Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• halides are valuable compounds with potent bioactivities [1][2][3][4][5] (Figure 1) and are utilized as crucial precursors for various metal-catalyzed cross-coupling reactions [6][7][8][9]. They are frequently used as synthetic intermediates in several value-added syntheses of natural products

• requires the use of a solid acid catalyst [52], apart from the use of high-cost, high-end milling equipment which limits to laboratory scale only. Therefore, developing an operationally simple, environmentally benign protocol, potentially useful for the batch-scale synthesis of aryl halides is highly

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

• -dihydrobenzo[d][1,2]azaphosphole 2-oxide (55), which was further alkylated with alkyl halides in the presence of NaH, affording 1-alkyl-2-phenyl-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides 56. Alternatively, under heating, methyl 2-aminobenzyl(phenyl)phosphinate (53) underwent a transmethylation from the O

• ]azaphosphole 2-sulfide (59). Sulfide 59 was similarly transformed to 1-alkyl-2-phenyl-1,3-dihydrobenzo[d][1,2]azaphosphole 2-sulfides 60 by treatment with alkyl halides in the presence of NaH. All 1,3-dihydrobenzo[d][1,2]azaphosphole 2-sulfides 60 were converted into the corresponding 1,3-dihydrobenzo[d][1,2

• ], the strategy is the dearomatizing anionic cyclization of diaryl-N-alkyl-N-benzylphosphinamides by treatment with sec-butyllithium followed by reactions with different electrophiles, such as water, alcohols, alkyl halides, aldehydes, etc. They first realized the dearomatizing anionic cyclization of

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• difluorocarbene adduct 5 was detected by high resolution mass spectrometry in addition to products 2, 3, and 4. As already mentioned, SmI2 is a well-known one-electron reducing reagent, and has been used to generate PhSCF2 radicals and perfluoroalkyl radicals from PhSCF2Br and perfluoroalkyl halides, respectively

• the formation of adduct 4 to some extent (from 0% to 14% yield) as shown in Table 3. Therefore, iPrOH seems to promote the radcal addition rather than reduction although the reason has not been clarified yet. Reaction mechanism Although the cathodic reduction of perfluoroalkyl halides usually involves

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

• (RSeSeR) and selanyl halides (RSeX) have been widely used as Se sources in these reactions. However, they have poor commercial availability and require complicated synthetic routes. Therefore, an alternative approach using the commercially available and easy-to-handle Se powder has attracted significant

• powder with imidazopyridine and aryl iodides or alkyl halides in the presence of Na2CO3 (2 equiv) using the NiBr2/2,2-bipyridine system to give aryl or alkyl imidazopyridinyl selenides [24]. In these reactions, aryl iodides, arylboronic acids, and alkyl halides are coupled with Se powder to form diaryl

Palladium-catalyzed solid-state borylation of aryl halides using mechanochemistry

• Koji Kubota,
• Emiru Baba,
• Tamae Seo,
• Tatsuo Ishiyama and
• Hajime Ito

Beilstein J. Org. Chem. 2022, 18, 855–862, doi:10.3762/bjoc.18.86

• , Japan 10.3762/bjoc.18.86 Abstract This study describes the solid-state palladium-catalyzed cross-coupling between aryl halides and bis(pinacolato)diboron using ball milling. The reactions were completed within 10 min for most aryl halides to afford a variety of synthetically useful arylboronates in

• organic materials, typically through Suzuki–Miyaura coupling [1][2][3][4][5][6][7]. The palladium-catalyzed boryl substitution of aryl halides with boron reagents, termed Miyaura–Ishiyama borylation, is an efficient method for synthesizing arylboronates with high functional group compatibility [8][9][10

• ][11][12][13][14]. To date, many palladium-based catalytic systems in solution for the borylation of aryl halides have been reported [8][9][10][11][12][13][14]. However, these solution-based reactions usually require long reaction times and significant amounts of dry and degassed organic solvents

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• processes. To evaluate the scope of the disclosed reaction a set of isoxazoles 1 was prepared using approaches shown in the Scheme 3 and Scheme 4. Isoxazoles 11a–f were prepared by cycloaddition of nitrile oxides, generated from N-hydroxyimidoyl chlorides 7a–f, to propargyl halides [29], followed by the

