On the strong difference in reactivity of acyclic and cyclic diazodiketones with thioketones: experimental results and quantum-chemical interpretation

• Andrey S. Mereshchenko,
• Alexey V. Ivanov,
• Viktor I. Baranovskii,
• Grzegorz Mloston,
• Ludmila L. Rodina and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2015, 11, 504–513, doi:10.3762/bjoc.11.57

• stage of the cycloaddition process. Keywords: diazocarbonyl compounds; 1,3-dipolar cycloaddition; 1,3-oxathioles; thiiranes; thiocarbonyl ylides; thioketones; Introduction Dipolar cycloadditions of diazo compounds have been of great interest for a long time as they provide a means for the preparation

• -thioxocyclobutanone (2b) as dipolarophiles (Figure 1). The calculations were performed at the density functional theory (DFT) level using the 6-31G(d) basis set. For reactions of diazo compounds 1a–f with thiobenzophenone (2a), the solvent was simulated using the polarizable continuum model (PCM) [22], and for the

• transition states) on the potential energy surface of the reaction of the diazo compounds 1a–f with thiobenzophenone (2a) were located. The optimized structures of reagents, intermediates, and products were found to be characterized by the absence of the imaginary part of the frequency, and transition states

Azirinium ylides from α-diazoketones and 2H-azirines on the route to 2H-1,4-oxazines: three-membered ring opening vs 1,5-cyclization

• Nikolai V. Rostovskii,
• Mikhail S. Novikov,
• Alexander F. Khlebnikov,
• Galina L. Starova and
• Margarita S. Avdontseva

Beilstein J. Org. Chem. 2015, 11, 302–312, doi:10.3762/bjoc.11.35

• ring opening into atropoisomeric oxazolium betaines and cyclization. Azirinium ylides generated from 2,3-di- and 2,2,3-triaryl-substituted azirines give rise to only 2-azabuta-1,3-dienes and/or 2H-1,4-oxazines. Keywords: 2-azabuta-1,3-dienes; azirines; diazo compounds; nitrogen ylides; 2H-1,4-oxazines

• the carbanion center. From these results it follows that 1,5-cyclization of azirinium ylides is a general stabilization route for ylides derived from diazo compounds containing an α-keto group. However, azirenooxazoles 10 reversibly formed in these reactions could not be detected in the absence of an

• rearrangement into a ketene derivative. To obtain experimental evidence for the formation of azirenooxazole intermediates 10 in the reactions of azirines 1 with α-diazo-β-ketoesters, we reacted azirine 1g with a mixture of two diazo compounds, ethyl diazoacetoacetate (2d) and diazoacetylacetone (2c), in the

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• Theoretical and experimental studies of the reaction of isoxazoles with diazo compounds show that the formation of 2H-1,3-oxazines proceeds via the formation of (3Z)-1-oxa-5-azahexa-1,3,5-trienes which undergo a 6π-cyclization. The stationary points corresponding to the probable reaction intermediates

• ; isoxazoles; isoxazolium N-ylides; 2-azabuta-1,3-dienes; 2H-1,3-oxazines; Introduction Isoxazoles are versatile building blocks, which have found extensive use in organic synthesis [1][2][3]. However, reactions of isoxazoles with diazo compounds have scarcely been studied [1][2][3][4][5]. In 2008 Davies and

• the exclusive formation of (3Z)-1-oxa-5-azahexa-1,3,5-trienes due to geometrical reasons. The first aim we set ourselves in the present work was to gain insight into the mechanism of the reaction of isoxazoles with diazo compounds by answering the two following questions: “Are isoxazolium N-ylides

Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Viktoriia V. Pakalnis,
• Roman O. Iakovenko and
• Dmitry S. Yufit

Beilstein J. Org. Chem. 2014, 10, 784–793, doi:10.3762/bjoc.10.74

• application of the reaction is the nonselective mode of the Wolff rearrangement of the unsymmetrical diazo compounds. This generates a mixture of isomeric oxoketenes [27][28][29] and, as a result, a complex mixture of products is formed [22]. Moreover not all diazo compounds give oxoketenes easily [27][28][29

