A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• . Thus, further work is needed to develop a novel strategy for an efficient synthesis of such a versatile synthon. On the other hand, diethyl (2-oxoindolin-3-yl) phosphates 2 were easily prepared by the base-catalyzed phospha-Brook rearrangement of isatins 1 with diethyl phosphite [28][29]. This compound

• rearrangement under Brønsted base catalysis and the subsequent acidolysis with haloid acids. The mild reaction conditions, simple operation, good yield, and readily available and inexpensive starting materials make this protocol a valuable method for the preparation of various 3-halooxindoles on a large-scale

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• state is characterized by the change of the segment distribution from a parabolic to a step profile and a rearrangement of the chain ends [126]. This collapse can be described by the classical Flory–Huggins model. It follows that this vertical collapse above the LCST or below the UCST is merely a

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• -hydrogen in the diallylsulfoxide (123) did not allow any Pummerer rearrangement [88][89]. Selenides In 1997, Showalter synthesized bis(indol-2-yl)selanes (or selenides) 130 having potential tyrosine kinase inhibitor activities [90][91]. The synthesis was achieved by reacting diselenium dichloride with (R

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

• 3-amino-2-naphthoic acid (97) to a Sandmeyer reaction and obtained 98. Then, a Curtius rearrangement of 98 by using diphenylphosphoryl azide (DPPA) yielded 3-iodonaphthalen-2-amine, that was subjected to a Suzuki cross-coupling with potassium vinyltrifluoroborate resulting in aminostyrene 99. The

• key step was borylative cyclization of precursor 99 and the subsequent treatment with LiAlH4 or MeLi, which resulted in BN anthracene 100a or 100b. On the other hand, the authors obtained BN anthracenes 105a and 105b by oxidation followed by Curtis rearrangement of the commercially available 1,4

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

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

• a high diastereoisomeric control and in most cases with good enantioselectivity of the products. It becomes even more attractive, since it allows an in situ rearrangement of the acyl group that can be used in other functionalization methodologies. However, it presents a limitation relative to the

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

• was then converted to a 5,6-fused seco-prezizaane scaffold through an α-ketol rearrangement promoted by a strong base and after secondary alcohol protection with TBSCl, a Fe-catalyzed C–H activation reaction promoted a second lactonization to afford (+)-pseudoanisatin (Scheme 28B). In 2016, Chirik and

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

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• ]metaparacyclophane and a cyclohexadienone cyclophane. Keywords: cyclophane; metaparacyclophane; nitration; paracyclophane; rearrangement; Introduction Cyclophanes have been described as having bent and battered benzene rings [1] due to a structure that involves one, or more, aromatic rings linked by aliphatic

• (2) (31 kcal mol−1 and 13 kcal mol−1, respectively) [33][34]. [2.2]Metaparacyclophane (3) was first isolated by Cram et al., the pioneer of [2.2]cyclophane chemistry, by the acid-catalyzed rearrangement of [2.2]paracyclophane (1) [35][36]. This methodology furnished the non-substituted cyclophane. A

• signal at 5.80 ppm, along with the unusual splitting of the bridgehead protons (H1, 2, 9 and 10) was unlike any [2.2]paracyclophane derivative we had observed. It was clear that we had isolated a cyclophane, but we suspected rearrangement [61][62]. The structure of the other side-product, 6, was even

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• compound. Once the crucial 1,3-syn-diol moiety had been obtained, attention shifted to functionalization and differentiation of the terminal carbon atoms for the synthesis of the two C5 fragments. Intermediate 4 was subjected to the Pummerer rearrangement by treatment with TFAA in collidine at 0 °C

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• between C-2′ and C-4′. The synthesis of the aimed nucleoside 122 started from the nucleoside 119 which in turn was synthesized from uridine in six steps following a literature procedure [68]. The olefinic nucleoside 119 was subjected to a RhCl3-mediated allyl rearrangement to give nucleoside 120 as a

