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This paper shows a novel oxidative functionalization of α-amino ketones to yield the corresponding α-ketoamides and α-acylimidates. The reaction proceeds via oxygen delivery from water/alcohols in conjunction with an electron acceptor and 4-dimethylaminopyridine (DMAP). Mechanistic study indicates that DMAP exhibits a dual function of nucleophilic catalysis and proton abstraction. [ABSTRACT FROM AUTHOR]

C–N bonds play a critical role in pharmaceutical, agrochemical, and materials sciences, necessitating ever-better methods to forge this linkage. Here we report a simple procedure for direct C(sp3)–H azidation using iron or manganese catalysis and a nucleophilic azide source. All reagents are commercially available, the experimental procedure is simple, and we can use the C–H donor substrate as the limiting reagent, a challenge for many C–H azidation methods. Preliminary experiments are consistent with a hydrogen atom transfer (HAT)/radical ligand transfer (RLT) radical cascade mechanism and a wide variety of substrates can be azidated in moderate to high yields. [ABSTRACT FROM AUTHOR]

Catalysis by trivalent nucleophilic organophosphines has emerged as an essential tool in organic synthesis. Several new organic transformations promoted by phosphines substantiate and complement the existing synthetic chemistry tools. Mere design of the substrate and reagent combinations has introduced new modes of reactivity patterns, which are otherwise difficult to achieve. These design considerations have led to the rapid build-up of complex molecular entities and laid a solid foundation to synthesise bioactive natural products and pharmaceuticals. This article presents an overview of some of the conceptual advances, including our contributions to nucleophilic organophosphine chemistry. The scope, limitations, mechanistic insights, and applications of these metal-free transformations are discussed elaborately. [ABSTRACT FROM AUTHOR]

Asymmetric catalysis holds a prominent position among the important developments in chemistry during the 20th century. This was acknowledged by the 2001 Nobel Prize in chemistry awarded to Knowles, Noyori, and Sharpless for their development of chiral metal catalysts for organic transformations. The key feature of the catalysts was the crucial role of the chiral ligand and the nature of the metal ions, which promoted the catalytic conversions of the substrates via direct coordination. Subsequently the development of asymmetric organic catalysis opened new avenues to the synthesis of enantiopure compounds, avoiding any use of metal ions. Recently, an alternative approach to asymmetric catalysis emerged that relied on the catalytic functions of the ligands themselves boosted by coordination to metal ions. In other words, in these hybrid chiral catalysts the substrates are activated not by the metal ions but by the ligands. The activation and enantioselective control occurred via well-orchestrated and custom-tailored non-covalent interactions of the substrates with the ligand sphere of chiral metal complexes. In these metal-templated catalysts, the metal served either as a template (a purely structural role), or it constituted the exclusive source of chirality (metal-centred chirality due to the spatial arrangement of achiral or chiral bi-/tridentate ligands around an octahedral metal centre), and/or it increased the Brønsted acidity of the ligands. Although the field is still in its infancy, it represents an inspiring combination of both metal and organic catalysis and holds major unexplored potential to push the frontiers of asymmetric catalysis. Here we present an overview of this emerging field discussing the principles, applications and perspectives on the catalytic use of chiral metal complexes that operate as "organocatalysts in disguise". It has been demonstrated that these chiral metal complexes are efficient and provide high stereoselective control in asymmetric hydrogen bonding catalysis, phase-transfer catalysis, Brønsted acid/base catalysis, enamine catalysis, nucleophilic catalysis, and photocatalysis as well as bifunctional catalysis. Also, many of the catalysts have been identified as highly effective catalysts at remarkably low catalyst loadings. These hybrid systems offer many opportunities in the synthesis of chiral compounds and represent promising alternatives to metal-based and organocatalytic asymmetric transformations. [ABSTRACT FROM AUTHOR]

