Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• amination by oxidative C−H bond functionalizations. These methods showed significant improvement with respect to the substrate scope and reaction conditions. However, mostly they are restricted to substrates containing hydrogen [13][14], alkyl [14][15], or (substituted) phenyl moieties [14][16][17] as N

A versatile way for the synthesis of monomethylamines by reduction of N-substituted carbonylimidazoles with the NaBH₄/I₂ system

• Lin Chen,
• Xuan Zhou,
• Zhiyong Chen,
• Changxu Wang,
• Shunjie Wang and
• Hanbing Teng

Beilstein J. Org. Chem. 2022, 18, 1032–1039, doi:10.3762/bjoc.18.104

• the methylation reagents and the reductive amination reactions by using formaldehyde or paraformaldehyde as the “indirect” alkylation reagents [16][17][18][19]. Recently, a variety of promising methylating agents or C1 sources such as formic acid [20][21], methanol [22][23][24][25][26][27][28][29][30

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• reductive amination/cyclization of enantiopure cis-cyclopropane dicarbonyls [26]. The strategy based on azomethine ylide cycloadditions to cyclopropenes enables ready access to a wide range of spiro-fused 3-azabicyclo[3.1.0]hexanes (Scheme 1a). Inspired by our recent achievements, we have focused on

New synthesis of a late-stage tetracyclic key intermediate of lumateperone

• Mátyás Milen,
• Bálint Nyulasi,
• Tamás Nagy,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2022, 18, 653–659, doi:10.3762/bjoc.18.66

• -toluenesulfonate followed by reduction of the N-methylated quaternary ammonium salt 25 with sodium borohydride gave tetrahydroquinoxaline 26. Since N-amination of the latter with hydroxylamine-O-sulfonic acid [14] had been unsuccessful, we tried to achieve our target via the N-nitroso derivative 27, which was

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• Dongming Zhang Bin Lv Pan Gao Xiaodong Jia Yu Yuan College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, P. R. of China 10.3762/bjoc.18.65 Abstract An efficient Cu-catalyzed strategy for the direct C–H amination of arenes in high yields using N-hydroxyphthalimide as

• the amidyl radical precursor under air is reported. A possible mechanism is proposed that proceeds via a radical reaction in the presence of CuBr and triethyl phosphite. Keywords: amination; copper; N-hydroxyphthalimides; radical reactions; triethyl phosphite; Introduction Practical methods for

• applied in amination reactions [17][18][19][20][21][22][23][24]. Especially, N-hydroxyphthalimide can react with arenes directly in the presence of palladium [25] or gold [26] (Scheme 1, reactions 1 and 2). Recently, we found that iron catalyzes the amination of arenes with N-hydroxyphthalimide under air

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• direct C–H amination is vital to provide many amine derivatives by sustainable methods [36][37]. The dehydrogenative C–N cross-coupling reactions from unreactive N–H and C–H bonds can lead to various nitrogen-containing heterocycles [32][38]. Herein, we disclose the DDQ-mediated oxidative C–N coupling

Substituent effect on TADF properties of 2-modified 4,6-bis(3,6-di-tert-butyl-9-carbazolyl)-5-methylpyrimidines

• Irina Fiodorova,
• Tomas Serevičius,
• Rokas Skaisgiris,
• Saulius Juršėnas and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 497–507, doi:10.3762/bjoc.18.52

• -9H-carbazol-9-yl)-5-methyl-2-methylthiopyrimidine (tCbz-mPYR) as a starting material for the synthesis of 2-substituted pyrimidine emitters (Scheme 1). Compound tCbz-mPYR was synthesized by using the palladium-catalyzed Buchwald–Hartwig amination reaction of 4,6-dichloro-5-methyl-2-methylpyrimidine

Comparative study of thermally activated delayed fluorescent properties of donor–acceptor and donor–acceptor–donor architectures based on phenoxazine and dibenzo[a,j]phenazine

• Saika Izumi,
• Prasannamani Govindharaj,
• Anna Drewniak,
• Paola Zimmermann Crocomo,
• Satoshi Minakata,
• Leonardo Evaristo de Sousa,
• Piotr de Silva,
• Przemyslaw Data and
• Youhei Takeda

Beilstein J. Org. Chem. 2022, 18, 459–468, doi:10.3762/bjoc.18.48

• mono-functionalized compound DBPHZ-OTf, the target compound 1 was successfully synthesized through a Pd-catalyzed Buchwald–Hartwig amination with phenoxazine (POZ) in a good yield as red-brown solid (Scheme 1). The D–A–D counterpart POZ-DBPHZ was synthesized according to the previously reported process

Synthesis of piperidine and pyrrolidine derivatives by electroreductive cyclization of imine with terminal dihaloalkanes in a flow microreactor

