Ruthenium‐catalyzed formal alkyl group transfer: Synthesis of quinolines from nitroarenes and alkylammonium halides

Nitroarenes are reductively cyclized with an array of tetraalkylammonium halides and trialkylarnmonium chlorides in the presence of a catalytic amount of a ruthenium catalyst along with tin(II) chloride dihydrate at 180° to afford the corresponding quinolines in moderate to good yields. The addition of tin(II) chloride dihydrate is necessary for the effective formation of quinolines and toluene is the solvent of choice. A reaction pathway involving initial reduction of nitroarenes to anilines and conversion of alkylammonium halides to alkylamines, alkyl group transfer from alkylamines to anilines to form an imine, dimerization of imine, and heteroannulation is proposed for this catalytic process.     

Nickel-Catalyzed Amination of (Hetero)aryl Halides Facilitated by a Catalytic Pyridinium Additive

An efficient and operationally simple Ni-catalyzed amination protocol has been developed. This methodology features a simple Ni^II salt, an organic base and catalytic amounts of both a pyridinium additive and Zn metal. A diverse number of (hetero)aryl halides were coupled successfully with primary and secondary alkyl amines, and anilines in good to excellent yields. Similarly, benzophenone imine gave the corresponding N-arylation product in an excellent yield.     

Designing multistep transformations using the Hammett equation: imine exchange on a copper(I) template

Herein, we quantify how imine exchange may be used to selectively transform one metallo-organic structure into another. A series of imine exchange reactions were studied, involving a set of 4-substituted anilines, their 2-pyridylimines and 1,10-phenanthrolyl-2,9-diimines, as well as the copper complexes of these imine ligands. Electron-rich anilines were found to displace electron-poor anilines in all cases. Linear free energy relationships (LFERs) were discovered connecting the electron-donating or -withdrawing character of the 4-substituent of an aniline, as measured by the Hammett sigma(para) parameter, to that aniline's ability to compete with unsubstituted aniline to form imines. The quality of these LFERs allowed for quantitative predictions: to obtain the desired degree of selectivity in an imine exchange between anilines A and B, the required sigma(para) differential could be predicted using a variant of the Hammett equation, log(K(AB)) = rho(sigma(A) - sigma(B)). We validated this methodology by designing and executing a three-step transformation of a series of copper(I)-containing structures. Each step proceeded in predictably high yield, as calculated from sigma differentials. At each step in the series of transformations, macrocyclic structures could be created or destroyed through the selection of mono- or di-amines as subcomponents. The same methodology could be used to predict the formation of a diverse dynamic library of helicates from a set of four aniline precursors, as well as the collapse of this library into one helicate upon the addition of a fifth aniline.     

Selective palladium-catalyzed amination of β-chloroacroleins by substituted anilines

β-Chloroacroleins can undergo a selective amination on their chloro position under palladium catalysis; in those conditions, no imine formation was observed. Their coupling with anilines carrying electron-donating or electron-withdrawing substituents proceeds in moderate to good yields and steric hindrance does not seem to be a limitation as o-substituted anilines react readily.     

Synthesis of Stannylated Aryl Imines and Amines via Aryne Insertion Reactions into Sn−N Bonds

The reaction of in situ generated arynes with stannylated imines to provide ortho-stannyl-aniline derivatives is reported. The readily prepared trimethylstannyl benzophenone imine is introduced as an efficient reagent to realize the aryne σ-insertion reaction. The imine functionality is an established N-protecting group and insertions proceed with good yields and good to excellent regioselectivities. The product anilines are valuable starting materials for follow-up chemistry thanks to the rich chemistry offered by the trimethylstannyl moiety.     

