Electrocatalytic C(sp³)–H/C(sp)–H cross-coupling in continuous flow through TEMPO/copper relay catalysis

• Bin Guo and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2021, 17, 2650–2656, doi:10.3762/bjoc.17.178

• temperatures [3][4][5], prompting the development of mild conditions by merging photoredox catalysis with copper catalysis (Scheme 1B) [8][9]. Notwithstanding of these outstanding achievements, noble metal-based catalysts and chemical oxidants are employed under these photochemical conditions. Organic

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• ) revealed that toluene is the most suitable solvent. Next, we targeted to make the reaction more time economical under mild conditions. For this purpose, the reaction was performed at different concentrations of the reaction mixture (Table 1, entries 8–11). It was observed that time required for completion

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

• good yields (24 to >99%) with poor to moderate ee (9 to 55%). A complete reversal of stereoselectivity was observed on introducing a benzoyl group in cinchonine and cinchonidine. It was demonstrated that racemization occurred in suitable solvents under mild conditions due to retro-MR of the initially

• -Michael addition of 2-tosylaminoenones with unsaturated pyrazolones using squaramide as catalyst. The reaction proceeded smoothly under mild conditions to afford the corresponding spiro[pyrazolone-tetrahydroquinolines] in high yields (up to 99%) with excellent diastereoselectivities (up to >25:1 dr) and

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

• alkylation Under mild conditions, copper salts are able to catalyze olefinic C–H functionalization or allylic alkylation, thus allow introducing alkenyl or allyl groups into organic molecules. Alkenylation and allylation reactions have been extensively investigated under thermal conditions. However, only few

• salts or the substitution of thermal heating for LED irradiation resulted in a low yield of the cross-coupling products 22 and 23, indicating the necessity of the copper salt and LED irradiation. Mild conditions, such as Pd-free and high reaction yields at room temperature, make this method a very

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

• oxidative C–H/N–H coupling of ferrocenes with free amines to provide mono-aminated ferrocenes exclusively under mild conditions (Scheme 1b). During the preparation of the manuscript of this article, a nice report on Cu-catalyzed C–H amination of ferrocenes directed by 8-aminoquinoline was reported by

• -determining step. Conclusion To summarize, we have reported a copper-catalyzed direct ortho-C–H/N–H coupling reaction of ferrocenes with alkyl amines directed by 8-aminoquinoline. Fruitful mono-aminated ferrocenes were obtained in moderate to good yields and the mild conditions offered the possibility to the

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

• mild conditions (Scheme 12) [55]. The reaction was performed in CH2Cl2 at ambient conditions in the presence of 2.0 equiv of K2CO3. Substrates bearing electron-donating or electron-withdrawing groups were compatible under standard conditions to give the highly substituted pyrroles in moderate to good

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• developed a straightforward metal-free procedure for the synthesis of bis-arylated 2,5-dichlorobenzoquinones. The reaction is tolerant towards a wide range of functional groups, occurs under mild conditions in an environmentally benign solvent and does not require further purification of the reaction

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

• -amino C(sp3)–H bonds using di-tert-butyl peroxide (DTBP) or dicumyl peroxide (DCP) as the methyl source under mild conditions [93]. Based on the substrate structure and peroxide choice, the authors developed four sets of reaction conditions (Scheme 29) [93]. In these reaction conditions, photocatalyst

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

• Brønsted acids and Lewis acids as catalysts (Table 1) to develop an intramolecular FCA protocol with activating alkenes effectively and economically in order to obtain some originally substituted arylxanthenes under mild conditions for the first time. We found that, among these acids, trifluoroacetic 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

• widely applied as catalysts for this matter, including in the synthesis of bioactive substances. Although catalysts based on these metals, are known to be efficient in C–H bond activation reactions affording the products in good yields and mild conditions, they are also known to be usually expensive

• also been reported for the direct C(sp3)–H fluorination. Chen and co-workers [94] described a fluorination method employing Selectfluor as fluorine source and the commercially available V2O3 to give fluorine-containing compounds under mild conditions and with moderate to good yields (Scheme 10B,C). The

• , operating under mild conditions without the need of directing groups, using traceless electrons as sole redox reagents, presenting high scope and chemoselectivity. The robustness of the reaction was proved by the late-stage modification of pharmaceutically relevant compounds by promoting the azidation of a

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

• , olefins, silyl enol ethers, vinyl acetates, sulfides and so on, under mild conditions with high selectivity and yields [29][30][31][32]. All these reactions could be carried out routinely using standard glassware in normal laboratory environments and without any specialist training. Some interesting

• , Grignard reagents, and aromatic compounds under mild conditions. In each case Selectfluor gave the corresponding fluorinated products in good to high yields (Scheme 34). As can be seen in Figure 3 and Figure 4, two years later (1994), Banks et al. reported mono- and difluorinations of various 1,3

• F2/N2 system, but failed. Reagent 20-3 was synthesized using cesium fluoroxysulfate in 1991 (see section 1-15). Reagent 20-2 proved useful for the fluorination of both neutral and anionic nucleophiles under mild conditions. Scheme 45 illustrates some pertinent examples. Phenyl Grignard reagent

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

• -triazoles. The postfunctionalization of disubstituted 1,2,3-triazole was also explained with a range of C–C- and C–N-bond-forming reactions. A number of fully substituted 1,2,3-triazoles was provided from different compounds in moderate to high yield under mild conditions. In the last years, the

