Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• , this method is not viable for N-benzylated indoles, where reduction in liquid ammonia with sodium is usually used as a standard protocol instead, even though successful reports are rare [41]. Other methods involve strongly basic and oxidative conditions [42], which are not tolerated by the CH2 group in

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

• Tianri Du Xiangmu Wei Honghong Xu Xin Zhang Ruiru Fang Zheng Yuan Zhi Liang Yahui Li Key Laboratory of Agri-Food Safety of Anhui Province, School of Resources and Environment, Anhui Agricultural University, Hefei 230036, China 10.3762/bjoc.18.9 Abstract The selective acylation of indoles often

• requires sensitive and reactive acyl chloride derivatives. Here, we report a mild, efficient, functional group tolerant, and highly chemoselective N-acylation of indoles using thioesters as a stable acyl source. A series of indoleamides have been obtained with moderate to good yields. In addition

• cannabinoid (hCB1) receptor [3] (Figure 1). Indole has multiple reactive sites, and chemoselective N- or C-functionalization of indoles is a challenging and important task [4][5]. Acylation of indoles frequently takes place at the C3 position because of the relatively strong electron cloud density. As N

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

• essential for promoting this reaction (Scheme 12). Both electron-rich and electron-deficient indoles afforded the desired products in good yields. The major advantages of this method include high regioselectivity, mild reaction conditions, and reusability of the catalyst. Two years later, in 2014, Ackermann

• heteroarenes such as thiophenes, benzofurans, furans, and indoles were found suitable substrates and afforded the desired products with high chemo- and site-selectivity. A possible mechanism for the reaction was also described. The first step of the catalytic cycle involves the formation of a cationic complex

• mechanism for the ruthenium-catalyzed aerobic oxidative cyanation. RuCl3-catalyzed oxidative cyanation of tertiary amines using acetone cyanohydrin as the cyanating agent. Cyanation of indoles using K4[Fe(CN)6] as cyano source and Ru(III)-exchanged NaY zeolite (RuY) as catalyst. Cyanation of arenes and

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• necessary for their biosynthesis. Prenylated indoles are widely distributed among bacteria, fungi and plants, and all seven positions are subject of prenylation except for the bridgehead carbons [34]. Compound 6 is the acetylated derivative of 6-(3,3-dimethylallyl)-ʟ-tryptophan from Streptomyces sp. SN-593

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

• methodology was extended to the carbosilylation of olefins with carbon nucleophiles 108 including indoles, pyrroles, and 1,3-dicarbonyls. The scope of the reaction was broad and could tolerate a variety of functional groups; however, electron-deficient alkenes afforded the products in slightly diminished

• sterically demanding alkyl groups. Overall, when the protocol was applied towards the synthesis of pyrrolo[1,2-a]indoles 135, product yields were slightly diminished; however, the scope was equally as broad and tolerated most functional groups. Sterically demanding peresters were shown to react poorly with

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

• 2019, Li and co-workers developed a synthetic strategy for the atroposelective construction of phenylindole 20 by the chiral phosphoric acid-catalyzed cross-coupling of quinones 18 and indoles 19. In this reaction, the chiral phosphoric acid (R)-CPA 6 acts as a bifunctional catalyst to activate indoles

• -workers showed that azo groups enable the organocatalytic asymmetric arylation of indoles. The nucleophilic aromatic substitution between the azobenzene derivative 24 and indoles 25 was carried out in the presence of 2.5 mol % chiral phosphoric acid (CPA 8, Scheme 9a), leading to the intermediate I-4

• the reaction of 2-substituted indoles with azobenzenes proceeded smoothly in the presence of the chiral phosphoric acid catalyst (R)-CPA 9. At a catalyst loading of 0.2 mol %, the intermediate I-5 was simultaneously cyclized to I-6, followed by β-H elimination and chirality transfer to afford another

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

• of prolinol silyl ether (cat. 120) and benzoic acid (A1) catalysts to bring about reaction between 3-formyl-substituted indoles or pyrroles 118 and diverse electrophiles, including carbonyls, imines and other Michael acceptors (Scheme 5) [69]. The reaction with secondary amines occurred via the

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

• found with Pd(OAc)2/bpy as the catalyst, N-methylacetamide as the solvent, and a temperature of 80 °C. Variously substituted indoles as well as esters of 118 (R = aryl, alkyl, vinyl) were generally well tolerated, but oxa- (X = O) and azo- (X = NR) cyclobutanes met with limited success. Alternative

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 cyanamides) has also been described [53]. A similar base-induced cyclization of N-(alkoxycarbonylmethyl)-7-formylindoles to give pyrrolo[3,2,1-hi]indoles is also of interest [54]. Acid-induced cyclization akin to ours, and also assuming an in situ E to Z isomerization under the reaction conditions

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

• ] discovered the asymmetric cross-coupling of racemic tertiary alkyl halides 43 with carbazoles or indoles 44 in the CuI/chiral phosphine system. Under irradiation conditions, excitation of the copper–nucleophile complex A results in the excited state species B that engages in the electron transfer with the

• undergoes radical addition with the N-substituted maleimide (Scheme 25). In 2017, Wu and co-workers [94] reported the α-amino C−H functionalization of aromatic amines 51 with nucleophiles, including arynes or aromatic olefins 52, indoles, acyclic β-ketoester 53, and β-diketone 54 (Scheme 26). Mechanistic

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

• powerful nitrogen source for the synthesis of various N-heterocycles, such as isoquinolines, quinolines, pyridines, pyrroles, indoles, azoles, and azepines [40][41][42][43][44][45]. 1,3-Enyne, as a powerful Michael acceptor, is a wonderful synthon for the synthesis of N-heterocycles via tandem addition and

