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

The mechanochemical synthesis of quinazolin-4(3H)-ones by controlling the reactivity of IBX

• Md Toufique Alam,
• Saikat Maiti and
• Prasenjit Mal

Beilstein J. Org. Chem. 2018, 14, 2396–2403, doi:10.3762/bjoc.14.216

• aniline derivative with moderate reactivity. Therefore, we anticipate that the controlled reactivity of IBX under mechano-milling conditions led to successful reaction with 2-aminobenzamide. Finally, a large scale synthesis was performed to prove the synthetic utility of this methodology. By taking

Hypervalent iodine compounds for anti-Markovnikov-type iodo-oxyimidation of vinylarenes

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Mikhail A. Syroeshkin,
• Alexander A. Korlyukov,
• Pavel V. Dorovatovskii,
• Yan V. Zubavichus,
• Gennady I. Nikishin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2018, 14, 2146–2155, doi:10.3762/bjoc.14.188

• %) without column chromatography (Scheme 4). The synthetic utility of the obtained products 3aa and 3ab was demonstrated by the substitution of the iodine atom with O- (methanol), S- (benzenesulfinate) and N- (azide) nucleophiles (Scheme 5). It is noteworthy that the reaction of compound 3aa with sodium

• –ka, 3ab–db, 3fb, 3hb, and 3kb. The proposed mechanism of iodo-oxyimidation of styrene (1a) using the NHPI/I2/PhI(OAc)2 system with the formation of product 3aa. Gram-scale synthesis of compound 3aa. Synthetic utility of the iodo-oxyimides 3aa and 3ab. Optimization of the synthesis of iodo

Thiocarbonyl-enabled ferrocene C–H nitrogenation by cobalt(III) catalysis: thermal and mechanochemical

• Santhivardhana Reddy Yetra,
• Zhigao Shen,
• Hui Wang and
• Lutz Ackermann

Beilstein J. Org. Chem. 2018, 14, 1546–1553, doi:10.3762/bjoc.14.131

• products, the amidated thiocarbonylferrocene 3aa could be easily transformed into the corresponding synthetically useful aminoketone 4aa (Scheme 6), illustrating the unique synthetic utility of our strategy. Mechanochemical molecular synthesis has attracted recent renewed attention as an attractive

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• enantioselectivities (90–94% ee), as shown in Scheme 5. The synthetic utility of this novel methodology was demonstrated through the total synthesis of the natural product (−)-psychotriasine (Scheme 5) and the biologically active compound AG-041R (Scheme 1). By using another type of organocatalyst, such as L

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• ]. Here, symmetrical diaryliodonium salts 1 were used in a palladium-catalysed cross-coupling reaction with sodium tetraphenylborate (Scheme 3). This reaction not only provides excellent yields of the respective biphenyls 3 but also exhibits a high AE (57% for Ar = Ph). However, its general synthetic

• utility is limited since it requires highly reactive boron compounds as nucleophiles. Symmetrical biphenyls 3’ can be generated from the corresponding symmetrically substituted diaryliodonium salts 1 and bis(pinacolato)diboron as demonstrated by Muñiz and co-workers [25]. In the first step, a mild carbon

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• [43][44]. Due to the particular significance of cyclic peptides, chemists pay considerable attention to the efficient synthesis of cyclic peptides [45]. In the second part of the investigation of the synthetic utility of the FPID/(4-MeOC6H4)3P system, we tested this system in the cyclic peptide