A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• are relatively common, access to photo-responsive modifications of backbone N–H bonds is quite limited. This letter describes a new photocleavage pathway, affording N-formyl amides from vinylogous nitroaryl precursors under physiologically relevant conditions via a formal oxidative C=C cleavage. The N

• pathways involving the intermediacy of 8. To provide additional support for this analysis, and to assess the stability of N-formyl amides formed in this reaction, we irradiated alkenyl amide 10, which contains a 2-phenylethyl substituent that allowed easier isolation of N-formyl 11 (Figure 4). After

• then account for the isolation of the acetylated analogue 9. The photochemical pathway described here represents a formal oxidative olefin cleavage of vinylogous nitroaryl-modified amides and ethers. The pathway adds to the diversity of photochemical pathways known for 2-nitrophenyl systems, and the

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• includes the reaction of readily available anthranilic amides or hydrazides with pent-4-yn-1-ols or -carboxylic acids promoted by PdCl4 [15], Au(І) [16][17][18] or Cu(ІІ) [19] salts. In another version, the target compounds were obtained by iodine-catalyzed reaction of the aforementioned anthranilic acid

• ][40] including from properly functionalized arenes and alkenes [41][42][43][44][45][46][47][48][49][50][51][52][53]. In the case of such substrates having oxygen-containing functional groups, PIFA attacked the double bond first [41][42][43]. With unsaturated amides or hydroxamates, oxidation of the

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

• characterization impossible. Therefore, the crude aminomethyl compounds 17a–g were directly converted to the corresponding amides 9a–i using different anhydrides or acid chlorides 11a–c. The resulting amides were stable and gained mediocre to good yields except for amides 9a and 9d (Table 2). The yield of 9d was

• shown with compound 12g (R1 = -CH2CO2Et), being reduced to compound 17g (R1' = -(CH2)2OH) and acylated to 9i with R1'' = -(CH2)2OCOMe. The last step in the synthesis of the target compounds 5a–i included the cleavage of the triazene unit of the amides 9 with subsequent cyclization to the final pyrazolo

• viability of HeLa cells, their regioisomers 13a and 13d–h decreased the viability at high micromolar concentrations. A slightly increased cytotoxicity of some derivatives of compound class 12 compared to 13 was observed for 12b and 12c. The amides 9 had no influence on the viability except for derivate 9b

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

• secondary and tertiary amines, amides/lactams/carbamates, and nitrile. The test reactions were monitored by thin-layer chromatography (TLC) and, where deemed necessary, results were further verified by GC–MS. The reagents employed encompassed tritylium tetrafluoroborate [50], H2O2/HBr [42], ceric ammonium

• /reagent combinations employed. The reaction of the secondary N-methylamine 2b with CBr4 [22] gave fluorenone (3) in 6% yield (determined by GC–MS), while tertiary amines, amides, and the γ-lactam 2e did not yield any. Formation of fluorenone (3) was also confirmed after applying a modified version of one

• fluorenone (3) in 30% yield (determined by GC–MS). TLC analysis further revealed that fluorenone formation does not occur when treating tertiary amides 2h and 2i, γ-lactam derivative 2e, and carbamate 2j with this reagent (Table 1, entries 5, 8, 9, and 10). The reaction does, however, also work with tertiary

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

• isomerization of N-allyl amides [20], but still possess drawbacks, especially for stereoselective synthesis of tri- and tetrasubstituted enamides. Recently, we have reported a triflic acid-mediated reaction of N-fluoroalkyl-1,2,3-triazoles leading to (Z)-β-enamido triflates [21] and Lewis acid-mediated reaction

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• [21], this variation of the reaction draws considerably less attention in comparison to the usage in the synthesis of amides or lactams. As presented in Figure 2, after initial formation of the azidohydrine by addition of hydrazoic acid to the ketone, the reaction can undergo two pathways. In the

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

• overviews the literature published during the last 10 years concerning the asymmetric aza-MR of amines and amides catalysed by organocatalysts. Both types of the organocatalysts, i.e., those acting through non-covalent interactions and those working through covalent bond formation have been applied for the

• aromatic amines, amides, imides, etc. require the use of an appropriate catalyst to undergo a Michael addition with a suitable acceptor. In view of this, chemists endeavoured to develop different types of catalysts, particularly the chiral catalysts to accomplish asymmetric aza-MRs. The development of

• compounds; however, in order to comply with the requirements of a mini review, additions of amines and amides only will be included. 1. Non-covalent bonding organocatalytic aza-Michael reactions Organocatalysts catalyzing aza-MRs through mainly hydrogen bonding include cinchona alkaloids, squaramide

