RESUMEN

While the oxidation of phenols and BINOLs is well documented to lead to a broad range of useful organic scaffolds, that of NOBINs is far less explored. We investigate herein their oxidation with a number of standard chemical oxidants, leading upon skeletal rearrangement to the corresponding α-spiropyrrolidones, which represent a rare and highly valuable heterocyclic core.

RESUMEN

A visible-light-induced photocatalytic deoxygenative benzylation of quinoxalin-2-(1H)-ones is herein described. This novel approach provides a mild, simple, and practical route to 3-benzylquinoxalin-2(1H)-ones from ubiquitous and safe carboxylic acid anhydrides. A wide range of substrates with different substituents were well-tolerated and efficiently transformed to various functionalized 3-benzylquinoxalin-2(1H)-ones with great potential for valuable applications in drug discovery. Mechanistic investigations suggest H2O as a proton source, while hydroxyl-containing quinoxalin-2(1H)-ones may be key intermediates of the photocatalytic deoxygenative process.

RESUMEN

The oxidative formation of N-N bonds from primary amides has been recently reported and then retracted in the journal Nature Communications by Kathiravan, Nicholls, and coauthors, utilizing a hypervalent iodane reagent. Unfortunately, the authors failed to recognize the Curtius reaction taking place under the described reaction conditions. Thus, the claimed N-N coupling products were not formed. Instead, the Curtius rearrangement urea coupling products were obtained. We demonstrate this herein by means of NMR and x-ray analysis, as well as with the support of an alternative synthetic route.

RESUMEN

Redox active phenotellurazine catalysts have been recently utilized in two different cross-dehydrogenative coupling reactions. In this study, we revisit the design of the phenotellurazine redox catalysts. In particular, we investigate the level of cooperativity between the Te- and N-centers, the effect of secondary versus tertiary N-centers, the effect of heterocyclic versus non-heterocyclic structures, and the effect of substitution patterns on the redox catalytic activity.

RESUMEN

The synthetic control of atropoisomerism along C-N bonds is a major challenge, and methods that allow C-N atroposelective bond formation are rare. This is a problem because each atropoisomer can feature starkly differentiated biological properties. Yet, among the three most practical and applicable classical amination methods available: 1) the Cu-catalyzed Ullmann-Goldberg reaction, 2) the Pd-catalyzed Buchwald-Hartwig reaction, and 3) the Cu-catalyzed Chan-Evans-Lam reaction, none has truly been rendered atroposelective at the newly formed C-N bond. The first ever Chan-Evans-Lam atroposelective amination is herein described with a simple copper catalyst and newly designed PyrOx chiral ligand. This method should find important applications in asymmetric synthesis, in particular for medicinal chemistry.

RESUMEN

Invited for the cover of this issue is the group of Frederic W. Patureau at the RWTH Aachen University. The image depicts atropoisomerism, in particular through the helix-shaped vines in the forefront focus. This metaphorically illustrates the importance of atroposelectivity in biologically active molecules, such as in the 5-hydroxyindoles that were accessed through the first enantioselective Nenitzescu indole synthesis. Read the full text of the article at 10.1002/chem.202300279.

RESUMEN

A practical NaI/PPh3-catalyzed decarboxylative radical cascade cyclization of N-arylacrylamides with redox-active esters is described, which is mediated by visible light irradiation. A wide range of substrates bearing different substituents and derived from ubiquitous carboxylic acids, including α-amino acids, were synthesized and examined under this very mild, efficient, and cost effective transition-metal-free synthetic method. These afforded various functionalized oxindoles featuring a C3 quaternary stereogenic center. Mechanistic experiments suggest a radical mechanism.

RESUMEN

In the past decade, compounds bearing a stereogenic C-N axis have gained significant attention in fields ranging from ligand to drug design. Yet, the atroposelective synthesis of these molecules remains a considerable challenge. In contrast to recent methods using more advanced chiral catalysts, a very simply accessed Jacobsen-type chromium(III)-salen complex was used here as a chiral enantiopure Lewis acid catalyst for a highly atroposelective Nenitzescu indole synthesis. Mild reaction conditions afforded various 5-hydroxybenzo[g]indoles in up to 97 % yield. Moreover, through a simple work-up, very high enantiomeric excesses of up to 99 % could be obtained.

RESUMEN

The Pd-catalyzed highly selective synthesis of mono- and di-2-fluoroallylic amines from gem-difluorocyclopropanes and ubiquitous unprotected primary anilines is herein described. Initial kinetic investigations suggest a first order in the gem-difluorocyclopropane substrate, as well as a circa zeroth order in the aniline coupling partner. The newly produced fluoroallylic motifs should find important applications in synthetic as well as medicinal chemistry and stimulate the further development of coupling methods based on strained cyclic building blocks.

Asunto(s)

RESUMEN

The unprecedented photochemical late-stage defluorinative gem-difluoroallylation of aryl sulfonium salts, which are formed site-selectively by direct C(sp2)─H functionalization, is herein disclosed. This method is distinguished by its mild reaction conditions, wide scope, and excellent site-selectivity. As showcase examples, a Flurbiprofen and Pyriproxyfen derivatives could be late stage C(sp2)─H gem-difluoroallylated with high yields. Experimental and computational investigations were conducted.

