Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• oxidizing agent serves to generate oxime radicals from oximes and perform one-electron oxidation of 1,3-dicarbonyl compounds 45. The formation of oxime radicals under the reaction conditions was confirmed by EPR spectroscopy [46]. 1,3-Diketones and 1,3-ketoesters with easily oxidizable groups, such as allyl

• Kharash peroxidation of 1,3-dicarbonyl compounds [88][89][90][91][92][93] did not occur, and a selective formation of the C–O product with oximes was observed. Benzylmalononitrile (47) was introduced into the oxidative C–O coupling with diacetyl oxime (19) analogously to 1,3-dicarbonyl compounds [46], but

• , including oximes, was demonstrated [44]. In contrast to the cross-dehydrogenative coupling of oximes with 1,3-dicarbonyl compounds, both one-electron oxidants (Fe(ClO4)3, (NH4)2Ce(NO3)6) and two-electron oxidants (PhI(OAc)2, Pb(OAc)4), that vary greatly in properties, are applicable for this process. After

Emission solvatochromic, solid-state and aggregation-induced emissive α-pyrones and emission-tuneable 1H-pyridines by Michael addition–cyclocondensation sequences

• Natascha Breuer,
• Irina Gruber,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 2684–2703, doi:10.3762/bjoc.15.262

• be isolated in 30% yield, while the aniline derivative was not formed (Scheme 3). There are only a few known methods for the synthesis of this kind of 1H-pyridines. In a cyclocondensation, starting from 1,3-dicarbonyl compounds, Elnagdi and co-workers synthesized 1H-pyridines with an additional cyano

In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5-a]pyrimidines

• Irina G. Tkachenko,
• Sergey A. Komykhov,
• Vladimir I. Musatov,
• Svitlana V. Shishkina,
• Viktoriya V. Dyakonenko,
• Vladimir N. Shvets,
• Mikhail V. Diachkov,
• Valentyn A. Chebanov and
• Sergey M. Desenko

Beilstein J. Org. Chem. 2019, 15, 2390–2397, doi:10.3762/bjoc.15.231

• was assayed with 1,1-diphenyl-2-picrylhydrazyl. Keywords: 5-aminotetrazole; antioxidant activity; 1,3-dicarbonyl compounds; multicomponent synthesis; tetrazolo[1,5-a]pyrimidines; Introduction Tetrazolo[1,5-a]pyrimidines and their partially hydrogenated derivatives are known for their interesting

• promising for further detailed studies. Conclusion The three-component method which is based on the in-water reaction of 5-aminotetrazole with 1,3-dicarbonyl compounds and aliphatic aldehydes, like formaldehyde or acetaldehyde, under microwave activation, was applied for the preparation of low-molecular

• -mass 4,7-dihydrotetrazolo[1,5-a]pyrimidines. The use of acetoacetic ester derivatives as 1,3-dicarbonyl compounds in the reaction showed high selectivity under catalyst-free conditions, whereas in the case of acetylacetone the formation of a side product was observed. The desired product could be

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• ) complexes as catalyst for the Michael addition of 1,3-dicarbonyl compounds to nitroalkenes [47][48][49][50][51][52][53][54]. This reaction was used as a key stage in the synthesis of non-racemic analogues of GABA and substituted pyrrolidinones with neurotropic activity [47][51][52][54]. It should be noted

• proposed mechanism for 1,3-dicarbonyl compounds [47] to explain how Ni catalysts are able to activate the substrates. The postulated catalytic cycle is summarized in Scheme 1. We assume that the β-ketosulfone coordinates to the Ni complex generating Ni-enolate B. The nitroalkene is activated by

• coordination to Ni. The complex B regenerates after the conjugate addition via transition state C and coordination of a new β-ketosulfone molecule to Ni. TS1 and TS2 are proposed by analogy with 1,3-dicarbonyl compounds [47] to rationalize the asymmetric induction. As illustrated in Scheme 2, β-ketosulfone is

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• - and meta-substituted anilines 2 did not produce isoindolinones 32, and aliphatic amines only reacted when p-toluenesulfonic acid was present. The reaction has also been applied to 1,3-dicarbonyl compounds, however, only residual amounts of isoindolinones 32 were detected and deamination products

• can intramolecularly attack the ester function, giving rise to lactam 32. As pointed out above, unfortunately this methodology did not work properly when it was first applied to 1,3-dicarbonyl compounds. Nevertheless, more recently, two research groups have disclosed, nearly simultaneously, the three

• -component cyclization of 2-formylbenzoic acids, primary amines and a 1,3-dicarbonyl compounds. The first proposal uses 2-formylbenzoic acid 33 (R = H, conditions A, Scheme 9), cyclic aliphatic and aromatic diketones 34 such as dimedone (R2R3 = -CH2CMe2CH2-) as the 1,3-dicarbonyl partner and a variety of

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• another molecule Mn(OAc)3 [48]. Later, Shi et al. demonstrated an oxidative annulation of MCPs 1 with 1,3-dicarbonyl compounds 7 using manganese(III) catalysis under room temperature conditions, which afforded 4,5-dihydrofuran derivatives 8 as [3 + 2] annulation products (cyclopropyl retained adducts) in

• oxidative radical ring-opening/cyclization of cyclopropane derivatives. Mn(OAc)3-mediated oxidative radical ring-opening and cyclization of MCPs with malonates. Mn(III)-mediated oxidative radical ring-opening and cyclization of MCPs with 1,3-dicarbonyl compounds. Heat-promoted ring-opening/cyclization of

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• -dicarbonyl compounds, and ammonium acetate promoted by acid under aerobic conditions [37][38]. Furthermore, Brønsted- and Lewis-acid-catalyzed cyclization reactions between β-enamino esters (derived from β-ketoesters and ammonium acetate) and alkynones/α,β-unsaturated carbonyls/in situ generated α,β

• construction of pyridines bearing a carboxylate or CN group at C3 position has been a lucrative target for chemists due to the pharmaceutically privileged status (Figure 1). In this context, Rodriguez’s group successfully established a one-pot three-component reaction between β,γ-unsaturated α-ketoesters, 1,3

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• another published article by this research group, silica-supported sulfonated 1,4-diazabicyclo[2.2.2]octane 71 was used for the one-pot tandem Knoevenagel–Michael cyclization reaction between isatin derivatives 32 or acenaphthenquinone (33), barbituric acid derivatives 73, and 1,3-dicarbonyl compounds 20

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