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

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• dihydropyridine, hydantoin, imidazole, indole, isoquinoline, isoxazole, oxazole, 4H-pyran, pyrazine, pyridazine, pyridine, pyridinone, pyrimidine, pyrimidone, pyrrole, 3H-quinazolin-4-one, quinoline, 1H-quinolin-4-one, and thiophene. For heterocycles that are composed of a fused aromatic ring, such as

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• (see Figure 3, Figure 4 and Supporting Information File 2 for details of X-ray study of compounds 4a,o,p). According to the XRD data, the molecules of compound 4a are non-planar with the Ph substituent turned toward the oxazole ring by a 51° angle and the imidazole ring turned toward the oxazole moiety

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• enantiopure phosphine catalyst 27 in order to generate the coupled product 30 with both high ee and dr (Scheme 6) [31]. Presumably, the allenyl stereochemistry is destroyed upon 1,4-addition of the phosphine catalyst, resulting in chiral phosphonium adduct 29 that further reacts with deprotonated oxazole 28

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• pathways but is found across proteins of all sizes so will not be discussed here. Review Thiazole and oxazoles Thiazoles and oxazoles are found in a huge number of bacterial RiPPs, which are often loosely defined as thiazole/oxazole-modified microcins [24] (TOMMs), although these can be subdivided more

• there remains a wealth of unexplored pathways to discover and characterise. Schematic of RiPP biosynthesis. Thiazole/oxazole formation is represented by the blue heterocycle (X = S, O), lanthionine formation is represented by the purple cross-link (X = S) and macrolactam (X = N) or macrolactone (X = O

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• formed. Instead, we isolated the trisubstituted oxazole derivative 6 in 55% yield. The scope of this reaction has not been studied by us, however it is known in the literature that enamides can undergo related oxidative cyclizations to oxazoles in the presence of the reagent cocktail employed or under

• methoxylation of compound 3a we unexpectedly observed the formation of the 5-acetyl-substituted oxazole derivative 6. However, precursor 3i was smoothly available from acetylacetone 1a. It could smoothly be transformed into the desired bipyridine derivative 4i, but also into the related pyrimidine and

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• Na a174 yielded a new class of halogenated pyrrole–oxazole compounds 14–18 (Figure 8). Pyrronazols A (14), A2 (15) and B (16), synthesized by Ari7, additionally include an α-pyrone moiety [48]. This is worth noting, since the non-cyclic alkyl moiety in the pyrronazols C1 (17) and C2 (18), found in

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• exhibit an unusual molecular architecture featuring two oxazole rings connected by a two-carbon tether and a terminal 2,4-pentadienylamine moiety. Feeding experiments as well as biosynthetic reasoning indicated that the siphonazoles originate from a mixed PKS/NRPS pathway [125]. Both bisoxazoles were

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• functionalization with nitrogen nucleophiles, including amides, sulfonamides and primary arylamines. In addition, the oxazole-based DG could be easily deprotected to provide the corresponding benzoic acid 44 by heating in EtOH in the presence of KOH (Scheme 13). As another easily available N-containing aromatic

• , was reported by Dai and Yu et al. [83]. As outlined in Scheme 26, the presence of the oxazole-based DG was found to be the main factor in tuning the selective formation of 101. Related control experiments suggested that the formation of intermediate 102 acquired from the copper-catalyzed C(sp2)–C(sp3

• for lactam synthesis. Copper-catalyzed amidation/sulfonamidation of aryl C–H bonds. C–H amidation of pyridinylbenzenes and indoles. Mechanism of the Cu-catalyzed C2-amidation of indoles. Copper-catalyzed, 2-phenyl oxazole-assisted C–H amidation of benzamides. DG-assisted amidation/imidation of indole

Investigation on the reactivity of α-azidochalcones with carboxylic acids: Formation of α-amido-1,3-diketones and highly substituted 2-(trifluoromethyl)oxazoles

• Kandasamy Rajaguru,
• Arumugam Mariappan,
• Rajendran Suresh,
• Periasamy Manivannan and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2015, 11, 2021–2028, doi:10.3762/bjoc.11.219

• . This is illustrated with one reaction in which 3 was subjected to treatment with triphenylphosphine in the presence of iodine and triethylamine in dry dichloromethane at room temperature (Scheme 4) [34][35]. As expected, compounds 3 are converted to 2,4,5-substituted oxazole 7 regiospecifically in good

• investigation of the structure of 8a indicated that the compound is a highly substituted 2-(trifluoromethyl)oxazole. With different α-azidochalcones, differently substituted 8 have been isolated (Figure 5). It should be mentioned that oxazole formation is observed only at low temperature with trifluoroacetic

• , the solvent was removed in vacuo, and the residue was directly purified by column chromatography on silica gel (hexane/ethyl acetate 9:1) to yield oxazole 7. Synthesis of 8: In a dry two neck round bottom reaction vessel equipped with a calcium guard tube and a magnetic bar, α-azidochalcone (1.0 equiv

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

A new and efficient procedure for the synthesis of hexahydropyrimidine-fused 1,4-naphthoquinones

• Marcelo Isidoro P. Reis,
• Vinícius R. Campos,
• Jackson A. L. C. Resende,
• Fernando C. Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2015, 11, 1235–1240, doi:10.3762/bjoc.11.137

• naphthoquinones (Figure 1) such as naphtho[2,3-b]furan [5][6][7][8][9][10][11][12][13][14], naphtho-pyran [15][16][17][18], benzo[f]indole [19][20][21][22][23][24], benzo[g]quinolone [25], benzo[b]carbazole [26], naphtho[2,3-b]thiophene [27][28][29][30][31][32][33] and naphtho[2,3-b]]oxazole [34] have been