Dinitrogen Extrusion Research Articles

Ru(II)-Catalyzed Cross-Coupling of Cyclopropenes with Diazo Compounds: Formation of Olefins from Two Different Carbene Precursors.

Formal carbene dimerization is a convergent method for the synthesis of alkenes. Herein, we report a Ru(II)-catalyzed carbene dimerization of cyclopropenes and diazo compounds. The yields are up to 97% and the stereoselectivity are up to >20:1. Mechanistically, it has been experimentally demonstrated that the catalyst reacts with cyclopropene first to generate a Ru(II)-carbene species, which is attacked by nucleophilic diazo substrate, followed by dinitrogen extrusion to form the double bond.

Vinyldiazo Reagents and Metal Catalysts: A Versatile Toolkit for Heterocycle and Carbocycle Construction

AbstractOver the past decade, vinyldiazo compounds have provided mild, efficient, and highly selective methods for the construction of heterocycles and carbocycles. Dinitrogen extrusion with suitable catalysts provides the carbon framework for [3+n] cycloaddition with a large variety of dipolarophiles. This minireview, covering the latest achievements in the field of metal‐catalyzed cyclization reactions with vinyldiazo reagents, focuses on reagent‐ or catalyst‐dependent chemodivergence: different vinyldiazo reagents or metal catalysts direct reactions to different cyclization pathways that give different reaction outcomes. Accordingly, metal‐catalyzed cyclization reactions of vinyldiazo compounds with nitrosoarenes, nitrones, indoles, and other diazo compounds are chosen to showcase the controllable versatility of the combination of vinyldiazo reagents and metal catalysts.

Photoreactions of Phenylborylene with Dinitrogen and Carbon Monoxide.

Formal removal of two bonding partners from boranes, BR3, yields borylenes, RB, which have been inferred as reactive intermediates in a number of reactions. Phenylborylene (R = C6H5; 1) is accessible from phenyldiazidoborane by photochemical extrusion of dinitrogen under matrix isolation conditions. Concomitantly, the nitrene PhNBN is formed via phenyl rearrangement. Here we used a combination of UV/vis, IR, and ESR spectroscopy under cryogenic matrix isolation conditions to investigate the properties and reactivity of phenylborylene. We detected an absorption band of phenylborylene at 375 nm (S0 → S2) and tentatively assigned the S0 → S1 transition to a very weak band at 518 nm. We also show for the first time that an electrophilic borylene such as 1 can react with N2 reversibly and with CO irreversibly under photochemical conditions. The corresponding photoproducts PhBNN and PhBCO have triplet electronic ground states. Their small E values are in agreement with the linear arrangements Ph-B-N-N and Ph-B-C-O obtained by density functional theory computations. The D values decrease in the series PhNBN > PhBNN > PhBCO and approach the value for phenylcarbene (PhCH). Indeed, the boron center in PhBCO is isoelectronic with the carbene center in PhCH. The compounds are the first examples of boron analogues of diazoalkanes (R2CNN) and ketenes (R2CCO), and their formation may serve as a demonstration of the high reactivity of phenylborylene.

A Benzoquinone Imine Assisted Ring‐Opening/Ring‐Closing Strategy of the RCOCHN1N2 System: Dinitrogen Extrusion Reaction to Benzimidazoles

A mild, three‐component dinitrogen extrusion reaction proceeding at room temperature to give different 1,2‐disubstituted benzimidazoles from 2‐oxoaldehydes, 4‐azidophenol, and benzotriazoles was successfully developed. Mechanistically, this transformation occurs through the benzoquinone imine assisted ring opening/ring closing of a highly unstable RCOCHN1N2 system.

Thermal Ring Contraction Reactions of 9-Aryl-5H,7H-[1,2,5]thiadiazolo[3,4-h][2,3,4]benzothiadiazepine 6,6-Dioxides. Experimental and Computational Studies for Understanding the Course of the Transformations.

