Electrochemical vicinal oxyazidation of α-arylvinyl acetates

• Yi-Lun Li,
• Zhaojiang Shi,
• Tao Shen and
• Ke-Yin Ye

Beilstein J. Org. Chem. 2022, 18, 1026–1031, doi:10.3762/bjoc.18.103

• development of a green, efficient, and sustainable protocol for the synthesis of azidoketones is of great significance [7][8][9]. Retrosynthetically, the nucleophilic substitution of α-bromoketones by sodium azide [10] and oxidation of the azido alcohols [11] are among the most straightforward methods to

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• 1-substituted 2-ethoxy-1,2-azaphospholidine-4-carboxylate 2-oxides 203 were synthesized in 70% and 39% yields, respectively, from ethyl 2-((chloro(ethoxy)phosphoryl)methyl)acrylate (202) and benzyl- and adamantylmethylamines via aza-Michael addition and intramolecular nucleophilic substitution. The

• synthetic method showed very limited substrate scope. Only less bulky primary amines underwent the first aza-Michael addition and then intramolecular nucleophilic substitution. However, aromatic amines, aniline, 2,3-dihydro-1H-inden-4-amine, and the bulky aliphatic primary amine adamantylamine did not

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• inexpensive and easy to handle Se powder as the Se source. The reaction proceeded with terminal alkynes having various substitutions, such as aryl, vinyl, and alkyl groups. The obtained alkynyl imidazopyridinyl selenide was found to undergo nucleophilic substitution reaction on Se atom using organolithium

• phenyllithium in THF at −78 °C led to a nucleophilic substitution reaction with the elimination of the ethynyl group to form the desired phenylimidazopyridinyl selenide 6a in 49% yield. In the reaction with n-butyllithium, alkyl derivative 6b was isolated in the same way. The reaction of 4aa with the Ruppert

• synthesized using a simple operation that can be performed under aerobic conditions. Moreover, the results showed that the obtained compounds underwent nucleophilic substitution reactions involving the elimination of the alkyne moiety on Se atoms to form aryl or alkyl imidazopyridinyl selenides and

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• envisioned the bimolecular nucleophilic substitution between an α-halopropiophenone as the “dummy group” scaffold and the corresponding perfluorinated sodium sulfinate salt – also visualized as the installation of the photocleavable moiety onto the perfluoroalkyl chain [15][16][17][18][19]. The precursory

• obtain the corresponding sulfinate in limited yield, the decomposition of this compound after several days at 4 °C, and within a few minutes under heating deemed its applicability impractical. After this first step, we proceeded to test the nucleophilic substitution between our perfluoroalkylsulfinate

• under thermal conditions afforded product 5 in only 30% yield and underscored the sluggish reactivity of these sulfinate derivatives towards undergoing nucleophilic substitution (Scheme 2). To solve this problem, we turned to the use of α-iodopropiophenone (6), generated from its bromide counterpart

A trustworthy mechanochemical route to isocyanides

• Francesco Basoccu,
• Federico Cuccu,
• Federico Casti,
• Rita Mocci,
• Claudia Fattuoni and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 732–737, doi:10.3762/bjoc.18.73

• attributed to their probable reaction mechanism where the nitrogen atom not only promotes the enolate derivative formation as already described in literature [33][34] but it may also generate a positively charged intermediate at the transition state [35], enhancing the nucleophilic substitution. Obviously

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

• nucleophilic substitution of the methylsulfonyl group with sodium cyanide and 4-(tert-butyl)thiophenol. The thorough photophysical analysis was carried out to assess the impact of different substituents in position 2 of the pyrimidine ring. It was shown that HOMO–LUMO overlap and the resulting ΔEST can be

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• the R2O- part of the carbamate group does not modify the structure of linezolid (1), because this molecular moiety is cleaved during the intramolecular nucleophilic substitution in the final reaction step (Scheme 2). The catalysts derived from ligands Ia, IIa, IIIa, and IV were also tested in the

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

• , azides, halides and alkenes, oxidation of remote C–H bonds and alkenes, and substitution reactions involving ring-opening cyclization of epoxides, nucleophilic substitution of allylic chlorides, and hydrolysis reactions. The product selectivity is interpreted as the consequence of the space shape and

• could mimic the catalysis behavior of the active sites of enzymes. In 2012, the Fujita group reported a site-selective nucleophilic substitution reaction of allylic chlorides mediated by cage host J (Figure 12) [74]. Usually, this reaction occurs both at the α and γ positions of the allylic chloride

• . Site-selective monoepoxidation of α,ω-dienes mediated by the water-soluble cavitand host E. Site-selective ring-opening reaction of epoxides mediated by cavitand I with an inwardly directed carboxylic acid module. Site-selective nucleophilic substitution reaction of allylic chlorides mediated by cage

