Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96

• -closing metathesis (RCM), Clauson–Kaas and Ullmann-type coupling reactions as key steps. Moreover, we have also assembled some other interesting heterocyclic systems possessing oxazole, imidazole, benzimidazole, and benzoxazole in the framework of truxene. Additionally, the preliminary photophysical

• the hexaalkylated tribromotruxene 5 by means of Ullmann-type reaction in the presence of copper powder using pristine imidazole (13) and benzimidazole (15), respectively (Scheme 5). Moreover, we have successfully constructed the C3-symmetric oxazole containing truxene derivative 20 along with

• the required triformyltruxene 19 as a major product along with a minor amount of diformyltruxene 18 (Scheme 6). Later, both the di- and triformylated truxene systems 18/19 were subjected to oxazole formation involving p-toluenesulfonylmethyl isocyanide (TosMIC) in Van Leusen fashion to provide the

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• converted to novel oxazole-fused derivatives 19 and 20, respectively, by condensation with benzaldehyde and subsequent 2,3-dichloro-5.6-dicyano-p-benzoquinone (DDQ)-mediated oxidation (Scheme 3). Aldehyde building block 16 was a versatile starting material for further cyclization reactions. Synthesis of

• . Electrophilic aromatic substitution of 6-hydroxybenzofuro[2,3-b]pyridine (13). Synthesis of isomeric oxazole-fused derivatives. Fused derivatives from 16. Supporting Information Supporting Information File 164: Experimental part as well as 1H and 13C NMR data. Funding We thank the KU Leuven for financial

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• Bidyut Kumar Senapati Department of Chemistry, Prabhat Kumar College, Contai, 721404, India, Tel.: +91 8145207480 10.3762/bjoc.17.7 Abstract The inthomycin family of antibiotics, isolated from Streptomyces strains, are interesting molecules for synthesis due to their characteristic common oxazole

• , and i) [21][22][23][24]. The first racemic synthesis of inthomycin A ((rac)-1), alternatively known as phthoxazolin A, was reported in 1999 [19]. The key steps include i) the synthesis of intermediate dienyl iodide (rac)-20, ii) the synthesis of intermediate oxazole vinylstannane 24, and iii) the

• Stille coupling between oxazole vinylstannane 24 and dienyl iodide (rac)-20 as the final step. The synthesis began with alcohol (Z)-15a, which was readily prepared in 65% yield from propargyl alcohol (14) by using a copper(I)-catalyzed methyl Grignard addition followed by in situ iodinolysis. The Swern

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• azidochalcones, when treated with potassium thiocyanate in the presence of potassium persulfate, lead to 2,4,5-trisubstituted oxazoles in good yields. Incidentally, 2-aminothiazoles are the products when ferric nitrate is employed instead of persulfate in the above reaction. Keywords: aminothiazole; oxazole

• -azirine, an efficient source of nitrogen, was employed as starting material for the synthesis of oxazole with various coupling partners such as aldehyde, trifluoroacetic acid, etc. [8][45][46][47][48][49][50] (Scheme 1). Thiazole is a common structural motif that is found in a wide variety of naturally

• with a highly substituted oxazole skeleton with a thiol group is expected to have potential synergetic bioactivity [70]. During the exploration of the reactivity of azidochalcones with thiocyanate in the presence of the oxidizing agent, 1i was chosen as the model α-azidochalcone to react with potassium

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• . Keywords: bromotrimethylsilane; McKenna reaction; organophosphorus acid; oxazole; phosphonate ester; Introduction The McKenna reaction is a tool for the synthesis of organophosphorus acids from their esters and known for over 40 years [1][2]. The importance of this class of compounds is widely recognized

• problem. Section 1: Formation of oxazoles from propargylamides One of the most intriguing side reactions was observed when compounds comprising a propargyl amide group were treated with BTMS. Besides the products of addition of HBr, we observed the formation of oxazole. In order to study this process, we

