Novel photochemical reactions of carbocyclic diazodiketones without elimination of nitrogen – a suitable way to N-hydrazonation of C–H-bonds

• Liudmila L. Rodina,
• Xenia V. Azarova,
• Jury J. Medvedev,
• Dmitrij V. Semenok and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2018, 14, 2250–2258, doi:10.3762/bjoc.14.200

• . Results and Discussion The starting diazocyclopentanediones (DDK, 1a–f) were synthesized from the corresponding 1,3-dicarbonyl compounds [31][32][33] employing a diazotransfer reaction [34][35][36][37][38][39]. Diazocyclopentenedione 1g was prepared by thermal cycloelimination from diazodiketones 1d,e [38

Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives

• Zheng-Yi Li,
• Hong-Xiao Tong,
• Yuan Chen,
• Hong-Kui Su,
• Tangxin Xiao,
• Xiao-Qiang Sun and
• Leyong Wang

Beilstein J. Org. Chem. 2018, 14, 1901–1907, doi:10.3762/bjoc.14.164

• convenience and good stereoselectivity [5][6]. Accordingly, different versions of this reaction have been extensively studied. Notably, the Michael addition reaction of 1,3-dicarbonyl compounds to conjugated nitroalkenes is very important for the synthesis of chiral nitro carbonyl compounds, such as bioactive

• of ortho- or para-halogenated substrates. Mechanism study There are two possibilities for the bifunctional thiourea-catalyzed asymmetric Michael addition reaction mechanism as has been summarized by Wang and co-worker [41]. In case of 1,3-dicarbonyl compounds or nitroolefins as substrates in the

• organocatalysts for the enantioselective Michael reactions of nitroolefins to 1,3-dicarbonyl compounds. Under the optimal conditions, catalyst 2 smoothly catalyzed the reactions in mixed solvent of toluene and water (v/v = 2:1) at room temperature to afford the products in high yields (90–99%) and with moderate

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• series of calixarene-based chiral bifunctional tertiary amine–thiourea organocatalysts 54–56 have been synthesized by us and Genc et al. (Scheme 15) [52][53]. Among them, 54a,b were applied to the asymmetric Michael addition of 1,3-dicarbonyl compounds 34 and 57 to a variety of nitroolefins. Although

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• high yields (89–99%) and enantioselectivities (92–99% ee). A lower yield (78%) albeit combined with a high enantioselectivity (94% ee) was obtained in the reaction of a dihalogenated isatin imine (R1 = 4,7-Cl2). The scope of the process was also extended to 1,3-dicarbonyl compounds other than

• symmetrical pentane-2,4-dione, such as 1,3-diphenylpropane-1,3-dione (R2 = R3 = Ph), that also led by reaction with the unsubstituted isatin imine (R1 = H) to the corresponding product in high yield (93%) and enantioselectivity (96% ee). Furthermore, unsymmetrical 1,3-dicarbonyl compounds, such as methyl

• -isatin imines with ethyl nitroacetate (2) catalyzed by a cinchona alkaloid followed by denitration and synthesis of AG-041R. Mannich reaction of N-Boc-isatin imines with 1,3-dicarbonyl compounds catalyzed by a cinchona alkaloid-derived squaramide. Mannich reaction of N-alkoxycarbonylisatin imines with

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• and pregabalin [9][10]. Later, hydrogen-bonding activation proved to be more general for obtaining Michael adducts via the addition of 1,3-dicarbonyl compounds to nitroalkenes. Chiral thioureas and squaramides, particularly those with the bifunctional mode of action, served as excellent catalysts in

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• -aminopyrazole derivatives 16/126 with β,γ-unsaturated-γ-alkoxy-α-ketoesters 175 for the regioselective synthesis of pyrazolo[1,5-a]pyrimidines 177 in refluxing ethanol. The reaction provided high regioselectivity compared to other 1,3-dielectrophiles like 1,3-dicarbonyl compounds. The reaction was proposed to

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

• Alexey M. Starosotnikov,
• Dmitry V. Shkaev,
• Maxim A. Bastrakov,
• Ivan V. Fedyanin,
• Svyatoslav A. Shevelev and
• Igor L. Dalinger