When refluxing with sodium hydrogen carbonate in acetonitrile, 7-chloro-5-(4-fluorophenyl)-1,3-dihydro-2,3,4-benzothiadiazepine 2,2-dioxide afforded, after loss of dinitrogen and subsequent ring contraction, the corresponding sulfone in 83% yield. Similar treatment of the related thiadiazolo-fused tricycles, i.e. 9-aryl-5H,7H-[1,2,5]thiadiazolo[3,4-h][2,3,4]benzothiadiazepine 6,6-dioxides, resulted in a substantially different product mixture: formation of sultines and benzocyclobutenes was observed, while only small amounts of the sulfones were formed, if any. Density functional theory calculations support the mechanism proposed for the transformations involving a zwitterionic intermediate formed by the tautomerization of the thiadiazepine ring followed by dinitrogen extrusion. When starting from 7-chloro-substituted 2,3,4-benzothiadiazepine 2,2-dioxide, the formation of sulfone via o-quinodimethane is the preferred pathway from the zwitterion. However, in the case of thiadiazolobenzothiadiazepine 6,6-dioxides it has been found that the ring closure of the zwitterion leading to the formation of sultines was kinetically preferred over the loss of sulfur dioxide leading to o-quinodimethane, which is the key intermediate to benzocyclobutene-type products. The calculations explain the differences observed between the product distributions of the chloro-substituted and the thiadiazolo-fused derivatives.

Diverse Pathways in Catalytic Reactions of Propargyl Aryldiazoacetates: Selectivity between Three Reaction Sites.

Three catalyst-dependent divergent reaction pathways for reactions of propargyl aryldiazoacetates are disclosed. Transition metal catalysts including those of rhodium(II), palladium(0 and II), silver(I), mercury(II), copper(I and II), platinum(II), and cationic gold(I) are effective for reactions that proceed through dinitrogen extrusion, carbene/alkyne metathesis, and aromatic substitution to form fused indeno-furanones, and use of tetrakis(acetonitrile)copper(I) provides indeno-furanones in the highest product yields. A Lewis acid catalyzed pathway that forms furan-2-ones is uncovered with FeCl3, ZnBr2, and BF3·Et2O as catalysts that proceed through activation of the aryldiazoacetate ester for arylpropargyl cation dissociation followed by recombination through cation addition to the diazo carbon. Neutral gold catalysts selectively activate the triple bond of propargyl aryldiazoacetates, resulting in the formation of allenic aryldiazoesters that further undergo uncatalyzed rearrangement.

Syntheses of Tetrahydropyridazine and Tetrahydro-1,2-diazepine Scaffolds through Cycloaddition Reactions of Azoalkenes with Enol Diazoacetates.

Catalyst-dependent [4 + 2]-cycloaddition reactions of azoalkenes from α-halohydrazones with enol diazoacetates have been developed. A [4 + 2]-cycloaddition of enol diazoacetates with in situ formed azoalkenes produces tetrahydropyridazinyl-substituted diazoacetates promoted by only Cs2CO3. In contrast, donor-acceptor cyclopropenes, which are formed in situ from enol diazoacetates by Rh2(OAc)4-catalyzed dinitrogen extrusion, undergo [4 + 2]-cycloaddition with azoalkenes to yield bicyclo[4.1.0]tetrahydropyridazines. These stable cycloaddition products undergo subsequent one-step transformations to form 6-alkylidenetetrahydropyridazines and 4,5,6,7-tetrahydro-1,2-diazepine derivatives in good yields.

ChemInform Abstract: NBS‐Mediated Dinitrogen Extrusion of Diazoacetamides under Catalyst‐Free Conditions: Practical Access to 3‐Bromooxindole Derivatives.

A synthetically useful transformation arises from NBS-mediated dinitrogen extrusion of N-aryl diazoacetamides under catalyst-free conditions, which gives 3-bromooxindoles in high to excellent yields with high selectivity via a non-carbene process.

ChemInform Abstract: Versatile Donor—Acceptor Cyclopropenes in Metal Carbene Transformations

AbstractReview: [28 refs.

Versatile Donor‐Acceptor Cyclopropenes in Metal Carbene Transformations

AbstractSelect transition metal compounds catalyze metal vinylcarbene formation from cyclopropenes, and their documented reactions include both intermolecular and intramolecular C−H insertion and cyclopropanation, as well as [3+3]‐cycloaddition. Although known to undergo carbene‐like transformations for decades, the uses of cyclopropenes as reactive alternatives to diazo compounds under mild conditions has been limited. However, recently developed donor‐acceptor cyclopropenes that are conveniently accessed from enoldiazoacetates and enoldiazoacetamides are effective metallo‐vinylcarbene precursors. They provide entry to highly stereoselective metal carbene transformations under reaction conditions that are milder than those required for dinitrogen extrusion from diazo compounds.

NBS-mediated dinitrogen extrusion of diazoacetamides under catalyst-free conditions: practical access to 3-bromooxindole derivatives

A synthetically useful reaction via NBS-mediated dinitrogen extrusion of N-aryl diazoacetamides under catalyst-free conditions is disclosed, which gives the 3-bromooxindoles in high to excellent yields with high selectivity via a non carbene process.