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

• vinylogous amides such as 11, however, we fortuitously found substituted 2,3-dihydro-1H-pyrrolizines 12 as unexpected products when intermediates 11 were exposed to acidic conditions, including treatment with acetic acid or even during chromatography on silica gel (Scheme 1) [18]. In these cyclizations the

• 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

• N-phenacyl analogue 11 (Ar = Ar’ = Ph), the ester-containing enaminone 15a proved to be completely stable during chromatography on silica gel or upon dissolution in acetic acid at room temperature (conditions under which we had observed cyclization of vinylogous amides 11 [18]), and spontaneous

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

• alkyl halide to generate a copperII–nucleophile complex C and an alkyl radical. The formation of the R–Nu bond might occur through an in-cage pathway involving complex C (Scheme 20). In addition to carbazoles, the authors further described the C–N coupling of organic halides 45 with amides [83] and

• . Aerobic oxidative C(sp)–S coupling reaction. Copper-catalyzed alkylation of carbazoles with alkyl halides. C–N coupling of organic halides with amides and aliphatic amines. Copper-catalyzed C–X (N, S, O) bond formation reactions. Arylation of C(sp2)–H bonds of azoles. C–C cross-coupling of aryl halides

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

• , including bioactive molecules, were successfully installed to the ortho-position of ferrocene amides with high efficiency under mild conditions. A range of functionalized ferrocenes were compatible to give the aminated products in moderate to good yields. The gram-scale reaction was smoothly conducted and

• amination occurred selectively at the ortho position to the N-quinolinyl amides with acceptable yields (3f–l). Notably, free alcohol was also compatible with this protocol, exclusively giving the mono-aminated product in 73% yield (3m) without the observation of any competitive alkoxylation product [38][57

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

• discovered the synergistic combination of nickel catalysis and benzaldehyde for the arylation of C(sp3)–H bonds adjacent to nitrogen or sulfur in amides 6 and thioethers 28, respectively, under UVA light irradiation [68]. As shown in Scheme 16, both primary and secondary C(sp3)–H bonds of amides were

• bonds are not limited to tertiary amines/amides. Secondary amides could also be arylated, as reported by Montgomery, Martin and co-workers [72]. The authors discovered that the combination of Ir[dF(CF3)ppy]2(dtbbpy)PF6, NiBr2·diglyme, 5,5’-dimethyl-2,2’-bipyridine (5,5’-diMe-bpy), and K3PO4 in dioxane

• under irradiation of blue LEDs at ambient temperature afforded the desired α-arylation products 32 from secondary amides 31 and (hetero)aryl bromides 3 (Scheme 18) [72]. The method showed a broad substrate scope for both amides and aryl bromides. The authors also realized the enantioselective variant 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

• (III) salts and AlMe3 as a base for the regioselective ortho functionalization of aromatic secondary amides has been recently reported [121]. The reaction is performed with 1–2 mol % of CrCl3 or Cr(aca)3, a stoichiometric amount of AlMe3 and bromoalkynes (Scheme 15B), allyl bromide or 1,4-dihydro-1,4

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

• malonates and Grignard reagents were largely improved to up to 81% and 50%, respectively. The carbanions of aromatics, ketones, nitroalkanes, amides, etc. could also be reasonably well fluorinated and this study showed great progress. However, although these fluorinating agents were stable and easy-to

• -alkylarenesulfonamides 4-1 [26] and Umemoto’s N-fluoropyridinium salts 5-4 [29][32]. 1-7. N-Fluoroperfluoroalkanesulfonimides In 1987, DesMarteau et al. reported the synthesis of a series of N-fluoroperfluoroalkanesulfonimides 7-1. These were prepared by reacting N,N-bis(perfluoroalkanesulfonyl)amides with 100% F2 at

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• File 1, third paragraph). Despite the poverty of means, Guareschi established a laboratory in Livorno, carrying out independent research in the realm of organic chemistry. In 1874, Guareschi reported the reduction of amides to aldehydes and alcohols with sodium amalgam [23], nowadays an obsolete

Photoinduced post-modification of graphitic carbon nitride-embedded hydrogels: synthesis of 'hydrophobic hydrogels' and pore substructuring

• Cansu Esen and
• Baris Kumru

Beilstein J. Org. Chem. 2021, 17, 1323–1334, doi:10.3762/bjoc.17.92

• stretching at 1620 cm−1 is typical for carbonyl groups of amides (Figure 1a). Thereupon, characteristic hydrogel vibrations explicitly vary according to the applied processes. The major difference between HG and HGCM is the significant peak sharpness around 3274 cm-1, which can be related to –NH2 functional