Ruthenium‐catalyzed formation of quinolines via reductive cyclization of nitroarenes with tris(3‐hydroxypropyl)amine in an aqueous medium

Nitroarenes react with tris(3‐hydroxypropyl)amine in an aqueous medium (dioxane/H₂O) at 180° in the presence of a catalytic amount of a ruthenium catalyst and tin(II) chloride along with isopropanol as hydrogen donor to afford the corresponding quinolines in good yields. The presence of tin(II) chloride is essential for the formation of quinolines. A reaction pathway involving initial reduction of nitroarenes to anilines, propanol group transfer from tris(3‐hydroxypropyl)amine to anilines to form 3‐anilino‐1‐propanols, N‐alkylation of anilines by 3‐anilino‐1‐propanol to form 1,3‐dianilinopropane and intramolecular heteroannulation of 1,3‐dianilinopropane is proposed for this catalytic process.     

Preparation of 2- and 4-arylmethyl N-substituted and N,N-disubstituted anilines via a "green", multicomponent reaction

[reaction: see text] A new, green, regioselective, one-step, multicomponent reaction of an aldehyde possessing a nonenolizable carbonyl function, cyclohex-2-enone (or a derivative thereof), and primary or secondary amines afforded 2-N-substituted arylmethyl anilines or 4-N,N-disubstituted arylmethyl anilines, respectively. Yields and regioselectivities were good. Evidence for a pathway involving imine and iminium intermediates is presented along with examples demonstrating amenability of the process to combinatorial chemistry.     

Addition des ylures de carbonyle derives de gem-dicyanoepoxydes sur les benzylidene anilines substituees

The reaction of substituted benzylidene anilines with 1,1-dicyano or 1-cyano 1-ethoxycarbonyl epoxides gives oxazolidines, the structures of which is established by NMR spectroscopy. The formation of oxazolidines proceeds via regiospecific addition of epoxide derived ylid to imine. The influence of ylid substituants and imine substituants on the reaction may be interpreted by interactions of the frontier orbitals.     

Facile Synthesis of Dihydro-1,2,4-benzotriazepin-5-ones

Direct interaction between model anilines and an 1,3-dipolar nitrile imine, derived from 2-[N′-(1-chloro-2-oxopropylidine)hydrazine]benzoic acid, yielded the respective acyclic amidrazones. The latter adducts underwent CDI-induced cyclocondensation involving the hydrazone–NH terminus and the activated carboxy group to produce the corresponding dihydro-1,2,4-benzotriazepin-5-ones.     

N-Heterocyclic Carbenes and Imidazole-2-thiones as Ligands for the Gold(I)-Catalysed Hydroamination of Phenylacetylene

Gold(I) complexes of 1-[1-(2,6-dimethylphenylimino)alkyl]-3-(mesityl)imidazol-2-ylidene (C^Imine(R) ), 1,3-dimesitylimidazol-2-ylidene (IMes) and of the corresponding thione derivatives (S^Imine(R) and IMesS) were prepared and structurally characterised. The solid-state structure of the C^Imine(R) and S^Imine(R) gold(I) complexes showed monodentate coordination of the ligand and a dangling imine group that could bind reversibly to the metal centre to stabilise otherwise unstable catalytic intermediates. Interestingly, reaction of C^Imine(tBu) with [AuCl(SMe(2) )] led to the formation of [(C^Imine(tBu) )AuCl], which rearranges upon crystallisation into the unusual complex cation [(C^Imine(tBu) )(2) Au](+) , with AuCl(2) (-) as the counterion. The activity of the gold complexes in the hydroamination of phenylacetylene with substituted anilines was tested and compared to control catalyst systems. The best catalytic performance was obtained with [(C^Imine(tBu) )AuCl], with the exclusive formation of the Markovnikov addition product in excellent yield (>95?%) regardless of the substituents on aniline.     

Facile Synthesis of Dihydro-1,2,4-benzotriazepin-5-ones

Summary. Direct interaction between model anilines and an 1,3-dipolar nitrile imine, derived from 2-[N′-(1-chloro-2-oxopropylidine)hydrazine]benzoic acid, yielded the respective acyclic amidrazones. The latter adducts underwent CDI-induced cyclocondensation involving the hydrazone–NH terminus and the activated carboxy group to produce the corresponding dihydro-1,2,4-benzotriazepin-5-ones.     

