Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• ], and sulfonic acids [31]. On the other hand, nitrogen-based nucleophiles amenable to this reaction manifold have thus far been limited to nitriles in the context of Ritter-type iodo(III)amidation [29]. In light of the significance of vinylated azoles, our attention was attracted to the feasibility of

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• 109 (Scheme 12A) [58]. The formed products all contained a pendant primary iodide group and the synthesis was additionally shown to be tolerant of functional groups including protected amines (in 110c), protected alcohols (in 110d) and nitriles (in 110e). Grygorenko and co-workers accessed fluorine

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• oxidation, whereas in Nicewicz's report, the alkene is oxidized. This modification allows for a significantly larger reaction scope (Scheme 29). Terminal alkenes and several functional groups such as ethers (163), esters (165), ketones (166), nitriles (167), and enones (170) are tolerated. The

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• example, Wan and co-workers developed a cascade reaction of α-diazo esters, nitriles, and carboxylic acids via the generation of nitrile ylides and Mumm rearrangement affording unsymmetric diacyl α-amino acid esters as products (Scheme 1a) [39]. In 2017, Zhang, Hu, and co-workers developed a Cu-catalyzed

• [42][43][44][45][46][47][48][49], we sought to develop reactions of the unexplored β-trifluoromethyl β-diazo esters. We hypothesized that nitrile ylides, in situ generated from nitriles and β-trifluoromethyl β-amino esters, could also react with carboxylic acids to give nitriliums, which then could

• undergo a Mumm rearrangement to provide unsymmetrical β-trifluoromethyl diacyl-β-amino esters as products (Scheme 1c). Herein, we report our results on the design of β-trifluoromethyl β-diazo esters and their application in a three-component reaction with nitriles and carboxylic acids under mild

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• diaryliodonium salts [29][31], as well as Pd-catalysed methods for synthesizing N-aryl carbazoles [32]. Similar procedures were published for the Cu-catalysed synthesis of aryl carbazoles from amines as well as other heterocycles such as N-acyl acridanes with nitriles using cyclic iodonium salts by Wen and Chen

• with a 47% yield. A method for the synthesis of similar annulated N-heterocycles from iodanes with nitriles is described by Chen et al. [34]. Next, we investigated O-bridged dibenzo[b,e][1,4]iodaoxin-5-ium salts as substrates, as was shown in a recent work [29]. Following the trend, we already observed

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• -bromo-N-acetylhydrazones gave higher yields than the corresponding α-bromo-N-benzoylhydrazones. Also, substituents present in the MBH nitriles of isatins showed marginal effects on the yields. The obtained spiro[indoline-3,5'-[1,2]diazepines] 3a–m were fully characterized by various spectroscopic

• -toluenesulfonylhydrazones 6 have a much higher reactivity compared to that of α-halogenated benzoylsulfonylhydrazones 1 in this reaction. The desired spiro[indoline-3,5'-[1,2]diazepines] 7a–n were obtained in satisfactory yields of 58–83% and the substituents in MBH nitriles of isatins showed only marginal effects on the

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• conditions were later replaced by the use of unstable or toxic radical initiators/chain carriers such as peroxides, azo-nitriles, or very prominently Bu3SnH [88][89]. Only recently have PRC methods emerged, that mostly relied on the use of metal-based photocatalysts and high energy UV/near-UV light [90][91

Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO₂F₂)

• Xian-Lin Chen and
• Hua-Li Qin

Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68

• the construction of a range of δ-olefin-containing aliphatic nitriles with (E)-configuration selectivity. This new method features wide substrate scope, mild conditions, and direct N–O activation. Keywords: direct N–O activation; E-selectivity; nitrile synthesis; ring-opening cross-coupling; sulfuryl

• ][26][27][28][29], a synthesis method for δ-olefin-containing aliphatic nitriles by the radical C–C bond cleavage of cycloketone oxime ester derivatives was developed by Shi’s group (Scheme 2a) [30], which emerged as an efficient strategy to construct C(sp2)–C(sp3) bonds [31][32][33]. Later, Xiao [34

