Ambivalent role of metal chlorides in ring opening reactions of 2H-azirines: synthesis of imidazoles,pyrroles and pyrrolinones

2H-Azirines were found to react with imines, enaminones and enaminoesters in the presence of metal salts. Imidazoles, pyrroles and new pyrrolinones derivatives are isolated in good overall yields. The role of metal salts was investigated as they can act as Lewis acids or electron donors. Mechanisms are proposed suggesting that imidazoles arise from addition of azirine to imines via radical or ionic mechanism; pyrroles and pyrrolinones are obtained from azirines with enamino derivatives when the salt acts as a Lewis acid. In the latter case the properties of the metallic compound influence the reaction regioselectivity.     

Aromatic hydrocarbons as ligands. Recent advances in the synthesis,the reactivity and the applications of bis(η6-arene) complexes

Synthetic procedures for bis(η⁶-arene) metal derivatives and aspects of their reactivity are reviewed. Attention is focused on early transition metals (Groups 4–6) but, when necessary, reference will be made to arene derivatives of Groups 7–10, lanthanides and actinides.After a short historical presentation of bis(η⁶-arene) derivatives, aimed at illustrating the relevance of this class of compounds to the origin and the evolution of organometallic chemistry, the synthetic procedures to bis(η⁶-arenes) will be discussed in the light of the most recent results. As far as the reactivity of bis(η⁶-arene) compounds is concerned, particular attention is given to the electron transfer reactions occurring with or without arene displacement; data are reported for the use of low-valent bis(η⁶-arene) compounds as a useful entry into the inorganic and coordination chemistry of the corresponding metal in non aqueous systems.The use of bis(η⁶-arene) derivatives of transition metals in low oxidation states (0, +1) as precursors to catalytic systems for the oligomerisation and polymerization of unsaturated monomers and as starting compounds for the preparation of molecule-based magnets, ordered crystals and new materials and supports is described.     

Kinetic Resolution of 2H‐Azirines by Asymmetric Imine Amidation

Highly efficient kinetic resolution of 2H‐azirines by an asymmetric imine amidation was achieved in the presence of a chiral N,N′‐dioxide/Sc^III complex, thus providing a promising method to obtain the enantioenriched 2H‐azirine derivatives and protecting‐group free aziridines at the same time. It is rare to find an example of N1 of an oxindole participating in a reaction over C3. Moreover, chiral 2H‐azirines were stereospecifically transformed into an unprotected aziridine and α‐amino ketone.     

Enantioselective Reaction of 2H‐Azirines

2H‐Azirines are useful precursors for the synthesis of a variety of chiral aziridine and amine derivatives with a range of biological activities. Owing to the ring strain and the presence of a C=N double bond, 2H‐azirines are more reactive than other types of ketimine, and undergo a range of enantioselective reactions, including reduction and Diels–Alder reactions, as well as nucleophilic addition to the C=N double bond. Therefore, the enantioselective reactions of 2H‐azirines has become a hot topic, in particular within the last few years. In this Minireview, we focus on the enantioselective reactions of 2H‐azirines by using catalytic or stoichiometric amounts of chiral additives, the reaction mechanisms, and the applications of these reactions of 2H‐azirines and related compounds in organic synthesis.     

1-Aminoalkylphosphonium Derivatives: Smart Synthetic Equivalents of N-Acyliminium-Type Cations,and Maybe Something More: A Review

N-acyliminium-type cations are examples of highly reactive intermediates that are willingly used in organic synthesis in intra- or intermolecular α-amidoalkylation reactions. They are usually generated in situ from their corresponding precursors in the presence of acidic catalysts (Brønsted or Lewis acids). In this context, 1-aminoalkyltriarylphosphonium derivatives deserve particular attention. The positively charged phosphonium moiety located in the immediate vicinity of the N-acyl group significantly facilitates C_α-P⁺ bond breaking, even without the use of catalyst. Moreover, minor structural modifications of 1-aminoalkyltriarylphosphonium derivatives make it possible to modulate their reactivity in a simple way. Therefore, these types of compounds can be considered as smart synthetic equivalents of N-acyliminium-type cations. This review intends to familiarize a wide audience with the unique properties of 1-aminoalkyltriarylphosphonium derivatives and encourage their wider use in organic synthesis. Hence, the most important methods for the preparation of 1-aminoalkyltriarylphosphonium salts, as well as the area of their potential synthetic utilization, are demonstrated. In particular, the structure–reactivity correlations for the phosphonium salts are discussed. It was shown that 1-aminoalkyltriarylphosphonium salts are not only an interesting alternative to other α-amidoalkylating agents but also can be used in such important transformations as the Wittig reaction or heterocyclizations. Finally, the prospects and limitations of their further applications in synthesis and medicinal chemistry were considered.     