• ]. In particular, unsubstituted acylketenes, the reactivity of which towards azirines is until now unknown, cannot be generated from diazo compounds. An alternative source of acylketenes can be furan-2,3-diones, which have been used in reactions with nucleophiles and various cycloadditions [30][31][32

• ]. Aiming to broaden the scope of the reaction of acylketenes with 2H-azirines we tried to use furan-2,3-diones instead of diazo compounds as the source of ketenes. Results and Discussion Unexpectedly, with a new source of acylketenes in addition to predictable products (derivatives of 5,7-dioxa-1

Use of activated enol ethers in the synthesis of pyrazoles: reactions with hydrazine and a study of pyrazole tautomerism

• Denisa Tarabová,
• Stanislava Šoralová,
• Martin Breza,
• Marek Fronc,
• Wolfgang Holzer and
• Viktor Milata

Beilstein J. Org. Chem. 2014, 10, 752–760, doi:10.3762/bjoc.10.70

• ), 1,3-dipolar cycloaddition with diazo compounds as a source of N–N linkage, degradation of fused pyrazoles or rearrangement of other monocyclic heterocycles under chemical, thermal or photochemical conditions [4]. Upon reaction of hydrazine with symmetrical enol ethers, only a single product is formed

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• been reported [59]. Preformed 2-(1-alkynyl)arylaldimines 27 have been used in a MCR involving tandem cyclization/three-component reactions with diazo compounds 37 and water or alcohols 38 in the presence of dirhodium acetate and silver triflate cooperative catalysis resulting in excellent yields of

Less reactive dipoles of diazodicarbonyl compounds in reaction with cycloaliphatic thioketones – First evidence for the 1,3-oxathiole–thiocarbonyl ylide interconversion

• Valerij A. Nikolaev,
• Alexey V. Ivanov,
• Ludmila L. Rodina and
• Grzegorz Mlostoń

Beilstein J. Org. Chem. 2013, 9, 2751–2761, doi:10.3762/bjoc.9.309

• compounds takes place, but at room temperature the reaction proceeds very slowly [7][8]. Within the framework of our longstanding research interest in the synthesis of heterocycles by using diazo compounds [4][9][10][11][12][13], we have recently performed a comprehensive study of a variety of reactions of

• . Results and Discussion Two cycloaliphatic thioketones that were previously studied in similar reactions with diazo compounds [14], were selected as dipolarophiles for the present study, namely 2,2,4,4-tetramethyl-3-thioxocyclobutanе-1-one (1a) [15] and adamantane-2-thione (1b) [16] (Figure 1). As for the

• representatives 2h–i, neither these diazo compounds nor the corresponding acylketenes generated by their thermolysis [18][19] reacted with thioketone 1a (as proved by 1H NMR spectroscopy) (Table 1, entry 6). Irrespective of the reaction temperature (rt or 80 °C), methyl diazoacetoacetate (2с) reacted with

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• sphere of the metal”. Indeed, the present radicals led to less side-reactions – in particular, oligomerization in the case of alkenes as substrates –, which shows that they exhibit “restricted reactivity” in comparison with “that of free radicals initiated by peroxides or diazo compounds and by

Gold(I)-catalyzed enantioselective cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2013, 9, 2250–2264, doi:10.3762/bjoc.9.264

• eleven, gold has also demonstrated to be an efficient promoter of intermolecular carbene transfer reactions from diazo compounds to unsaturated systems such as alkenes or alkynes, resulting in cyclopropanation processes [44][45]. The development of an enantioselective variant of this type of reactions

• -workers reported another example of a highly enantioselective gold-catalyzed cyclopropanation reaction by using diazo compounds as a source of gold carbenes. In particular, the authors demonstrated that the chiral bisgold complex Au6, derived from the spiroketal bisphosphine ligand, was a very efficient