• substituted triazoles under mild conditions starting from readily available starting materials, showing broad structural diversity (Scheme 47) [68]. The authors proposed a reasonable mechanism for this process. First, 1-alkyltriazene 176 and azide 177 are coordinated to the iridium center to form intermediate

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

• -biphenyl)]Cl as a catalyst (Scheme 8) [41]. Under mild conditions, functionalized five and six-membered lactams 14 were synthetized in excellent yields (90–99%), including those of the lactams in which a quaternary center was constructed. Only exo-trig cyclization products were obtained, and substrates

• of MHAT reactions is the high tolerance to the presence of other functional groups in the reactants due to the mild conditions usually employed. At the end of the 1980s and the middle of the 1990s, Mukaiyama published a series of seminal works reporting the use of silanes as reducing agents (hydride

• strategy in total synthesis can be found [82][83][84][85][86][87][88][89][90]. The reaction’s mild conditions and high chemoselectivity allowed its use even in advanced steps in a total synthesis route when diverse functional groups were present in the intermediates. Two representative examples of the

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

• , such as 5 and 6, available via [3 + 2]-cycloadditions [21][22][23][24][25] or [3 + 3]-annulations [26] of trifluoroacetonitrile imines 7, respectively, were reported (Scheme 2). Noteworthy, the latter 1,3-dipoles are easily generated under mild conditions via base-mediated dehydrobromination of the

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• unsymmetrical 3,3'-diindolylmethanes (DIMs) with a quaternary carbon center has been developed via iodine-catalyzed coupling of trifluoromethyl(indolyl)phenylmethanols with indoles. In contrast to previously reported methods, the new procedure is characterized by chemoselectivity, mild conditions, high yields

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

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• radical initiator under mild conditions. A wide range of structurally diverse nitrogenous heterocyclic compounds including indolines, oxindoles, isoquinolinones, and isoquinolinediones have been accessed in high yields. This heterogeneous protocol features base- and transition metal-free, good catalyst

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• , which can provide the desired biguanides in one-step under relatively mild conditions. Given the moderate yields of the reported procedure, the reaction conditions should be reexamined in an exhaustive and systematic study. In addition, the development of new “biguanidilation” agents presenting other

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

• -metal catalysts, such as in the Suzuki–Miyaura and Heck coupling reactions. Methodologies for forming different C–C bonds have recently been developed in the field of single-electron chemistry [63][64][65]. Considering that EDA-complex-initiated free-radical reactions are carried out under mild

• conditions, more attention has been paid to this efficient strategy for C–C-bond formation. In 2015, Yu and colleagues [27] proposed a method for direct C–H trifluoromethylation of aromatic hydrocarbons through an EDA complex. Trifluoromethylated product 61 was synthesized by employing tryptamine derivative

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• formation of an unexpected product, i.e., β-triazolylenone. Being inspired by the results, we intended to use 1,3-dicarbonyl compounds as detosylative alkylating agents that would lead to the formation of β-triazolylenones in a highly regioselective manner under mild conditions (Scheme 1d). Results and

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

• kinetics, cost of metals, toxicity, difficulty in catalyst reusing and need of downstream processing. Significant efforts have thus been made to develop greener and sustainable catalytic systems featuring high efficiency under mild conditions. The use of sodium carbonate or bicarbonate as ecofriendly

Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes

• Xiaojuan Li,
• Qiang Zhang,
• Weigang Zhang,
• Jinzhu Ma,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49

• successfully studied. However, the disproportionate dithiolation of alkenes is unknown. Herein, a transition-metal-free protocol is presented for the vicinal trifluoromethylthio–thiolation of unactivated alkenes via a radical process under mild conditions with a broad substrate scope and excellent tolerance

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• respect, a bifunctional quinine-derived sulfonamide organocatalyst was developed to catalyze the asymmetric sulfa-Michael reaction of naphthalene-1-thiol with trans-chalcone derivatives. The target sulfa-Michael adducts were obtained with up to 96% ee under mild conditions and with a low (1 mol

• synthetic organic chemistry [22]. Thus, the SMA with thiols and α,β-unsaturated ketones are generally carried out at low temperatures and with high catalyst loading [23][24][25][26]. The studies that employ mild conditions and low catalyst loading use thiophenol derivatives or simple alkylthiols as

• sulfa-Michael additions of thiols to chalcones with sulfonamide-type organocatalysts in the literature [30][31], in this study, a new quinine sulfonamide organocatalyst derivative was developed to catalyze the enantioselective SMA of naphthalene-1-thiol to trans-chalcones under mild conditions and with

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

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

• -dioxaphospholane-4,5-dicarboxylate (168) gave the corresponding phosphonodepsipeptides 169 in 65–86% yields under mild conditions. Although the diisopropyl ester was applied instead of diethyl ʟ-tartrate, a low diastereoselectivity (ratios varied from 55:45 to 67:33) was observed as well. Acetophenone (170

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• . A series of substituted products was obtained in SNAr reactions between 2,6-bistriazolylpurine derivatives and O- and C-nucleophiles under mild conditions. The products were isolated in yields up to 87%. The developed C–O and C–C bond forming reactions clearly show the ability of the 1,2,3-triazolyl

• 4a. Also hydrolysis of 2c into 4b proceeded under mild conditions and only gentle warming to 50 °C was required. 2,6-Bistriazolylpurine derivatives in SNAr reactions with C-nucleophiles Next, SNAr reactions between 2,6-bistriazolylpurine 2c and C-nucleophiles offered an easy way for the C–N bond