Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• ), the corresponding products 8b–g were obtained in only moderate yields with decreased selectivity. Replacing the Boc-protecting group on the imine site by a Cbz group led to a largely decreased selectivity (8h). For a series of substrates with various substituents on the 5, 6, or 7-position, including

• disrupted by 4-substitution, and only trace conversion was observed for the 4-chloro or 4-bromo-substituted substrate (8o,s). This was probably caused by a steric effect as the 4-substituent is close to the imine reactive site and accordingly blocked it toward activation and nucleophilic attack

• , a plausible catalytic mechanism is represented in Figure 2. The MAHT substrate is deprotonated by one of the tertiary amine sites, and the formed enolate intermediate can be stabilized by hydrogen bonding-mediated ion-pair interaction within the macrocyclic cavity. The imine substrate is activated

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

• available imine and terminal dihaloalkanes in a flow microreactor. Reduction of the substrate imine on the cathode proceeded efficiently due to the large specific surface area of the microreactor. This method provided target compounds in good yields compared to a conventional batch-type reaction

• . Furthermore, piperidine and pyrrolidine derivatives could be obtained on preparative scale by continuous electrolysis for approximately 1 hour. Keywords: electrochemical synthesis; electrocyclization; flow microreactor; heterocyclic amines; imine; Introduction Heterocycles are a very important class of

• starting imine 1 in the first reduction step. The nucleophilic attack of the radical anion on the terminal dihaloalkane 2a is the second step, which forms a radical. These sequential steps are followed by a further one-electron reduction at the cathode to provide an anion intermediate. The last step is

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• and efficient organocatalyst. Recent promoted reactions by the resorcin[4]arene capsule include the intramolecular ether cyclization [34], the synthesis of bis(heteroaryl)methanes [35], the imine formation [36], the Michael addition reactions of N-methylpyrrole on methyl vinyl ketone [37], the

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• conformer. Aiming to generalize the discovered transformation, a brief scope of the reaction with respect to the N-tert-butanesulfinyl imine substrate was next performed (Figure 2). The protecting group R1 on the oxindole nitrogen atom was found to have a moderate effect on the reactivity, with R1 = Bn

• intermediate spontaneously turns into the carbanion C, thus realizing the imine umpolung and allowing the cross-coupling reaction with the remaining electrophilic ketimine 1. The complete diastereoselectivity would arise from the mutual approach of the two oxindole nuclei from the less hindered side, that is

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

• recovered and reused, but it could also result in a reduced metal contamination of the products. However, most of the immobilized catalysts suffer from some problems like catalyst deactivation, low turnover numbers, and also leaching of metal. A new heterogeneous cobalt catalyst (Co@imine-porous organic

• polymer) (Co@imine-POP) has been synthesized by immobilizing cobalt onto a nitrogen-rich porous organic polymer (Scheme 20) [35]. Using scanning electron microscopy, the surface morphology of the catalyst was evaluated. Nowadays, covalent organic frameworks (COF) were found to be a suitable support in

• catalysis. The catalytic activity of Co@imine-POP was investigated in a Sonogashira coupling of bromobenzene and phenylacetylene under different reaction conditions. The optimized reaction conditions were found to be 1.7 mol % of the Co@imine-POP catalyst, PEG as solvent and 80 °C reaction temperature

Tenacibactins K–M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum

• Yasuhiro Igarashi,
• Yiwei Ge,
• Tao Zhou,
• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku and
• Agus Trianto

Beilstein J. Org. Chem. 2022, 18, 110–119, doi:10.3762/bjoc.18.12

• [30], terminal blocking by acylation [29][31][32], formation of sugar ester [33], imine oxide [34], oxime [35], or functional group transformation into a hydroxy [33] or nitro group [35]. To the best of our knowledge, compounds 1–3 are the first to have a hydroxamic acid terminus. Similar to the

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

• in the presence of electrophilic reagents [18][19] (Scheme 1d). Aziridines can be considered as the NCC structural fragment after ring-opening and have been applied in the synthesis of aziridine-imine-containing chiral tridentate ligands [20], 2-alkylideneoxazolidines [21], and N-vinylamides [22]. We