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• rhodium catalyst in dioxane, in the presence of 2 equivalents of MeOH, at 65 °C, leading to compounds 65 with high diastereomeric ratio. Crude amides 65 were converted into the corresponding pyrrolidines 66 in high yield by stirring at room temperature for 1 h in presence of 2.0 equivalents of LiHMDS

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• -coupling reactions [28][29][30][31][32][33][34][35]. The thio-substitution of amides with LR is an efficient and straightforward method, because the amide substrates and LR are readily available and the reactions are easily operated [8][9][36][37][38][39][40]. With thio-substitution of amides as a model

• reference data. Melting points were determined on a Büchi M-565 apparatus. All reagents were obtained from commercial suppliers and used without further purification. The reactions were monitored by thin-layer chromatography. Column chromatography was performed using silica gel (300–400 mesh). Amides 1a–l

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• form the EDA complex, affording acylation product 123 under blue-light irradiation (Scheme 42). The quantum yield of the reaction was determined to be 0.08, suggesting that the reaction proceeded via radical coupling rather than a radical propagation. Moreover, the reaction was compatible with amides

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• defined combinations of chiral epoxides and chiral amides. This represents a very rare example of an oxidative geminal C–C/C–O difunctionalization next to carbonyl groups. The resulting dioxygenated allylic amides are subsequently subjected to persistent radical effect-based 5-exo-trig radical cyclization

• step [55]. Radical 5-exo or 5-endo cyclizations of substituted N-allyl or N-vinyl α-halo amides VIII [56][57][58][59][60][61] or X [62][63][64][65][66] using atom transfer and other chain reactions, as well as non-chain methods [67][68][69][70][71][72][73] have been used to approach diverse γ-lactam

• access to complex target molecules [74][75]. The principle is illustrated for a merger of nucleophilic opening of allylepoxides 1 with silylacetamides 2/Brook rearrangement [76][77][78] and oxygenation with TEMPO (3) leading to γ-(silyloxy)-α-(aminoxy)amides 5, which can be subsequently subjected to

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• conditions. For instance, for polyesters, alcoholysis may provide mixed monomers formally derived from transesterification reactions [89][90], while aminolysis provides amides and alcohols [91][92]. In the search of “greener” technologies for plastic recycling, catalytic hydrogenolysis processes have been

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

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

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• inhibiting activity, was prepared in yields varying mostly from 70 to 97% and always surpassing those obtained by other published methods. The method includes an Eschenmoser coupling reaction, which is very feasible (even without using a thiophile except tertiary amides) and scalable. The (Z)-configuration

• nitriles, amides, amide acetals, and imidoesters [1][2][3][5][11][14] or from their independently prepared 3-chloromethylidene- [4][9][15][16][17], 3-hydroxymethylidene- or 3-(alkoxymethylidene)oxindoles [2][5][6][18][19][20] and the appropriate amines. Recently, original methods involving the construction

• also Supporting Information File 1). The primary thiobenzamides 2a–d were prepared by the magnesium chloride-catalyzed thiolysis of commercially available benzonitriles [53] and the secondary thiobenzamides 3a–h were obtained by the thionation of the corresponding N-substituted amides [54] using

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• trifluorometylated compounds is essential for future progress in areas that eventually improve the quality of life. In this context, N-trifluoromethylated compounds (amines, amides and nitrogen heterocycles) are a relatively underexplored group of molecules with a high potential in medicinal chemistry [29][30

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• reviewed, including the phosphonylation of hydroxy esters with phosphonochloridates, the condensation of phosphonic monoesters and hydroxy esters, the alkylation of phosphonic monoesters with 1-(alkoxycarbonyl)alkyl halides or sulfonates, multicomponent condensation of amides, aldehydes, and

• transpeptidase, which catalyzes the transfer of the γ-glutamyl group of glutathione and related γ-glutamyl amides to amino acids and peptides (transpeptidation) or to water (hydrolysis). For this purpose, N-Cbz-aminophosphonic acid 91 was first transformed to the corresponding dichloride 92, which underwent a

• -hydroxyglutarate (84) in a Mitsunobu reaction to generate the γ-phosphonodepsipeptide 79 in a high yield of 66% (Scheme 27) [28]. Synthesis of phosphonodepsipeptides via the multicomponent condensation of amides, aldehydes, and phosphites followed by alcoholysis with hydroxy esters Previously, the Mannich-type