ChemInform Abstract: Dinitrogen Extrusion from Enoldiazo Compounds under Thermal Conditions: Synthesis of Donor—Acceptor Cyclopropenes.

AbstractA convenient, metal‐free protocol for the quantitative transformation of various N‐alkyl and N‐benzyl substituted enoldiazoacetamides into donor‐acceptor cyclopropenes is examined.

Palladium-catalyzed C-H functionalization of acyldiazomethane and tandem cross-coupling reactions.

Palladium-catalyzed C-H functionalization of acyldiazomethanes with aryl iodides has been developed. This reaction is featured by the retention of the diazo functionality in the transformation, thus constituting a novel method for the introduction of diazo functionality to organic molecules. Consistent with the experimental results, the density functional theory (DFT) calculation indicates that the formation of Pd-carbene species in the catalytic cycle through dinitrogen extrusion from the palladium ethyl diazoacetate (Pd-EDA) complex is less favorable. The reaction instead proceeds through Ag2CO3 assisted deprotonation and subsequently reductive elimination to afford the products with diazo functionality remained. This C-H functionalization transformation can be further combined with the recently evolved palladium-catalyzed cross-coupling reaction of diazo compounds with aryl iodides to develop a tandem coupling process for the synthesis of α,α-diaryl esters. DFT calculation supports the involvement of Pd-carbene as reactive intermediate in the catalytic cycle, which goes through facile carbene migratory insertion with a low energy barrier (3.8 kcal/mol).

Dinitrogen extrusion from enoldiazo compounds under thermal conditions: synthesis of donor-acceptor cyclopropenes.

Donor-acceptor cyclopropenes are formed quantitatively or in high yield from enoldiazoacetates and enoldiazoacetamides under moderate thermal conditions. They are more versatile than their corresponding enoldiazocarbonyl compounds as carbene precursors.

N‐Bromosuccinimide‐Mediated Radical Cyclization of 3‐Arylallyl Azides: Synthesis of 3‐Substituted Quinolines

AbstractVisible light irradiation of N‐bromosuccinimide serves as an effective means to convert methyl 2‐(azidomethyl)‐3‐arylpropenoates and 2‐(azidomethyl)‐3‐arylacrylonitriles to the corresponding iminyl radicals via α‐hydrogen abstraction and subsequent extrusion of dinitrogen. Thus formed iminyl radicals then undergo intramolecular ortho attack on the aryl ring, affording methyl quinoline‐3‐carboxylates and quinoline‐3‐carbonitriles respectively.magnified image

The [3 + 3]-cycloaddition alternative for heterocycle syntheses: catalytically generated metalloenolcarbenes as dipolar adducts.