Ethyl diazoacetate synthesis in flow

• Mariëlle M. E. Delville,
• Jan C. M. van Hest and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2013, 9, 1813–1818, doi:10.3762/bjoc.9.211

• conditions, a production yield of 20 g EDA day−1 was achieved using a microreactor with an internal volume of 100 μL. Straightforward scale-up or scale-out of microreactor technology renders this method viable for industrial application. Keywords: diazo compounds; diazotization; ethyl diazoacetate (EDA

• ); flow chemistry; microreactor technology; Introduction Diazo compounds are frequently used versatile building blocks in organic chemistry [1][2]. From this class of compounds diazomethane and ethyl diazoacetate (1, EDA) are arguably the synthetically most useful ones. Due to the potentially explosive

• nature of diazomethane and EDA [3][4][5], however, synthetic routes that involve large scale batchwise handling of such diazo compounds is generally avoided in industrial processes. With the advent of continuous processing over the past decade, new approaches have appeared to conceptually change the way

α-Bromodiazoacetamides – a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C–H insertion reactions

• Åsmund Kaupang and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2013, 9, 1407–1413, doi:10.3762/bjoc.9.157

• cycloaddition, ylide formation, cyclopropanation and C–H insertion reactions [1][2][3]. A generally useful modification of diazo compounds is the substitution of the α-hydrogen for an electrophile. This substitution can be effected in the presence of a base or starting from the metalated diazo compound, and

• et al. reported the syntheses of an α-halodiazomethyl phosphonic acid dimethyl ester and an α-halodiazomethyl diphenyl phosphoxide, starting from the silver salts of the respective diazo compounds [10]. More recently, two novel protocols for the halogenation of diazoesters and -phosphonates have been

• in the case of more labile diazo compounds [14][22][23][67]. Recent examples of thermolyses of diazocarbonyl compounds, include the preparation of arylcyclopropanes (cyclopropanation) and α-arylamino esters (N–H insertion) by thermolysis of aryldiazoacetates in trifluorotoluene under reflux [68][69

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

Intramolecular carbenoid ylide forming reactions of 2-diazo-3-keto-4-phthalimidocarboxylic esters derived from methionine and cysteine

• Marc Enßle,
• Stefan Buck,
• Roland Werz and
• Gerhard Maas

Beilstein J. Org. Chem. 2012, 8, 433–440, doi:10.3762/bjoc.8.49

• reaction. Keywords: α-aminoacids; carbonyl ylides; cycloaddition; α-diazo-β-ketoesters; sulfonium ylides; Introduction The synthetic potential of diazo compounds, in particular of α-diazoketones and α-diazoesters, is greatly widened by the ability of the derived carbene or metal-carbene intermediates to

Continuous gas/liquid–liquid/liquid flow synthesis of 4-fluoropyrazole derivatives by selective direct fluorination

• Jessica R. Breen,
• Graham Sandford,
• Dmitrii S. Yufit,
• Judith A. K. Howard,
• Jonathan Fray and
• Bhairavi Patel

Beilstein J. Org. Chem. 2011, 7, 1048–1054, doi:10.3762/bjoc.7.120

• . Pyrazoles are also useful intermediates for many industrial products and it is, therefore, not surprising that many synthetic methods have been developed for the preparation of such heterocyclic systems, for example, through 1,3-dipolar cyclo-additions of diazo compounds and the direct condensation of 1,3

Gold-catalyzed naphthalene functionalization

• Pedro J. Pérez,
• M. Mar Díaz-Requejo and
• Iván Rivilla

Beilstein J. Org. Chem. 2011, 7, 653–657, doi:10.3762/bjoc.7.77

• photochemical route for the functionalization of benzene using diazo compounds to provide a carbene moiety. The first step of this transformation consists of the addition of such a unit to the aromatic double bond to give a norcaradiene intermediate that spontaneously undergoes ring opening to afford the more

