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

• through a gram-scale synthesis, one-pot three-component reactions and further transformation experiments of the products. Keywords: asymmetric catalysis; cyclization reaction; Michael addition; one-pot three-component reaction; spirobarbiturates; Introduction Indane scaffolds exist in various

• the basic reaction conditions (Scheme 5b). A one-pot reaction of three available starting materials was tested using CH2Cl2 as the solvent. The one-pot reaction of 1,3-dimethylbarbituric acid (6), benzaldehyde (7), and 2-isothiocyanato-1-indanone (1a) proceeded smoothly to provide the desired product

• 3aa in 80% yield with 95% ee and >20:1 dr (Scheme 6a). In addition, the one-pot reaction of 1,3-dimethylbarbituric acid (6), m-bromobenzaldehyde (8), and 2-isothiocyanato-1-indanone (1a) was also investigated, and the reaction yield (80%) was lower than before, but the stereoselectivity (>20:1 dr, >99

Stepwise PEG synthesis featuring deprotection and coupling in one pot

• Logan Mikesell,
• Dhananjani N. A. M. Eriyagama,
• Yipeng Yin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2021, 17, 2976–2982, doi:10.3762/bjoc.17.207

• one pot. The deprotonation step, and the isolation and purification of the intermediate product after deprotection using existing approaches are no longer needed when the one-pot approach is used. Because the stepwise PEG synthesis usually requires multiple PEG elongation cycles, the new PEG synthesis

• group, PEG elongation is achieved in two steps – deprotection and coupling – in only one pot (Scheme 1). There is no need to isolate and purify the intermediate between deprotection and coupling, and the deprotonation step is not needed. Our results show that the synthesis is far more convenient than

• known methods, and high quality of monodisperse PEGs can be obtained in acceptable to high yields. Results and Discussion For a base-labile protecting group to be useful in PEG synthesis using the one-pot PEG elongation approach, it needs to meet two criteria: (1) The protecting group can be removed

Total synthesis of the O-antigen repeating unit of Providencia stuartii O49 serotype through linear and one-pot assemblies

• Tanmoy Halder and
• Somnath Yadav

Beilstein J. Org. Chem. 2021, 17, 2915–2921, doi:10.3762/bjoc.17.199

• involving the [1 + (1 + 1 = 2)] assembly, followed by a one-pot synthesis involving [1 + 1 + 1] strategy from the corresponding monosaccharides. The one-pot method provided a higher yield of the protected trisaccharide intermediate (73%) compared to the two step synthesis (66%). The protected trisaccharide

• was then deprotected and N-acetylated to finally afford the desired trisaccharide repeating unit as its α-p-methoxyphenyl glycoside. Keywords: capsular polysaccharide; carbohydrate vaccines; O-antigen; oligosaccharide synthesis; one-pot synthesis; Introduction O-antigens or O-specific

• co-worker accomplished the total synthesis of a O-polysaccharide of Providencia alcalifaciens O22 via a one pot assembly of the oligosaccharide unit [36]. Recently in 2020 Werz and co-workers completed the total synthesis of a tri-, hexa-, and heptasaccharide of the O-polysaccharide of Providencia

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• methyl ethyl ketone (MEK) was as effective. In addition, in situ-generated α-bromo-δ-valerolactone was directly converted into a sulfur-substituted functional lactone without difficulty by reacting it with a sulfur nucleophile in one pot without isolation. This new bromination system is expected to

• facilitate the industrial use of α-bromolactones as important intermediates. Keywords: α-bromolactone; metal-free; one-pot operation; tetraalkylammonium hydroxide; two-phase system; Introduction Lactones are important heterocycles in the organic chemistry, materials science, and medicinal chemistry fields

• through ring-closing reactions that involve the elimination of HBr; notably, ring-closure is successfully promoted in a two-phase system (Scheme 1b). Furthermore, we also report the simple one-pot transformations of lactone derivatives using α-bromolactones as key intermediates. Results and Discussion We

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

• 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

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• unsaturated moieties. The known literature exceptions included synthesis of 2-alkynylquinazolines via acylation of anthranilamides with alkynylcarboxylic acids and further cyclocondensation under alkaline conditions [36], as well as formation of 2-alkenyl counterparts by a one-pot Yb(OTf)3-catalyzed microwave

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• mixture of two rotamers in a ≈2:1 ratio at 25 °C, probably caused by the Cbz-protecting group (see Supporting Information File 1, page S26). It is worth mentioning that the attempts to prepare polyhydroxylated pyrrolidine 2 directly from epoxide 5 by the one pot Cbz-removal/aminocyclization under

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• produce the chiral oxathiolane precursor 68 of lamivudine (1) from a mixture of isomers, i.e., 67, the reaction occurred in a single-phase aqueous system, which may be considered a green chemistry approach. Recently, Zhang and co-workers [63] developed a one-pot enzymatic synthesis of enantiopure 1,3