Nucleophilic phosphine catalysis is a practical and powerful tool for the synthesis of various heterocyclic compounds with the advantages of environmentally friendly, metal-free, and mild reaction conditions. The present report summarizes the construction of four to eight-membered heterocyclic compounds containing nitrogen, oxygen and sulphur atoms through phosphine-catalyzed intramolecular annulations and intermolecular [2+2], [3+2], [4+1], [3+1+1], [5+1], [4+2], [2+2+2], [3+3], [4+3] and [3+2+3] annulations of electron-deficient alkenes, allenes, alkynes and Morita–Baylis–Hillman carbonates. [ABSTRACT FROM AUTHOR]

The hydrolysis reaction of methyltrimethoxysilane MeSi(OMe)3 under neutral conditions and the catalytic role of the fluoride ion in this reaction have been re-examined using DFT theoretical methods in methanol solution. Contrary to the common opinion, formation of pentacoordinate silicon fluoride, either free or complexed with a water molecule, proceeds with a free energy barrier. A hypercoordinate silicon intermediate is in equilibrium with the ion–dipole complex with fluoride, which is usually lower in energy than the pentacoordinate species. A comparison of the hydrolysis pathways of uncomplexed silanes, MeSi(OMe)3−n(OH)n, n = 0–3, and the corresponding ion–dipole complexes with fluoride and pentacoordinate silicon fluorides showed that both complexes hydrolyze more easily than the uncomplexed silanes. The pathway involving ion–dipole complexes is kinetically preferred. The catalytic effect of fluorine in the hydrolysis of these complexes is of a basic nature, i.e., fluoride acts as a base, withdrawing a proton from the attacking water, thus increasing its nucleophilicity. However, since both intermediates are in equilibrium, nucleophilic catalysis may become significant under specific conditions, when the concentration of the pentacoordinate silicon–fluoride complex is higher. [ABSTRACT FROM AUTHOR]

Proteomic profiling using bioorthogonal chemical probes that selectively react with certain amino acids is now a widely used method in life sciences to investigate enzymatic activities, study posttranslational modifications and discover novel covalent inhibitors. Over the past two decades, researchers have developed selective probes for several different amino acids, including lysine, serine, cysteine, threonine, tyrosine, aspartate and glutamate. Among these amino acids, cysteines are particularly interesting due to their highly diverse and complex biochemical role in our cells. In this feature article, we focus on the chemical probes and methods used to study cysteines in complex proteomes. [ABSTRACT FROM AUTHOR]

After seminal Tsuji–Trost reactions (palladium catalyzed allylation of nucleophiles viaπ-allyl intermediates as electrophiles), the idea of reversal reactivity of π-allyl intermediates (i.e.π-allyl as nucleophiles) has been stated since the eighties. Thanks to different transition metal sources and the modification of their electronic environment through the use of additives and ligands, such ‘reactivity switch’ of π-allyl intermediates proved its powerfulness allowing high control in regio-, diastereo- and enantio-selectivities. These methodologies have thus emerged as efficient methods in the catalytic enantioselective allylation of carbonyl compounds and imines with a deep impact on natural product and/or drug elaboration. This tutorial review highlights the concept of ‘umpoled’ reactivity of π-allyl intermediates, relying on selected recent examples. [ABSTRACT FROM AUTHOR]

A practical and environmentally attractive methodology for the direct diversification of N-heterocycles at ambient temperature under open-air conditions was developed. The obvious advantage of the process is that no toxic reagent, transition metal, base or other additive is employed, thus greatly reducing costs, facilitating post-reaction neutralization and purification and minimizing the environmental impact. [ABSTRACT FROM AUTHOR]

A visible light driven catalytic cycle for hydrocarboxylation of alkenes with CO2 was established using a combination of a Rh(i) complex as a carboxylation catalyst and [Ru(bpy)3]2+ (bpy = 2,2′- bipyridyl) as a photoredox catalyst. Two key steps, the generation of Rh(i) hydride species and nucleophilic addition of π-benzyl Rh(i) species to CO2, were found to be mediated by light. [ABSTRACT FROM AUTHOR]

