Diazoalkenes: From an Elusive Intermediate to a Stable Substance Class in Organic Chemistry

Over decades diazoalkenes (R₂C=C=N₂) were postulated as reactive intermediates in organic chemistry even though their direct spectroscopic detection proved very challenging. In the 1970/80ies several groups probed their existence mainly indirectly by trapping experiments or directly by matrix-isolation studies. In 2021, our group and the Severin group reported independently the synthesis and characterization of the first room-temperature stable diazoalkenes, which initiated a rapidly expanding research field. Up to now four different classes of N-heterocyclic substituted room-temperature stable diazoalkenes have been reported. Their properties and unique reactivity, such as N₂/CO exchange or utilization as vinylidene precursors in organic and transition metal chemistry are presented. This review summarizes the early discoveries of diazoalkenes from their initial postulation as transient, elusive species up to the recent findings of the room-temperature stable derivatives.     

New Methods of Preparative Organic Chemistry. Transfer of Diazo Groups

When an arenesulfonyl azide, particularly p-toluenesulfonyl azide, reacts, in the presence of a base, with a compound containing an active methylene group, the two hydrogen atoms of the active methylene group are replaced by a diazo group to form a diazo compound and an arenesulfonamide. The method may be used for the synthesis of the diazo derivatives of cyclopentadienes, cyclohexadienes, 1,3-dicarbonyl, 1,3-disulfonyl, and 1,3-ketosulfonyl compounds, ketones, carbonic acid esters, and β-iminoketones. Secondary reactions can lead to azo compounds and heterocycles such as 1,2,3-triazoles, 1,2,3-thiadiazoles, and pyrazolin-4-ones. Azidinium salts react in the same way, but in this case an acidic reaction medium is necessary, a fact that is sometimes advantageous.     

Mild Diazo Transfer Reaction Catalyzed by Modified Clays

Abstract

A very mild method for the preparation of various 2‐diazo‐1,3‐carbonyl compounds in the presence of environmentally attractive solid acids such as clays in a heterogeneous manner in moderate to good yield is reported.     

Trapping the elusive aza-oxyallylic cation: new opportunities in heterocycloaddition chemistry

The aza-oxyallylic cation is a reactive intermediate that undergoes a [4+3] cycloaddition with dienes to form seven-membered heterocycles. Although this type of intermediate was proposed over 50 years ago, only recently has experimental evidence been obtained to support its existence. This review highlights the historical studies of aza-oxyallylic cations and their recent development as intermediates for the synthesis of heterocycles and polyheterocyclic scaffolds.     

Cooperative Bimetallic Catalysis via One-Metal/Two-Ligands: Mechanistic Insights of Polyfluoroarylation-Allylation of Diazo Compounds

Metal/ligand in situ assembly is crucial for tailoring the reactivity & selectivity in transition metal catalysis. Cooperative catalysis via a single metal/two ligands is still underdeveloped, since it is rather challenging to harness the distinct reactivity profiles of the species generated by self-assembly of a single metal precursor with a mixture of different ligands. Herein, we report a catalytic system composed of a single metal/two ligands for a three-component reaction of polyfluoroarene, α-diazo ester, and allylic electrophile, leading to highly efficient construction of densely functionalized quaternary carbon centers, that are otherwise hardly accessible. Mechanistic studies suggest this reaction follows a cooperative bimetallic pathway via two catalysts with distinct reactivity profiles, which are assembled in situ from a single metal precursor and two ligands and work in concert to escort the transformation.     

Efficient Solid/Liquid Phase-Transfer Catalytic Diazo Transfer Synthesis

A simple and efficient solid/liquid phase-transfer catalytic diazo transfer reaction for the synthesis of diazocarbonyl, diazophosphonyl, and diazophosphinyl compounds is reported.     

Inclusion Complexation of Diphenylamine-4-diazonium Chloride and p-Sulfonatocalix[4]arene

Inclusion complexation of p-sulfonatocalix[4]arene (SC4A) and diphenylamine-4-diazonium chloride (DDC) in aqueous solution was investigated in this study. The inclusion of DDC in the cavity of SC4A leads to ¹H NMR chemical shifts of DDC moving towards higher magnetic field. The complexation of SC4A also results in a bathochromic shift and a decrease in optic intensity of the absorption spectrum of DDC. In the presence of SC4A, the thermal stability of DDC in aqueous solution increases significantly while its photosensitivity still remains high.     

