Α-diazocarbonyl Compounds Research Articles

N-Alkylation of Nitrogen Heterocycles with α-Diazocarbonyl Compounds

Examples of the use of α-diazocarbonyl compounds in the N–H insertion reactions with the formation of the products of selective N-alkylation of various five-membered nitrogen heterocycles and their derivatives are considered. The literature data is systematized according to the number of N atoms in the heterocycle. The review contains information published in the period from 2003 to 2020.

Taking diazo transfer to water: α-diazo carbonyl compounds from in situ generated mesyl azide

Mesyl azide generated in situ in aqueous medium converted a range of active methylene substrates into the corresponding diazo compounds in good yields and high purity with no need for chromatographic purification. The products thus obtained are suitable for the subsequent RhII-catalyzed O–H insertions with no need for chromatography in the interim.

Direct Observation of Ylide and Enol Intermediates Formed in Competition with Wolff Rearrangement of Photoexcited Ethyl Diazoacetoacetate.

The photoexcitation of α-diazocarbonyl compounds produces ketenes by both concerted and stepwise Wolff rearrangements. The stepwise mechanism proceeds through singlet carbene intermediates which can also participate in bimolecular reactions such as ylide formation with nucleophiles. Here, ultrafast transient infrared absorption spectroscopy is used to show competitive production of singlet carbene and ketene intermediates from the photoexcitation of ethyl diazoacetoacetate. We provide direct spectroscopic evidence for ylide formation by singlet α-carbonyl carbene capture in aprotic nucleophilic solvents (with ylide bands at 1625 cm-1 in acetonitrile and 1586 and 1635 cm-1 in tetrahydrofuran) and report an enol-mediated pathway for singlet α-carbonyl carbene reaction with alcohols (ethanol or tert-butanol) identified by an absorption band at 1694 cm-1; however, we find no evidence for a previously proposed ylide pathway. The α-carbonyl carbene is monitored by using a band with solvent-dependent wavenumber in the range 1627-1645 cm-1. A computed two-dimensional cut of the potential energy surface for the reaction of the singlet α-carbonyl carbene with methanol shows that the enol forms without a barrier and that this reaction is promoted by an intermolecular hydrogen bond from methanol to the carbonyl oxygen atom. The corresponding ylide structure lies higher in energy, with a barrierless downhill path to isomerization to the enol.

Synthesis, Structure, and Reactivity of Gold(I) α-Oxo Carbenoid Complexes

The trifluoromethanesulfonate α-oxo carbenoid complexes (IPr)AuCH(OTf)COR [R = OEt (1a), p-tolyl (1b)] were isolated from reactions of (IPr)Au(OTf) with the corresponding α-diazo carbonyl compounds...

The Use of α-Diazo-γ-butyrolactams in the Büchner–Curtius–Schlotterbeck Reaction of Cyclic Ketones Opens New Entry to Spirocyclic Pyrrolidones

The only cyclic α-diazocarbonyl compound employed in the Büchner–Curtius–Schlotterbeck ring expansion of cyclic ketones to date was α-diazo-γ-butyrolactone. Encouraged by the recent success using α-diazo acetamides in related Tiffeneau–Demjanov type ring expansions, we extended this approach to various α-diazo-γ-butyrolactams, which produced, under BF3·OEt2-promoted conditions, spirocyclic seven-membered ketones. These findings substantially enhance the possibilities offered by cyclic α-diazocarbonyl compounds in constructing privileged spirocyclic scaffolds for drug design.

Rh(III)-Catalyzed Relay Double Carbenoid Insertion and Diannulation of Sulfoximine Benzamides with α-Diazo Carbonyl Compounds: Access to Furo[2,3-c]isochromenes.

An efficient rhodium-catalyzed construction of furo[2,3-c]isochromene scaffolds through tandem double carbenoid insertion and diannulation of sulfoximine benzamides with α-diazo carbonyl compounds has been developed. Mechanistic studies revealed that the alkyl-rhodium intermediate generated by carbenoid insertion was directly trapped with another molecule of carbene species, followed by subsequent intramolecular cyclization reactions. Sulfoximine was released in situ, featuring a traceless directing fashion. The reactions proceeded smoothly under mild conditions with wide functional group tolerance.