Mechanistic investigation of the iridium-catalysed alkylation of amines with alcohols

The [Cp*IrCl(2)](2)-catalysed alkylation of amines with alcohols was investigated using a combination of experimental and theoretical methods. A Hammett study involving a series of para-substituted benzyl alcohols resulted in a line with a negative slope. This clearly documents that a positive charge is built up in the transition state, which in combination with the measurement of a significant kinetic isotope effect determines hydride abstraction as being the selectivity-determining step under these conditions. A complementary Hammett study using para-substituted anilines was also carried out. Again, a line with a negative slope was obtained suggesting that nucleophilic attack on the aldehyde is selectivity-determining. A computational investigation of the entire catalytic cycle with full-sized ligands and substrates was performed using density functional theory. The results suggest a catalytic cycle where the intermediate aldehyde stays coordinated to the iridium catalyst and reacts with the amine to give a hemiaminal which is also bound to the catalyst. Dehydration to the imine and reduction to the product amine also takes place without breaking the coordination to the catalyst. The fact that the entire catalytic cycle takes place with all the intermediates bound to the catalyst is important for the further development of this synthetic transformation.     

Precipitation-driven self-sorting of imines

Judicious choice of precipitation conditions can lead to self-sorting of equilibrating mixtures of aromatic aldehydes and substituted anilines into a handful of imine products. The selectivity of this process is caused by the solubility differences among possible imines in the EtOH-H(2)O solvent mixtures used in precipitation.     

A computational investigation of the hydrogenation of imines catalyzed by rhodium thiolate complexes

The mechanism of imine hydrogenation catalyzed by thiolate complexes of Rh(III) bearing a hydrotris(3,5‐dimethylpyrazolyl)borato ligand has been investigated via the density functional theory calculations. The overall catalytic cycle for heterolytic cleavage of H₂ and hydrogenation of N‐benzylidenemethylamine by the model catalyst [TpRh(bdt)MeCN)] is presented in detail. The results show that the reaction proceeds via an ionic mechanism through three steps: formation of dihydrogen complex, protonation of imine and the hydride transfer process. Protonation of imine occurs after the formation of Rh(H)‐S(H) moiety. For the whole catalytic cycle, the heterolytic splitting of dihydrogen is the step with the highest free energy barrier. © 2014 Wiley Periodicals, Inc.     

Intramolecular hetero Diels-Alder (Povarov) approach to the synthesis of the alkaloids luotonin A and camptothecin

[reaction: see text] Pyrrolo[3,4-b]quinolines can be formed through the coupling of anilines with N-propargylic substituted heterocyclic aldehydes in the presence of mild Lewis acid catalysts (Ln(OTf)3). The coupling proceeds through sequential imine formation and a formal intramolecular aza-Diels-Alder (Povarov) reaction. This approach was applied in a total synthesis of luotonin A and a formal synthesis of camptothecin.     

Ruthenium-catalyzed propargylic substitution reactions of propargylic alcohols with oxygen-, nitrogen-, and phosphorus-centered nucleophiles

The scope and limitations of the ruthenium-catalyzed propargylic substitution reaction of propargylic alcohols with heteroatom-centered nucleophiles are presented. Oxygen-, nitrogen-, and phosphorus-centered nucleophiles such as alcohols, amines, amides, and phosphine oxide are available for this catalytic reaction. Only the thiolate-bridged diruthenium complexes can work as catalysts for this reaction. Results of some stoichiometric and catalytic reactions indicate that the catalytic propargylic substitution reaction proceeds via an allenylidene complex formed in situ, whereby the attack of nucleophiles to the allenylidene C(gamma) atom is a key step. Investigation of the relative rate constants for the reaction of propargylic alcohols with several para-substituted anilines reveals that the attack of anilines on the allenylidene C(gamma) atom is not involved in the rate-determining step and rather the acidity of conjugated anilines of an alkynyl complex, which is formed after the attack of aniline on the C(gamma) atom, is considered to be the most important factor to determine the rate of this catalytic reaction. The key point to promote this catalytic reaction by using the thiolate-bridged diruthenium complexes is considered to be the ease of the ligand exchange step between a vinylidene ligand on the diruthenium complexes and another propargylic alcohol in the catalytic cycle. The reason why only the thiolate-bridged diruthenium complexes promote the ligand exchange step more easily with respect to other monoruthenium complexes in this catalytic reaction should be that one Ru moiety, which is not involved in the allenylidene formation, works as an electron pool or a mobile ligand to another Ru site. The catalytic procedure presented here provides a versatile, direct, and one-step method for propargylic substitution of propargylic alcohols in contrast to the so far well-known stoichiometric and stepwise Nicholas reaction.     

