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

• ). Conclusion In summary, a concise, simple, clean and efficient synthesis of paullone isomer C was achieved in 4 steps with a crucial transformation, the Fischer indole ring-closure reaction, at the early stage of the synthesis (Scheme 6). The synthetic utility of the elaborated route was validated by gram

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• -isothiocyanato-1-indanones with barbiturate-based olefins have been developed to afford chiral dispiro[indene-pyrrolidine-pyrimidine]s. Through this strategy, the target products could be obtained in good to excellent yields with excellent stereoselectivities. In addition, the synthetic utility was verified

• , >99% ee), which indicated this strategy shows promising prospects for mass production. Moreover, two different transformations of the product 3ah are shown to validate synthetic utility of the reaction. As demonstrated in Scheme 5, the dispiro[indene-pyrrolidine-pyrimidine] 3ah could be easily

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

• ligand and its appropriate steric properties are thought to be crucial to the success of the reaction [71]. The authors showed the in situ-formed 1,3-dienylmagnesium species 33 can also be trapped by a variety of electrophiles, demonstrating the synthetic utility of the reaction. In 2016, Fürstner and

• catalysis [132]. Electron-rich alkyl iodides did not produce the desired product with only perfluorinated and ester-containing alkyl iodides 20 working well. Despite the limited applicability of nucleophiles, the reaction was extremely fast, typically finishing in under 10 minutes. To show the synthetic

• utility of their reaction, the authors studied the one-pot conversion of the vinyl azides to 2H-azirines 161. The carboazidation reaction for the aryl alkynes was completed in a comparable amount of time. A myriad of different functionalized π-systems was tolerated by the reaction, demonstrating its

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• synthetic utility of this protocol was also demonstrated in the synthesis of difluoroalkylated diarylmethane 5 and diarylmethane ketone derivatives 6 and 7, which are important core structures in natural products and medicines. Keywords: chemoselective reactions; diarylmethyl sulfones; dual role

• ; isonitrile diarylmethane; synthetic utility; Introduction Sulfones are ubiquitous units commonly found in marketed drugs and natural products. Because of their unique electronic and structural properties, they are often used in medicinal chemistry programs to search for anti-inflammatory, anti-HIV

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

• . Furthermore, the synthetic utility of this protocol was demonstrated in the successful synthesis of the antitumor agent CWJ-a-5 in gram scale. Keywords: 1-aminoisoquinolines; CWJ-a-5; intramolecular cyclisation; 2-(2-oxo-2-phenylethyl)benzonitriles; nucleophilic addition; Introduction Heterocyclic compounds

• found to be compatible with the present protocol delivering the corresponding 1-aminoisoquinolines (5v–x) in good yields (Scheme 4). The synthetic utility of this method was further extended towards the gram-scale synthesis of the antitumor agent CWJ-a-5. Accordingly, 2-(2-oxo-2-phenylethyl)benzonitrile

• to yield the product 5. Conclusion In summary, an efficient Me3Al-mediated domino nucleophilic addition with a subsequent intramolecular cyclisation on 2-(2-oxo-2-phenylethyl)benzonitriles with amines was developed allowing access to widely substituted 1-aminoisoquinolines. Furthermore, the synthetic

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

• 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

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

• in 50% yield (Scheme 4b, 1.32 g). For synthetic utility, the directing group was conveniently removed by refluxing with KOH in EtOH and the benzyl-protected ester 5 was obtained in 75% yield. We also conducted several deuteration experiments to shed a preliminary insight into the mechanism. No H/D

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

• strategy presented here does not involve isolating these reactive substrates, the potential risk is minimized. The procedure was safely repeated for the synthesis of 3o on a 10 mmol (2 g) scale without altering the yield. We further demonstrated the synthetic utility of the method by successfully

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• of HBr in these processes. The influence of steric and electronic factors from both the perspective of the nucleophile and electrophile were investigated and levels of enantiocontrol up to 90% ee obtained. The synthetic utility of the methodology was demonstrated via the concise enantioselective

• the SN2 alkylation of methylene ester-substituted 2-oxindole 4 [31]. The utility of this methodology has been demonstrated through the total synthesis of (−)-debromoflustramine B (Scheme 1B). In an attempt to devise variants of this reaction of greater versatility and synthetic utility; we sought to

