Evidencing an inner-sphere mechanism for NHC-Au(I)-catalyzed carbene-transfer reactions from ethyl diazoacetate

• Manuel R. Fructos,
• Juan Urbano,
• M. Mar Díaz-Requejo and
• Pedro J. Pérez

Beilstein J. Org. Chem. 2015, 11, 2254–2260, doi:10.3762/bjoc.11.245

• of a gold(I) source and a diazo compound. It was not until 2005 that the first example of this transformation was reported by our group [15][16], when the complex IPrAuCl (1) (IPr = 1,3-bis(diisopropylphenyl)imidazole-2-ylidene), in the presence of NaBArF4 (BArF4− = tetrakis(3,5-bis(trifluoromethyl

• the well-known instability of some of the diazo reagents. The reactions shown in Scheme 2 and Scheme 3 have been explained through the appearance of a [LAu=CR1R2]+ intermediate, not detected nor isolated, that further reacts with a non-coordinated nucleophile (i.e., by means of an outer-sphere

• mechanism). Those intermediates are quite reactive, in contrast to similar but low reactive gold–carbene complexes recently and independently described by the groups of Fürstner [19] and Straub [20]. Scheme 4a shows a generally accepted mechanism for the metal-catalyzed carbene transfer from diazo compounds

Olefin metathesis in air

• Lorenzo Piola,
• Fady Nahra and
• Steven P. Nolan

Beilstein J. Org. Chem. 2015, 11, 2038–2056, doi:10.3762/bjoc.11.221

• reaction with styrene, avoiding the use of hazardous diazo compound 7 [82]. Towards the end of 2013, a report by Olszewski, Skowerski and co-workers showed how a variety of commercially available catalysts (Figure 12) could be employed in air with nondegassed ACS grade green solvents. Their results were in

Synthesis of quinoline-3-carboxylates by a Rh(II)-catalyzed cyclopropanation-ring expansion reaction of indoles with halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2015, 11, 1944–1949, doi:10.3762/bjoc.11.210

• transition metal-catalyzed C–H functionalization by diazo compounds [5][6][7][8]. The reactions of indoles with electrophilic metal-bound carbenes, or carbenoids, generated from diazo compounds, takes place under mild reaction conditions. The reaction has been studied for the three principle classes of

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• precursor 333 was obtained from diazo ester 331 in five steps. Further, the RRM of 333 with catalyst 2 furnished the required pyran derivative 334 (71%). Next, the fused ether 334 was transformed into the desired intermediate 335 in eight steps, which is a key intermediate required for the synthesis of

Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application to the synthesis of SF₅-substituted phenylboronic esters and iodobenzenes

• George Iakobson,
• Junyi Du,
• Alexandra M. Z. Slawin and
• Petr Beier

Beilstein J. Org. Chem. 2015, 11, 1494–1502, doi:10.3762/bjoc.11.162

• for an efficient reaction. Alkali metal acetates are known to facilitate decomposition of aryldiazonium salts by the formation of diazoacetates and diazo anhydrides, which decompose to aryl radicals [76]. These additives were used in Meerwein arylation of isopropenyl acetate [77]. In our case, two

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• density. Synthesis of glycoconjugate DNA by diazo-coupling. β-Galactose-modified deoxyuridine phosphoramidite used for solid-phase DNA synthesis and DNA display of glycan. (NHS)-carboxy-dT phosphoramidite as a general entry for the solid-phase synthesis of glycan–DNA conjugates. Preparation of the DNA

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

• , Poland 10.3762/bjoc.11.57 Abstract The 1,3-dipolar cycloaddition of acyclic 2-diazo-1,3-dicarbonyl compounds (DDC) and thioketones preferably occurs with Z,E-conformers and leads to the formation of transient thiocarbonyl ylides in two stages. The thermodynamically favorable further transformation of C

• , carbocyclic diazodiketones are much less reactive under similar conditions due to the locked cyclic structure and are unfavorable for the 1,3-dipolar cycloaddition due to the Z,Z-conformation of the diazo molecule. This structure results in high, positive values of the Gibbs free energy change for the first

• 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

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

• , rhodium carbenoids derived from α-diazocarbonyl compounds transform 2H-azirines 1 to azirinium ylides 5 (Scheme 1) which undergo facile N–C2 bond cleavage to give 2-azabuta-1,3-dienes 3. Recently we showed that the use of α-diazo-β-ketoesters 2 in these reactions, which are finished by 1,6-cyclization of

• 5-acyl-substituted 2H-1,4-oxazines. They could, in principle, be prepared from azirines and α-diazo ketones or 2-diazo-1,3-diketones via ring opening across the N–C2 bond in the intermediate azirinium ylides to form 2-azabuta-1,3-dienes and subsequent cyclization of the latter into 2H-1,4-oxazines

Three-component synthesis of C₂F₅-substituted pyrazoles from C₂F₅CH₂NH₂·HCl, NaNO₂ and electron-deficient alkynes

• Pavel K. Mykhailiuk

Beilstein J. Org. Chem. 2015, 11, 16–24, doi:10.3762/bjoc.11.3

• AS-136A [55]) (Scheme 3). Conclusion In summary, a novel approach to C2F5-substituted pyrazoles has been elaborated by a three-component reaction between C2F5CH2NH2·HCl, NaNO2 and electron-deficient alkynes. This method is highly practical: it does not require a) the pre-isolation of toxic diazo

Enantioselective synthesis of polyhydroxyindolizidinone and quinolizidinone derivatives from a common precursor

• Nemai Saha and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2014, 10, 3104–3110, doi:10.3762/bjoc.10.327