Réaction de réformatsky sur les azirnes: synthesés d'aziridines esters et de pyrrolinones

Addition of Reformatsky reagents 1 to two azirines is reported. From 2-phényl-3,3-dimethyl azirine 2, aziridines esters 3 are obtained. 2-Phenyl-3-methyl azirine 4 gives aziridines esters 5 and diazepinones 6. Δ-3-Pyrrolinones or 5-methylene pyrrolidones are obtained from Grignard reagents and aziridines esters 3 and 5. The reaction mechanism is discussed; compounds 7,8,9,11 and 12 result from an aza-1-oxo-2-bicyclo-pentane (2,1,0) intermediate.     

Diversity in Gold‐Catalyzed Formal Cycloadditions of Ynamides with Azidoalkenes or 2H‐Azirines: [3+2] versus [4+3] Cycloadditions

Gold‐catalyzed cycloadditions of ynamides with azidoalkenes or 2H‐azirines give [3+2] or [4+3] formal cycloadducts of three classes. Cycloadditions of ynamides with 2H‐azirine species afford pyrrole products with two regioselectivities when the C_β‐substituted 2H‐azirine is replaced from an alkyl (or hydrogen) with an ester group. For ynamides substituted with an electron‐rich phenyl group, their reactions with azidoalkenes proceed through novel [4+3] cycloadditions to deliver 1H‐benzo[d]azepine products instead.     

Reactivity of ionic liquids

Ionic liquids are becoming widely used in synthetic organic chemistry and yet relatively little attention has been paid to the intrinsic reactivity of these low temperature molten salts. Clues to the non-innocent nature of many ionic liquids are contained in the reports of altered reactivity of dissolved substrates, unexpected catalytic activity and unforeseen by-product formation. In this review, we focus on the reactivity of ionic liquids, as opposed to reactivity in ionic liquids (although discussion of the latter is often included where it aids understanding of the former).     

An efficient catalytic system for the hydrogenation of quinolines

A new catalytic system ([Ru(p-cymene)Cl₂]₂/I₂) has been developed for the hydrogenation of quinoline derivatives with high reactivity. For the 2-methyl-quinoline, the hydrogenation reaction can proceed smoothly at an S/C of 20,000/1 with complete conversion. The iodine additive is important for the reactivity.     

Early metal bis(phosphorus-stabilised)carbene chemistry

Since the discovery of covalently-bound mid- and late-transition metal carbenes there has been a spectacular explosion of interest in their chemistry, but their early metal counterparts have lagged behind. In recent years, bis(phosphorus-stabilised)carbenes have emerged as valuable ligands for metals across the periodic table, and their use has in particular greatly expanded covalently-bound early metal carbene chemistry. In this tutorial review we introduce the reader to bis(phosphorus-stabilised)carbenes, and cover general preparative methods, structure and bonding features, and emerging reactivity studies of early metal derivatives (groups 1-4 and the f-elements).     

Reaction of difluorocarbene with 2H-azirines: generation and transformations of strained azomethine ylides -- aziriniodifluoromethanides

The reaction of difluorocarbene with azirines affords a new type of azomethine ylides, viz., strained aziriniodifluoromethanides. 1,3-Dipolar cycloadditions of ylides derived from 2-unsubstituted 3-arylazirines to dimethyl acetylenedicarboxylate and aldehydes give derivatives of 2,2-difluoro-1-azabicyclo[3.1.0]hex-3-ene-3,4-dicarboxylic acids and 1,4-oxazin-3(4H)-ones, respectively. Ylides derived from 2-mono- and 2,2-disubstituted azirines undergo isomerization to 2-aza-1,3-diene derivatives. 2,2-Difluoro-1-azabicyclo[3.1.0]hex-3-enes are transformed into 2-fluoropyridine derivatives in high yields and react with amines to give 2,4-diamino-1-azabicyclo[3.1.0]hex-2-ene derivatives.     

Synthesis and characterization of N-alkyl 1,3-diamino-4,6-diamidobenzenes

A new preparation of N-substituted 1,3-diamino-4,6-diamidobenzenes has been achieved. This synthesis affords the first N-alkylamino derivatives for which a fine-tuning of the NR¹R² substituents should modify the reactivity of the amine functions.     

Recent progress in the chemistry of heterocycles incorporated oxazolo[4,5-b]pyridine and oxazolo[5,4-b]pyridine skeletons

Abstract

The present study describes recent advances in the chemistry of heterocycles incorporated oxazolo[4,5-b]pyridine and oxazolo[5,4-b]pyridine skeletons. The main sections included the synthesis of the investigated compounds from readily accessible aminopyridinol derivatives or aminopyridines. The reactivity of substituents attached to ring carbon or nitrogen atoms were discussed. In addition, the synthetic and biological evaluation of the inspected oxazolopyridines were highlighted. The purpose of this review is to discuss the chemistry of the title so far. The present study will support researchers in the fields of organic and medicinal chemistry to design and develop new protocols for the construction of new biological components.     