This work introduces a luminescent dinuclear Au(i) complex with a cyclic PNNP ligand ((AuCl)2L) as a “host” molecule with two binding sites, “upper” and “lower”. The “upper” binding site is nucleophilic due to two preorganized Au–Cl moieties, while the “lower” one is electrophilic due to positive partial charges of hydrogen atoms of P–CH2–N moieties. The “host–guest” binding is a reason for both solvent- and substrate-induced tuning of the complex luminescence. Organic cations, namely N-methylpyridinium and trimethylammonium, are revealed as substrates able to bind via the “upper” site of the complex. Acetone, diphenylketone, DMSO, DMF and acetonitrile exemplify substrates able to bind with both the binding sites of the complex. The binding via“lower” sites leads to changes in mutual arrangement of pyridyl moieties and P–Au bonds of the complex, which results in a more pronounced effect on the excited state energy relative to the binding via the “upper” site. Substrate-induced tuning of the luminescence is affected by the nature of the solvent due to competitive “host–guest” binding of (AuCl)2L with solvent molecules. [ABSTRACT FROM AUTHOR]

A highly efficient, environmentally benign and reusable heterogeneous bentonite–gold nanohybrid catalyst was designed and synthesized. This heterogeneous catalyst could efficaciously catalyse the oxidation of organosilanes to silanols. The reaction is 98.7% atom economical and the products were obtained in excellent yield without the formation of disiloxanes as byproducts. The catalyst was also well applicable for the gram scale preparation of silanols. [ABSTRACT FROM AUTHOR]

Peroxiredoxins catalyze the reduction of peroxides, a process of vital importance to survive oxidative stress. A nucleophilic cysteine, also known as the peroxidatic cysteine, is responsible for this catalytic process. We used the Mycobacterium tuberculosis alkyl hydroperoxide reductase E (MtAhpE) as a model to investigate the effect of the chemical environment on the specificity of the reaction. Using an integrative structural (R116A – PDB URL URL="HTTP://XLINK.RSC.ORG/?PDB=4XIH"4XIH/URL; F37H – PDB URL URL="HTTP://XLINK.RSC.ORG/?PDB=5C04"5C04/URL), kinetic and computational approach, we explain the mutational effects of key residues in its environment. This study shows that the active site residues are specifically oriented to create an environment which selectively favours a reaction with peroxides. [ABSTRACT FROM AUTHOR]

The developed method for monitoring GST, an important drug metabolic enzyme, could greatly facilitate researches on relative biological fields. In this work, we have developed a SERS technique to monitor the absorbance behaviour of 6-mercaptopurine (6-MP) and its glutathione-S-transferase (GST)-accelerated glutathione (GSH)-triggered release behaviour on the surface of gold nanoflowers (GNFs), using the GNFs as excellent SERS substrates. The SERS signal was used as an indicator of absorbance or release of 6-MP on the gold surface. We found that GST can accelerate GSH-triggered release behaviour of 6-MP from the gold surface. We speculated that GST catalyzes nucleophilic GSH to competitively bind with the electrophilic substance 6-MP. Experimental results have proved that the presented SERS protocol can be utilized as an effective tool for accessing the release of anticancer drugs. [ABSTRACT FROM AUTHOR]

The chemoselective [4+2] vs. [2+2] cycloaddition between allenoates and dithioesters can be controlled by switching the nucleophilic amine catalyst. The two modes of cyclizations represent the first example of controllable and chemoselective annulations between allenoates and dienophiles catalyzed by amine. These cyclizations are useful in offering a divergent synthesis of sulfur-containing heterocycles. On the basis of this investigation, it can be realized that dithioesters with a vicinal electron-withdrawing group can react not only like a Michael acceptor but also as a ketone or imine. [ABSTRACT FROM AUTHOR]

A phosphine-catalyzed dearomatizing [3+2] annulation of isoquinolinium methylides with allenoates or allenones yields highly functionalized pyrroloisoquinolines with high regioselectivity and in viable yields. [ABSTRACT FROM AUTHOR]