ConspectusThe combination of two or more unsaturated structural units to form cyclic organic compounds is commonly referred to as cycloaddition, and the combination of two unsaturated structural units that forms a six-membered ring is formally either a [5 + 1]-, [4 + 2]-, [2 + 2 + 2]-, or [3 + 3]-cycloaddition. Occurring as concerted or stepwise processes, cycloaddition reactions are among the most useful synthetic constructions in organic chemistry. Of these transformations, the concerted [4 + 2]-cycloaddition, the Diels–Alder reaction, is by far the best known and most widely applied. However, although symmetry disallowed as a concerted process and lacking certifiable examples until recently, stepwise [3 + 3]-cycloadditions offer advantages for the synthesis of a substantial variety of heterocyclic compounds, and they are receiving considerable attention.In this Account, we present the development of stepwise [3 + 3]-cycloaddition reactions from virtual invisibility in the 1990s to a rapidly growing synthetic methodology today, involving organocatalysis or transition metal catalysis. With origins in organometallic or vinyliminium ion chemistry, this area has blossomed into a viable synthetic transformation for the construction of six-membered heterocyclic compounds containing one or more heteroatoms. The development of [3 + 3]-cycloaddition transformations has been achieved through identification of suitable and compatible reactive dipolar adducts and stable dipoles. The reactive dipolar species is an energetic dipolar intermediate that is optimally formed catalytically in the reaction. The stepwise process occurs with the reactive dipolar adduct reacting as an electrophile or as a nucleophile to form the first covalent bond, and this association provides entropic assistance for the construction of the second covalent bond and the overall formal [3 + 3]-cycloaddition. Organocatalysis is well developed for both inter- and intramolecular synthetic transformations, but the potential of transition metal catalysis for [3 + 3]-cycloaddition has only recently emerged. The key to the rapid development of the transition metal-based methodology has been recognition that certain catalytically generated vinylcarbenes are effective dipolar adducts for reactions with stable dipolar compounds, including aryl and vinyl ylides. In particular, metallo-enolcarbenes that are generated catalytically from conveniently prepared stable enoldiazoacetates or from donor–acceptor cyclopropenes are highly effective dipolar adducts for [3 + 3]-cycloaddition. The electron-donating oxygen of the silyl ether enhances electrophilic ring closure to the metal-bound carbon of the initial adduct from vinylogous addition, and this enhancement inhibits the alternative [3 + 2]-cycloaddition across the carbon–carbon double bond of the vinylcarbene.Catalytically generated metallo-enolcarbenes react under mild conditions with a broad spectrum of compatible stable dipoles, including nitrones, azomethine imines, ylides, and certain covalent precursors of stable dipoles, to form [3 + 3]-cycloaddition products having the β-ketoester functionality (in dihydrooxazines, tetrahydropyridazines, pyrazolidinone and pyraxole derivatives, dihydroquinolines, and quinolizidines, for example) in high yield. Two ways to access these metallo-enolcarbenes, either by dinitrogen extrusion from enoldiazoacetate esters or by rearrangement of donor–acceptor cyclopropenes, enhance the versatility of the process. The [3 + 3]-cycloaddition methodology is a complementary strategy to [4 + 2]-cycloaddition for the synthesis of heterocyclic compounds having six-membered rings. High levels of enantioselectivity are obtained with the use of chiral ligands on transition metal catalysts that include those on dirhodium(II) and silver(I).

Highly enantioselective dearomatizing formal [3+3] cycloaddition reactions of N-acyliminopyridinium ylides with electrophilic enol carbene intermediates.

Extrusion of dinitrogen from enol diazoacetates with a RhII catalyst generates metal enol carbenes. Subsequent vinylogous addition of these to N-acyliminopyridinium ylides results in an effective formal [3+3] cycloaddition to give highly substituted 1,2,3,6-tetrahydropyridazines in up to 98 % ee and high yield.

Synthesis of Hypervalent Iodonium Alkynyl Triflates for the Application of Generating Cyanocarbenes

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent reactions with azides to form cyanocarbene intermediates. The synthesis of hypervalent iodonium alkynyl triflates can be facile, but difficulties stem from their isolation and reactivity. In particular, the necessity to use filtration under inert atmosphere at -45 °C for some HIATs requires special care and equipment. Once isolated, the compounds can be stored and used in reactions with azides to form cyanocarbene intermediates. The evidence for cyanocarbene generation is shown by visible extrusion of dinitrogen as well as the characterization of products that occur from O-H insertion, sulfoxide complexation, and cyclopropanation. A side reaction of the cyanocarbene formation is the generation of a vinylidene-carbene and the conditions to control this process are discussed. There is also potential to form a hypervalent iodonium alkenyl triflate and the means of isolation and control of its generation are provided. The O-H insertion reaction involves using a HIAT, sodium azide or tetrabutylammonium azide, and methanol as solvent/substrate. The sulfoxide complexation reaction uses a HIAT, sodium azide or tetrabutylammonium azide, and dimethyl sulfoxide as solvent. The cyclopropanations can be performed with or without the use of solvent. The azide source must be tetrabutylammonium azide and the substrate shown is styrene.

Diazoacetoacetate enones for the synthesis of diverse natural product-like scaffolds.

Diazoacetoacetate enones are a new class of Michael acceptors that enable the efficient construction of natural product-like scaffolds. Through their Michael addition reactions, including those with silyl enol ethers, indoles, pyrroles, and amines, δ-functionalized diazoacetoacetates are formed in high yield and with overall operational efficiency. Subsequent catalytic dinitrogen extrusion reactions provide access to a diverse series of natural product-like carbo- and heterocyclic ring systems in only three steps from commercial materials.

Vinylogous Reactivity of Enol Diazoacetates with Donor–Acceptor Substituted Hydrazones. Synthesis of Substituted Pyrazole Derivatives

A regiospecific synthesis of multifunctional pyrazoleshas been developed from a cascade process triggered by Rh(II)-catalyzed dinitrogen extrusion from enol diazoacetates with vinylogous nucleophilic addition followed by Lewis acid catalyzed cyclization and aromatization.