RESUMEN

Phenochalcogenazines such as phenoxazines and phenothiazines have been widely employed as photoredox catalysts (PCs) in small molecule and polymer synthesis. However, the effect of the chalcogenide in these catalysts has not been fully investigated. In this work, a series of four phenochalcogenazines is synthesized to understand how the chalcogenide impacts catalyst properties and performance. Increasing the size of the chalcogenide is found to distort the PC structure, ultimately impacting the properties of each PC. For example, larger chalcogenides destabilize the PC radical cation, possibly resulting in catalyst degradation. In addition, PCs with larger chalcogenides experience increased reorganization during electron transfer, leading to slower electron transfer. Ultimately, catalyst performance is evaluated in organocatalyzed atom transfer radical polymerization and a photooxidation reaction for C(sp2)-N coupling. Results from these experiments highlight that a balance of PC properties is most beneficial for catalysis, including a long-lived excited state, a stable radical cation, and a low reorganization energy.

RESUMEN

A facile and environmentally friendly electrochemical protocol is herein reported for the C(sp2 )-C(sp3 ) cross dehydrogenative coupling between imidazopyridines and N,N-dimethylanilines. The broad functional group compatibility includes halogens, ester, alcohol, sulfone as well as thiophene. This methodology is also suitable for benzo[d]imidazo[2,1-b]thiazole, thiazoimidazole and tetrahydroisoquinoline, and can be scaled up to 5 mmol. Mechanistic insights are discussed.

Asunto(s)

RESUMEN

Very few elements in the periodic system can catalytically activate O2, such as in the context of cross-dehydrogenative couplings. The development of O2-activating catalysts is essential to enable new and sustainable reactivity concepts to emerge, because these catalysts also often feature specific activating interactions with the target substrates. In this context, the unprecedented Te(II)/Te(III) catalyzed dehydrogenative C3-C2 dimerization of indoles is described herein. The fact that O2 can be directly utilized as a terminal oxidant in this reaction, as well as the absence of any background reactivity without the redox-active Te catalyst, constitute very important milestones for the fields of cross-dehydrogenative couplings and tellurium catalysis.

RESUMEN

Phenoxazines, in particular N-arylated phenoxazines, represent an increasingly important scaffold in the material sciences. Moreover, the oxygen-gas-mediated dehydrogenative phenochalcogenazination concept of phenols has been developed and exemplified for X = sulfur and recently for X = selenium and tellurium. The smallest chalcogen, X = oxygen, is herein exemplified with various functional groups under a likewise trivial oxygen atmosphere.

Asunto(s)

RESUMEN

The late stage photochemical hydroxylation of biaryl sulfonium salts was enabled with a TEMPO derivative as a simple oxygen source, in metal free conditions. The scope and mechanism of this exceptionally simple synthetic method, which constructs important arylated phenols from aromatic C-H bonds, are herein discussed.

RESUMEN

The first non-directed dehydrogenative phenone coupling method of methylarenes with aromatic C-H bonds, displaying a large substrate scope, is herein reported. This reaction represents a far more direct atom- and step-efficient alternative to the classical Friedel-Crafts or Suzuki-Miyaura derived acylation reactions. The method can be carried out on a gram scale and was successfully applied to the synthesis of several Ketoprofen drug analogues.

Asunto(s)

RESUMEN

Oxidative clicklike reactions are useful for the late-stage functionalization of pharmaceuticals and organic materials. Hence, novel methodologies that enable such transformations are in high demand. Herein we describe a tellurium(II)-catalyzed cross-dehydrogenative phenothiazination (CDP) of aromatic amines. A key feature of this method is a cooperative effect between the phenotellurazine catalyst and the silver salt, which serves as a chemical oxidant for the reaction. This novel catalysis concept therefore enables a considerably broader scope compared with previous chemical oxidation methods.

RESUMEN

The triphenylphosphine-catalyzed dearomative [3 + 2] cycloaddition of benzoxazoles with 1,2-diphenylcyclopropenone is herein described. The reaction scope, mechanism, and possible future applications of this rare organocatalyzed cycloaddition are herein discussed.

RESUMEN

The relatively high electronegativity of nitrogen makes N-N bond forming cross-coupling reactions particularly difficult, especially in an intermolecular fashion. The challenge increases even further when considering the case of dehydrogenative N-N coupling reactions, which are advantageous in terms of step and atom economy, but introduce the problem of the oxidant in order to become thermodynamically feasible. Indeed, the oxidizing system must be designed to activate the target N-H bonds, while at the same time avoid undesired N-N homocoupling as well as C-N and C-C coupled side products. Thus, preciously few intermolecular hetero N-N cross-dehydrogenative couplings exist, in spite of the central importance of N-N bonds in organic chemistry. This review aims at analyzing these few rare cases and provides a perspective for future developments.

RESUMEN

A mild, facile, and environmentally friendly electrochemical protocol for the C(sp3)-H/O-H cross dehydrogenative coupling between various alcohols and tetrahydrofuran with H2 evolution is herein reported. This synthetic strategy does not require external oxidants nor catalysts. The broad functional group compatibility includes hydroxyl, halogens, olefins as well as an alkyne. Initial mechanistic investigations were conducted. The method provides a green and efficient hydroxyl group protection.