• Hz) and δ 6.94 ppm (q, 4JHH = 3.5 Hz) indicated the formation of oxazole 15. The presence of compound 15 was also confirmed by X-ray studies (see Figure S3 and Table S1 in Supporting Information File 1) and literature data [36]. Additionally, the formation of compounds 16 and 17 was observed

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

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

• oxazoles (17 examples, up to 87% yield) were difluoromethylated but a variety of other heteroarenes turned out to be suitable such as pyridine, imidazole, benzo[d]thiazole, benzo[b]thiophene, benzo[d]oxazole, thiazole and thiophene derivatives (Scheme 6). Copper-based CF2FG-containing reagents Besides the

Cation-induced ring-opening and oxidation reaction of photoreluctant spirooxazine–quinolizinium conjugates

• Phil M. Pithan,
• Sören Steup and
• Heiko Ihmels

Beilstein J. Org. Chem. 2020, 16, 904–916, doi:10.3762/bjoc.16.82

• +. Keywords: oxazole; oxidation; quinolizinium; spirooxazines; styryl dyes; Introduction Spiropyrans and spirooxazines are exemplary photochromic compounds that have gained great attention in the last decades because they allow to reversibly alter and control the physical and chemical properties of

• chemical shifts. The final product of the reaction was identified by additional NMR spectroscopic investigations (13C, COSY, HSQC, HMBC) and mass spectrometric analysis (ESI) as the oxazole derivative 4a (Scheme 3). The latter analysis confirmed the loss of one hydrogen atom from the substrate 3a at C2

• equiv of Cu2+ to 3b also resulted in the formation of the corresponding oxazole derivative 4b (Scheme 3), as shown by 1H NMR spectroscopic and mass spectrometric analysis. Additionally, the NMR spectroscopic analysis (1H and H,H-COSY) of a solution of 4a in MeCN after the addition of water revealed the

KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones

• Qiao Lin,
• Shiling Zhang and
• Bin Li

Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44

• proceeded well with heterocycle-containing chlorides such as 2-chloro-5-(chloromethyl)thiophene (4e), leading to 2-aminoethyl acetate product 3k in 66% yield which has potential as bifunctional monomer for polymerization. Furthermore, oxazole derivative 2,4,4-trimethyl-4,5-dihydrooxazole (2b) was also

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• a Zn-oxazole complex 148. Finally, ligand exchange with 2,2-bipyridine generated the desired 2-(diphenylphosphine)oxazole 149. Metallocenes have been used as ligand building blocks for many catalytic transformations. Especially, ferrocene has been used due to its high electron-donating capability

• amido alcohols 154. Cyclization in the presence of tosyl chloride/triethylamine yielded the analogous ferrocenyl phosphoryl oxazoles 155, which were further reduced to give the corresponding phosphine oxazole ligands 156. The ferrocenylphosphine oxazole ligand 156 is a fascinating example which contains

Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter

• Sachin S. Burade,
• Sushil V. Pawar,
• Tanmoy Saha,
• Navanath Kumbhar,
• Amol S. Kotmale,
• Manzoor Ahmad,
• Pinaki Talukdar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2019, 15, 2419–2427, doi:10.3762/bjoc.15.234

• and Research, Pune, Pune 411008, India 10.3762/bjoc.15.234 Abstract The intramolecular cyclization of a C-3-tetrasubstituted furanoid sugar amino acid-derived linear tetrapeptide afforded an oxazolone pseudo-peptide with the formation of an oxazole ring at the C-terminus. A conformational study of

An azobenzene container showing a definite folding – synthesis and structural investigation

• Abdulselam Adam,
• Saber Mehrparvar and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2019, 15, 1534–1544, doi:10.3762/bjoc.15.156

• , whereas platform 3a possesses two oxazole rings. Overall, both macrocycles feature four amino acid side chains (isopropyl groups), whereby all of them are of the same configuration (S). Therefore, they are presented on one face of the macrocycle in a convergent manner. Platform 3a was synthesized in a few