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• Abstract A new efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines via sequential Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution reaction has been developed. The three-component Passerini reactions of 2-azidobenzaldehydes 1, benzoic acid (2), and

• /addition/nucleophilic substitution reactions. Keywords: aza-Wittig reaction; 3,4-dihydroquinazoline; 4H-3,1-benzothiazine; nucleophilic substitution; Passerini reaction; Staudinger reaction; Introduction The chemistry of 3,4-dihydroquinazolines and 4H-3,1-benzothiazines is of constant interest owing to

• /nucleophilic substitution reactions. Compared with the synthetic method to 4H-3,1-benzothiazines in Scheme 1f, we provide another new sequential synthetic route to 4H-3,1-benzothiazines, especially for N,N-disubstituted 2-amino-4H-3,1-benzothiazines. Results and Discussion We initially selected 2

Synthesis of novel [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines and investigation of their fungistatic activity

• Anna V. Korotina,
• Svetlana G. Tolshchina,
• Rashida I. Ishmetova,
• Natalya P. Evstigneeva,
• Natalya A. Gerasimova,
• Natalya V. Zilberberg,
• Nikolay V. Kungurov,
• Gennady L. Rusinov,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2022, 18, 243–250, doi:10.3762/bjoc.18.29

• . Keywords: antifungal activity; nucleophilic substitution; oxidative cyclization; [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines; Introduction Azolo-annulated azines can be regarded as purine isosteres and are of great interest for modern medicinal chemistry as potential biologically active compounds. In

• carried out for the first time. The synthetic approach to new triazolotetrazines involves the preparation of 3,6-disubstituted 1,2,4,5-tetrazines 2a–i bearing the amidine moiety through nucleophilic substitution of the 3,5-dimethylpyrazol fragment in easily available compound 1, followed by oxidative

• ][1,2,4,5]tetrazines 3a,j, as well as triazolo[4,3-b][1,2,4,5]tetrazines [33][34][35], react with N- and O-nucleophiles to give the corresponding nucleophilic substitution products 4a–c, 5a–c, derived from the displacement of the azolyl group in the tetrazine ring (Scheme 3). These reactions can be used to

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• defining mechanisms of nucleophilic substitution at sulphur are known to the writer...”. Examination of this section of the text shows, however, that it is limited to a consideration of substitution at the sulfur of sulfinates and reactions of the general type illustrated in Equation 3 and reactions

• nucleophilic substitution taking place at the sulfur. 4. Consideration of evidence from applications of the extended Grunwald–Winstein equation Consistent with the bimolecular nature of the solvolyses of alkanesulfonyl chlorides and arenesulfonyl chlorides [49][55][56][57][58][59][60][61][62][63][64][65][66

Chemoselective N-acylation of indoles using thioesters as acyl source

• Tianri Du,
• Xiangmu Wei,
• Honghong Xu,
• Xin Zhang,
• Ruiru Fang,
• Zheng Yuan,
• Zhi Liang and
• Yahui Li

Beilstein J. Org. Chem. 2022, 18, 89–94, doi:10.3762/bjoc.18.9

• , heterocycles, such as carbazole, can also be used as nucleophiles in this reaction. Keywords: indole; N-acylation; nucleophilic substitution; thioesters; Introduction Molecules containing N-acylindoles have attracted wide attention in the synthetic polymers and pharmaceutical industry because of their unique

• acid (4) (Scheme 4, reaction 4). A plausible reaction mechanism has been proposed based on the results of the control experiments. As shown in Scheme 5, the reaction starts with a base-promoted deprotonation of indole forming intermediate A. In the next step nucleophilic substitution between

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• recognition of cholylglycine, which is a combination of cholic acid and glycine. The β-cyclodextrin/graphene oxide composite forms an inclusion complex with a β-NQS guest. The amino group of cholylglycine can bind to β-NQS by a nucleophilic substitution reaction, resulting in a decrease in the electrochemical

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• conditions, and its purity quickly deteriorated even when stored in a freezer with shading (see Supporting Information File 1), resulting in trace amounts of α-functionalized lactones using the above-mentioned two-step method. Hence, we focused on sequential nucleophilic substitution in a two-phase system

• then phase-transferred into the organic phase, with subsequent nucleophilic substitution at the α-position of 3a proceeding directly to produce a variety of α-substituted lactones, along with the regeneration of n-Bu4N+Br− (Scheme 5). To demonstrate the applicability of this protocol, we investigated

• 2a. Synthesis of α-functionalized lactones using the two-phase system. Synthesis of unsymmetrically functionalized sulfide 5 via the two-phase system-promoted intramolecular cyclization of 2b. Sequential nucleophilic substitution in the two-phase system. One-pot synthesis of 2-phenylthio-α

Synthesis of a novel aminobenzene-containing hemicucurbituril and its fluorescence spectral properties with ions

