Use of Stille-type cross-coupling as a route to oligopyridylimines

The new tin reagents, 2-(n-Bu₃Sn)-6-{C(R)OCH₂CH₂O}-C₅H₃N, (R=H a, Me b), have been employed in Stille-type cross-coupling reactions with a range of oligopyridylbromides generating, following a facile deprotection step, a series of formyl- and acetyl-functionalised oligopyridines. Condensation reactions with 2,6-diisopropylaniline has allowed access to families of novel sterically bulky multidentate N,N,N,N (tetradentate), N,N,N,N,N (pentadentate), N,N,N,N,N,N (sexidentate) and N,N,N,N,N,N,N (heptadentate) nitrogen donor ligands. This work represents a straightforward and rapid synthetic route for the preparation of oligopyridylimines, which are expected to act as useful components for the self-assembly of polymetallic complexes.     

[4+1] Cycloaddition of N-acylimine derivatives with isocyanides: efficient synthesis of 5-aminooxazoles and 5-aminothiazoles

[4+1] Cycloaddition reaction between isocyanides and N-acylimine derivatives generated from N-acyl N,O-acetals acting as isocyanophiles has been developed. These reactions proceeded smoothly and cleanly to afford the corresponding 5-aminooxazoles in high yields. This reaction was extended to the syntheses of 5-aminothiazoles by using N-thioacyl N,O-acetals. A wide range of N-acyl N,O-acetals, N-thioacyl N,O-acetals, and isocyanides were found to be applicable to this reaction.     

Recent Advances in the Chemical Biology of N-Glycans

Asparagine-linked N-glycans on proteins have diverse structures, and their functions vary according to their structures. In recent years, it has become possible to obtain high quantities of N-glycans via isolation and chemical/enzymatic/chemoenzymatic synthesis. This has allowed for progress in the elucidation of N-glycan functions at the molecular level. Interaction analyses with lectins by glycan arrays or nuclear magnetic resonance (NMR) using various N-glycans have revealed the molecular basis for the recognition of complex structures of N-glycans. Preparation of proteins modified with homogeneous N-glycans revealed the influence of N-glycan modifications on protein functions. Furthermore, N-glycans have potential applications in drug development. This review discusses recent advances in the chemical biology of N-glycans.     

Synthesis of polyfunctionalized methylphosphine oxides

N,N-Dialkylamino(diphenylphosphoryl)chloromethanes, a new type of organophosphorus compounds, were synthesized. On dissolving in polar and low polar solvents, N,N-dialkylamino(diphenylphosphoryl)chloromethanes dissociate spontaneously with the P??C bond cleavage to form the diphenylphosphinite anion Ph₂PO^?. This was confirmed by the reaction of N,N-dimethylamino(diphenylphosphoryl)chloromethane with electrophilic substrates to form the corresponding addition or substitution products of Ph₂PO^?. The capability of spontaneous generating the diphenylphosphinite anion considers accessible N,N-dimethylamino(diphenylphosphoryl)chloromethane as a synthetic equivalent of the diphenylphosphinite anion.     

Selective C-N bond oxidation: demethylation of N-methyl group in N-arylmethyl-N-methyl-α-amino esters utilizing N-iodosuccinimide (NIS)

Demethylation of N-methyl group in N-methyl-N-arylmethyl-α-amino esters was accomplished by the oxidation of the amino group using the N-iodosuccinimide (NIS)/acetonitrile system followed by treatment with O-methylhydroxylamine hydrochloride. This combination of reagents could provide a complementary method to catalytic hydrogenolysis, which certainly cleaves N-arylmethyl groups, in organic synthesis.     

Synthesis, characterization and crystal structures of boron-containing intermediates in the reductive amination of ferrocenecarboxaldehyde to a bis(ferrocenylmethyl) amine

Reaction of ferrocenecarboxaldehyde with aqueous methylamine leads to [(methylimino)methyl]ferrocene, which is reduced to N-(ferrocenylmethyl)-N-methylamine by NaBH₄. This amine reacts with ferrocenecarboxaldehyde and NaCNBH₃ to give the tertiary ammonium salt, di(N-(ferrocenylmethyl))-N-methylammonium cyanoborohydride. Hydrolysis of the NaCNBH₃ reaction mixture produces the free amine, di(N-(ferrocenylmethyl))-N-methylamine. Thermolysis of di(N-(ferrocenylmethyl))-N-methylammonium cyanoborohydride in refluxing tetrahydrofuran converts it to the cyanoborane adduct, di(N-ferrocenylmethyl)-N-methylamine-cyanoborane, with elimination of H₂. The new compounds are fully characterized by using spectroscopic and physical methods, including X-ray crystal structure determinations of di(N-(ferrocenylmethyl))-N-methylammonium cyanoborohydride, di(N-(ferrocenylmethyl))-N-methylamine, and di(N-(ferrocenylmethyl))-N-methylamine-cyanoborane.     