• -oxathiolane with Trichosporon laibachii lipase and a kinetic resolution. The synthesis of enantiopure ((R)-5-acetoxy-1,3-oxathiolan-2-yl)methyl benzoate (71) was carried out from the substrates 3a, 1,4-dithiane-2,5-diol (3q), and phenyl acetate via dynamic covalent kinetic resolution. This was a one-pot

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• after each step prompted us to apply a Mitsunobu and Staudinger reaction for the preparation of amine 2 (Scheme 1) [33]. This one-pot reaction gave the desired amine 2 in 56% yield. Then, the corresponding isothiocyanate 3a was prepared by reaction of amine 2 with CS2 and DCC according to the reported

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• high enantioselectivities (up to 65–91%) [40]. Rajasekar et al. developed an efficient one-pot tandem rhodium(II)/chiral squaramide relay catalysis for the enantioselective construction of dihydro-β-carbolines 37 from the Michael reaction of suitably substituted indole derivatives 34 with N-sulfonyl

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• reactions nevertheless accomplishes the same goal of connecting two carbon-skeleton alterations conveniently in one pot with a combined yield of 45%. α-Ketol rearrangements in biosynthetic reactions At the time of this review, only two enzymes have been identified that catalyze an α-ketol rearrangement as

• equivalent of aniline in the presence of a Brønsted acid undergoes a multistep rearrangement to form the indole group as part of the target tryptamine 110 (Figure 20). The one-pot conversions occurred successfully over a wide range of monosubstituted anilines, including various para-alkyl groups (65–72

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• reported C(sp3)–H allylic substitution reactions were mainly applied on the 2-alkyl-azaarenes containing strong electron-withdrawing groups. While the reactions with inactive alkyl-aza-arenes were rare [30][31]. Kim et al. have reported a K2CO3-promoted one-pot allylation reaction of 2-alkylpyridines with

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• converted to the corresponding acid 23 in 94% yield in the presence of KOH (2.0 equiv) in MeOH (Scheme 9). In 2011, Lee and co-workers reported a one-pot method for the construction of polysubstituted pyridines 29 via tandem sequential reactions of nitriles 26, Reformatsky reagents 27, and 1,3-enynes 28

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• diastereoisomers of tetrahydropyrrolo[3,4-c]carbazoles, which can be dehydrogenated by DDQ oxidation in acetonitrile at room temperature to give the aromatized pyrrolo[3,4-c]carbazoles in high yields. On the other hand, the one-pot reaction of 3-(indol-3-yl)-1,3-diphenylpropan-1-ones with chalcones or

• attractive strategy for the synthesis of carbazole derivatives [28][29][30][31][32][33][34][35][36][37][38][39][40]. In recent years, by using the one-pot domino synthetic strategy of in situ-generated 2-vinyl- or 3-vinylindolines and sequential Diels–Alder reaction with activated dienophiles, we have

• dehydrogenation reaction was carried out in acetonitrile at room temperature. A series of aromatized pyrrolo[3,4-c]carbazoles 4a–l were successfully synthesized by the one-pot two-step reaction and the results are summarized in Table 1. All reactions proceeded smoothly to give the corresponding pyrrolo[3,4-c

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• ]. Recently, a Hg(OTf)2-catalyzed one-pot cyclization of nitroalkyne 175 and alkyne had been reported to synthesize indole derivatives 176. Based on this strategy, the one-pot method to synthesize indole derivatives had been developed [112]. Similarly, benzo[c]isoxazole was also formed in excellent yields

• -methylenepiperidine. a) Preparation of indole derivatives through cycloisomerization of 2-ethynylaniline and b) its mechanism. a) Hg(OTf)2-catalyzed synthesis of 3-indolinones and 3-coumaranones and b) simplified mechanism. a) Hg(OTf)2-catalyzed one pot cyclization of nitroalkyne and b) its plausible mechanism

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

• effectiveness of our strategy, the necessity of isolating the potentially hazardous diazonium salt may be seen as an important disadvantage. Arylating the quinone starting directly from the aniline in a one-pot procedure would effectively avoid the need for isolation of the potentially explosive salt and

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• -workers reported a one-pot synthesis of substituted anthracenes 37 from o-tolualdehyde 34 and aryl iodides 35 via a palladium-catalyzed C–H arylation with a silver oxidant (Scheme 8) [42]. During optimization studies, the authors noted that steric and electronic effects strongly affected the cyclization

• . Although other methodologies were available, the authors chose to employ lithium aluminum hydride (LAH) to reduce the substituted anthraquinones 67 to the corresponding anthracenes 68, to obtain very good yields (81–90%) [48]. In 2016, Glöcklhofer and co-workers developed a versatile one-pot procedure for

