Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• diverse range of heteroaromatics. For instance, incorporation of a 4-methylpyrazole ring (64a) showed nearly complete conversion to product with no measurable starting substrate or hydrolytic byproducts. After producing these cryptophycin analogs utilizing the CrpTE, the selective epoxidation using wild

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• , this new method creates two C–N bonds simultaneously based on a mono-halogenated starting material, thus allowing heterocycle formation with diminished halogen waste. Keywords: carbazoles; heteroaromatics; iodanes; metal-catalyzed; one-pot reaction; Introduction N-Acyl carbazoles are effective

Lewis acid-promoted direct synthesis of isoxazole derivatives

• Dengxu Qiu,
• Chenhui Jiang,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2023, 19, 1562–1567, doi:10.3762/bjoc.19.113

• oxide E [23], which can be converted to the desired isoxazole with 1a through a 1,3-dipolar cycloaddition. Conclusion In conclusion, we have developed an efficient and concise synthesis of isoxazole nitrogen heterocycles by direct C–H-bond activation of methyl heteroaromatics. The method avoids using

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• promote the sunlight-induced reaction and hydrogen transfer CDC of heteroaromatics and several H-donors (including ethers) under mild conditions (Scheme 42) [122]. There have been no previous reports using this catalyst for the alkylation of aromatics. Subsequently, various photocatalytic CDC

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

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• heteroaromatics available for various applications. Fused polyheteroarenes, containing a pyrrole moiety, are widely present in natural products and pharmacologically important agents and have a significant importance in the development of new materials useful for bioimaging applications and chemosensor systems [3

• ][4][5][6][7][8][9][10][11][12][13]. Pyrroles with vicinal o-bromophenyl and heteroaryl substituents, which are readily accessible via reactions of the corresponding 2H-azirines and phenacylcycloiminium ylides [14][15][16][17][18][19], are excellent precursors for various fused aza-heteroaromatics via

• . Results and Discussion Although the intramolecular free-radical cyclization is widely used for the synthesis of heteroaromatic compounds [23][24][25][26], only a few examples of the successful use of radical cyclization for the synthesis of pyrrole-containing fused heteroaromatics are known in the

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

• )acetaldehydes or 3-(2-vinylphenyl)propanal by action with BF3 to generate benzyl carbenium ions that are captured by a Friedel–Crafts alkylation reaction with a range of electron-rich benzenes or heteroaromatics. The method has a relatively broad applicability allowing variation in the benzene ring as well as

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• wide variety of substrates including silyl enol ethers, heteroaromatics and alkynes using an electrophilic CF3+ source (8 or 9), opening new opportunities to access pharmaceutically relevant trifluoromethylated products under mild reaction conditions. The ligand-based SET step involved the

• trifluoromethylation of heteroaromatics with redox-active iminosemiquinone ligands. Reversal of helical chirality upon redox stimuli and enantioselective Michael addition with a redox-reconfigurable copper catalyst. Interaction of guanidine-copper catalyst with oxygen and representative coupling products. a4 mol

Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• trifluoroacetophenones did not significantly influence the yield of the reaction. The trifluoromethyl ketones having electron-rich heteroaromatics such as 2-(trifluoroacetyl)furan (2g) and 2-(trifluoroacetyl)thiophene (2h) gave the desired products 3g (97%) and 3h (98%) in excellent yields. Next, the role of fluorine in

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• group [68] used silicon-based Grignard reagents 189 to add to conjugated heteroaromatics 188, e.g., benzoxazole (as an extension to more commonly studies ketones, esters, imines, etc.), leading to products 190–194. The heterocycle played a crucial role, as in its absence, none of the expected product

Regioselective Pd-catalyzed direct C1- and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives

• Hai-Yun Huang,
• Haoran Li,
• Thierry Roisnel,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2019, 15, 2069–2075, doi:10.3762/bjoc.15.204

• heteroaromatics [38], we initially employed 1 mol % Pd(OAc)2 catalyst associated to KOAc as the base in DMA at 150 °C as the reaction conditions to promote the coupling of lilolidine with 3-bromobenzonitrile (Table 1, entry 1). Under these conditions a mixture of the α- and β-arylated lilolidines 1a and 1b was

Copper(I)-catalyzed tandem reaction: synthesis of 1,4-disubstituted 1,2,3-triazoles from alkyl diacyl peroxides, azidotrimethylsilane, and alkynes