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• ][18]. Because indoles are readily available materials, the direct extension of indoles to carbazole skeletons has a great advantage [19][20][21][22][23][24][25][26][27]. Therefore, the Diels–Alder reaction of activated 2-vinylindolines or 3-vinylindolines with diverse dienophiles has become the most

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• arylacetylenes 93, 95, and 97 yielded benzofurans 94, benzothiophenes 96, and indoles 98, respectively. When the carbonyl group was introduced between an aryl and a methoxy group (99) then six-membered isocoumarin ring 100 was formed, and when a carbonyl group was introduced in between an aryl and an alkyne

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

• -workers reported controllable mono- and dichlorooxidation of indoles with hypervalent iodine species in DMF/CF3CO2H/H2O at room temperature, which generated 3,3-dichlorooxindoles and 3-monochlorooxindoles, respectively (Scheme 1, reaction 3) [23]. Apart from these methods, most traditional approaches to 3

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

• these types of reactions. The first thiourea-catalyzed asymmetric intermolecular reaction with N-acyliminium chlorides was then also realized by the same group in 2009. Therein, nucleophilic addition of indoles 17 to the N-acyliminium chlorides was achieved with excellent enantiomeric excess (Scheme 4b

• have been provided by the group of Jacobsen in the nucleophilic addition of indoles 17 to pyranones 62 (Scheme 14a) [71], as well as in the enantioselective synthesis of α-allyl amino esters 67 by the reaction of α-chloro amino acid derivatives 65 with allyltin and allylsilane 66 nucleophiles [72

• -catalyzed intramolecular Pictet–Spengler-type cyclization of hydroxylactam-derived N-acyliminium chlorides and b) thiourea-catalyzed intermolecular hydroxy lactam-derived N-acyliminium chlorides with indoles. Enantioselective Reissert-type reactions of a) (iso)quinolines with silyl ketene acetals, and b

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

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

• a concise account of the same, although preparations of ionic bis(indolyl) metal salts will not be considered [24][25][26][27][28][29][30][31][32][33]. Review The pyrrole C2 and C3 linkages By virtue of the two available sites in its pyrrole substructure, two indoles can be attached to a central

• process, where hydrosilanes 41 were treated with an excess amount of indoles (Scheme 7a and Scheme 7b) [60]. Brookhart’s acid [H(OEt2)2]+[BArF4]− (42) was used to generate ether-stabilized silicon cations of type 46 and norbornene was added as a proton scavenger [64]. Following this procedure, Yonekura

• ). A repetition of the processes leads to the bis(indol-3-yl)silanes 40. Han described a Lewis acid-promoted C3-silylation of N-protected substituted indoles by a disproportionation mechanism of the latter. He used both B(C6F5)3 and Al(C6F5)3 in the reactions (Scheme 8a and Scheme 8c) which followed a

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

•  19D). In carbocyclic substrates the displacement of a C–F bond or ionization with a Lewis acid is difficult, but mesylates are stable and suitable for AlMe3 activation. As already mentioned, indoles are an important class of molecules with potential antidiabetic properties since they can act as GPR40

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

• -protected indoles led to reduced indole products (indolines 82f and 82g). The substitution of the acrylonitrile group for an acrylate unit completely inhibited the reaction, whereas the replacement with an unactivated trisubstituted olefin unit led to cyclized products in lower yields (Scheme 30, 82h–k

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

• derivatives have recently received increasing attention from synthetic organic chemists, biologists, and pharmacologists. In general, DIMs can be synthesized via electrophilic substitution of indoles by aldehydes or ketones in the presence of conventional Lewis or Brønsted acids as catalysts [19]. This

• electrophiles has emerged as a powerful strategy for constructing synthetically valuable indol-3-yl-containing molecules. In particular, the reaction of indol-3-ylmethanols with indoles has become a useful route for the preparation of tertiary unsymmetrical 3,3'-DIMs [26][27][28][29][30][31][32][33][34][35

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• -pyrido[3,4-b]indole (β-carboline) is the most naturally abundant, present for instance, in the alkaloid harmine, a well-known selective inhibitor of monoamine oxidase-A (MAO-A) [1]. On the contrary, 5H-pyrido[4,3-b]indoles (γ-carbolines) are comparatively less examined, although these heterocycles have

• substituted pyrrole-2-aldehydes to 5-azaindole transformation during a base-catalyzed imination reaction [31]. However, we envisioned that our methodology might be strategically applied towards the synthesis of substituted γ-carbolines as a C-3 nucleophilic attack is more favored in indoles than in pyrroles

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

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

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• the high nucleophilicity of the amino group in the substrate 23 to control the regioselectivity of the reaction (Scheme 9). 3 Indoles Indoles have a bicyclic structure consisting of a six-membered benzene ring fused with a five-membered nitrogen-containing pyrrole ring. Figure 3 depicts some of the

• synthesis of 3-functionalized indoles 34 by employing amines 32, arylglyoxal monohydrate 33 and cyclic 1,3-diketones 6 under microwave irradiation in the greener solvent system EtOH/H2O (Scheme 10). A plausible mechanism (Scheme 11) suggests a TFA-catalyzed Knoevenagel condensation between 4-hydroxy-6

• opening resulting in imine intermediate E. A consecutive intramolecular cyclization and tautomerization yields azepino[5,4,3-cd]indoles 143b. 9 Quinolines Quinolines are bicyclic aromatic heterocycles consisting of a fused pyridine and benzene ring. Quinoline and its derivatives are important both from