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• reductive coupling of acid halides with ketones [36][37] and acetolyses of α-phenoxy-α-diazoketones [38] were also employed. Recently, F. P. Cossío et al. [39] have described a method for the preparation of benzo[b]furans by thermal heating of a dispersion of α-phenoxyketones in Al2O3. We involved the

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

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

• reduction of organic halides [35][36]; therefore, 1,4-dibromobutane (2a) was more easily reduced than 1 at the Ag cathode, which resulted in the recovery of a large amount of unreacted 1. Linear sweep voltammetry (LSV) experiments revealed that the reduction of 2a occurred at a lower potential than the

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

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• is shown in Scheme 5. Non-green protocols Nakamura et al. disclosed an Fe-catalyzed Sonogashira coupling between an alkynyl unit with primary and secondary alkyl halides (Scheme 6) [24]. They reported the coupling of an unactivated alkyl halide with the Fe catalyst can switch its chemoselectivity

• , Balla and co-workers discussed the scope of the reaction by the utilization of in-situ generated α-Fe2O3 nanoparticles with several activated and unactivated halides (Scheme 13) [30]. They also examined the effect of concentration of fluorescent aggregates of HPB, i.e., the size of the generated

• , recyclable, and selective for the coupling between aryl halides and phenylacetylene in PEG as the solvent (Scheme 22). The effect of various reaction parameters such as solvent, base, temperature, and catalyst loading was assessed by the model reaction between bromobenzene and phenylacetylene. Optimization

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

• . The solvolyses of these additional types of sulfur(VI) substrates will be the topics of a future review. Keywords: correlation; Grunwald–Winstein equation; Hammett equation; mechanism; solvolysis; sulfonyl halides; Review 1. Introduction to solvolyses of sulfonyl halides In medicinal chemistry

• (1961–1971), Hambly and co-workers, published a series of eight papers (Solvolysis of Sulfonyl Halides, Parts I through VIII) [16][17][18][19][20][21][22][23]. In the initial study [16][17] of the solvolysis of the parent benzenesulfonyl chloride and the p-methyl, p-bromo-, and p-nitro derivatives in

• was considered to indicate more bond breaking at the transition state for the departure of the chloride ion in the hydrolyses of the sulfonyl chlorides. The sulfonyl halides are not ideal substrates for studies of this type since they range from poorly soluble to almost insoluble in water. The parent

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

• transthioesterification of aryl halides for the synthesis of thioethers and thioesters [17] (Scheme 1, C). In addition, we also used this reagent to trap alkylcopper(I) intermediates and to form C−S bonds [18]. To the best of our knowledge, thioesters have not been developed as indole N-amidation reagent. Based on our

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

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

• , alkynes, and halides were compatible with this strategy. A photoredox-catalyzed oxidative coupling of 4-alkyl-3,4-dihydroquinoxalin-2(1H)-ones with nucleophiles was reported by Hong and co-workers [42]. The reaction was performed using 20 mol % of Ru(bpy)3Cl2.6H2O in methanol under CFL light irradiation

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• and co-workers demonstrated the generation of highly reductant CO2 radical anions through potassium formate hydrogen atom abstraction promoted by DABCO [25] (Figure 2c). This species was then used for reduction of (hetero)aryl and alkyl halides, and subsequent carboarylation of several styrenes

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

• first Fe-catalyzed cross-coupling reaction between Grignard reagents and vinyl halides [37]. As of late, the development of Fe-catalyzed cross-coupling methodology and mechanistic rationales have burgeoned [38]. Today, the rate of growth within the field of iron catalysis is much greater than that

• iron-catalyzed cross-coupling reactions of alkyl halides began in 2004 when Nakamura first reported the TMEDA-mediated Fe-catalyzed cross-coupling reaction between secondary bromides with aryl Grignard reagents [52]. Since then, several reports of alkyl halide cross-coupling reactions have been

• . Similar to their previous report, primary and secondary alkyl halides were prone to undergoing direct cross-coupling rather than radical addition across the π-system. Consistent with the proposed mechanism, perfluorinated n-alkyl radicals performed well, suggesting ease of Giese addition is crucial [67

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

• sulfones is a valuable and appealing task in synthetic chemistry. Traditionally, diarylmethyl sulfones are synthesized by transition-metal-catalyzed deoxy C–S bond-coupling reaction of sodium arylsulfinates with diarylmethanols [11], C–H functionalization of alkyl sulfones with aryl halides [12], and via a