Phosha-Meerwein Reaction of Diazo Esters

Abstract

Diazo esters (la,b) react with trialkyl phosphates (2a–c) in the presence of BF₃.OEt₂ to give the corresponding phosphates (3a–e) in 42–58 % yields. The competed intra/intermolecular protonation in the reaction of la with dimethyl hydrogen phosphite leads to phosphonate. 4,and phosphite 5.     

From Dinitrogen to N-Containing Organic Compounds: Using Li2CN2 as a Synthon

Through the synergies of a heterogeneous synthetic approach and a homogeneous synthetic methodology, N-containing organic compounds can be synthesized via activated N-containing species prepared from N₂ gas and suitable carbon sources. From N₂, carbon, and LiH, we have previously succeeded in the high-yield preparation of Li₂CN₂ as the activated N-containing species. In this work, we applied Li₂CN₂ as a novel synthetic synthon for constructing N-containing organic compounds. A series of reaction models, including a substitution reaction, cycloaddition reaction, and transition metal-catalyzed coupling reaction, were successfully performed using Li₂CN₂ under mild conditions. Various valuable cyanamides, carbodiimides, N-aryl cyanamides and 1,2,4-triazole derivatives were readily synthesized in moderate to excellent yields. With this method, the ¹⁵N-labeled products, including oxazolidine derivatives with anti-cancer activity, could also be facilely prepared from ¹⁵N₂ gas.     

BF3-promoted reactions between aryl aldehydes and 3-diazoindolin-2-imines: Access to 2-amino-3-arylindoles

An efficient and highly regioselective synthesis of 2-amino-3-arylindoles via the BF₃-promoted reaction of 3-diazoindolin-2-imines with aryl aldehydes is described. This reaction could be carried out under mild reaction conditions with a broad scope of substrates. Moreover, the operation is of practical usage and could be scaled up.     

Synthesis and Reactivity of a Zinc Diazoalkyl Complex: [3+2] Cycloaddition Reaction with Carbon Monoxide

This work reports the synthesis, characterization, and reactivity of the first example of a well-defined zinc α-diazoalkyl complex. Treatment of zinc(I)-zinc(I) bonded compound L ₂Zn₂ [ L =CH₃C(2,6-ⁱPr₂C₆H₃N)CHC(CH₃)(NCH₂CH₂PPh₂)] or zinc(II) hydride L ZnH with trimethylsilyldiazomethane affords zinc diazoalkyl complex L ZnC(N₂)SiMe₃. This complex liberates N₂ in the presence of a nickel catalyst to form an α-zincated phosphorus ylide by reacting with the pendant phosphine. It selectively undergoes formal [3+2] cycloaddition with CO₂ or CO to form the corresponding product with a five-membered heterocyclic core. Notably, the use of CO in such a [3+2] cycloaddition reaction is unprecedented, reflecting a novel CO reaction mode.     

Crystalline Intermediates during Polycondensation Reactions in the C–N–Cl System – The Paddle‐Wheel Molecule N(C6N7Cl2)3

Solid state metathesis reactions between cyanuric chloride and C–N–H or alkali metal–(B–)C–N compounds, respectively, were carried out in the temperature range between 150 °C to 500 °C, studying intermediate stages of reactions and targeting the formation of carbon nitride materials by elimination of HCl or alkali metal chlorides. Although cyanuric chloride was reacted with quite a number of different reaction partners such as melamine, cyanamide, lithium nitride, lithium or sodium carbodiimide, lithium nitridoborate or sodium dicyandiamide, always the same intermediate compounds appeared in the reactions mixtures. Colorless, needle‐shaped crystals of the tertiary amine N(C₃N₃Cl₂)₃ ( 1 ) were obtained at temperatures around 200–250 °C. Temperatures as high as 400 °C yielded yellow, plate‐like crystals of the heptazine compound C₆N₇Cl₃ ( 2 ). At even higher temperatures, the reaction products were of poorer crystallinity, but evidence of the formation of another crystalline intermediate was given by X‐ray powder diffraction and electron diffraction experiments. This third intermediate is assumed to be a tertiary amine, quite similar to 1 , however, having heptazine ligands instead of triazine ligands and is assigned with the formula N(C₆N₇Cl₂)₃ ( 3 ). Theoretical calculations were performed for the structures and the vibrational spectra of 1 and 3 . Theoretical calculations and a structure refinement based of X‐ray powder diffraction data yielded a plausible structural model for compound 3 .     