Although nucleophilic phosphine-catalysis is a powerful tool for the construction of various carbocycles and heterocycles, the reactions in which phosphines are incorporated into the final product are rare, and the reports on phosphine addition to highly electrophilic arynes are scarce. Herein, we report the phosphine triggered multicomponent reaction of arynes and aldehydes, which takes place via the formal [3+2] cycloaddition of an initially generated 1,3-phosphonium zwitterion from phosphines and arynes with aldehydes. The reaction resulted in the formation of a diverse range of stable pentacovalent phosphoranes in good yields based on the benzooxaphosphole system. [ABSTRACT FROM AUTHOR]

The ionic nucleophilic character of ammonium betaine catalysts allows for controlling the ROP of L-LA for DP as high as 750 with very narrow dispersity values (≤1.18). Compared to ionic nucleophilic and hydrogen-bonding based catalysts for ROP, meta-betaine combines the positive aspects of both processes in terms of kinetics and selectivity. The versatility of ammonium betaines was evidenced by varying the nature of the initiating alcohol and monomer used. [ABSTRACT FROM AUTHOR]

The mechanisms for the formation of a cationic methylene complex [(PONOP)Ir(CH2)]+ (PONOP = 2,6-bis(di-tert-butylphosphinito)pyridine) viaα-hydride abstraction from a neutral methyl complex [(PONOP)Ir(CH3)] and its reactivity with ethyl diazoacetate, a Lewis base (PMe3) and dihydrogen have been studied computationally with the aid of density functional theory (DFT). The calculation results show that the η2-alkene complex can be formed via a direct C–C coupling reaction involving the methylene ligand and ethyl diazoacetate. A ylide compound is given for the reaction of this cationic methylene complex with PMe3. In addition, hydrogenolysis of the Ir=CH2 moiety of this cationic methylene complex results in a hydride iridium complex. Our calculations could provide new insights into the reactivity of methylene complexes. [ABSTRACT FROM AUTHOR]

Nucleophilic phosphine catalysis of allenes with electrophiles is one of the most powerful and straightforward synthetic strategies for the generation of highly functionalized carbocycle or heterocycle structural motifs, which are present in a wide range of bioactive natural products and medicinally important substances. The reaction topologies can be controlled through a judicious choice of the phosphine catalyst and the structural variations of starting materials. This Tutorial Review presents selected examples of nucleophilic phosphine catalysis using allenes and electrophiles. [ABSTRACT FROM AUTHOR]

We report the effect of DNA-templation on aniline-catalyzed N-acylhydrazone formation. The reaction occurs in both twocomponent and three-component systems. Through systematic catalyst modifications, we are able to increase the efficiency of the DNA-templated variant to 85-fold above that of the uncatalyzed reaction at physiological pH. [ABSTRACT FROM AUTHOR]

The nucleophilic catalysis by a pyridyl group in ester/phosphate ester hydrolysis was modulated by the microenvironmental hydrophobicity around the catalyst. The catalytic efficiency was enhanced thousands or tens of thousands of times and the activity was maintained well below the pKa of the pyridyl group. [ABSTRACT FROM AUTHOR]

The mobility and rearrangement of the C4H7+ system over Chabazite were studied using ab initio molecular dynamics. The results indicated the high mobility of the cations, which can rearrange within picosecond time intervals. Experimental studies of nucleophilic substitution supported the theoretical findings. [ABSTRACT FROM AUTHOR]

The asymmetric synthesis of 3-indolylglycine derivatives was achieved by an oxidative heterocoupling reaction. This method for the selective C-3 functionalization of unprotected indoles with the chiral equivalent of a nucleophilic glycine nickel(ii) complex afforded adducts with high diastereoselectivities. The decomposition of adducts readily afforded 3-indolylglycine derivatives in high yields. [ABSTRACT FROM AUTHOR]

The back cover of the October 2016 issue of the journal "Chemical Communications" is presented.