Efficient Approaches for the Synthesis of Diverse α-Diazo Amides

Metal-catalysed carbenoid chemistry can be exploited for the synthesis of diverse ranges of small molecules from α-diazo carbonyl compounds. In this paper, three synthetic approaches to α-diazo amides are described, and their scope and limitations are determined. On the basis of these synthetic studies, recommendations are provided to assist the selection of the most appropriate approach for specific classes of product. The availability of practical and efficient syntheses of diverse α-diazo acetamides is expected to facilitate the discovery of many different classes of bioactive small molecules.

A gold(i)-catalysed chemoselective three-component reaction between phenols, α-diazocarbonyl compounds and allenamides

Gold(i) catalysts are considered to be efficient in promoting sp2 C-H bond insertion at the para position of unprotected phenols because of the exceptionally chemical reactivity of gold-stabilized carbophilic carbocations. Herein, we present a gold(i)-catalysed three-component reaction between phenols, diazocarbonyl compounds and allenamides, affording the corresponding three-component reaction products with excellent geometric selectivity (E : Z > 20 : 1) in moderate to high yields (up to 90%) under mild conditions. Additionally, a gram-scale transformation and diverse transformations of the resulting product show the high synthetic utility of the present three-component protocol.

3+2]-Cycloaddition of α-Diazocarbonyl Compounds with Arenediazonium Salts Catalyzed by Silver Nitrate Delivers 2,5-Disubstituted Tetrazoles

[3+2]-Cycloaddition of arenediazonium salts with diazo compounds (earlier exemplified only for trimethylsilyldiazomethane and 2,2,2-trifluorodiazoethane) has been developed to include a wide range of readily available α-diazocarbonyl compounds. The resulting 2-aryl-5-acyl-2H-tetrazoles are of high value in medicinal chemistry.

Cp*Ir(III)-Catalyzed C-H/O-H Functionalization of Salicylaldehydes for the Synthesis of Chromones at Room Temperature.

Herein, we report Cp*Ir(III)-catalyzed C-H/O-H-bond functionalization of salicylaldehydes with α-diazocarbonyl compounds for the synthesis of chromones under redox-neutral conditions. The reaction proceeds at room temperature and displays excellent functional group tolerance along with high yields of the corresponding products. The developed reaction protocol was successfully applied for the late-stage functionalization of estrone derivative.

Fused vs. spiro: Kinetic, not thermodynamic preference may direct the reaction of α-carbonyl oxonium ylides

Rh(II)-catalyzed decomposition of certain cyclic α-diazocarbonyl compounds in the presence of cyclic ethers has been shown to give bicyclic ring expansion products. These are thought to arise from a [1,4]-alkyl shift toward the carbonyl oxygen atom and are in contrast with the recently observed spirocyclic products of a Stevens-type [1,2]-alkyl shift within the postulated oxonium ylide intermediate. Quantum chemical calculations performed at the B3LYP/6-31G* level of theory showed that the former reaction pathway (toward fused bicycles) is kinetically preferred.

Rh(III)-Catalyzed Cascade Reactions of Sulfoxonium Ylides with α-Diazocarbonyl Compounds: An Access to Highly Functionalized Naphthalenones.

An unprecedented cascade reaction of benzoyl sulfoxonium ylides with α-diazocarbonyl compounds leading to the formation of highly functionalized naphthalenones containing a β-ketosulfoxonium ylide moiety is presented. Promisingly, the naphthalenone derivative thus obtained was found to be a versatile intermediate toward diversely functionalized naphthalene derivatives including substituted 1-naphthol, 2-hydroxynaphthalen-1(2 H)-one, naphthalen-1,2-dione, and 2-(methylsulfinyl)naphthalen-1-ol.

3 + 3]-Cycloaddition of α-Diazocarbonyl Compounds and N-Tosylaziridines: Synthesis of Polysubstituted 2 H-1,4-Oxazines through Synergetic Catalysis of AgOTf/Cu(OAc)2.

An impressive and new [3 + 3]-cycloaddition of α-diazocarbonyl compounds with N-tosylaziridines via synergetic catalysis of AgOTf and Cu(OAc)2 has been well described, which offers efficient access to highly substituted 2 H-1,4-oxazine derivatives. A variety of α-diazocarbonyl compounds and N-tosylaziridines were compatible substrates with convenient operations under mild reaction conditions.