• % ee (Table 2, entry 10). Consistent with the goal of developing a protocol of the best possible synthetic utility; alkylating agents which would be easily modified after installation on the oxindole core – such as α-iodoesters – were also evaluated (Table 2, entries 10–12). Although, alkyl esters

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

• active nickel(0) catalyst 5-III. The synthetic utility of the photoredox nickel-catalyzed C‒H arylation was further elaborated to include C‒O electrophiles which could be readily derived from phenols, as disclosed by the Yu group [58]. Hence, they reported an arylation protocol for α-amino- and α-oxy C

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

• Reactions associated with carbon–carbon bond formations are explored for their synthetic utility in extending the carbon framework in organic molecules [1][2][3]. Among the known C–C bond forming methodologies the Friedel–Crafts reaction is the most utilized methodology. As a result of its broad scope of

• standard reaction conditions. Convincingly MBH adduct 5h (10 mmol) delivered the desired product 6h in 73% yield (1.28 g). The outcome of this practical scale synthesis demonstrates the synthetic utility of the stabilized reaction for large scale synthesis. The structure of the synthesised indene compounds

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• carbon-nucleophile. As expected, the 4-allyl-substituted tetrahydronaphthalen-2-ol 14ai was obtained, again, as a mixture of cis/trans-isomers in a ratio of 44:56. This example demonstrates the general synthetic utility of this cascade protocol. Encouraged by the success of using 13a as the substrate

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

• loss of photocatalytic activity when applied in the cyanomethylarylation of N-arylallylamine 1a with acetonitrile. We also utilized this strategy to test n-butyl nitrile under the standard conditions. As shown in Scheme 6a, the corresponding oxindole 11 was obtained in 45% yield. The synthetic utility

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

• , because of the influence of the bulky tert-butyl in the most stable conformation of the sulfinyl imine (Scheme 30). The authors also demonstrated the synthetic utility of compounds 100. Their reaction with thionyl chloride in methanol produced removal of the sulfinyl group and formation of the

Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines

• Geetanjali S. Sontakke,
• Rahul K. Shukla and
• Chandra M. R. Volla

Beilstein J. Org. Chem. 2021, 17, 485–493, doi:10.3762/bjoc.17.42

• and aliphatic triazoles were suitable substrates for the reaction and afforded 6b–d in good to excellent yield of 71–89%. In order to investigate the synthetic utility of the current methodology, a gram-scale reaction was carried out (Scheme 6a). Upon treating quinoline N-oxide (1a, 6.9 mmol, 1.0 g

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• activation parameters. Furthermore, the synthetic utility of the cycloadducts obtained was demonstrated. Keywords: Diels–Alder reaction; fluorine; nitrostyrene; norbornene; stereochemistry; Introduction Organofluorine compounds play an exceptionally important role in various fields of science and

• react. The activation parameters of the reaction of nitrostyrene 1h with CPD were estimated. In addition, the synthetic utility of the norbornenes obtained was demonstrated. All the structures obtained in this work were elucidated by NMR spectroscopy and elemental analysis or HRMS. The structure

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• decreased reactivity towards the larger I+ cation in comparison to the smaller Br+ cation (see Scheme 12 and Scheme 14), the absolute lack of reactivity with the even larger PhSe+ cation is not surprising. To study the synthetic utility of the obtained fluoroselenides, oxidative elimination of the

Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• these species in inhibiting aconitase [22] must be reconciled with synthetic utility. To that end, catalysis-based strategies to unmask the venerable α-fluorocarbonyl motif [23] from a terminal alkyne were considered (Figure 1). This general strategy was appealing given the commercial availability of

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• ) acetylation, (ii) azidation, and (iii) cycloaddition to produce IV–VIII. In spite of the broad scope and synthetic utility, it is evident that the multistep synthetic methodology is the only existing module for cycloaddition reactions. Our research group is focused on developing one-pot synthetic

• transformations employed quaternary phosphonium salts as favourable catalysts [36]. Their synthetic utility was not only confined to catalysis, but they were also used as intermediates for the synthesis of 1H-indazoles [37], as promoters for stereoselective rearrangements [38], and as temporary protectors of O,P