Beilstein J. Org. Chem. 2017, 13, 2854–2861, doi:10.3762/bjoc.13.277

• 10.3762/bjoc.13.277 Abstract 4-Aza-6-nitrobenzofuroxan (ANBF) reacts with 1,3-dicarbonyl compounds and other CH acids to give carbon-bonded 1,4-adducts – 1,4-dihydropyridines fused with furoxan ring. In the case of most acidic β-diketones, which exist mainly in the enol form in polar solvents, the

• , 1,3-dicarbonyl compounds, etc. on furoxans annelated with benzene or heterocyclic ring in the presence of base (Scheme 1). Mononitrobenzofuroxans as well as pyridofuroxan (4-azabenzofuroxan) react as mentioned above [11][12][13][14]. At the same time in the case of highly electrophilic 4,6

• solvents (DMSO, MeCN) and therefore, the mechanism depicted on Scheme 7 seems reasonable. Adducts of 1,3-dicarbonyl compounds to ANBF are generally enolic. At the same time ratios of enolic and diketonic forms depend on the nature of certain CH acid. In case of most acidic diketones (Table 1, entries 3, 4

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• -dicarbonyl compounds has been reported previously by Sasson’s group [73]. We propose that with a strong base like KOH, direct α-bromination of 2a occurs instead of relaying the Br through an α-bromination shuttle as observed in our previous studies [20][21][22]. Other strong bases like NaH and KOEt also

• obtained (Table 1, entries 2 and 3). These results are not surprising as the substrate 1a is a weaker dinucleophile than aminopyridine and thiourea used previously [20][21][22]. However, 56% yield of 3a was obtained with KOH (Table 1, entry 4). The use of KOH as a base in the α-bromination of 1,3

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• their reactions with enolates. Thus, our group has demonstrated that nitrosoacetals of nitrosoalkenes (N,N-bis(silyloxy)enamines 3) smoothly react with 1,3-dicarbonyl compounds in the presence of TBAF or DBU to give the corresponding oximes 6 in moderate to good yields (Scheme 3) [24]. The process is

• oxidative [4 + 1]-annulation of nitrosoalkenes with 1,3-dicarbonyl compounds (Scheme 37). Optimized reaction conditions require 2 equivalents of silver carbonate as oxidizer and K2CO3 as a base to generate nitrosoalkene from a halooxime precursor 1. The plausible mechanism involves the initial conjugate

• nitrosoalkenes. Precursors of nitrosoalkenes NSA. Reactions of cyclic α-chlorooximes 1 with 1,3-dicarbonyl compounds. C-C-coupling of N,N-bis(silyloxy)enamines 3 with 1,3-dicarbonyl compounds. Reaction of N,N-bis(silyloxy)enamines 3 with nitronate anions. Reaction of α-chlorooximes TBS ethers 2 with ester

One-pot multistep mechanochemical synthesis of fluorinated pyrazolones

• Joseph L. Howard,
• William Nicholson,
• Yerbol Sagatov and
• Duncan L. Browne

Beilstein J. Org. Chem. 2017, 13, 1950–1956, doi:10.3762/bjoc.13.189

• designed a 2-step reaction related to our recent work on liquid assisted grinding effects of the fluorination of 1,3-dicarbonyl compounds, in which the dicarbonyl will initially form a pyrazolone in the first reaction prior to undergoing difluorination in the second step (Scheme 1) [17]. Notably this

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• bases like NaOH, KOH, NaOEt etc. have been used as catalyst for the Michael addition of 1,3-dicarbonyl compounds to α,β-unsaturated ketones. In 2004, Wang and co-workers first reported a mechanochemical Michael reaction of 1,3-dicarbonyl compounds with chalcones and azachalcones using the mild base

• desired product at 25 Hz within 30 min (Scheme 13) [69]. The oxidant DDQ was added in portions at 7 min intervals to get better yields. Different active methylene compounds like diethylmalonate, dibenzylmalonate, malonitrile, and unsymmetrical 1,3-dicarbonyl compounds were explored for the CDC reaction

• and co-workers reported bromination of phenol derivatives, chalcones, 1,3-dicarbonyl compounds using NaBr as bromine source and oxone as oxidant under ball-milling conditions [96]. Within 1 h they could isolate more than 90% of mono or poly-brominated products of phenol and 1,3-dicarbonyl compounds