Azodicarbonsäureester und Diazoessigester als Reaktionspartner des Ferriophosphaalkens [Cp*(CO)2FeP=C(Ph)NMe2]

Azodicarboxylates and Diazoacetates as Reactants of the Ferriophosphaalkene [Cp*(CO)₂FeP=C(Ph)NMe₂] Reaction of equimolar amounts of the ferriophosphaalkene [Cp*(CO)₂FeP=C(Ph)NMe₂] ( 1 ) and diethyl azodicarboxylate afforded the complex (C₅Me₄CH₂)(CO)₂Fe ( 3 ) as the result of a cheletropic [1+4] cycloaddition with subsequent transprotonation. The diazoacetates N₂=CHCO₂R ( 8a :=tBu; 8b :Et) and 1 gave rise to the formation of the N‐metallated 1, 2, 3‐diazaphospholes [Cp*(CO)₂Fe‐ ] ( 11a, b ). Compounds 3, 11a and 11b were characterized by means of elemental analyses and spectroscopy (IR, ¹H, ¹³C{¹H}, ³¹P{¹H}‐NMR). The molecular structure of 11a was determined by X‐ray diffraction analysis.     

Chemoselectivity for Alkene Cleavage by Palladium-Catalyzed Intramolecular Diazo Group Transfer from Azide to Alkene

Alkenes can be cleaved by means of the (3+2) cycloaddition and subsequent cycloreversion of 1,3-dipoles, classically ozone (O₃), but the azide (R−N₃) variant is rare. Chemoselectivity for these azide to alkene diazo group transfers (DGT) is typically disfavored, thus limiting their synthetic utility. Herein, this work discloses a palladium-catalyzed intramolecular azide to alkene DGT, which grants chemoselectivity over competing aziridination. The data support a catalytic cycloreversion mechanism distinct from other known metal-catalyzed azide/alkene reactions: nitrenoid/metalloradical and (3+2) cycloadditions. Kinetics experiments reveal an unusual mechanistic profile in which the catalyst is not operative during the rate-controlling step, rather, it is active during the product-determining step. Catalytic DGT was used to synthesize N-heterocyclic quinazolinones, a medicinally relevant structural core. We also report on the competing aziridination and subsequent ring expansion to another N-heterocyclic core structure of interest, benzodiazepinones.     

Elucidating the Underlying Reactivities of Alternating Current Electrosynthesis by Time-Resolved Mapping of Short-Lived Reactive Intermediates

Alternating current (AC) electrolysis is an emerging field in synthetic chemistry, however its mechanistic studies are challenged by the effective characterization of the elusive intermediate processes. Herein, we develop an operando electrochemical mass spectrometry platform that allows time-resolved mapping of stepwise electrosynthetic reactive intermediates in both direct current and alternating current modes. By dissecting the key intermediate processes of electrochemical functionalization of arylamines, the unique reactivities of AC electrosynthesis, including minimizing the over-oxidation/reduction through the inverse process, and enabling effective reaction of short-lived intermediates generated by oxidation and reduction in paired electrolysis, were evidenced and verified. Notably, the controlled kinetics of reactive N-centered radical intermediates in multistep sequential AC electrosynthesis to minimize the competing reactions was discovered. Overall, this work provides direct evidence for the mechanism of AC electrolysis, and clarifies the underlying reasons for its high efficiency, which will benefit the rational design of AC electrosynthetic reactions.     

A Convergent,Modular Approach to Trifluoromethyl-Bearing 5-Membered Rings via Catalytic C(sp3)−H Activation

Trifluoromethyl-bearing 5-membered rings are prevalent in bioactive molecules, but modular approaches to these compounds by functionalization of robust C(sp³)−H bonds in a direct and selective manner are extremely challenging. Herein we report the rhodium-catalyzed α-CF₃-α-alkyl carbene insertion into C(sp³)−H bonds of a broad range of substrates to access 7 types of CF₃-bearing saturated 5-membered carbo- and heterocycles. The reaction is particularly effective for benzylic C−H insertion exerting good site-, diastereo- and enantiocontrol, and applicable to the synthesis of chiral CF₃ analogues of bioactive molecules. Ruthenium α-CF₃-α-alkyl carbene complexes underwent stoichiometric reactions to give C−H insertion products, lending evidence for the involvement of metal α-CF₃-α-alkyl carbene species in the catalytic cycle. DFT calculations revealed that the π⋅⋅⋅π attraction and intra-carbene C−H⋅⋅⋅F hydrogen bond elucidate the origin of selectivity of the benzylic C−H insertion reactions.     