• Qingkai Zeng,
• Qiumeng Long,
• Jihong Lu,
• Li Wang,
• Yuting You,
• Xiaoting Yuan,
• Qianjun Zhang,
• Qingmei Ge,
• Hang Cong and
• Mao Liu

Beilstein J. Org. Chem. 2021, 17, 2840–2847, doi:10.3762/bjoc.17.195

• intensity. Conclusion In summary, we have presented a novel type of hemicucurbituril derivative modified with aminobenzene. Based on the fragment coupling strategy, the nitrobenzene-containing hemicucurbituril 9 was synthesized by nucleophilic substitution reaction with two fragments 7 and 8. The desired

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• standard conditions, the desired products 3b or 4b were obtained with yields of 92% and 88%, respectively. Second, the sulfonylated diarylmethane 3b obtained through the C–S bond-cleavage sulfonylation reaction is a versatile building block for preparing diarylmethane derivatives through a nucleophilic

• substitution process. For example, compound 3b reacted with difluoroenolate to form the difluoroalkylated diarylmethane 5 in 83% yield via a Cu(OAc)2-catalyzed hydrodifluoroalkylation reaction [52]. Two other examples were the use of photoredox catalysis to generate acyl anions in situ from aromatic carboxylic

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

• the development of several approaches for the efficient construction of these heterocyclic frameworks (Scheme 1). Traditional preparations for 1-aminoisoquinolines include nucleophilic substitution of 1-haloisoquinolines with amines either employing a base [31][32][33][34][35] or a transition metal

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• (sp3)–H allylic alkylation of 2-alkylpyridines with Morita–Baylis–Hillman (MBH) carbonates is described. A plausible mechanism of the reaction might involve a tandem SN2’ type nucleophilic substitution followed by an aza-Cope rearrangement. Various alkyl substituents on 2-alkylpyridines were tolerated

• demonstrated a direct C(sp3)–H allylic alkylation reaction of 2-alkylpyridines with MBH carbonates with mild and simple operation. The process does not need either a base or a transition metal catalyst. The mechanism of this reaction was envisioned involving a tandem SN2’ type nucleophilic substitution

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• challenge in chemistry. In order to achieve this goal, and on the basis of our previous experiences in the functionalization of oxindoles [33][34], we herein designed a nucleophilic substitution method of an isatin-derived 3-phosphate-substituted oxindole with haloid acids, leading to 3-monohalooxindoles

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• )pyrimidin-2-amine (5) was obtained from the aromatic nucleophilic substitution reaction of intermediate PAPP via the formation of a diazonium salt with 84% yield, which was characterized, and its data agreed with those in the literature [29]. The carbonyl nucleophilic substitution reaction between

• obtained from the nucleophilic substitution reaction of intermediate 8 in 85% yield. The 1H and 13C NMR spectra of compounds 8 and 9 were similar, but in the IR spectrum of intermediate 9, it was possible to observe the characteristic stretching of the azide group at 2103 cm−1. The 1,3-dipolar

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• alcohols with diaryliodonium salts [26], the Sc(OTf)3-catalyzed domino reaction [27], and the iodine-catalyzed nucleophilic substitution reaction of xanthen-9-ol [28]. As an example of an intramolecular hydroarylation of an olefin, 9,10-dihydroacridines, which are N derivatives of xanthenes, were

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• usually achieved by a nucleophilic substitution of an alkyl halide by the deprotonated malonate [12][13][14][15][16][17][18][19], but other strategies could be envisioned: Cu-catalyzed arylation reactions for aryl-substituted MAHOs [20][21][22][23]; Knoevenagel/reduction sequences for benzyl-substituted

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• was described by Sun et al. [46]. In this method, the catalyst (DHQ)2PYR 42 reacts with tert-butyl 2-bromoacetate, and then an ylide is formed by the base Cs2CO3. After a conjugated addition of this intermediate to the coumarin 43 followed by nucleophilic substitution, the corresponding cyclopropa[c

• described an allylic alkylation reaction between 3-cyano-4-methylcoumarins 39 and Morita–Baylis–Hillman (MBH) carbonates 40 [45]. In this case, the catalyst (DHQ)2PYR 42 activates the MBH substrate and generates the dienolate in the vinylogous coumarin moiety, acting as a base. After the nucleophilic

• substitution reaction between the coumarin and the activated MBH substrate, it is possible to obtain functionalized coumarins 41 (Scheme 13). Furthermore, the absolute configuration of the stereogenic center was determined by X-ray crystallography. The enantioselective synthesis of cyclopropa[c]coumarins 45

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• followed by the nucleophilic substitution of alkylating reagent R2–X to selectively give the desired N-1 regioisomer 68. It is likely that a mixture of the solvent-separated ion pairs 65 and 66 predominate, when using polar solvents such as DMF [24]. Furthermore, precluding tight ion pair formation through