Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• Discussion The reason why we investigated the reaction under mild basic conditions was because nitrile oxides are often generated by dehalogenation of hydroximoyl chlorides in situ under basic conditions or by dehydration of nitroalkanes [30]. So we were wondering whether we could take advantage of that

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• -unsaturated carbonyl compounds catalyzed by bifunctional squaramide catalysts has been developed. This methodology offers both enantiomers of β-silyl nitroalkanes in good to excellent yields (up to 92%) and enantioselectivities (up to 97.5% ee) under solvent-free conditions at room temperature. Control

• experiments reveal that the presence of a β-silyl group in the enones is crucial for high reactivity under the optimized reaction conditions. Keywords: β-silyl α,β-unsaturated carbonyl compounds; β-silyl nitroalkanes; chiral organosilanes; organocatalysis; solvent-free synthesis; Introduction

• organosilanes [29][37][38], we present herein an organocatalyzed conjugate addition reaction of nitromethane to β-silyl enones to afford chiral β-silyl nitroalkanes (Scheme 1). Notably, the developed method was not only carried out under solvent-free conditions at room temperature but was found to be tolerant

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• malonates and Grignard reagents were largely improved to up to 81% and 50%, respectively. The carbanions of aromatics, ketones, nitroalkanes, amides, etc. could also be reasonably well fluorinated and this study showed great progress. However, although these fluorinating agents were stable and easy-to

Organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones

• Chandrakanta Parida and
• Subhas Chandra Pan

Beilstein J. Org. Chem. 2021, 17, 1447–1452, doi:10.3762/bjoc.17.100

• development of catalytic asymmetric conjugate addition reactions [3][4][5]. In particular, the conjugate addition of nitroalkanes and their derivatives to enones has drawn the attention of organic chemists as the corresponding products can be chemoselectively converted to a variety of useful structures [6

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Nitroalkene reduction in deep eutectic solvents promoted by BH₃NH₃

• Chiara Faverio,
• Monica Fiorenza Boselli,
• Patricia Camarero Gonzalez,
• Alessandra Puglisi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2021, 17, 1041–1047, doi:10.3762/bjoc.17.83

• nitroalkanes, valuable precursors of amines. A variety of nitrostyrenes and alkyl-substituted nitroalkenes, including α- and β-substituted nitroolefins, were chemoselectively reduced to the nitroalkanes, with an atom economy-oriented, simple and convenient experimental procedure. A reliable and easily

• ammonia borane in the chemoselective reduction of a variety of nitrostyrenes and alkyl-substituted nitroalkenes to the corresponding nitroalkanes, without any catalyst or additive [13]. We thought that the combination of an atom economic, very convenient and inexpensive reagent such as BH3NH3 in bio-based

• eutectic mixtures as biorenewable alternative solvents in the synthesis of nitroalkanes, valuable precursors of amines, would represent a significant step towards the development of more sustainable synthetic organic methodologies for the preparation of valuable molecules. In the present communication, we

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• , USA 10.3762/bjoc.16.239 Abstract Imidazo[1,5-a]pyridines were efficiently prepared via the cyclization of 2-picolylamines with nitroalkanes electrophilically activated in the presence of phosphorous acid in polyphosphoric acid (PPA) medium. Keywords: cyclization; heterocycles; imidazo[1,5-a

• ]pyridines; nitroalkanes; polyphosphoric acid; Introduction It is hard to overstate the importance of imidazo[1,5-a]pyridines in modern organic and medicinal chemistry. Several natural alkaloids possessing this core were isolated from marine sponges, for example, cribrostatin 6 (Figure 1) [1][2][3]. The

• ][37]. However, given the importance of these targets, new preparative methods are still in high demand. Herein we demonstrate a new synthetic approach towards imidazo[1,5-a]pyridines, taking advantage of the unusual electrophilic properties of nitroalkanes activated by PPA. Results and Discussion

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• -catalyzed acetylation of these alcohols, which gave the corresponding acetates 2a–d [59]. The nitrenones 3a–d were finally obtained in an acceptable yield by reacting the acetate derivatives with the appropriate nitroalkanes [60]. The next step was the transformation of the nitro group of 3a–d via the Nef

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• this sense, while the addition of hard organometallic nucleophiles, such as lithium dialkylcuprates or Grignard reagents, failed, softer nucleophiles such as nitroalkanes cleanly added to the β-position, providing the Michael adduct 61. Unexpectedly, the conjugate addition reaction resulted in