• other. The isolation of the desired container was achieved by column chromatography followed by HPLC. It is noteworthy that the synthesis of this container showing two different Lissoclinum cyclopeptides only took a couple of steps starting from an imidazole and an oxazole building block, an azobenzene

A three-component, Zn(OTf)₂-mediated entry into trisubstituted 2-aminoimidazoles

• Alexei Lukin,
• Anna Bakholdina,
• Anna Kryukova,
• Alexander Sapegin and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2019, 15, 1061–1064, doi:10.3762/bjoc.15.103

• which makes it a useful tool for library array synthesis. The investigation of other metal-catalyzed transformations of propargylureas is underway in our laboratories and will be reported in due course. Examples of imidazole (1 and 2) and oxazole (3) syntheses from propargylamides previously reported

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• ]. Alternatively, the conversion of PM44 into oxime PM46 or a van Leusen oxazole synthesis [51] of PM48 with tosylmethyl isocyanide giving PM49 were possible. The synthesis of pyrimidine derivative PM49 with three heterocyclic substituents is remarkable and stresses the flexibility of the methods presented here

• above with the pyrimidine derivatives, see Scheme 13) was not examined so far, however, it should be possible. Hence, the pyrimidine N-oxides may also be used in other palladium-catalyzed processes in order to introduce new substituents at C-5 of the heterocycles. Synthesis of oxazole derivatives By

• brief heating with trifluoroacetic acid β-ketoenamides KE with acid-labile alkoxy substituents OR1 underwent an unexpected formation of 5-acetyl-substituted oxazole derivatives OX (Scheme 22) [42][45]. This useful transformation proceeds with benzyloxy-, p-methoxybenzyl-, 2-tetrahydropyranyl- and 2

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• [2 + 3] cycloadditions, one leading to a spiroacetal, which led to the undesired ethyl 5-(benzamidomethyl)isoxazole-3-carboxylate. The addition of ethyl nitroacetate on a 5-methylene-4,5-dihydrooxazole using cerium(IV) ammonium nitrate was also explored and the synthesis of other oxazole-bearing α

• NMR analysis of the crude reaction mixture. Indeed, a slow ring-opening reaction took place upon standing in solution to mainly give the isoxazole isomer 28 along with much less of the target oxazole-bearing α-hydroximino ester 29. Extensive trials to alter the selectivity of the ring opening using

• few byproducts were noticed. A control experiment omitting the ethyl nitroacetate (4) allowed us to identify amongst these: the oxazole derivative 31 resulting from an isomerization of 25 as well as alcohol 32 resulting from an oxidation of compound 25. Accordingly, this greatly dampened our hope to

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

• ). The reaction uses 2H-azirines and aldehydes to access the functionalised heterocycles [61]. Unlike the pyrrole-forming reaction, this protocol requires an oxidising agent, DDQ, for the desired oxazole to be obtained. This means that access to the corresponding 2,5-oxazolines is also possible

• the anti-configuration in all cases. In addition, the option for oxidation to the oxazole or thiazole is always enticing as a way of easily accessing a diverse set of molecules. Immediately akin to the oxazole moiety is the oxadiazole heterocycle, which exhibits similar properties. There are several

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• acids – potent xanthine oxidoreductase inhibitors [40] or even 3,4-unsubstituted pyrazoles [16]. Both pyrazole carboxylic groups can be also modified to hydrazides and oxazole rings [26] or a new condensed pyridazine ring [27]. Less reactive dipolarophiles such as dibenzoylacetylenes (1,4-diphenylbut-2

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• described by Christol’s group through the oxidation of benzocyclopheptene 245 with SeO2 in 35% yield (Scheme 38) [160]. Galantay’s group described a novel synthetic protocol for benzotropolones using the oxazole-benzo[7]annulenes 247 and 248, which may be easily obtained from the reaction of α-oximino

