Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• the formation of N-substituted indole derivatives from N-substituted anilines. The direct PdI2/KI oxidative carbonylation of 2-alkynylanilines does not lead to the formation of indole-3-carboxylic esters but to the formation of acyclic carbamates. For this reason, they performed the reaction in the

• ) and the corresponding urea derivatives as byproducts. In the middle of the same year, Wu’s group succeeded in using N-(2-bromobenzoyl)indoles in the reaction with alcohols and anilines to achieve a Pd-catalyzed diasteroselective carbonylative cyclodearomatization [62]. The synthesis proceeded best

• when the reaction was performed in the presence of 10 mol % of Pd(OAc)2 and dppp as catalyst system, Na2WO4∙2H2O (1 or 2 equiv) as base and an excess of nucleophile (alcohols or anilines) in toluene as reaction solvent under 5 bar of CO at 100 °C. Also, 20 mol % of LiBr were added as additive when

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• efficiently scaled-up to gram scale. Noteworthy, 1-substituted tetrazole-5-carbaldehydes are almost elusive from chemical literature [25][26][27][28][29]. Moreover, all synthesis routes described so far are lengthy and involve dangerous chemicals. The 4-step procedure of Sun et al. starts from anilines and

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• reactions of substituted anilines VI, VII or N-arylamidines VIII are frequently employed for synthesizing C2-substituted quinazolines (Scheme 1), thereby influencing the spatial arrangement of the desired substituents [13][14]. Moreover, there have been recent advancements in efficient C–H activation

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• sterically crowded 6,8-di-tert-butyl-3H-phenoxazin-3-one (1) that afforded a series of 6,8-di-tert-butyl-2-(arylamino)-3H-phenoxazin-3-ones 4 prepared in 68–93% yield (Scheme 2). Using o-amino-, o-hydroxy- and o-mercapto-substituted anilines in this process allowed to pursue both principal reaction pathways

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• -dihydronaphthalenes 47 with yields of up to 92%, as depicted in Scheme 21 [38]. The key aspect of the approach involved the simultaneous cleavage of dual C–C bonds and a single N–O bond, which was facilitated by the utilization of LiI/PPh3 as the photoredox system. Amination Anilines play important roles in both

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• morpholine as solvent (0.4 M) and 0.4 equiv LiHMDS as a base at 75 °C for 48 h. The only byproducts observed are anilines as a result of thermal decomposition of the organic azides via reactive nitrene species. No other byproducts were observed by TLC or crude 1H NMR. The volatility of the gem

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• thiolating reagent was used by another research team for the arylthiolation of arylamines 76 in acetonitrile as a solvent under metal-free conditions (Scheme 66) [96]. A broad spectrum of mono-, or diarylthiolated anilines 153 was obtained in low to excellent yields. Arylthiolation occurred predominantly at

• of the product, while benzoyl peroxide (BPO) gave a low yield. Various nucleophiles 161, including ammonia, alkylamines, hydrazines, alcohols and alkoxides, indole, N-alkylpyrrole, N-substituted anilines, PhSH, and PhMgBr worked well under these conditions. Asymmetric thiolation of 4-substituted

Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates

• Olfa Mhasni,
• Jalloul Bouajila and
• Farhat Rezgui

Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93

• , Yang et al. [18][19] have developed a catalytic system involving Pd/Ti(OiPr)4 or Pd/carboxylic acid for the direct allylation of anilines with alcohols. The synthesis of N-allylimidazole derivatives 3 has been previously carried out using acyclic MBH adducts bearing good leaving groups, such as bromide

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• to obtain the products with satisfactory enantioselectivities. The reaction was compatible with a broad range of substrates using para-substituted phenyl rings as the nitrogen substituents in anilinies 59. Two examples were shown with N-benzyl and N-methyl-substituted anilines which afforded the

• N-aryl-substituted anilines 59 which decreased in case of N-alkyl-substituted anilines. This observation led to the development of a plausible transition state of the stereoselective electrophilic addition which included dual H-bonding interactions between both the substrates and the catalyst along

• . Functionalization of the carbocyclic ring of substituted indoles. Aza-Friedel–Crafts reaction between unprotected imines and aza-heterocycles. Anilines and α-naphthols as potential nucleophiles. Solvent-controlled regioselective aza-Friedel–Crafts reaction. Generating central and axial chirality via aza-Friedel