Stereoselective Synthesis of Iminosugar-C-Glycosides through Addition of Organometallic Reagents to N-tert-Butanesulfinyl Glycosylamines: A Comprehensive Study

A comprehensive study of the preparation and reactivity of N-tert-butanesulfinyl glycosylamines with simple Grignard and organo lithium reagents in batch vs. continuous flow chemistry is reported. As they readily react as latent imine equivalents with a variety of carbon nucleophiles, these carbohydrate derivatives constitute very useful precursors for the diastereoselective synthesis of bioactive compounds such as iminosugar-C-glycosides. A hybrid protocol, involving the addition of benzylmagnesium chloride to a (S_R)-arabinofuranosylamine substrate in flow, at room temperature, combined with a cyclization protocol in batch is also described for the first time. Of note, this semi-continuous flow process shortens the synthesis of imino-C-glycoside scaffolds to a single workday.     

Aminophosphines: their chemistry and role as ligands and synthons

In recent years, research in organophosphorus chemistry has mainly focused in designing newer and better phosphorus ligands for synthesizing novel metal complexes with improved catalytic activities. Aminophosphines [tricoordinate phosphorus(III)–nitrogen systems] are considered as versatile compounds owing to the presence of nitrogen centres which, in principle, can influence additional reactivity features. They are quite sensitive to air and moisture due to the presence of polar P? N bond(s). In spite of this, research in aminophosphine chemistry is gaining momentum day‐by‐day and this is due mainly to one reason: their rich behaviour as ligands in metal complex chemistry and subsequently in catalysis. Their role as synthons in inorganic heterocyclic chemistry has also helped produce new types of heterocycles. In this paper, the chemistry of simple acyclic aminophosphines (synthesis, characterization, reactivity and applications) is covered and particular focus is given to their ability to form chalcogenides along with their role played as ligands in coordination chemistry and as synthons in inorganic heterocyclic chemistry. Copyright © 2009 John Wiley & Sons, Ltd.     

Advances in the Chemistry of 2,4,6-Tri(thiophen-2-yl)-1,3,5-triazine

Heterocyclic systems are now considered to be an integral part of material chemistry. Thiophene, selenophene, furan, pyrrole, carbazole, triazine and others are some such examples worth mentioning. 2,4,6-Tri(thiophen-2-yl)-1,3,5-triazine is a C_3h-symmetric system with thiophene as the donor unit and s-triazine as the acceptor unit. This review gives an insight into the advances made in the thienyl-triazine chemistry over the past two to three decades. The synthetic pathways for arriving at this system and all its important derivatives are provided. The major focus is on the materials synthesized using the thienyl-triazine system, including star molecules, linear and hyperbranched polymers, porous materials and their diverse applications. This review will play a catalytic role for new dimensions to be explored in thienyl-triazine chemistry.     

Synthesis of a constrained tricyclic scaffold based on trans-4-hydroxy-l-proline

Drug discovery research has taken advantage of peptidomimetic chemistry in order to achieve new leads possessing structural and functional characteristics of bioactive peptides together with enhanced metabolic resistance towards proteases. Herein is reported the synthesis of a tricyclic peptidomimetic scaffold derived from the combination of trans-4-hydroxy-l-proline and tartaric acid derivatives by means of amidation and acid trans-acetalisation reactions. Further manipulations of the hydroxylic function on the pyrrolidine ring gave access to a new set of amino acid scaffolds possessing high rigidity and a fixed arrangement of the functional groups.     

Development of effective Lewis acids for the catalytic Diels-Alder reaction of α,β-unsaturated lactones with cyclopentadiene

We found that ‘Tf₂CH₂ + Me₃Al’ systems are effective catalytic systems for the DA reaction of less reactive α,β-unsaturated lactone derivatives, compared to α,β-unsaturated ester derivatives, with cyclopentadiene. Mononuclear aluminum methide complex, Tf₂CHAlMe₂, as an active species is formed in these catalytic systems. Effects of lactone ring-size on the reactivity and stereoselectivity were also examined. By expanding ring-size, reactivity of α,β-unsaturated lactones reduced but endo-selectivity notably increased.     

Stille reaction over cis-halocyclohexadienediol derivatives

Stille reaction was performed with several halo cis-diol derivatives by reaction with allyltributyltin in the presence of a palladium catalyst forming allyl cis-dihydrodiol derivatives. These couplings were conducted with conventional heating as well as with microwave irradiation. Allylbenzene cis-dihydrodiol was obtained with excellent yield using mild conventional heating. However, if the diol moiety is protected with the isopropylidene group, the expected product is obtained only under microwave irradiation. The unusual reactivity observed for the polyoxygenated derivatives suggests assistance of the free hydroxyls in the catalytic cycle.     

Merging Visible-Light Catalysis for the Direct Late-Stage Group-16–Trifluoromethyl Bond Formation

The use of visible light activation/photoredox chemistry for the generation of radical-centered chalcogen–CF₃ has gained widespread interest in the last past three years. Its subsequent reactivity for the synthesis of new chalcogen–CF₃-containing building blocks gained much attention. To date several methodologies have been developed addressing several challenges in modern organofluorine chemistry and enabled substantial progress in substrates scope and reaction conditions. This review describes these advancements with a particular focus on the reaction mechanisms.