• ). The synthetic utility of the reaction was further extended to ortho-vanillin and para-bromobenzaldehyde to afford the corresponding halomethylcoumarins (4b/c). However, this regiospecific transformation was restricted only to the MBH adducts derived from salicyladehydes and tert-butyl acrylate [52][53

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• that the PhSO2CF2Cu species might be prepared from difluoromethylphenylsulfone (PhSO2CF2H) and used it to functionalize an array of (hetero)aromatic boronic acids [62] (Scheme 12). The transformation showed a good functional group tolerance (aldehyde, CN, halogens). Note that the synthetic utility of

• different approaches developed to synthesize CF2CH3-containing molecules, Wang, Hu and co-workers demonstrated the possibility to use 1,1-difluoroethylsilane (TMSCF2CH3) as a precursor for the in situ generation of the corresponding CuCF2CH3 species [64]. The synthetic utility of this copper-based reagent

• either from the pre-isolated (K(DMF))Cu(Ot-Bu)2 or in situ from CuCl, t-BuOK in DMF in a nearly quantitative yield. The copper reagent was used for the pentafluoroethylation of a panel of (hetero)aryl iodides and bromides (up to 99% 19F NMR yield) and its synthetic utility was further demonstrated with

Bipyrrole boomerangs via Pd-mediated tandem cyclization–oxygenation. Controlling reaction selectivity and electronic properties

• Liliia Moshniaha,
• Marika Żyła-Karwowska,
• Joanna Cybińska,
• Piotr J. Chmielewski,
• Ludovic Favereau and
• Marcin Stępień

Beilstein J. Org. Chem. 2020, 16, 895–903, doi:10.3762/bjoc.16.81

• ], with FeCl3 being particularly notable for its versatility, ease of use, and low price [5]. Nevertheless, the synthetic utility of oxidative couplings is often limited by several factors [6]. Consequently, incomplete ring fusion and various side reactions, e.g., chlorination [7], or unexpected

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

• Anna R. Bockman and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46

• Anna R. Bockman Jeffrey M. Pruet Department of Chemistry, Valparaiso University, 1710 Chapel Dr, Valparaiso, IN 46383, USA 10.3762/bjoc.16.46 Abstract The synthetic utility of pterins is often hampered by the notorious insolubility of this heterocycle, slowing the development of medicinally

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• [Cu(I)(dap)2]Cl under green light irradiation (Scheme 5) [21]. Fluorinated sultones are important scaffolds for pharmaceutical syntheses. To illustrate the synthetic utility of the method, a novel benzoxathiin analog was synthesized using this reaction as the key step. The authors suggested a similar

• , acrylates, enol acetates, and enamines. The functional group tolerance of the transformation was fairly decent and demonstrated the synthetic utility of this reaction manifold. To explain the reaction outcome, the authors suggested the following mechanism: The excited copper catalyst reduces the CF3SO2Cl

• moderate to good yields. Notably, alkyl iodides were also suitable substrates. The methodology proved to be compatible with a broad range of functional groups. To demonstrate the synthetic utility of the process, the reaction was developed under continuous flow conditions to afford an easy and

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• Pauson–Khand conditions (Table 1,entry 14). The synthetic utility of the spiro derivatives resulting from the combined KA2/Pauson–Khand process to generate second-generation molecular scaffolds was tested on compound 5 by applying representative reactions on the enone structural motif (Scheme 3). The

Regioselective addition of Grignard reagents to N-acylpyrazinium salts: synthesis of substituted 1,2-dihydropyrazines and Δ⁵-2-oxopiperazines

• Valentine R. St. Hilaire,
• William E. Hopkins,
• Yenteeo S. Miller,
• Srinivasa R. Dandepally and
• Alfred L. Williams

Beilstein J. Org. Chem. 2019, 15, 72–78, doi:10.3762/bjoc.15.8

• adding to 2-cyano-6-morpholinylpyrazine [21]. As a part of our continued exploration into the synthetic utility of N-acylpyrazinium salts, herein we report the regioselective addition of Grignard reagents to mono- and disubstituted N-acylpyrazinium salts towards the synthesis of 1,2-dihydropyrazines and

• -oxopiperazines. These compounds can potentially serve as templates for making substituted 2-oxopiperazines. The investigation into the synthetic utility of this reaction is currently underway and will be reported in due course. Regioselective addition of Grignard reagents to mono- and disubstituted pyrazinium