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

• Josef Jansa,
• Ramona Schmidt,
• Ashenafi Damtew Mamuye,
• Laura Castoldi,
• Alexander Roller,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2017, 13, 895–902, doi:10.3762/bjoc.13.90

• most common strategies employ reactions of 1,3-dicarbonyl compounds or α,β-unsaturated carbonyl compounds with substituted hydrazines [4][6][19]. To overcome the drawbacks of this method, namely insufficient regioselectivity [20], other accesses such as, for instance, regioselective metalations of N

Et₃B-mediated and palladium-catalyzed direct allylation of β-dicarbonyl compounds with Morita–Baylis–Hillman alcohols

• Ahlem Abidi,
• Yosra Oueslati and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2402–2409, doi:10.3762/bjoc.12.234

• interesting synthesis of bicyclic dienones in a one-pot process involving the reaction of 2-(acetoxymethyl)cyclohex-2-enone with 1,3-dicarbonyl compounds using K2CO3 as a weak base. Later, Chamakh and Amri [38] have described a one-pot synthesis of (E)-4-alkylidene-2-cyclohexen-1-ones through a cross coupling

• -enone (1a) and acyclic ethyl 2-(hydroxymethyl)acrylate (1b), under the action of 1,3-dicarbonyl compounds 2, in the presence of an appropriate palladium catalyst and Et3B as a Lewis acid promoter, into the allylation compounds 3–8 with the formation of only water as a byproduct. These derivatives can be

• optimized conditions (Table 1, entry 4), we examined the scope of the catalytic system, Et3B/ Pd(OAc)2/PPh3, for a wide range of 1,3-dicarbonyl compounds and related derivatives (pKa = 9–14) [29][31] using two typical MBH alcohols 1a and 1b. The results of this study are summarized in Table 2. Like diethyl

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• -azolyl-1,3-dicarbonyl compounds with hydroxylamine and cyanomethylazoles with hydroxamoyl chlorides are used for the synthesis of a few representatives of 4-(azol-5-yl)isoxazoles [1][4][12][13][14][15][16]. Cycloaddition reactions of azolylacetylenes with nitrile oxides are an alternative method for the

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• not isolable and spontaneously recyclized to dihydropyridinylphosphonate 150 (Scheme 32) [46]. In this way, the reaction of 6-methyl-3-formylchromone (75) with cyclic 1,3-dicarbonyl compounds such as dimedone (151), 1-phenylpyrazolidine-3,5-dione (153) or barbituric acid (155) afforded the fused

• oxidative domino three-component reaction of α-ketophosphonates 290, ammonium acetate and various 1,3-dicarbonyl compounds 289 to give pyridinylphosphonates 291 has been described. This method allowed the synthesis of highly functionalized pyridinylphosphonates 291 in 63–80% yields in refluxing AcOH/toluene

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• efficacy. We also examined an alternative approach to β-ketoenamides by the addition of carboxylic acid amides to alkynones. This approach can potentially lead to products that are formally derived from unsymmetrically substituted 1,3-dicarbonyl compounds. The best result was obtained with picolinic acid

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• dichloromethane at 15 °C (Scheme 15) [48]. Although high yields were obtained in all cases, the best enantioselectivity was provided by the bifunctional cis-aminoindanol-based squaramide 43. Under these conditions, several 1,3-dicarbonyl compounds 36 reacted with many different nitrostyrene derivatives 3 with

• very low catalytic charge (1 mol %), affording a broad scope of the enantiomerically enriched β-nitroalkyl products 38. A possible drawback of the method would be the low diastereoselectivity generally achieved for the nonsymmetrical 1,3-dicarbonyl compounds 36. In order to understand the role of the

• the proposed transition state TS12. Addition of 3-oxindoles 39 to 2-amino-1-nitroethenes 40, catalyzed by 41. Michael addition of 1,3-dicarbonyl compounds 36 to the nitroalkenes 3 catalyzed by the squaramide 43. Asymmetric aza-Henry reaction catalyzed by the aminoindanol-derived sulfinyl urea 50

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• (Scheme 42) [62]. The resulting (R)-3-nitro-2H-chromene was isolated in rather moderate optical purity. In 2010, a domino Michael hemiacetalization reaction was reported between cyclic 1,3-dicarbonyl compounds 134 and β-unsaturated α-ketoesters 87 utilizing a novel tyrosine-derived thiourea 135 (Scheme 43