2,3,7‐Triazabicyclo[3.3.0]octenes Prepared by Tandem Cascade Reaction of Allyl Azides and Olefinic Dipolarophiles

Tandem cascade reactions of allylazides and olefinic dipolarophiles to give cis‐fused 2,3,7‐triazabicyclo [3.3.0]octenes ( 5, 6 or 7 ) are reported. Therein, an intermolecular dipolar cycloaddition of azide and alkene gave a triazoline which was followed by isomerization of the triazoline to a diazoester ( 4 ) and then an intramolecular dipolar cycloaddition from the diazo functional group and the double bond in 4 to give 5 . Compound 5 may further more undergo a Michael addition to give 7‐substituted‐ 2,3,7‐ triazabicyclo [3.3.0]oct‐2‐ene ( 6 ) or a tautomerization to give 2,3,7‐triazabicyclo[3.3.0]oct‐3‐ene ( 7 ). The reaction may be manipulated to stop at a particular stage by adopting a suit able solvent or an appropriate temperature.     

Thermal and Photochemical Cycloelimination of Nitrogen

Cyclic azo compounds including heteroaromatics with a N?N bond of strong double-bond character can eliminate molecular nitrogen on addition of sufficient thermal energy or on electronic excitation. Some substrates decompose spontaneously, others are moderately or even extremely resistant to N₂-elimination. From a preparative point of view this type of reaction opens a variety of interesting possibilities, e.g. the synthesis of small carbocycles or heterocycles, strained bi- and polycycles, as well as cage compounds. From a theoretical mechanistic viewpoint, current importance attaches to the primary fragments such as carbenes, diradicals, trimethylene, trimethylenemethane, dipoles, ylides, antiaromatic 4π-systems, unstable cycloalkynes, and arynes.     

Halogen-Incorporated Sn Catalysts for Selective Electrochemical CO2 Reduction to Formate

Electrochemically reducing CO₂ to valuable fuels or feedstocks is recognized as a promising strategy to simultaneously tackle the crises of fossil fuel shortage and carbon emission. Sn-based catalysts have been widely studied for electrochemical CO₂ reduction reaction (CO₂RR) to make formic acid/formate, which unfortunately still suffer from low activity, selectivity and stability. In this work, halogen (F, Cl, Br or I) was introduced into the Sn catalyst by a facile hydrolysis method. The presence of halogen was confirmed by a collection of ex situ and in situ characterizations, which rendered a more positive valence state of Sn in halogen-incorporated Sn catalyst as compared to unmodified Sn under cathodic potentials in CO₂RR and therefore tuned the adsorption strength of the key intermediate (*OCHO) toward formate formation. As a result, the halogen-incorporated Sn catalyst exhibited greatly enhanced catalytic performance in electrochemical CO₂RR to produce formate.     

Innentitelbild: A Phosphine‐Mediated Conversion of Azides into Diazo Compounds (Angew. Chem. 13/2009)

Im Jahr 1919 berichteten H. Staudinger und J. Meyer über die reduktive Fragmentierung eines Azids zu einem Amin. Auf S. 2395 ff. stellen nun E. L. Myers und R. T. Raines ein ergänzendes Verfahren vor: die Spaltung der anderen N‐N‐Bindung eines Azids unter Bildung einer Diazoverbindung. Weil in beiden Umsetzungen ein Phosphor(III)‐Reagens zur Anwendung kommt, wurde als Hintergrund das Bild The Alchymist, in Search of the Philosopher's Stone, Discovers Phosphorus aus dem Jahr 1771 gewählt, in dem Joseph Wright die Entdeckung des Phosphors durch Hennig Brandt im Jahr 1669 darstellt. (Gestaltung: H. Adam Steinberg)