• Muhammad Israr,
• Changqing Ye,
• Munira Taj Muhammad,
• Yajun Li and
• Hongli Bao

Beilstein J. Org. Chem. 2018, 14, 2916–2922, doi:10.3762/bjoc.14.270

• ring, five-membered heteroaromatics (ethynylthiophenes) have also been used, and afforded the desired products 3s and 3t in up to 76% yield. Terminal aliphatic alkynes were then examined and it was found that they could smoothly deliver the corresponding 1,2,3-triazoles 3u–z with high yields

Calixazulenes: azulene-based calixarene analogues – an overview and recent supramolecular complexation studies

• Paris E. Georghiou,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Hidetaka Nishimura,
• Jaehyun Lee,
• Atsushi Wakamiya and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2018, 14, 2488–2494, doi:10.3762/bjoc.14.225

• reported in the literature [7]. Besides the classical calixarene phenolic subunits linked by methylene groups, “calixarenes” incorporating other subunits include, but are not limited to, resorcinol [8], hydroquinone [9], naphthols [10], pyrrole [11], heteroaromatics [12] and triptycene [13] in their cavity

One-pot synthesis of epoxides from benzyl alcohols and aldehydes

• Edwin Alfonzo,
• Jesse W. L. Mendoza and
• Aaron B. Beeler

Beilstein J. Org. Chem. 2018, 14, 2308–2312, doi:10.3762/bjoc.14.205

• (29–32). Other notable functionalities include heteroaromatics 34, alkenes 36, halides 33 and 37, and a benzyl protected alcohol 38. Furthermore, electron-donating groups were tolerated in all positions on the aryl groups (41–44). Although the Corey–Chaykovsky reaction has been well studied, nearly

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• , heteroaromatics and aliphatics all seen. However, the variation in the alkyne partner is limited, with only examples of esters and nitriles shown. The yields are variable (15–98%), with no general explanation being offered to rationalise this by the authors. An example of the reaction of two asymmetric substrates

• . Aliphatic and heteroaromatic substituents on the 2H-azirine were not tolerated. The aldehyde substituents are much more diverse, with a variety of substituted benzenes, heteroaromatics, carbonyls and aliphatic side chains undergoing the cycloaddition. Overall, these two methods provide much more mild

• , scalable and environmentally friendly reaction conditions than the traditional methods employed for making these highly substituted heteroaromatics. Access to the saturated oxazolines and thaziolines from amides and thioamides, respectively, has been described by Nicewicz who used acridinium salt

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• generated trifluoromethyl anion and suppress its rapid decomposition (Scheme 2). S-(Trifluoromethyl)diphenylsulfonium salts, as commonly used electrophilic trifluoromethylation reagents, were orginally developed by the group of Yagupolskii [14]. When iodo-substituted aromatics and heteroaromatics were

Reactivity of bromoselenophenes in palladium-catalyzed direct arylations

• Aymen Skhiri,
• Ridha Ben Salem,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2017, 13, 2862–2868, doi:10.3762/bjoc.13.278

• recent years, the Pd-catalyzed arylation, via a C–H bond activation, of a broad range of heteroaromatics using aryl halides as reaction partners was demonstrated to be particularly effective for the preparation of bi(hetero)aryls [22][23][24][25][26][27][28][29][30][31]. Among the reported results, a few

• allowed the coupling of several heteroaromatics such as thiazole, pyrrole, furan or imidazole derivatives with aryl bromides [36]. 2-Bromoselenophene, which was easily prepared by reaction of selenophene with N-bromosuccinimide [37], and 2-ethyl-4-methylthiazole were employed as model substrates for our

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

• Alexey M. Starosotnikov,
• Dmitry V. Shkaev,
• Maxim A. Bastrakov,
• Ivan V. Fedyanin,
• Svyatoslav A. Shevelev and
• Igor L. Dalinger

Beilstein J. Org. Chem. 2017, 13, 2854–2861, doi:10.3762/bjoc.13.277

• base to give the σ-adducts. Earlier it was found that an aza analog of DNBF – 4-aza-6-nitrobenzofuroxan (1, ANBF) ranks among the most electrophilic heteroaromatics known to date [17][18]. Compound 1 gives a remarkably stable hydrate in aqueous solution and forms Diels–Alder cycloadduts 2 with dienes