• Yuki Naito,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 350–359, doi:10.3762/bjoc.18.39

• ]. Conventional synthetic methods for piperidine derivatives include nucleophilic substitution (route (1) in Scheme 1), reductive amination (route (2)), intramolecular cyclization of amines and alkenes (route (3)), the Diels–Alder reaction and subsequent reduction (route (4)), and the radical cyclization reaction

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• ligands (Figure 7a). The normally used analogous smaller-sized host was assembled with naphthalene-walled ligands, which had been used widely in mediating various reactions, including dehydration reaction [65], aza-Darzens reaction [66], and reductive amination [67], etc. [28]. The anionic cage host

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• antitumor agents, several synthetic methodologies have been developed to prepare these compounds. Amination using primary [6][8][9][10][11][12][13] or secondary [14][15][16] amines and 4-chloroquinazolines is among the most employed procedures. Electron-rich amines (e.g., primary aliphatic amines or hydroxy

• -methoxy-N-methylaniline was not efficient under various reaction conditions and afforded the desired product in low yields even in basic medium (AcONa). To address this issue, we investigated a microwave-mediated base-free amination strategy involving a mixture of THF and water (1:1) as solvent system

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

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• ) will be obtained by treatment of the deprotected pyrrolidine 2 with formaldehyde under reductive amination conditions. As described in Scheme 2, isoxazolidine-4,5-diol 3 was readily synthesized in four steps according to our procedure [16], starting from commercially available (E)-4

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

• catalyst [36][37][38][39][40]. However, pre-functionalization of isoquinolines to the corresponding halogenated isoquinolines is the main limitation associated with these protocols as they require noxious halogenated acids for their starting materials preparation. Alternative strategies include, amination

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• desirable. In this sense, Tan and co-workers (2020) developed the first chiral phosphoric acid-catalyzed atroposelective C–H amination of arenes for the synthesis of N-arylcarbazole structures. The atroposelective N-arylcarbazoles 58 were prepared by C–H amination of azonaphthalene derivatives 54 and

• high loading of 20 mol % CPA 18 with a 1-pyrenyl group at the 6,6’-position of the spiro backbone was preferred as the best catalyst for this transformation. Encouragingly, the double atroposelective C–H amination reaction took place and afforded the desired 1,5-dicarbazole naphthalene derivative 63 in

• context, Bai and co-workers (2019) developed the direct intermolecular enantioselective C–H amination of N-aryl-2-naphthylamines 92 with azodicarboxylates 93 to prepare N–C atropisomers of nonbiaryl naphthalene-1,2-diamine 94. In the presence of chiral phosphoric acids (CPA 15), the desired product 94 was

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

• frequently and at various positions in fluorenones from nature. The model cyclization precursors were prepared in two step syntheses by Suzuki coupling [58] of commercially available ortho-substituted areneboronic acids 7 and bromobenzenes 6, 12, and 13 followed by either reductive amination [59] in the case

• Suzuki cross-coupling reactions, followed by reduction or reductive amination. The oxidative cyclization conditions are compatible with many functional groups on the aromatic rings (methoxy, chloro, cyano, nitro, and phenol protecting groups like TBS and SEM – but not benzyl and methylenedioxy

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• et al. They carried out asymmetric conjugate amination of tert-butylbenzyloxycarbamate (50) to β-nitrostyrene 51 under neutral phase-transfer conditions in the presence of chiral bifunctional tetraalkylammonium bromide (cat. 52) in water-rich biphasic solvent. The reaction proceeded with high ee

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• substrate for the synthesis of the decarboxylated derivative 12 and simultaneously 10 was the expected product of its reaction with 4% HCl. The amine 10 was obtained by reductive amination of veratral (2f) with 2,3-dimethoxybenzylamine (9) with 57% yield and subsequently alkylated with bromoacetaldehyde

• diethyl acetal (11) to give 12 with 73% yield. Additionally, the aminoacetal 12 was also synthesized via another route involving a double reductive amination of the aldehydes 2a and 2f with aminoacetaldehyde acetal (1) with 59% yield. The aminoacetal 12 was then treated with 4% HCl in THF at reflux but in

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• , Zhengzhou University, Zhengzhou, 450001, China School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, He’nan, 453007, China 10.3762/bjoc.17.165 Abstract A copper-catalyzed mono-selective C–H amination of ferrocenes assisted by 8-aminoquinoline is presented here. A range of amines

• the directing group could be removed easily under basic conditions. Keywords: amination; C–H activation; copper; ferrocene; mono-selectivity; Introduction Ferrocene-based compounds have broad applications from asymmetric catalysis to medicinal discovery [1][2][3][4][5][6][7][8]. Therefore, the