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

• isomerization involves two routes: one through the hydrolysis of 22 leading to lawsone (4) and the subsequent addition of arylamines in position C2, and the other involves the addition of arylamines at position C2 of 22, leading to 24 with two equivalents of arylamine, which after hydrolysis of the imine at

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

• corresponding imine. Finally, oxidative dehydrogenation results in the formation of the nitrile. Conclusion This review summarizes the recent progress in ruthenium-catalyzed cyanation reactions. Due to the wide application of nitrile compounds in pharmaceutical and biological fields, cyanation reactions have

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

• thermal conditions or through the Fe redox cycle, can abstract the aldehydic hydrogen to form the acyl radical 71. Subsequent radical addition to the alkene 68 to form 72 followed by cyclization with the nitrile affords the iminyl radical 73 which can abstract a hydrogen atom to form the more stable imine

• 74. Hydrolysis of the imine affords the final product 69. In 2020, Sun and Liu reported the iminyl cyclization could also be achieved with DMSO as a methyl-radical precursor [88]. In 2017, the Zhu group developed an Fe(acac)3-catalyzed cyanoalkylative dearomatization of N-phenylcinnamamides 75 for

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• were no significant differences in the chemical shift values between the quinoline precursor and new Schiff bases regarding the aromatic resonances in the 1H NMR and 13C NMR data. Studies in the literature have reported that the imine group may exist as E/Z geometrical isomers in the –CH=N double bond

• ultraviolet range, the observed transitions can be attributed to the π → π* transitions and refer to the heterocyclic ring. Transitions above 350 nm can be attributed to the n → π* transition referring to the imine moiety, causing an intramolecular charge-transfer type (ICT) transition [27]. Complementary

• , according to Temel and co-workers who studied a similar scaffold, namely, 4-bromo-2-((quinoline-8-yl)methyl)phenol [27], no imine–hemiaminal tautomer peak transition was observed for the Schiff bases 3. In general, there were slightly significant changes in the transitions according to the changes in the

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

• ) condenses with amine/aniline in the presence of Me3Al to afford imine intermediate A. Intermediate A then underdoes an intramolecular cyclisation to afford intermediate B. This intermediate B then undergoes an N-[1,3]-shift leading to the generation of intermediate C, which subsequently abstracts a proton

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

• 69 and 70 in high yields (up to 89%) with excellent enantioselectivity (up to 98% ee, Scheme 22) [78]. The primary amino group in the N1-(aryl)benzene-1,2-diamines reacts with the carbonyl group in 67 to give imine intermediate I-15 mediated by the chiral phosphoric acid. Meanwhile, isomerization of

• accelerating imine formation (I-19), and under the catalysis of a chiral phosphoric acid, intramolecular nucleophilic addition occurs to form I-20, followed by oxidative dehydrogenation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). In the presence of 10 mol % chiral phosphoric acid CPA 7, the axially

• with α-methylene carbonyl derivatives 78 catalyzed by a chiral phosphoric acid. In the presence of (R)-CPA 9, the Friedländer heteroannulation reaction between aromatic amines 77 and the carbonyl derivative 78 was carried out to form imine I-21, which tautomerized to generate intermediate I-22. Under

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• features the 1,2-shift of an alkyl or aryl group. In the process, the hydroxy group is converted to a carbonyl and the aldehyde/ketone or imine is converted to an alcohol or amine. Such α-ketol/α-iminol rearrangements are used in a wide variety of synthetic applications including asymmetric synthesis

• rearrangements. Inspired by the use of a BOROX catalyst in a series of asymmetric imine reactions, the group performed a catalyst screen for the conversion of 97 to 98 (Figure 18) [3]. Out of nearly twenty catalysts tested, (R)-VANOL Zr (99) produced the best results, with 5 mol % in toluene at 80 °C for 1 hour

• ring strain from cyclobutane derivatives has been developed by Cheng et al. to prepare functionalized α-amino cyclopentanones [31]. In the presence of a palladium catalyst, an electron-rich heteroarene 115 first adds to the nitrile group in a 1-cyanocyclobutyl ester 116 to give a tetrahedral imine

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

• observations revealed a new avenue for copper-based photocatalysis. The transformation was initiated by a SET process from the amine to the CuII ion to generate the visible-light-driven species I [CuI-NH•+]. Under visible-light irradiation, the intermediate [CuI-NH•+] was oxidized to the imine 60 by O2. Next