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• various substituted anilines, primary arylamides, and sufonylamides 20 and 2,5-DMTHF (2) in the presence of 10 mol % MgI2 etherate in MeCN at 80 °C (Scheme 9a). MgI2 etherate is a main-group Lewis acid catalyst that selectively activates electron-rich aromatic amines. This is a mild, efficient, and highly

• were selected and used for the synthesis of 20 examples of N-substituted pyrroles in yields of 62–98%. In this study, it was observed that anilines with electron‐withdrawing groups (i.e., NO2, CF3, F, Cl, Br) deactivated arylamine and gave the corresponding pyrroles in moderate yields, while anilines

• aniline having electron withdrawing and electron donating substituents on the aromatic ring. However, this protocol did not produce a product with aliphatic amines and satirically hindered o-substituted anilines. A plausible mechanism for the formation of N-arylpyrroles is depicted in Scheme 18b. In 2014

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• with ortho-substituted anilines is also reported. The key features of the protocol include the use of a green oxidant, a short reaction time (30 min), chromatography-free isolation, scalability, and economical, delivering N-arylsulfonylimines in excellent yields of up to 96%. While the oxidation of N

• approach, a gram-scale synthesis and a “one-pot” tandem synthesis of pharmaceutically relevant N-heterocycles by the reaction of in situ-generated N-arylsulfonylimines with various ortho-substituted anilines were also developed. The mechanism of the oxidation is believed to occur via hydrogen atom

• synthetic utility of the developed protocol, a tandem “one-pot” synthesis of N-heterocycles was successfully executed (Scheme 3). Thus, exposition of substrates 1 under the optimized reaction conditions followed by the addition of ortho-substituted anilines 3 and K2S2O8 (1 equiv) and heating the reaction

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• electron-donating and electron-withdrawing groups, as well as N-aryl and N-alkylamines (Scheme 15). Lam et al. [58] expanded on the multicomponent method to form substituted dihydropyridobenzazepines 80–82 wherein vinylpyridines 77 are coupled with boronate ester anilines 78 in a Suzuki reaction

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

Dissecting Mechanochemistry III

• Lars Borchardt and
• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1454–1456, doi:10.3762/bjoc.18.150

• José G. Hernández Bochum, Medellín, October 2022 ORCID® iDs Lars Borchardt - https://orcid.org/0000-0002-8778-7816 José G. Hernández - https://orcid.org/0000-0001-9064-4456 a) Mechanochemical PEG-400-assisted halogenation of phenols and anilines using NXS. b) Halogenation of azobenzenes with NXS

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

• catalyst-free halogenation of phenols and anilines via liquid-assisted grinding using PEG-400 as the grinding auxiliary. A series of mono-, di-, and tri-halogenated phenols and anilines was synthesized in good to excellent yields within 10–15 min in a chemoselective manner by controlling the stoichiometry

• catalyst-free methods, the use of costly and low boiling hexafluoroisopropanol (HFIP) as solvent offered the para-selective halogenation of activated aromatic systems (Scheme 1c) [44]. It is noteworthy to mention that over-halogenation of activated systems like phenols and anilines, due to the high

• desired monobromo derivative 2z was achieved only after 30 min of rigorous grinding. However, a negligible conversion was observed for p-xylene or mesitylene even after grinding for an hour. Therefore, we restricted our study to the halogenation of phenols and anilines only. Subsequently, a short series

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

• -arylaminopropyl(methyl)phosphinic acids 45 under reduced pressure. The reactions of 1,2-oxaphospholane 2-oxides 47/2-sulfides 50 and anilines 48 generated 1-aryl-2-methyl-1,2-azaphospholidine 2-oxides 49 and 46a as well, while the reaction of 1,2-thiaphospholane 2-sulfide (51) with aniline (48a) gave

• with anilines. Synthesis of 1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides/sulfides from 2-aminobenzyl(phenyl)phosphinic acid. Synthesis of 1,3-dihydrobenzo[d][1,2]azaphosphole 2-sulfide (59) from zwitterionic 2-aminobenzyl(phenyl)dithiophosphinic acid (58). Synthesis of 1,3-dihydrobenzo[d][1,2