Rh(II)-Catalyzed Spirocyclization of α-Diazo Homophthalimides with Cyclic Ethers.

Rh(II)-catalyzed decomposition of α-diazo homophthalimides in the presence of cyclic ethers gave spirocyclic products of Stevens-type [1,2]-alkyl shift within the postulated oxonium ylide intermediate. Such a reaction pathway is in line with thermodynamic predictions obtained from quantum chemical calculations performed at the B3LYP/6-31G* and B3LYP/6-311++G** levels of theory. These findings represent the first systematically investigated case of spirocyclization of cyclic α-diazocarbonyl compounds with cyclic ethers.

Reactions of 5-Aminoisoxazoles with α-Diazocarbonyl Compounds: Wolff Rearrangement vs N-H Insertion.

A highly chemoselective reaction between 5-aminoisoxazoles and α-diazocarbonyl compounds has been described. Both Wolff rearrangement and N-H insertion products can be obtained selectively by the judicious choice of reaction conditions. In the case of the Wolff rearrangement reactions, the N-isoxazole amides are accessed as the sole products under thermal conditions. On the other hand, α-amino acid derivatives of N-isoxazolescan be obtained through N-H insertion reactions in the presence of catalytic Rh2(Oct)4. Both reactions proceed under mild reaction conditions and feature a broad substrate scope.

Enynone-enabled migratory insertion and Schmittel cyclization cascade for the synthesis of furan-fused fluorenes

A new method for the synthesis of furan-/benzo-fused fluorenes through copper(i)-catalyzed coupling of conjugated enynones or α-diazocarbonyl compounds with dialkynylbenzenes has been developed.

Rhodium(i)-catalyzed vinylation/[2 + 1] carbocyclization of 1,6-enynes with α-diazocarbonyl compounds.

A sequential Rh(i)-catalyzed vinylation/[2 + 1]carbocyclization between enynes and diazo compounds has been developed. This transformation features a wide range of enynes and acceptor/acceptor diazo compounds, providing easy access to versatile vinyl-substituted azabicyclo[3.1.0]hexanes having a broad tolerance to functional groups.

Progress in N-H Insertion Reaction of α-Diazocarbonyl Compounds

Progress in N-H Insertion Reaction of α-Diazocarbonyl Compounds

2 + 1 + 1] Assembly of spiro β-lactams by Rh(ii)-catalyzed reaction of diazocarbonyl compounds with azirines/isoxazoles.

A domino synthesis of dispiro-fused N-vinyl β-lactams from diazo-Meldrum's acid and 2H-azirines or 5-alkoxyisoxazoles via the "2-azabuta-1,3-diene formation/Staudinger ketene-imine cycloaddition" sequence is described. The Rh2(Piv)4-catalyzed formation of the 2-azabuta-1,3-diene intermediates in the first stage of the reaction sequence proceeds via addition of the rhodium carbenoid to the azirines/isoxazoles and provides the first example of the generation of iminium-type ylides from diazo-Meldrum's acid. This methodology was extended to monospiro-β-lactams, which were synthesized in two steps using acyclic α-diazocarbonyl compounds in the stage of the formation of 2-azabuta-1,3-dienes. The method allows for the rapid assemblage of the carbon part of the azetidin-2-one system from diazo compounds only and affords spiro- and dispiro-β-lactams in moderate yields. A bromine atom in the 2-bromoalkenyl moiety of the synthesized β-lactams can be easily substituted by hydrogen under catalytic hydrogenation conditions or by 2-pyridyl-substituent via the Stille cross-coupling reaction.

Phosphoric Acid Catalyzed [4 + 1]-Cycloannulation Reaction of ortho-Quinone Methides and Diazoketones: Catalytic, Enantioselective Access toward cis-2,3-Dihydrobenzofurans.

A highly straightforward route to enantiomerically highly enriched cis-2,3-dihydrobenzofurans has been achieved via addition of α-diazocarbonyl compounds to in situ generated o-QMs catalyzed by a chiral Brønsted acid. This catalytic strategy provides a direct access to 2,3-dihydrobenzofurans in high yields and with up to 91:9 dr and 99:1 er at ambient temperature. Moreover, a unique phenonium-type rearrangement accounts for product formation with an inverted 2,3-substitution pattern.