CuCl-catalyzed radical cyclisation of N-α-perchloroacyl-ketene-N,S-acetals: a new way to prepare disubstituted maleic anhydrides

The copper-catalyzed radical cyclization (RC) of N-α-perchloroacyl cyclic ketene-N,X(X=O, NR, S)-acetals was studied. While the RC of N-acyl ketene-N,O-acetals was unsuccessful, the 5-endo cyclization of the other ketene acetals provided much better results, with the following order of cyclization efficiency: hexa-atomic cyclic ketene-N,NR-acetals<penta-atomic cyclic ketene-N,S-acetals<hexa-atomic cyclic ketene-N,S-acetals. Invariably the catalytic cycle begins with the formation of a carbamoyl methyl radical. This leads to a cascade of reactions, including a radical polar crossover step, which ends with the formation of the maleimide nucleus, or precursors of this. Products from the RC of the hexa-atomic cyclic ketene-N,S-acetals, were efficiently transformed into disubstituted maleic anhydrides.     

Redox-responsive conformational alteration of aromatic amides bearing N-quinonyl system

Redox-induced conformational alteration of N-aryl-N-phenylamides, in which the N-aryl group consists of a hydroquinone–p-quinone system, was examined. The reduced form bearing a dihydroxyphenyl or dimethoxyphenyl group exists mainly in the E-form, whereas the oxidized form bearing a N-benzoquinone moiety takes the Z-form both in the crystal and in solution. This redox-induced conformational alteration is associated with a marked change in optical properties. This system appears to have suitable properties for use in external redox stimulus-responsive functional switching.     

Sialylation reactions with N,N-dibenzylthiosialoside donor

A new sialyl donor, N,N-dibenzyl-protected p-toluenethiosialoside, was synthesized and its sialylation reaction was investigated. This reaction proceeded in a preactivation manner and preferred to provide β-anomeric coupling products. The β-selectivity was rationalized based on the assumption that N,N-dibenzylamino group could serve as an oriented group to activate the hydroxyl group of acceptor from β-face.     

Recent progress in controlled radical polymerization of N-vinyl monomers

This review summarizes recent advances in the controlled radical polymerization of N-vinyl monomers, such as N-vinylcarbazole, N-vinylindole derivatives, N-vinylpyrrolidone, N-vinylcaprolactam, N-vinylformamide, N-vinylacetoamide derivatives, N-vinyl(na)phthalimides, N-vinylimidazolium salts, and N-vinyltriazoles. Recent significant progress of controlled radical polymerization of these N-vinyl monomers has allowed for the synthesis of well-defined functional polymers having various architectures, including block copolymers, branched polymers (stars, star block copolymers, miktoarm star copolymers, and graft copolymers), and hybrids. Characteristic properties, assembled structures, and three-dimensional architectures of these functional polymers derived from N-vinyl monomers are briefly introduced.     

2-Halogeno-N-phenacylimidazolium salts and their reactions with active methylene species,arylamines and thiocyanate ions

This study describes the reactivity of 2-halogeno-N-phenacylimidazolium salts towards active methylene species, arylamines and thiocyanate ions. The 2-chloro-N-phenacylimidazolium salt undergoes unexpected reactions in the presence of active methylene species and a tertiary amine as the base. The reaction of 2-bromo-N-phenacylimidazolium salts with arylamines led to a mixture of the corresponding 2-(arylamino)-N-phenacylimidazolium salts and imidazolone. The reaction of 2-bromo-N-phenacylimidazolium bromide with KSCN led to the corresponding imidazole-2-thione. The crystal structures of five compounds are reported.     

A novel method for the one-pot conversion of carboxylic acids to N,N-dimethylamides

A simple, efficient, and new method has been developed for the preparation of N,N-dimethylamides from carboxylic acids. As described below, treatment of a variety of aromatic carboxylic acids with N,N-dimethylsulfamoyl imidazole or N,N-dimethylsulfamoyl chloride in the presence of a mixture of methanesulfonic acid/phosphorus pentoxide (2:1, v/w) proceeded effectively to afford the corresponding N,N-dimethylamides in moderate to good yields. This method is easy, rapid, and good yielding for the synthesis of N,N-dimethylamides from carboxylic acids.     

A Journey from June 2018 to October 2021 with N,N-Dimethylformamide and N,N-Dimethylacetamide as Reactants

A rich array of reactions occur using N,N-dimethylformamide (DMF) or N,N-dimethylacetamide (DMAc) as reactants, these two amides being able to deliver their own H, C, N, and O atoms for the synthesis of a variety of compounds. This account highlights the literature published since June 2018, completing previous reviews by the author.     