• 2012, Singh and co-workers performed green syntheses of oxa-aza-benzo[a]anthracene and oxa-aza-phenanthrene derivatives 151 and 152 via a sequential one-pot reaction in an aqueous micellar system (Scheme 34) [68]. This methodology comprised reactions of isoquinoline (147), phenacyl bromides 148 bearing

Correction: One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2021, 17, 2026–2027, doi:10.3762/bjoc.17.130

• 10.3762/bjoc.17.130 Keywords: antiproliferative activity; 1,2-dihydropyridines; green Hantzsch synthesis; heterogeneous catalysis; one-pot multicomponent reaction; The authors noticed that the E-factor (E) was calculated using a wrong Equation 2 in the original publication: The correct Equation 2 should

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• (6mer, 8mer, 10mer and 12mer) following a convergent preactivation-based iterative strategy [135]. These compounds were subsequently conjugated to keyhole limpet hemocyanin, revealing that the length of the glucans affected the immunogenic properties. A pre-activation-based iterative one-pot

• COS, which requires tedious purification steps. Furthermore, degradation of natural chitin often lacks proper control over the pattern of acetylation (PA). Acetolysis also often leads to heterogeneous mixtures [232][233][234][235]. A controlled acetolysis of chitin, followed by the one-pot trans-N

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• acid (4) as catalyst [30]. Based on this pioneer work, our research group described an efficient, highly stereoselective, one-pot process comprising an organocatalytic conjugate addition of dimedone or 4-hydroxycoumarin 1 to α,β-unsaturated aldehydes 2 followed by an intramolecular isocyanide-based

• obtained with good to excellent yields and enantiomeric excesses. Besides, the one-pot synthesis of coumarins followed by the Michael addition step was proven to be a good alternative, affording the desired product with excellent yield and ee. The applicability of the methodology was also demonstrated by a

• stereoselective one-pot procedure for the synthesis of five-membered annulated coumarins 28 was described by the group of Enders [40]. Using dual catalysis, with a cinchona primary amine derivative 22 and silver carbonate, a series of functionalized coumarin derivatives 28 were obtained in good yields (up to 91

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• were found to be unreactive, probably due to steric hindrance. The one-pot difunctionalization of arenes involving a sequential C–O cleavage and C(sp2)–H activation mediated by chromium was recently reported by Luo and Zeng [124]. The reaction allows an ortho-directed diarylation of o

• target lactone in 61% yield over two steps. The final steps involved a one-pot ozonolysis with quenching under Pinnick oxidation conditions to afford the carboxylic acid derivative in 83% yield, followed by White’s selective C–H oxidation (Scheme 26B). White’s selective C–H oxidation was also applied in

• behaves as a terminal oxidant to form α-aminoalkyl radicals, whereas the formation of an Fe-peroxo species in the catalytic cycle was confirmed using a combination of EPR and ESI mass spectrometry experiments (Scheme 31D). One-pot processes for the synthesis of benzo[b]furans from aryl- or alkylketones

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• etherate and thus solved the problem with a simple two-step one-pot method; (step 1) fluorination of a mixture of DABCO and 1.5 molar equivalents of H2SO4 with 10% F2/N2 in acetonitrile at −20 °C, and (step 2) treatment of the resulting reaction mixture with 2.1 molar equivalents of BF3 etherate at −20 °C

2,4-Bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines: synthesis and photophysical properties

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli,
• Noureddine Chaaben,
• Kamel Alimi,
• Stefan Jopp and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 1629–1640, doi:10.3762/bjoc.17.115

• properties. Herein, starting from readily available anthranilic acid, an efficient synthesis of 2,4-bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridine derivatives was accomplished via a one-pot double Sonogashira cross-coupling method. The UV-visible absorption and emission properties of the synthesized

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• aniline (Scheme 5) [40]. A one-pot and multicomponent route to 1,4,5-trisubstituted 1,2,3-triazoles 11 containing a carboxylic ester group on the triazole ring was reported by Zhao et al. This strategy generates desired products from the reaction of readily available primary amines 10, 1,3-dicarbonyl

• the faster hydrolysis of the in situ generated imine intermediates, aromatic aldehydes containing electron-withdrawing substituents afforded no product in the reaction. It was proved that a variety of aliphatic primary amines can efficiently produce the triazole products (Scheme 14) [45]. This one-pot

• enone 46 reacted with aryl and vinyl azides to afford a moderate to high yield of the triazole products (Scheme 16) [46]. A simple one-pot two-stage strategy for the synthesis of disubstituted 4-chloro-, 4-bromo-, and 4-iodo-1,2,3-triazoles 50 from the reaction of the corresponding nonactivated alkynes

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• latter synthetic steps towards 5, an alternative, one-pot three-component procedure (H2N-OH, NaN3 and catalytic [(NH4)4Ce(SO4)4]) was attempted from the crude C6-aldehyde [17]. TLC analysis indicated C6-nitrile formation was evident after 36 h, however, the desired C6-tetrazole 5 was not observed