• heteroaromatics combining several pharmacophoric moieties in the same molecule, interesting from the standpoint of design of novel pharmaceuticals. The work continues our ongoing project on the synthesis of complex hybrid molecules – furoxan-containing potential NO donors [19][20][21][22][23][24]. Results and

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• nitrogen heteroarenes. Keywords: aerobic oxidation; bioinspired Flavin mimics; nitrogen heteroarenes; organo catalytic; oxidative dehydrogenation; Introduction By virtue of their presence in bioactive natural products and active pharmaceutical ingredients, nitrogen heterocycles and heteroaromatics form

• oxidative dehydrogenation, a stoichiometric amount of oxidant is applied in the reaction that gets associated with the nitrogen and facilitates subsequent proton abstraction and elimination in the ring to afford the desired heteroaromatics. Various organic oxidants such as 2-iodoxybenzoic acid (IBX), 2,3

• dehydrogenation Metal-free organocatalytic aerobic oxidative dehydrogenation of heterocycles is another atom economical and green strategy of accessing various heteroaromatics. Not very many reports are present in the literature to demonstrate this. Hence, the available few render special attention. One such

1-Imidoalkylphosphonium salts with modulated C_α–P⁺ bond strength: synthesis and application as new active α-imidoalkylating agents

• Jakub Adamek,
• Roman Mazurkiewicz,
• Anna Węgrzyk and
• Karol Erfurt

Beilstein J. Org. Chem. 2017, 13, 1446–1455, doi:10.3762/bjoc.13.142

• work-up procedure. Obviously, Olah’s imidoalkylating procedure and other similar imidoalkylating systems using strong acids as catalysts and solvents cannot be applied to aromatics or heteroaromatics of basic character, such as tertiary aromatic amines or azines. In the present paper we report the

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• then generated on the outer layers of the core. Surface passivation by TTDDA can now take place via either incorporation of TTDDA into the surface heteroaromatics or amide bond formation. Amide formation can occur either through surface-bound carboxylic acids reacting directly with an amine (e.g

A convenient route to symmetrically and unsymmetrically substituted 3,5-diaryl-2,4,6-trimethylpyridines via Suzuki–Miyaura cross-coupling reaction

• Dariusz Błachut,
• Joanna Szawkało and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2016, 12, 835–845, doi:10.3762/bjoc.12.82

• unsymmetrically substituted diarylpyridines, difficult to access by other methods. Keywords: arylpyridines; cross coupling reaction; heteroaromatics; one-pot reaction; palladium catalyst; Introduction Nitrogen heterocycles are an important class of compounds widely present in agrochemical products [1][2] and

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• Alkenes containing N-heteroaromatics are known to be poor partners in cross-metathesis reactions, probably due to catalyst deactivation caused by the presence of a nitrogen atom. However, some examples of ring-closing and cross-metathesis involving alkenes that incorporate N-heteroaromatics can be found

• in the literature. In addition, recent mechanistic studies have focused on the rationalization of nitrogen-induced catalysts deactivation. The purpose of this mini-review is to give a brief overview of successful metathesis reactions involving olefins containing N-heteroaromatics in order to

• of N-heteroaromatics containing olefins in metathesis has been less documented. In this review, we would like to give an overview of successful metatheses involving alkenes that possess N-heteroaromatics in order to delineate some guidelines. Some mechanistic insights dealing with catalyst

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• . Heteroaromatics provided the desired dimers in pleasing yields. With α-substituted arylacetic acids (R1 and/or R2) the outcome depended critically on the type of substituent. Racemic α-fluorophenylacetic acid was converted to two stereoisomeric dimers 39 (R1 = F, R2 = H) in an excellent combined yield of 90

A new and convenient synthetic way to 2-substituted thieno[2,3-b]indoles

• Roman A. Irgashev,
• Arseny A. Karmatsky,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2015, 11, 1000–1007, doi:10.3762/bjoc.11.112

• inhibitors of acetylcholine esterase and butyrylcholine esterase [5], compounds of this series exhibit as well anti-tuberculosis [6] and anti-inflammatory activities [7]. Another promising area for the use of thieno[2,3-b]indoles, as electron-rich heteroaromatics, is the design of photo- and electroactive