Continuous flow synthesis of azobenzenes via Baeyer–Mills reaction

• Jan H. Griwatz,
• Anne Kunz and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2022, 18, 781–787, doi:10.3762/bjoc.18.78

• reliable synthesis of symmetric ABs in high yields via a Cu-catalyzed oxidative coupling of aniline derivatives [17]. This synthesis can be also used for the formation of non-symmetric AB, however, only for a selected set of anilines. One of the most applied methods to access non-symmetric azobenzenes is

• based on the condensation of nitrosobenzenes with anilines (Scheme 1). This so-called Baeyer–Mills reaction, which was first published by Baeyer in 1874 and further investigated by Mills, proceeds best for electron-rich anilines with electron-poor nitrosobenzenes. The reactivity can be rationalized by

• excellently for most of the electron-rich anilines due to their increased nucleophilicity. A comparison of ortho-, meta- and para-substituted derivatives revealed that for electron-rich anilines, the para-substituted ABs are formed in better yields as their ortho- and meta-analogues. For example, 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

• the reaction of bromopropargylic alcohol 1a and phenols 2b–i. Reaction of bromopropargylic alcohol 1b and phenols 2a and 2d. Reaction of bromopropargylic alcohol 1c and phenol (2a). Reaction of chloropropargylic alcohol and phenol (2a). Reaction of bromopropargylic alcohol 1a and anilines. Control

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• -, meta-, and para-substituted N-methylanilines as well as substituted anilines and furnished the corresponding 4-anilinoquinazolines in good yields. Preliminary screening of the synthesized compounds against tumor cells (HCT-116 and T98G) showed promising antiproliferative properties. Keywords: 4

• -substituted anilines) [6][9] readily react with 4-chloroquinazolines to give 4-aminoquinazolines in moderate to good yields under milder reaction conditions (Scheme 1a). On the other hand, long reaction times and low yields may be observed when electron-poor amines are applied in these reactions [17][18

• ]. These limitations can be overcome by using microwave irradiation [12][13][18][19][20], which promotes fast and efficient anilination reactions when a wide range of anilines bearing both electron-donating and electron-withdrawing groups are employed as nucleophiles (Scheme 1b) [12][13]. Moreover, 4

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

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

• the substrate scope of this protocol. Initially, 2-(2-oxo-2-phenylethyl)benzonitrile (3a) was treated with various anilines under the optimized reaction conditions (Scheme 2). The yields of the reactions were not influenced significantly by the electronic effects of the substituents. However, the

• huge impact on the reaction efficiency and efficacy, where para- and meta-substituents have minimal impact on the yields of the reaction delivering the corresponding products in comparable yields (Scheme 2). While least yields were observed with ortho-substituted anilines (Scheme 2, 5h and 5k), which

• can be rationalized by the steric hindrance created by the ortho-substituents. It is also worth mentioning that secondary anilines also reacted with 2-(2-oxo-2-phenylethyl)benzonitrile (3a) and delivered the corresponding product 5m, albeit in lesser yields. Later, the substrate scope of 2-(2-oxo-2

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

• groups were tolerated [7]. In 2020, Tan and co-workers disclosed the phosphoric acid-catalyzed atroposelective arene functionalization of nitrosonaphthalene with indoles to form atropisomeric indole-naphthalenes 39 and indole-anilines 40 by a nucleophilic aromatic substitution reaction [61] (Scheme 13

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

• bifunctional thioureas Thioureas constitute one of the most important class of organocatalysts [49]. Wang et al. reported a cascade aza-Michael/Michael reaction of anilines 60 to nitroolefin enoates 61 using chiral bifunctional thiourea as catalyst (cat. 62). It provided a mild and efficient approach to the

• -quinolones 92 in very good yields (67–95%) with high ee (82–97%) (Table 20) [59]. Following a similar approach, Yang et al. reported asymmetric aza-Michael additions of anilines 94 to β-nitrostyrenes 93 using a chiral binol-derived phosphoric acid diester catalyst (cat. 95). They succeeded in preparing β

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

• equivalent of aniline in the presence of a Brønsted acid undergoes a multistep rearrangement to form the indole group as part of the target tryptamine 110 (Figure 20). The one-pot conversions occurred successfully over a wide range of monosubstituted anilines, including various para-alkyl groups (65–72