Continuous multistep synthesis of 2-(azidomethyl)oxazoles

• Thaís A. Rossa,
• Nícolas S. Suveges,
• Marcus M. Sá,
• David Cantillo and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2018, 14, 506–514, doi:10.3762/bjoc.14.36

• integration; vinyl azides; Introduction Oxazoles are an important class of five-membered aromatic heterocycles containing one oxygen and one nitrogen atom in their structures. The oxazole moiety is relatively stable and is found widely in nature [1][2][3]. Naturally occurring oxazoles include compounds with

• antibiotic or antimicrobial properties such as pimprinine [4] or phenoxan [5] (Figure 1a). Also many synthetic active pharmaceutical ingredients (API) contain the oxazole as an active moiety [1][2][3]. Oxaprozin, for example, is an important non-narcotic, non-steroidal anti-inflammatory drug [6][7

• ]. Important drawbacks observed in the generation of compounds of type 7 include the instability of the halide intermediate 6, which might be difficult to isolate due decomposition reactions, as well as selectivity issues during the generation of the oxazole ring. It has been shown that problems associated

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

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

• haloselenophene. Wipf et al. reported in 2014 that using ethyl oxazole-4-carboxylate as reaction partner, the corresponding 2,5-bis(oxazol-2-yl)selenophene derivative was formed in 45% yield (Scheme 1c) [17]. Moreover, to our knowledge the Pd-catalyzed direct heteroarylation of 2-bromoselenophene has not yet been

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• cannot exclude an alternative route when the carbenoid interacts with the cyano group to yield an oxazole heterocycle [39][40][41][42][43][44][45]. Herein we present the first detailed results of this study. Results and Discussion To determine the scope and limitations of these reactions, several

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• [32][33][34][35][36]. Gao and co-workers described the I2-catalyzed cyclization of β-acylaminoketones using tert-butyl hydroperoxide as the oxidant; notably, adding DBU led to oxazole formation whereas adding K2CO3 generated oxazolines [37][38]. Our proposed new approaches to oxazoline formation

Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid

• Kohei Yamada,
• Naoto Kamimura and
• Munetaka Kunishima

Beilstein J. Org. Chem. 2017, 13, 1478–1485, doi:10.3762/bjoc.13.146

• one-pot oxazole synthesis/Suzuki–Miyaura coupling sequence has been developed. One-pot formation of 5-(triazinyloxy)oxazoles using carboxylic acids, amino acids and a dehydrative condensing reagent, DMT-MM, followed by Ni-catalyzed Suzuki–Miyaura coupling with boronic acids provided the corresponding

• 2,4,5-trisubstituted oxazoles in good yields. Keywords: one-pot oxazole synthesis; Suzuki–Miyaura coupling; triazine; 5-(triazinyloxy)oxazole; trisubstituted oxazole; Introduction Oxazoles are found in numerous natural products and are used as a broad range of artificial compounds [1][2]. In

• synthetic strategies (Scheme 1a). i) The cyclization method: many methods, such as the Robinson–Gabriel oxazole synthesis using α-acylaminoketone [3][4], the Davidson oxazole synthesis with α-acyloxyketone [5], and modifications of these [6][7], have been developed. Moreover, cycloaddition of two starting

Derivatives of the triaminoguanidinium ion, 5. Acylation of triaminoguanidines leading to symmetrical tris(acylamino)guanidines and mesoionic 1,2,4-triazolium-3-aminides

• Jan Szabo,
• Julian Greiner and
• Gerhard Maas

Beilstein J. Org. Chem. 2017, 13, 579–588, doi:10.3762/bjoc.13.57

• is supported inter alia by recent theoretical studies using DFT calculations, Natural Bond Orbital analysis and Natural Resonance Theory calculations for mesoionic systems of the 1,3-oxazole, 1,3-diazole and 1,3-thiazole type [39]. As 1,2,4-triazolium-3-aminides have not yet been studied in depth