• , the imine 60 transferred a single electron to the CuII ion, thereby providing intermediate II [CuI-N•+]. [CuI-N+•] was equal to CuI and N+• of the imine, which is activated for the nucleophilic addition. With the help of O2, CuI regenerates CuII to complete the catalytic cycle (Scheme 27). A series of

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

• anhydrous ethanol and the formed imine was then reduced in situ with sodium borohydride to give the product 3a with 98% yield. The synthesis of further N-benzylated aminoacetaldehyde acetals 3b–e was performed in these reaction conditions in EtOH or MeOH to provide the desired products with high overall

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

• and Gandhi reported an Ag-catalyzed cascade cyclization of 6-hydroxyhex-2-en-4-ynals 42 and primary amines to give the 2-(α-hydroxyacyl)pyrroles 43 in moderate to good yield (Scheme 17) [62]. The proposed mechanism involves the condensation of amine and aldehyde to give the imine 44 and the AgNO3

• -promoted 5-exo-dig cyclization of imine to form a zwitter ion intermediate 45. In 2017, the Reddy group also reported a method for the construction of 2-carbonylpyrroles 46 through Au/Ag-catalyzed intramolecular oxidative aza-annulation of 1,3-enynyl azides 1 (Scheme 18) [63]. The method is very applicable

• previously reported methods is proposed in Scheme 22. Firstly, the hydrocupration of enyne 54 with LCuH 57 provides propargylcopper intermediate 58. The 1,3-isomerization of 58 and the following nitrile addition produces imine intermediate 60, which subsequently undergoes intramolecular cyclization, a 1,5

Facile and innovative catalytic protocol for intramolecular Friedel–Crafts cyclization of Morita–Baylis–Hillman adducts: Synergistic combination of chiral (salen)chromium(III)/BF₃·OEt₂ catalysis

• Karthikeyan Soundararajan,
• Helen Ratna Monica Jeyarajan,
• Raju Subimol Kamarajapurathu and
• Karthik Krishna Kumar Ayyanoth

Beilstein J. Org. Chem. 2021, 17, 2186–2193, doi:10.3762/bjoc.17.140

• arrangement would facilitate the intramolecular Friedel–Crafts cyclization of the MBH adducts. Cycloaddition of azomethine imine 7a with 2-substituted-1H-indenes 6b and 6c was attempted to ascertain the structure of the synthesized 1H-indenes (Scheme 3). The azomethine imine, 1-benzylidene-3-oxopyrazolidin-1

• -ium-2-ide (7a) was synthesised at room temperature by treating methyl acrylate, hydrazine hydrate and benzaldehyde in a yield of 67%. On treating the synthesised azomethine imine 7a (1.2 mM) and 2-substituted-1H-indenes 6b and 6c (1 mM) in toluene at 70 °C affords 8a and 8b via [3 + 2] cycloaddition

• ]+ calcd for C20H17N3O, 315.1372; found, 315.1397. Literature-reported approaches to synthesise indene from MBH adducts [10][11][12][13][14]. Proposed model for the intramolecular Friedel–Crafts cyclization. Reactions of azomethine imine 7a with 2-substituted 1H-indenes 6a and 6b. Optimization of reaction

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• of α-substituted glutamates and pyroglutamates via a cyclopropenimine-catalyzed Michael addition of amino ester imines is described. Enantioselectivities of up to 94% have been achieved, and a variety of functional groups were found to be compatible. The impact of the catalyst structure and imine

• only up to 84% ee [36]. Phase-transfer catalysis has been employed for the enantioselective addition of an alanine imine derivative, although the selectivity achieved in this case was only 64% ee [37]. In a related work, enantioselectivities of up to 90% ee were realized, but the procedure required an

• optimize this process, we selected the addition of alanine imine 1 to methyl acrylate as our test reaction (Table 1). We found that the previously reported cyclopropenimine 4 catalyzed this transformation with 90% conversion and 84% ee in 24 hours at ambient temperature (Table 1, entry 1). The desired