An Autocatalytic System of Photooxidation‐Driven Substitution Reactions on a FeII4L6 Cage Framework

The functions of life are accomplished by systems exhibiting nonlinear kinetics: autocatalysis, in particular, is integral to the signal amplification that allows for biological information processing. Novel synthetic autocatalytic systems provide a foundation for the design of artificial chemical networks capable of carrying out complex functions. Here we report a set of Fe^II₄L₆ cages containing BODIPY chromophores having tuneable photosensitizing properties. Electron‐rich anilines were observed to displace electron‐deficient anilines at the dynamic‐covalent imine bonds of these cages. When iodoaniline residues were incorporated, heavy‐atom effects led to enhanced ¹O₂ production. The incorporation of (methylthio)aniline residues into a cage allowed for the design of an autocatalytic system: oxidation of the methylthio groups into sulfoxides make them electron‐deficient and allows their displacement by iodoanilines, generating a better photocatalyst and accelerating the reaction.     

Cross-dehydrogenative coupling strategy for phosphonation and cyanation of secondary N-alkyl anilines by employing 2,3-dichloro-5,6-dicyanobenzoquinone

The cross-dehydrogenative coupling strategy for metal-free phosphonation and cyanation of secondary N-alkyl anilines has been developed firstly under mild reaction conditions. Based on detailed optimization of reaction conditions, the substrate generality of N-alkyl anilines and various hydrogen phosphonates has been investigated, and a series of versatile α-aminophosphonates and α-aminonitriles were therefore furnished in good to excellent yields. A plausible collective reaction mechanism through dehydrogenation to imine formation, then to respective α-aminophosphonates and α-aminonitriles was proposed.     

Mimicking transition metals in borrowing hydrogen from alcohols

Borrowing hydrogen from alcohols, storing it on a catalyst and subsequent transfer of the hydrogen from the catalyst to an in situ generated imine is the hallmark of a transition metal mediated catalytic N-alkylation of amines. However, such a borrowing hydrogen mechanism with a transition metal free catalytic system which stores hydrogen molecules in the catalyst backbone is yet to be established. Herein, we demonstrate that a phenalenyl ligand can imitate the role of transition metals in storing and transferring hydrogen molecules leading to borrowing hydrogen mediated alkylation of anilines by alcohols including a wide range of substrate scope. A close inspection of the mechanistic pathway by characterizing several intermediates through various spectroscopic techniques, deuterium labelling experiments, and DFT study concluded that the phenalenyl radical based backbone sequentially adds H⁺, H˙ and an electron through a dearomatization process which are subsequently used as reducing equivalents to the C–N double bond in a catalytic fashion.

An efficient method is developed for harvesting hydrogen, its storage and catalytic transfer by an odd alternant hydrocarbon. The strategy is reminiscent of transition metals in borrowing hydrogen mediated processes.     

An efficient synthesis of N-arylated, orthogonally protected racemic aspartates

A brief and efficient synthesis of variously N-arylated racemic aspartates has been achieved by two consecutive reactions in one-pot, in which imine or equivalent, formed in situ from various anilines and ethyl glyoxylate, reacted with the Reformatsky reagent, tert-butyl 2-bromozinc acetate. Notably the two esters are orthogonally protected for the convenience of further derivatization.