• other reasons, several novel methodologies have been developed towards the synthesis of polyhydroxylated indolizidine and quinolizidine derivatives as analogues of natural products which involved RCM [21][22][23][24], dipolar cycloaddition [25][26], nucleophilic substitution [27][28], diazo insertion

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

• diazo esters with 5-alkoxyisoxazoles is a good approach to 1,4-di(alkoxycarbonyl)-2-azabuta-1,3-dienes. The reaction conditions for the preparation of aryl- and halogen-substituted 2H-1,3-oxazines and 1,4-di(alkoxycarbonyl)-2-azabuta-1,3-dienes from isoxazoles were investigated. Keywords: diazo esters

• ; 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

C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

• Sebastian Rabe,
• Johann Moschner,
• Marina Bantzi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 1564–1569, doi:10.3762/bjoc.10.161

• analog that still exhibits similar inhibitory activity on hedgehog-signaling. For the sake of brevity of the overall synthetic sequence we defined carbacyclopamine analog 2 (see Figure 1) as our primary target. Results and Discussion A retrosynthetic analysis identified diazo compound 3 as a key

• was thought to establish the C-nor-D-homo steroid system, and a gold-catalyzed amination/annulation/aromatization sequence was planned to install the pyridine F-ring. Diazo compound 3 originates from diene 4 through standard transformations, the latter being accessible from commercially available and

A tandem Mannich addition–palladium catalyzed ring-closing route toward 4-substituted-3(2H)-furanones

• Jubi John,
• Eliza Târcoveanu,
• Peter G. Jones and
• Henning Hopf

Beilstein J. Org. Chem. 2014, 10, 1462–1470, doi:10.3762/bjoc.10.150

• palladium catalysis afforded 4-substituted furanones in good to excellent yields. 4-Hydrazino-3(2H)-furanones could also be synthesized from diazo esters in excellent yields by utilising the developed strategy. We could also efficiently transform the substituted furanones to aza-prostaglandin analogues

• closure of the primary adduct to form the furanone. In this paper, we report our investigations that extend the reaction to heteroatom-containing electrophiles such as imines and diazo esters. Results and Discussion Following the work on nitrostyrenes, Yan et al. also reported a two-step asymmetric route

• entry 2 of Table 2 we can confirm that palladium catalyzes the reaction. The generality of the reaction was checked with different diazo esters 19a–c with 4-chloroacetoacetate esters 2a and 2b under the optimized conditions (diazo ester (1.0 equiv), 4-chloroacetoacetate (1.1 equiv), Pd(PPh3)4 (5 mol

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

• ][17][18][19][20][21]. 2H-Azirines can react with ketenes both with cleavage and preservation of the three-membered ring [22][23][24][25][26]. It was found that acylketenes, which are generated in situ from diazo ketones, undergo cycloaddition with 3-mono- and 2,3-disubstituted-2H-azirines to afford 2

• 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

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

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• formal [4 + 3] cycloaddition [82]. Starting from 4-methoxyphenol (90) Friedel–Crafts acylation and cyclization provided bicycle 91. Wittig olefination furnished benzofuran 92. Diazotransfer using p-ABSA yielded the crucial diazo compound 93, which was used in the following enantioselective

• ethyl vinyl ether. The necessary diazo moiety was installed using tosylazide as a diazo-transfer reagent to yield 134. Copper catalyzed intramolecular cyclopropanation furnished bicycle 135. Reduction of the carbonyl moiety and protection of the resulting alcohol was followed by ether cleavage and

• -catalyzed cyclopropanation of silyl-enol-diazo compound 101 and Boc-protected pyrrole 147 resulted in the formation of intermediate cis-divinylcyclopropane 148, that rearranged under the reaction conditions to give the corresponding highly substituted bridged cycloheptadiene 149. Deprotection of the enolate

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

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

• diazoalkanes, diazoesters and diazoketones [1][2][3][4]. Due to their high dipolarophilic reactivity thioketones were given the name ‘superdipolarophiles’ [3][4]. It might be expected that these highly reactive dipolarophiles could also easily react with the deactivated 1,3-dipoles of 2-diazo-1,3-dicarbonyl

• 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

• diazodicarbonyl compounds with arylsubstituted (aromatic) thioketones to establish their suitability for the preparation of 1,3-oxathioles and other sulfur-containing heterocycles [7][8]. The main goal of the present study was to investigate the scope and limitations of cycloaddition reactions of 2-diazo-1,3

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

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• Rh(II)-catalyzed C–H and OH insertion reactions (Scheme 4). The preparation of both enantiomeric furanose building blocks commenced with the Rh2(OAc)4-catalyzed OH insertion of 39, respectively 40 into the α-diazo-β-ketoester 40. A tandem [3,3]/[1,2]-rearrangement cascade, followed by reductive

Gold-catalyzed regioselective oxidation of propargylic carboxylates: a reliable access to α-carboxy-α,β-unsaturated ketones/aldehydes

• Kegong Ji,
• Jonathan Nelson and
• Liming Zhang

Beilstein J. Org. Chem. 2013, 9, 1925–1930, doi:10.3762/bjoc.9.227

• permits a safe and efficient access to α-oxo gold carbenes without resorting to the dediazotization strategy [3][4][5] using hazardous and potentially explosive diazo substrates (Scheme 1). Since then an array of versatile synthetic methods has been developed based on the general approach by us [2][6][7

• ratio of 5a-OAc and 5a-H in the gold-catalyzed oxidation of 4a (reaction conditions: 5 mol % gold catalyst, 1.5 equiv of 3, DCE, rt, 3 h). Natural charges at and the 13C chemical shifts of the alkynyl carbons in 4a. Generation of α-oxo gold carbenes via intermolecular oxidation of alkynes: a non-diazo

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