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

• amines enables both the formation of an imine ion with the enone and activation of the hydroxycoumarin by hydrogen bonding [41]. Despite the long reaction time (3 days), the desired products 3 were obtained with good to excellent yields and moderate enantiomeric excesses (Scheme 9). A new organocatalyst

• % ee) (Scheme 10). A catalytic asymmetric β-C−H functionalization of ketones 33 with 4-hydroxycoumarins 1 was developed by Zhu et al. [43]. The enamine, formed via reaction of the aminocatalyst 35 with the ketone, is oxidased by IBX resulting in the electrophilic imine, which in turn undergoes a

• -withdrawing and electron-donating substituents were well tolerated in either coumarin or imine portion, and electron-withdrawing substituents at ortho-position of the imine phenyl ring afforded the corresponding products with excellent yields and moderated to good ee. The asymmetric addition of malonic acid

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

• compounds to produce the corresponding biaryl products with high enantiopurity using vanadium chelated with chiral ligands, such as tridentate asymmetric imine ligands, have been reported. For instance, (S)-binol derivatives could be successfully prepared from 2-naphthols using a dimeric vanadium complex

• -methoxybenzaldehyde imine derivatives with phenyl Grignard reagents as coupling partners. As the catalyst CrCl2 is used and either 2,3-dichlorobutane (DCB) or 1,2-dichloropropane (DCP) are used as oxidant to give 2,5-diarylbenzaldehyde after imine hydrolysis (Scheme 16B). Although benzaldehyde is a basic structure

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

• active N-F fluorinating agents, chiral N-fluorosultams, were synthesized by Lang and co-worker [52]. A camphor-derived imine was reduced or methylated, followed by direct fluorination (10% F2/N2) to give optically active N-F reagents 9-1 and 9-2 in 75% and 80% yield, respectively (Scheme 21). These N

• of 2-benzyl-α-tetralone was treated with 27-8. As summarized in Scheme 61, Takeuchi et al. prepared the enantiomers of cyclic N-F sulfonamide 27-6 by the approach used by Lang for N-fluorosultams [53]. A cyclohexyl ring was introduced nucleophilically into imine 27-3 and the resulting 27-4 was

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• compounds 9, and tosyl azide through a cycloaddition process in DCM as solvent and HOAc as additive at 90 °C in moderate to excellent yield (Scheme 6) [41]. As illustrated in Scheme 7, imine intermediate 12 was generated via the reaction between amine 10 and 1,3-dicarbonyl compound 9. Then, tautomerization

• of the imine intermediate produces the intermediate enamine 13. The 1,3-dipolar cycloaddition of enamine 13 with azide produces intermediate 1,2,3-triazoline 14. In continuation, a ring-opening process is promoted by acetic acid to afford the intermediate 16. Afterward, triazene intermediate 17 was

• is imine–enamine-tautomerized to afford the intermediate 27. Then, the final triazole compound, as major isomer, is achieved through an intermolecular cyclization process and elimination of one unit of TsNH2 [23]. A general strategy was described for the synthesis of 1,4,5-trisubstituted glycosyl

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• ]. This approach allowed the synthesis of alkylated benzofurans and benzothiophenes (Scheme 27). Investigations of the substrate scope revealed that both electron-donating and electron-withdrawing group substituents at the aromatic portions of the imine substrate could afford the aromatic heterocycle in

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• exclusively [16]. Noteworthy, [3 + 2]-cycloadditions of nitrile imines to the C=O group of 1,4-quinones have not yet been reported. In a historical work by Rolf Huisgen et al., the first [3 + 2]-cycloadditions of some 1,4-quinones, e.g., 1,4-naphthoquinone (1a), with C,N-diphenyl nitrile imine (2) were

• ]. Results and Discussion In a preliminary experiment, the reaction of 1,4-naphthoquinone (1a) with N-phenyltrifluoroacetohydrazonoyl bromide (8a), used as an easy-to-handle precursor of nitrile imine 7a, was examined. The reaction was performed in selected aprotic organic solvents by using organic and

• reported by Huisgen [17], who in the reaction of nitrile imine 2 with the same dipolarophile obtained the expected [3 + 2]-cycloadduct to the C=C bond as a single regioisomer, which was isolated in 33% yield. The observed outcome suggests that the thermally generated nitrile imine 2 undergoes [3 + 2