• also reported the Co-catalyzed C–H alkoxylation of ferrocenes under nearly room temperature [38]. In comparison, despite the direct C–H amination of arenes with alkylamines has emerged as an efficient strategy to prepare substituted anilines [39][40][41][42][43][44][45][46][47][48][49], the application

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

• proposed mechanism of I2-mediated aza-annulation. Copper-catalyzed amination of (E)-2-en-4-ynyl azides 1. The proposed mechanism of copper-catalyzed amination. The derivatization of sulfonated aminonicotinates. Copper-catalyzed chalcogenoamination of (E)-2-en-4-ynyl azides 1. The possible mechanism of

Isolation and characterization of new phenolic siderophores with antimicrobial properties from Pseudomonas sp. UIAU-6B

• Emmanuel T. Oluwabusola,
• Olusoji O. Adebisi,
• Fernando Reyes,
• Kojo S. Acquah,
• Mercedes De La Cruz,
• Larry L. Mweetwa,
• Joy E. Rajakulendran,
• Digby F. Warner,
• Deng Hai,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2021, 17, 2390–2398, doi:10.3762/bjoc.17.156

• through deviation of the salimethyloxazolinyl-thioester intermediate 8 from the assembly line via an unusually facile C–N-bond opening of the ring to generate an ester bond, and followed directly by amination (+ NH3), the addition of histamine and phenethylamine units to form compounds 1, 2, and 3

• , respectively (Figure 3). Biochemical studies show that histamine and phenethylamine moieties were produced from histidine and phenylalanine substrates by a decarboxylase enzyme [41][42][43]. Pseudomobactin A (4) was proposed logically to have formed through direct amination of the unstable salimethyloxazolinyl

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• Buchwald amination led to the 4-amino-substituted compounds 158 or acids 159 after basic hydrolysis (Scheme 21) [108]. Compound 159c had the maximum potency against IDO1 and TDO with IC50 values of 2.72 mM and 3.48 mM, respectively compared to 159a and 159b, which is 15 and 28.5 times higher than that of

• were taken as partners in a Buchwald coupling (Scheme 22a) [44]. On the other hand, in 2015, Organ’s group performed a phosphine-ligand free Buchwald amination of 5-chloroindole (164) with amine 165 to give the desired product 167, where the use of the Pd-PEPPSI-IPentCl precatalyst 166 in presence of

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• applied in some very sophisticated protocols including several examples reported by the White group. In 2015, White and co-workers reported a new catalytic method using manganese tert-butylphthalocyanine [Mn(t-BuPc)Cl] for the chemoselective intramolecular amination of various C(sp3)–H bond types like

• isosteviol derivate furnished a useful and versatile oxathiazinane (46). The betulinic acid-derived sulfamate ester preferentially underwent amination at the γ primary C–H bond of the equatorial C23 methyl group with high site- and diastereoselectivity to furnish the oxathiazinane derivative in 76% yield

• (Scheme 17C). The White group also reported a series of manganese-catalyzed intermolecular benzylic C(sp3)–H amination reactions using 2,2,2-trichloroethyl sulfamate (TcesNH2) and PhI(OPiv)2 as the oxidant (Scheme 18A and 18B) [131]. The manganese perchlorophthalocyanine [MnIII(ClPc)Cl] catalyst enabled a

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• trans-diazide Mn(IV) complex was proposed to furnish the formation of the C–N3 bond. Manganese-catalyzed late-stage C–H amination The installation of amine functional groups onto biologically active molecules is regarded as a potentially versatile synthetic transformation for accessing diverse potent

• ® (antiplatelet), Gleevec® (anticancer), and augmentin (antibiotic), also contain the benzylic amine motif. Therefore, C–H amination is synthetically important for the diversification of biologically active molecules. Transition metal catalysis has set the stage for C–H amination processes in organic syntheses

• [49]. To date, there are several examples of late-stage C–H amination methods that utilize iron and manganese as 3d transition metal catalysts [50][51][52]. However, intermolecular benzylic C–H amination has rarely been explored due to the challenges associated with selectivity and reactivity. In 2018

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• functional groups as they were unveiled. The functionalized C5 fragments were coupled via reductive amination revealing the C10 carbon backbone. Deprotection of the alcohol and amine functional groups successfully provided ent-pavettamine as a TFA salt. Keywords: chiral sulfoxide; ent-pavettamine

• , whose values differ for the syn-1,3 diol when compared to the anti-1,3-diol as described after an extensive study by Rychnovsky et al. [21]. The reductive amination of the aldehyde with benzylamine allowed for the introduction of a protected terminal amine group to the C5 fragment, yielding 19 in a

• reductive amination employing sodium triacetoxyborohydride as the reducing agent. The desired product precursor 27 was successfully recovered as a yellow oil in a yield of 95%. HRMS showed the desired mass whilst NMR spectroscopy showing a single set of signals for each half of the structure, confirmed the