Versatile synthesis of oxindole-1,3-dicarboxamides

A new, high-yielding synthesis of oxindole-1,3-dicarboxamides was elaborated starting from 1-phenoxycarbonyl-3-ethoxycarbonyl-2-oxindole and 1,3-diphenoxycarbonyl-2-oxindole. This method permits also the preparation of N,N,N′-tri- and N,N,N′,N′-tetrasubstituted oxidole-1,3-dicarboxamides, families of compounds that are unknown in the literature. The scope and limitations of the methodology have also been investigated, and a remarkable selectivity has been observed among the amines used in the amidation steps.     

Über die Si3-N-bindung: XXXV. Darstellung von N-β-halogenäthyl-N,N-bis(trimethylsilyl)aminen

N-β-Haloethyl-N,N-bis(trimethylsilyl)amines, which can be used for the introduction of aminoethyl groups into organic or organosilicon compounds, are prepared in good yields from N-trimethylsilylaziridine and trimethylhalosilanes. This reaction is spontaneous with trimethylbromo- and -iodosilane, whereas it is necessary to run the reactions with trimethylchlorosilane in the presence of dipolar aprotic solvents and at higher temperatures.N-β-Bromoethyl-N,N-bis(trimethylsilyl)amine (II) is also obtained by silylation of N-β-bromoethylamine hydrobromide with trimethylsilyldiethylamine or with N-trimethylsilyl-N-methyl acetamide. Furthermore N-β-iodoethyl-N,N- bis(trimethylsilyl)amine is prepared by the reaction of II with MgI₂ or of aziridine and N-trimethylsilylaziridine respectively, with trimethylchlorosilane and MgI₂.From the silylation of N-β-bromoethylamine hydrobromide with trimethylsilyldiethylamine N,N-bis(trimethylsilyl)-N′,N′-diethylethylenediamine is isolated as a side product or, at higher temperatures, as the main product.     

Fluorogenic probes for detecting deacylase and demethylase activity towards post-translationally-modified lysine residues

Reversible enzymatic post-translational modification of the ε-amino groups of lysine residues (e.g. N-acylation reactions) plays an important role in regulating the cellular activities of numerous proteins. This study describes how enzyme catalyzed N-deprotection of lysine residues of non-fluorescent peptide-coumarin probes can be used to generate N-deprotected peptides that undergo spontaneous O- to N-ester transfer reactions (uncatalyzed) to generate a highly fluorescent N-carbamoyl peptide. This enables detection of enzyme catalyzed N-deacetylation, N-demalonylation, N-desuccinylation and N-demethylation reactions activities towards the N-modified lysine residues of these probes using simple ‘turn on’ fluorescent assays.

We developed “turn-on” fluorescent probes that detect enzymatic lysine deacylation and demethylation critical for epigenetic and other cellular phenomena, using intramolecular O- to N-ester transfer reactions.     

Recent Progress Concerning the N-Arylation of Indoles

This review summarizes the current state-of-the-art procedures in terms of the preparation of N-arylindoles. After a short introduction, the transition-metal-free procedures available for the N-arylation of indoles are briefly discussed. Then, the nickel-catalyzed and palladium-catalyzed N-arylation of indoles are both discussed. In the next section, copper-catalyzed procedures for the N-arylation of indoles are described. The final section focuses on recent findings in the field of biologically active N-arylindoles.     

Regioselective N-alkylation of imidazo[4,5-b]pyridine-4-oxide derivatives: an experimental and DFT study

Regioselectivities were determined for N-alkylations of imidazo[4,5-b]pyridine-4-oxide and 2-methyl-imidazo[4,5-b]pyridine-4-oxide with benzyl bromide or benzyl iodide at RT using K₂CO₃ in DMF as a base. Experimental attempts have shown that N-1/N-3 ratios slightly varied according to the substitution on C-2 position. This was confirmed by DFT calculations in solvent phase. This computational study has shown first that this N-benzylation reaction passed through a S_N2 mechanism. Moreover, regioselectivity of N-benzylation has appeared essentially governed by ‘steric approach control’. It explained that opposite N-1/N-3 ratios were obtained with imidazo[4,5-b]pyridine-4-oxide and its 2-methyl-substituted analog. Finally, regioselectivities slightly varied with the nature of benzyl halide.     

A modular approach to α,β-unsaturated N-aryl ketonitrones

A modular approach to α,β-unsaturated N-aryl ketonitrones has been developed. Specifically, condensation of anilines and enals followed by alkylation of the resulting α,β-unsaturated imines provided N-allyl anilines, which were subjected to oxidation with Oxone® to form α,β-unsaturated N-aryl ketonitrones. This modular approach is general and provides rapid access to diversely substituted α,β-unsaturated N-aryl ketonitrones with a single purification step in good yields.