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• of cytotoxic, antifungal, or antibiotic properties [10][11][12]. Modern stereoselective syntheses leading to highly substituted enamides include cross-coupling of vinyl (pseudo)halides or organoboron compounds [13], hydroamidation of alkynes [14][15][16], ynamide functionalization [17][18][19], or

• to (Z)-β-enamido fluorides [22] and halovinyl imidoyl halides [23]. In addition, Li and co-workers extended the scope of accessible (Z)-β-enamido triflates by denitrogenative reaction of N1-H-1,2,3-triazoles in the presence of acyl halides and sodium triflate [24]. These enamido triflates and halides

• bond of vinyl (pseudo)halides during the Suzuki coupling have been published [25][26][27][28][29]. Typically, inversion of configuration occurs on substrates containing a double bond in conjugation with an electron-withdrawing group, such as the carbonyl group in enones [27][30]. We hypothesized that

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• functionalization, organic halides functionalization, and alkyl C–H functionalization, are highlighted. Review 1. Special features of photoredox-catalyzed processes by copper complexes To understand photoredox-catalyzed processes, a discussion of the general mechanism of [Ru(bpy)3]2+ is needed [25][26][27]. When

•  9). In addition to perfluoroalkyl iodides, this protocol was further extended to alkyl halides, trifluoromethylthiolate, amines, cycloketone oxime esters, and carboxylic acid N-hydroxyphthalimide esters (NHPI). In 2018, Peters and Fu [57] explored the copper-catalyzed three-component coupling of

• alkyl halides 14, olefins, and trifluoromethylthiolate 15. Mechanistic studies demonstrated that the photoexcited CuI/binap/SCF3 complex generated in situ engages in electron transfer with the alkyl halides, thereby providing an alkyl radical and the CuII/binap/SCF3 species. Subsequently, the alkyl

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

• ]. Then, they also reported another CuH-catalyzed coupling reaction of 1,3-enynes 54 and nitrile to prepare polysubstituted pyrroles 55 (Scheme 21) [66]. The substrates 54 could be easily prepared by Sonogashira coupling of terminal alkynes and vinyl halides. It is worth mentioning that the addition of

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

• -monohalooxindoles involve the direct halogenation of oxindoles with various reactive halogenating reagents, including N-chloro-N-methoxybenzenesulfonamide [24][25], ammonium halides/oxone [13], Selectfluor® [26][27], and CuBr2 (Scheme 1, reaction 4) [15]. However, these protocols each have a certain scope and

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• the cationic reactive species. Keywords: anion binding; asymmetric catalysis; halide anions; hydrogen donors; noncovalent interactions; Introduction Halogens and the respective anionic halides occupy an essential role in natural and chemical processes [1][2][3][4]. While in chemical syntheses

• cavities. In this context, halides offer an advantage over various other anionic species because their spherical topology reduces the number of possible isomers or complexes upon interaction with the receptor. As a consequence, predictable cavity sizes based on the employed halide allows for easier

• spherical halides [10]. The key to hydrogen bonding of the halide anion resides in the polarized N–H bonds of these (thio)urea units, which have since served as a benchmark in the design and development of anion receptor catalysts [12][13][14]. Consequently, other synthetic anion receptors have been

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• , MacMillan and co-workers demonstrated an inspiring C(sp3)‒H arylation of dimethylaniline (1a) with a variety of aryl halides using the photoredox nickel catalysis [53]. Here, the combination of the iridium photocatalyst Ir[dF(CF3)ppy]2(dtbbpy)PF6 and the commercially available nickel catalyst NiCl2·glyme

• that the oxidative addition of the nickel(0) species 10-VII to aryl bromide 3 and subsequent steps to produce nickel(III) intermediate 10-IX could not be ruled out. The König group discovered that the arylation of α-amino C(sp3)–H bonds could be realized with aryl halides using mesoporous graphitic

• nature of their α-C–H also proved viable under slightly modified reaction conditions, as was reported by Hashmi in 2019 (Scheme 25) [68]. In a recent publication, the group of Martin enabled an intermolecular alkylation of α-amino C–H bonds of benzamides 31 with unactivated alkyl halides 40 [72]. In this

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

• with 5-iodoindole (182) in the presence of thiourea and a recyclable CuO nanoparticle catalyst (Scheme 26) [116]. This heterogeneous catalysis strategy bypasses the use of unpleasant aryl thiols, which are generally coupled with other aryl halides in the presence of transition-metal catalysts for