• activated intermediates for a variety of transformations [46][47][48][49][50][51][52][53][54][55][56][57][58]. Lately, we discovered the SO2F2-mediated transformation of primary alcohols to nitriles, involving an aldoxime sulfonyl ester intermediate (Scheme 2c) [59]. Drawing inspiration from these excellent

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• ). These structural features enable the construction of a five-membered ring upon treatment with alkenes [9], diazo compounds (reaction g) [10], and nitriles [11]. Several approaches are available for the synthesis of cyclopropanedicarboxylates 1a, which consist of three steps: 1) conjugate addition, 2

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• thiazole synthesis and elimination to nitriles) were identified. The key factor that enables the successful Eschenmoser coupling reaction involves the optimum balance in acidity of nitrogen and carbon atoms of the intermediary α-thioiminium salts. Keywords: Eschenmoser coupling reaction; Hantzsch thiazole

• sources [7][8][9], primary thioamides were ineffective as reaction components in ECR as they can easily transform into nitriles under the reaction conditions typical for ECR. In fact, there are even three different reaction pathways (Scheme 2) that can compete with the ECR when primary thioamides I react

• ammonium salts [22]. All experiments with salts 6a,b derived from 2b and thiobenzamide or thioacetamide showed that three of four possible products (thiazoles 8a,b, ECR products 9a,b and nitriles; cf. Scheme 3) are formed depending on the reaction conditions specified in Table 1 and Supporting Information

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• ). Thomas and Gunanathan independently reported the borane-catalysed double hydroboration of nitriles using either Me2S·BH3 or H-B-9-BBN, respectively, as the catalyst and HBpin as the turnover reagent (Scheme 9) [72][73]. Both reports proposed similar mechanisms for the Me2S·BH3- and H-B-9-BBN-catalysed

• hydroboration of imines [87][92][97], nitriles [92][98][99][100][101], carbodiimides [92][100][102], pyridine [92], and isocyanides [92] with HBpin (Scheme 23). These generally follow a similar proposed catalytic cycle; aluminium-mediated reduction, followed by Al‒N/B‒H exchange with HBpin (Scheme 23). The

• , acetals, aminals, and alkyl ethers (Scheme 26) [119][120][121]. The proposed mechanism was analogous to the GaI catalysis by Schneider, with an In‒O/B‒C exchange proposed to drive catalytic turnover. Nakazawa reported an iron–indium cooperative catalytic system for the hydroboration of nitriles with HBpin

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• example, the sequential hydrozirconation/carbonylation of propargylic ethers 18 reported by Donato [58] yielded α,β-unsaturated lactones 19. Beside the hydrozirconation/acylation sequence of nitriles utilizing acid chlorides published by Majoral/Floreancig [59][60], Cox revealed that terminal alkynes 16

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• . performed the dehydrosulfurization of thioamides and thioureas that provided nitriles and cyanamides [35]. Using bismuth compounds as desulfurization reagents for synthesizing heteroazoles, this paper presents the syntheses of 2-aryl- and 2-alkylbenzoxazoles through the ring-closure reaction of 2

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• , Chemical Development U.K., AstraZeneca, Macclesfield, SK10 2NA, United Kingdom Medicinal Chemistry, Early Oncology, AstraZeneca, Cambridge, CB4 0WG, United Kingdom 10.3762/bjoc.18.138 Abstract The reduction of nitriles to primary amines is a useful transformation in organic synthesis, however, it often

• relies upon stoichiometric reagents or transition-metal catalysis. Herein, a borane-catalysed hydroboration of nitriles to give primary amines is reported. Good yields (48–95%) and chemoselectivity (e.g., ester, nitro, sulfone) were observed. DFT calculations and mechanistic studies support the proposal

• ]. Traditionally, the reduction of nitriles to primary amines relied on stoichiometric hydride reagents [4]. Current catalytic methods for nitrile reduction, hydrogenation [5][6] or hydroboration [7][8], generally rely on metal catalysts, designer ligands, forcing reaction conditions (such as elevated temperatures