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• reaction in photocatalysis, the oxidation of N-aryl tetrahydroisoquinoline (Scheme 31) [45]. Upon oxidation, the in situ-formed iminium ion was reacted with nitroalkanes, enamines, and indoles. In all cases, the 1-substituted tetrahydroisoquinolines were isolated in good to excellent yields. The reaction

• α-amino radical that is then oxidized to the dihydroisoquinolinium species. Then, the latter reacted with the nucleophile (nitroalkanes, catalytically in situ-formed enamines and indoles) to furnish the product. 2.4 Proton-coupled electron transfer (PCET) The PCET reaction is an interesting and

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

• acceptors and aldehydes [27][28][29][30][31][32], ketones [33], α-cyano esters [34][35], β-keto esters [35], β-keto acids [36], thiomalonates [37], nitroalkanes [38], oxindoles [39] and thiols [40] as Michael donors. There are only few examples of the use of sulfones as Michael donors in asymmetric addition

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• chemistry set-up, which requires a large amount of optimisation itself. A range of nucleophiles including nitroalkanes, cyanides, malonates and phosphonates are used to modify different N-aryltetrahydroisoquinolines. These products have the potential for quite a range of subsequent reactions for elaboration

• benzofused heterocycles (indole etc.) – such as benzimidazoles or tetrazolopyridines are often seen in medicinal chemistry. Singh et al. reported a method for preparing 3-arylnitrobenzimidazoles from 2-aminopyridines and nitroalkanes, using green LED Eosin Y photocatalysis, with molecular oxygen as the

Mild and selective reduction of aldehydes utilising sodium dithionite under flow conditions

• Nicole C. Neyt and
• Darren L. Riley

Beilstein J. Org. Chem. 2018, 14, 1529–1536, doi:10.3762/bjoc.14.129

• piperidines [17], benzil groups [19], nitroarenes and nitroalkanes in the presence of dialkyl viologen electron transfer catalysts [20][21] and immobilized nitroarene’s under phase transfer conditions [22][23]. In this publication we report the efficient reduction of aldehydes under flow conditions utilising

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

• -aminobenzothiazole with acetophenones [55] or aldehydes and nitroalkanes [56]. Because the bicyclic structure of 2-aminobenzothiazole is more stable than aminopyridines and thioureas, the nucleophilicity of the aromatic N atom is reduced. A stronger base, KOt-Bu, is therefore needed for in situ bromination to form

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

• intramolecular cyclization to 5-aminoisoxazoles 88, which were obtained in moderate to good yields. Following this synthetic scheme, 5-aminoisoxazoles 88 can be readily accessed from available nitroalkanes in three steps. Recently, Tanimoto and co-workers [22] reported the addition of TMSCN to a nitrosoallene

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• catalytic amount of potassium iodide (0.2 mmol) and 0.25 mL of tert-butylhydroperoxide (TBHP, 70 wt %) in water (4 equiv) to afford the dihydroisoquinazoline 34a, which got oxidized to the quinazolium intermediate 34b. Hydroxylation of 34b afforded 34c, which was further reacted with nitroalkanes at 50 °C

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

• formation of only water as a side product. This method provides a straightforward and practical route to a range of allylated compounds. Further work is in progress in our laboratory to investigate the Pd catalysis of the reaction of the MBH adducts with various pronucleophiles including nitroalkanes

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• hypochlorite [58] or related electrophilic halogen precursors [59][60] may be used. However, most of these methods result in the formation of nitro derivatives along with the desired nitroso compounds. Relatively new methods for the conversion of nitroalkanes into geminal chloronitroso compounds involving

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

• , a wide scope of the N-Boc-protected imines 48, including aliphatic ones, reacted with an excess of the nitroalkanes 49 at low temperature. This afforded the corresponding products 51 with high yield, diastereomeric ratio and excellent enantioselectivity (Scheme 16) [55]. Some experimental results

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• ; elimination of the catalyst then generates the exo-methylene adduct. For example, Lu and co-workers have used β-ICPD to react isatin-derived MBH carbonates 18 with nitroalkanes 19 [29]. The resulting adducts 20 could be converted to the corresponding spiroxindole 21 via a Zn/HOAc mediated reduction of the