• stable cycloheptatriene product (Scheme 1) [2]. Nearly one century later, Teyssié and co-workers discovered the potential of dirhodium tetraacetate and related Rh2(L-L)4 compounds as catalysts for the decomposition of diazo compounds and subsequent transfer of the carbene moiety to several saturated and

• cyclopropanation, ring opening and the formal insertion of CHCO2Et into the aromatic C–H bonds were observed, with 2a being by far the major product (Scheme 2). In the course of our research, focussed on the development of group 11 metal-based catalysts for carbene transfer reactions from diazo compounds [10], we

Sequential Au(I)-catalyzed reaction of water with o-acetylenyl-substituted phenyldiazoacetates

• Lei Zhou,
• Yizhou Liu,
• Yan Zhang and
• Jianbo Wang

Beilstein J. Org. Chem. 2011, 7, 631–637, doi:10.3762/bjoc.7.74

• steps. Keywords: alkyne; carbene O–H insertion; cyclization; diazo compounds; gold catalysis; 1H-isochromene; Introduction Transition metal carbene complexes are versatile intermediates and can undergo diverse transformations, including X–H (X = C, O, S, N, etc.) insertions, cyclopropanations, ylide

• formation, and 1,2-migrations [1][2][3][4][5]. Among the various methods to generate metal carbene complexes, transition metal-catalyzed decomposition of diazo compounds is the most straightforward and is highly reliable. Various transition metals have been found to decompose diazo compounds and then

• transfer a carbene unit to saturated or unsaturated organic substrates [3]. However, compared to the other group 11 metals, i.e., copper and silver, there are only a few reports on gold-catalyzed carbene transfer reactions of diazo compounds [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. In 2005

The arene–alkene photocycloaddition

• Ursula Streit and
• Christian G. Bochet

Beilstein J. Org. Chem. 2011, 7, 525–542, doi:10.3762/bjoc.7.61

• photocycloaddition (Scheme 6). This was indeed the case, as very similar ratios of the two distinct stereoisomers C and D were found to be formed from the diazo compounds A and B as well as from the photocycloaddition of o-xylene to cyclopentadiene. This finding seems to indicate that a biradical structure is indeed

The catalytic performance of Ru–NHC alkylidene complexes: PCy₃ versus pyridine as the dissociating ligand

• Stefan Krehl,
• Diana Geißler,
• Sylvia Hauke,
• Oliver Kunz,
• Lucia Staude and
• Bernd Schmidt

Beilstein J. Org. Chem. 2010, 6, 1188–1198, doi:10.3762/bjoc.6.136

• alkylidene moiety originates from 2,2-diphenylcyclopropene, was soon replaced by the second version B [9], since the benzylidene ligand is more conveniently available from phenyldiazomethane. The obvious disadvantages of handling non-stabilized diazo compounds stimulated investigations into the use of

One-pot preparation of substituted pyrroles from α-diazocarbonyl compounds

• Fernando de C. da Silva,
• Mauricio G. Fonseca,
• Renata de S. Rianelli,
• Anna C. Cunha,
• Maria C. B. V. de Souza and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2008, 4, No. 45, doi:10.3762/bjoc.4.45

• purification of crude residues by column chromatography led to the pyrroles 7a–n in moderate to good yields. Their structures were confirmed mainly based on their 13C and 1H NMR spectral data which are depicted in the experimental section. Since the reactivities of the diazo compounds are different there were

Transition- metal/Lewis acid free synthesis of acyl benzothiophenes via C-C bond forming reaction

• Sarbani Pal,
• Mohammad Ashrafuddin Khan,
• P. Bindu and
• P. K. Dubey

Beilstein J. Org. Chem. 2007, 3, No. 35, doi:10.1186/1860-5397-3-35

• an expensive transition metal catalyst along with toxic carbon monoxide gas[13] or unstable diazo compounds,[18] or pyrophoric BuLi,[19][20] or a multistep synthesis of starting material.[14] The simplest and straightforward method for the synthesis of acyl benzothiophenes appeared to be the Friedel