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• applications. NiO2, on the other hand, was used to achieve the dehydrogenation of amines (to nitriles) and to perform the α,β dehydrogenation of ketones 61. 3.2.3 Using chemically active fixed beds (catalysts): Copper metal in the form of wires or turnings can also be inductively heated when placed inside flow

Unusual highly diastereoselective Rh(II)-catalyzed dimerization of 3-diazo-2-arylidenesuccinimides provides access to a new dibenzazulene scaffold

• Anastasia Vepreva,
• Alexander S. Bunev,
• Andrey Yu. Kudinov,
• Grigory Kantin,
• Mikhail Krasavin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2022, 18, 533–538, doi:10.3762/bjoc.18.55

• at the double bond underwent cyclization as the result of intramolecular interception of the rhodium carbene, which led to the formation of indolizine [6] or 2H-chromene [7] derivatives, respectively (Figure 1). At the same time, Rh2(esp)2-catalyzed reactions of DAS with nitriles and carbonyl

• with nitriles [8]. An unexpected and interesting result was the exclusive formation of indenes 3 during the catalytic decomposition of DAS containing an ortho-substituted phenyl group at the nitrogen atom (Table 1, entries 15–17). In all three cases, compounds 3 were obtained in moderate yields, while

Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

• Yelong Lei and
• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6

• synthesis of oxazoline derivatives [11][12]. They mainly include (1) cyclization of 2-amidoethyl halides or sulfonates, which are prepared from carboxylic acid derivatives and vicinal amino alcohols [8][9][10] (Scheme 1a); (2) direct condensation of carboxylic acid derivatives or nitriles with vicinal amino

• alcohols [13][14][15] (Scheme 1a); (3) oxidative condensation of aldehydes with vicinal amino alcohols [16] (Scheme 1b); (4) cyclization of N-allylamides in the presence of electrophilic reagents or radical initiators or catalysts [17] (Scheme 1c); (5) direct synthesis from alkenes and amides or nitriles

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• 2021. Keywords: cyanation; nitriles; photocatalyst; ruthenium; tertiary amines; Introduction Nitriles are a major class of organic compounds having wide significance in materials science, agrochemical and pharmaceutical industry [1]. They are the privileged compounds finding broad applications in

• natural product synthesis, pigments and dyes. Different variety of α-amino carbonyls [2], α-amino acids [3] and 1,2-diamines were prepared from the nitriles using homogeneous and heterogeneous catalysis [4][5][6]. One of the astonishing aspects of nitriles is that it can be easily converted to amines

• acceptance. The conventional approaches towards the synthesis of nitriles include Rosenmund–von Braun reactions, Sandmeyer reactions and industrial ammoxidation reactions [13][14]. But these strategies involve harsh reaction conditions and generation of large amount of heavy metal waste. These drawbacks

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• aliphatic nitriles explored, the reaction further demonstrated the synthetic potential of C(sp3)–H species within CDC methodology. In 2013, the Li group established a carbonyl-arylation of N-arylacrylamides 60 with alkyl and aryl aldehydes 65 (Scheme 11) [83]. Like Li’s report in 2013 (Scheme 10) [80], the

• rate-determining step of this transformation, as well as free radicals being involved in the reaction mechanism. In 2017, Luo and Li described a three-component Ag-mediated Fe-catalyzed 1,2-carboamination of alkenes 82 using alkyl nitriles 76 and amines 105 for the synthesis of γ-amino alkyl nitriles

Synthesis of new pyrazolo[1,2,3]triazines by cyclative cleavage of pyrazolyltriazenes

• Nicolai Wippert,
• Martin Nieger,
• Claudine Herlan,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2021, 17, 2773–2780, doi:10.3762/bjoc.17.187