• set up a 4π-electrocyclization, generating second intermediate 27. Elimination of the tertiary amine then gives γ-methylene cyclopentenone 28. 1,2-Addition reactions Henry reaction The use of cupreine and cupreidine derivatives in the addition of nitroalkanes to carbonyl compounds was first

Organocatalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones with bifunctional amine-thiourea catalysts bearing multiple hydrogen-bond donors

• Ming-Liang Zhang,
• Deng-Feng Yue,
• Zhen-Hua Wang,
• Yuan Luo,
• Xiao-Ying Xu,
• Xiao-Mei Zhang and
• Wei-Cheng Yuan

Beilstein J. Org. Chem. 2016, 12, 295–300, doi:10.3762/bjoc.12.31

• amino-alcohols, amino acids and carbonyl compounds [15]. Much attention has been devoted to the development of an efficient catalytic asymmetric version of this reaction from readily accessible nitroalkanes and carbonyl compounds [16], such as aldehydes [17][18][19], α-ketoesters [20], α

• quaternary stereocenters [35][36][37], we envisioned that the Henry reaction of nitroalkanes with 1H-pyrrole-2,3-diones should take place with a chiral bifunctional amine-thiourea catalyst, leading to 3-hydroxy-3-nitromethyl-1H-pyrrol-2(3H)-ones bearing quaternary stereocenters (Scheme 1) [14]. Notably, this

Recent developments in copper-catalyzed radical alkylations of electron-rich π-systems

• Kirk W. Shimkin and
• Donald A. Watson

Beilstein J. Org. Chem. 2015, 11, 2278–2288, doi:10.3762/bjoc.11.248

• recent examples from this emergent area, including copper-catalyzed alkylation reactions of nitroalkanes, alkenes and alkynes. Results and Discussion Additions to nitronate anions The selective C-alkylation of nitroalkanes with alkyl halide electrophiles is a long-standing challenge in organic synthesis

• (Scheme 1). This is mainly because of the propensity of nitronate anions to undergo alkylation at oxygen rather than carbon, a process that has been known for more than 60 years [15]. Recently, our group has developed a copper/diketimine catalyst system to selectively C-alkylate nitroalkanes [16]. While

• nitroalkanes using palladium catalysis were known, prior to our work, no general catalytic methods for the alkylation of nitroalkanes existed. We envisioned that the catalytic generation of an alkyl radical under copper catalysis in the presence of a nitronate anion could lead to C-alkylated products. In

Cathodic hydrodimerization of nitroolefins

• Michael Weßling and
• Hans J. Schäfer

Beilstein J. Org. Chem. 2015, 11, 1163–1174, doi:10.3762/bjoc.11.131

• Michael Wessling Hans J. Schafer Organisch-Chemisches Institut der Westfälischen Wilhelms-Universität, Correns-Straße 40, 48149 Münster, Germany 10.3762/bjoc.11.131 Abstract Nitroalkenes are easily accessible in high variety by condensation of aldehydes with aliphatic nitroalkanes. They belong to

• appears at the cathode, which disappears at the anode. This indicates the formation of coloured nitroalkyl anions and their decolourization by protonation. The nitroalkenes were obtained by condensation of aldehydes with nitroalkanes (Scheme 3, Table 3) [21][22]. For work-up unreacted aldehyde was removed

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• -unsaturated systems [13]. Most of the early work, including Michael’s, involved the use of stabilized or “soft” [14] nucleophiles such as malonates and nitroalkanes. Mechanistically, one can imagine a 1,2-addition of the nucleophile occurring versus the 1,4-addition if the EWG is a carbonyl compound, but this

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• coworkers reported a visible light-mediated aza-Henry reaction that harnesses the synthetic potential of iminium ions. Using only 1 mol % of [Ir(ppy)2(dtbbpy)](PF6) and visible light, a variety of N-aryltetrahydroisoquinolines were oxidatively coupled with nitroalkanes to provide the aza-Henry products in

• , including nitroalkanes, was shown to add to iminium ions. The authors proposed two possible mechanisms for the formation of iminium ions based on the two divergent pathways for the conversion of amine radical cations to iminium ions. The first mechanism is based on the pathway involving abstraction of a

• . König and coworkers showed that the same aza-Henry reaction can be catalyzed by the organic dye Eosin Y to afford the aza-Henry product 18 (Scheme 5) [67]. In addition to nitroalkanes, dialkyl malonates and malononitrile can be used as pronucleophiles to provide β-diester amine 19 and α-aminonitrile 20