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

• ], multicomponent reactions [8], ring-closing metathesis approaches [9][10], tandem reactions of 1,3-dicarbonyl compounds [11][12] and cyclocondenzation reactions of salicylic aldehydes with α,β-unsaturated carbonyl compounds [13][14][15]. The utility of some of these methods are limited by drawbacks such as

Fe(II)/Et₃N-Relay-catalyzed domino reaction of isoxazoles with imidazolium salts in the synthesis of methyl 4-imidazolylpyrrole-2-carboxylates, its ylide and betaine derivatives

• Ekaterina E. Galenko,
• Olesya A. Tomashenko,
• Alexander F. Khlebnikov,
• Mikhail S. Novikov and
• Taras L. Panikorovskii

Beilstein J. Org. Chem. 2015, 11, 1732–1740, doi:10.3762/bjoc.11.189

• -dicarbonyl compounds under relay catalysis [31]. Taking into account the facts discussed above, we envisioned that the synthesis of 5-alkoxycarbonylpyrrol-3-ylimidazolium salts 1 could be carried out starting from easily available 5-alkoxyisoxazoles 7 [32][33] and 1-alkyl-3-phenacyl-1H-imidazolium bromides 9

• alkyl 2H-azirine-2-carboxylates can be prepared by isomerization of 5-alkoxyisoxazoles under Fe(II)-salt catalysis [30]. Quite recently this isomerization has been used for the preparation of substituted pyrrole-2-carboxylic acid derivatives by the domino reaction of 3-aryl-5-methoxyisoxazoles with 1,3

Development of variously functionalized nitrile oxides

• Haruyasu Asahara,
• Keita Arikiyo and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2015, 11, 1241–1245, doi:10.3762/bjoc.11.138

• ], nitriles [6], and 1,3-dicarbonyl compounds [7] to afford the corresponding polyfunctionalized heterocyclic compounds, which are not easily obtained by other approaches. Although this protocol is expected to be useful for synthesizing polyfunctionalized compounds, it is limited by the need of a N

Highly selective palladium–benzothiazole carbene-catalyzed allylation of active methylene compounds under neutral conditions

• Antonio Monopoli,
• Pietro Cotugno,
• Carlo G. Zambonin,
• Francesco Ciminale and
• Angelo Nacci

Beilstein J. Org. Chem. 2015, 11, 994–999, doi:10.3762/bjoc.11.111

• by extending the coupling to a series of 1,3-dicarbonyl compounds and allylic carbonates (Table 2). For these reactions, to further simplify the operating procedure of the proposed protocol, we chose to use the palladium–carbene catalyst prepared in situ as reported above (Table 1, entries 20–22

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

• of a wide variety of nitrogen containing heterocyclic compounds [1][2][3][4][5]. These reactions are generally known for diazoalkanes and 2-diazocarbonyl compounds, whereas similar processes with 2-diazo-1,3-dicarbonyl compounds (DDC) are far less common [6][7][8][9][10], and reported literature data

• performed a detailed experimental study of reactions of a series of 2-diazo-1,3-dicarbonyl compounds 1 with aromatic and aliphatic thioketones 2, and it was established that they occurred in a varied manner: acyclic diazodicarbonyl compounds 1 readily reacted with thioketones 2, whereas carbocyclic

The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles

• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess and
• Viktor I. Saloutin

Beilstein J. Org. Chem. 2015, 11, 385–391, doi:10.3762/bjoc.11.44

• ; diethyl 2-ethoxymethylidenemalonate; 2-ethoxymethylidene-3-oxo esters; ethyl 2-ethoxymethylidenecyanoacetate; Introduction 2-Ethoxymethylidene-1,3-dicarbonyl compounds are widely recognized as valuable building blocks in designing various open-chain and heterocyclic compounds, including those used in

• ], antiviral [14], antimicrobial and antioxidant activity [15] have been found among them. The known tetrazolo[1,5-a]pyrimidines were synthesized by cyclocondensation of 5-AT with 1,3-dicarbonyl compounds or their derivatives [16]. Moreover, a convenient method for obtaining this heterocyclic skeleton is the