studies provide insight into the catalytic steps which highlight the impact of ligand choice to overcome challenges associated with low-pressure carbonylation methodologies, along with rational for the development of future methodologies.

In coordination chemistry, carbon and phosphorus elements play a preponderant role being at the origin of the development of a large variety of ligands including carbeniophosphines and phosphonium ylides located at both extremities of the donating ability scale.

Abstract

Carbeniophosphines [R₂C⁺−PR₂] and phosphonium ylides [R₃P⁺−CR₂ ⁻] are two complementary classes of carbon-phosphorus based ligands defined by their unique donor properties. Indeed, while carbeniophosphines are electron-poor P-ligands due to the positioning of a positive charge near the coordinating P-atom, phosphonium ylides are electron-rich C-ligands due to the presence of a negatively charged coordinating C-atom. Based on this knowledge, this account summarizes our recent contribution on these two classes of carbon-phosphorus ligands, and in particular the strategies developed to lower the donor character of carbeniophosphines and enhance that of phosphonium ylides. This led us to design, at both extremities of the donating scale, extremely electron-poor P-ligands exemplified by imidazoliophosphonites [R₂C⁺−P(OR)₂] and dicarbeniophosphines [(R₂C⁺)₂−PR], and extremely electron-rich C-ligands illustrated by pincer architectures exhibiting several phosphonium ylide donor extremities. In the context of carbon-phosphorus analogy, the closely related cases of ligands where the C-atom of a NHC ligand is in close proximity of two positive charges, and that of a phosphonium ylide coordinated through its P-atom are also discussed. An overview of the synthetic methods, coordinating properties, general reactivity and electronic structure of all these C,P-based species is presented here.

Publication date: 14 September 2023

Source: Chem, Volume 9, Issue 9

Author(s): Alan K. Wortman, Corey R.J. Stephenson

Nature Communications, Published online: 24 July 2023; doi:10.1038/s41467-023-40177-1

The Cover Feature illustrates the concept of cooperative catalysis between supported metal single atoms and nanoparticles, which could be operative in various conventional catalysts and is discussed by P. Serp in his Review. Different types of synergies can (co)exist, involving or not a communication between these two species, which are presented and discussed relative to their involvement in thermal-, electro- and photo-catalysis. More information can be found in the Review by P. Serp.

Nature Communications, Published online: 24 July 2023; doi:10.1038/s41467-023-40164-6