• = diisopropylamine. Cleavage of the triazene protective group and cyclization of the resulting diazonium intermediate yielding pyrazolo[3,4-d][1,2,3]-3H-triazine derivatives 5a–i. Synthesis of N-substituted pyrazoles 12 and 13. Synthesis of amides 9a–i via reduction of nitriles 12a–g to pyrazolo-ortho-methylamines

Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• of isoquinoline N-oxides [41][42], condensation of lithiated o‐tolualdehyde tert‐butylimines with nitriles [43], electrophilic cyclization of 2-alkynylbenzamides [44][45] or 2-alkynylbenzaldoximes [46][47][48][49][50][51][52][53][54], oxidative C–H functionalizations (coupling) on aryl and heteroaryl

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• of biaryl aldehyde intermediates 8, reduction [60] in the case of nitriles 14, or Boc deprotection [61] for 14k, m, o according to standard protocols (Schemes 4–7; for details, see Supporting Information File 1). Although it may seem counterintuitive to first convert aldehydes 8 and nitriles 14 into

• the corresponding amines 9 and 15 when fluorenones can be obtained directly from aldehydes [35][37] and, to a lesser extent, nitriles [54], it was our goal to characterize amine cyclization furnishing fluorenones specifically. Amine cyclization of this nature is only punctiformly described in the

AlBr₃-Promoted stereoselective anti-hydroarylation of the acetylene bond in 3-arylpropynenitriles by electron-rich arenes: synthesis of 3,3-diarylpropenenitriles

• Yelizaveta Gorbunova,
• Dmitry S. Ryabukhin and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2663–2667, doi:10.3762/bjoc.17.180

• obtained 3,3-diarylpropenenitriles in triflic acid CF3SO3H (TfOH) at room temperature for 1 h are cyclized into 3-arylindenones in yields of 55–70%. Keywords: aluminum bromide; hydroarylation; indenones; propenenitriles; propynenitriles; Introduction Conjugated acetylene nitriles (propynenitriles, R–C≡C

• take part in electrophilic [1][2] and nucleophilic [3][4][5][6] addition reactions onto the acetylene bond leading to various substituted nitriles. Reactions onto both acetylene and nitrile groups are widely used for the construction of various heterocyclic systems [7][8][9][10][11][12][13][14][15

• arenes under the action of the strong Lewis acids, aluminum halogenides AlX3 (X = Cl, Br) and the Brønsted superacid TfOH (CF3SO3H). Results and Discussion It was found that acetylene nitriles 1a–c reacted with arenes in the presence of excess AlBr3 (6 equiv) at room temperature for 0.5–2 h to afford E,Z

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• synthetic utility, we surmised that replacing the aroyl component of the N-phenacyl substituent by electrophilic groups such as esters, amides or nitriles might yield 2,3-dihydro-1H-pyrrolizin-6-ones 13 or their hydroxypyrrole tautomers 13’. Our findings with N-(ethoxycarbonylmethyl)enaminones 14 are

• conditions yielded pyrrolo[2,1-a]isoquinoline products. A somewhat comparable cyclization of N-benzylenaminones has been reported under superbasic conditions [52], while base-induced pyrrole formation from N-(ethoxycarbonylmethyl)enamino esters (vinylogous urethanes) and the corresponding nitriles

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• pyridine derivatives have been developed through the intramolecular or intermolecular tandem addition annulation/functionalization of alkynes with some N-containing compounds, such as nitriles, oximes, and imines [15][16][17][18][19]. The pyrrole structural motif is also an invaluable five-membered N

• converted to the corresponding acid 23 in 94% yield in the presence of KOH (2.0 equiv) in MeOH (Scheme 9). In 2011, Lee and co-workers reported a one-pot method for the construction of polysubstituted pyridines 29 via tandem sequential reactions of nitriles 26, Reformatsky reagents 27, and 1,3-enynes 28

• -aryl-substituted pyrroles 55 in moderate to good yield. In addition, the method could tolerate a wide range of functional groups, such as phenolic hydroxy, aryl bromide, ester, terminal olefin, aryl chloride, and silyl-protected alcohol moieties. Furthermore, both aromatic and aliphatic nitriles