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• prepared from carbonyl compounds and chloromethyl p-tolyl sulfoxide and were converted into alkynes via the sulfoxide/magnesium exchange reaction and subsequent Fritsch–Buttenberg–Wiechell (FBW) rearrangement of the resulting magnesium alkylidene carbenoids. The mechanism of the FBW rearrangement of

• magnesium alkylidene carbenoids was studied by using 13C-labeled sulfoxides and by using DFT calculations. Keywords: alkyne; 1-chlorovinyl p-tolyl sulfoxide; DFT calculation; Fritsch–Buttenberg–Wiechell rearrangement; magnesium alkylidene carbenoid; Introduction Alkynes are important compounds in organic

• –Wadsworth–Emmons (HWE) reaction of carbonyl compounds with organophosphorus reagents containing carbene sources and the 1,2-rearrangement of alkylidene carbenes and related species, referred to as Fritsch–Buttenberg–Wiechell (FBW) rearrangement [8][9]. While alkynes are synthesized from carbonyl compounds

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• cyclopentylmethanol and 5-hexenol. Since the half-life for the rearrangement of the 5-hexenyl and the cyclopropylmethyl radical are known, it could be concluded that under the reaction conditions, the half-life of the radical lost from C-4 was >1 μs. When the reaction was carried out in 17O-enriched water, the

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines

• Alexei N. Izmest’ev,
• Dmitry B. Vinogradov,
• Natalya G. Kolotyrkina,
• Angelina N. Kravchenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2021, 17, 1141–1148, doi:10.3762/bjoc.17.87

• -triazine-3-thiones with acetylenedicarboxylic acid dimethyl and diethyl esters (DMAD and DEAD) and subsequent base-catalyzed rearrangement of the obtained imidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazines into regioisomeric imidazo[4,5-e]thiazolo[2,3-c]-1,2,4-triazine derivatives. Keywords: amidine

• rearrangement; cyclocondensation; heterocycles; thiazolidine-4-one; 1,2,4-triazine; Introduction The thiazolidin-4-one heterocyclic system is a well-known, accessible and, as a consequence, a widely used pharmacophore in the chemistry of biologically active compounds possessing antimicrobial [1

• based on the sequential condensation of imidazo[4,5-e]-1,2,4-triazine-3-thiones 3 with DMAD or DEAD and skeletal rearrangement of linear imidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazines 4 into isomeric imidazo[4,5-e]thiazolo[2,3-с]-1,2,4-triazines 5 having an angular structure. Results and Discussion We

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

• rearrangement, N-silyllithiumenamide 35 was formed. This strongly nucleophilic species could be traped by the chiral imine (RS)-14, producing 2-chloro-2-aroylaziridines via and aza-Darzens reaction [73]. Importantly, the structure of the final aziridine is determined by the silyl group, and the order of the

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• desolvation penalty associated with binding of hydrophilic natural carbohydrates [8], and (2) create additional contacts with the binding cavity via electrostatic and dipolar interactions with C–F bonds [9][10], new intermolecular hydrogen bonds [11], or rearrangement of hydrogen bond-mediating water

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• ) [11]. Another possible use of this catalytic system was demonstrated by the groups of Lautens and Hashmi [4]. The starting enone, prepared by the Au(I)-catalysed Rautenstrauch rearrangement, was subjected to the addition reaction with phenylboronic acid (Scheme 15). Without isolation of the

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• epoxidation of (−)-α-pinene (6), carried out with meta-chloroperoxybenzoic acid (MCPBA), followed by a base-catalyzed allylic rearrangement mediated by aluminium isopropoxide (Al(OiPr)3). The resulting allylic alcohol 7 was reacted with trichloroacetyl isocyanate, followed by alkaline treatment, delivering

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• mixture of mannosides α-3r and α-3s was obtained when cyclopropylmethanol (2r) was applied. The cyclopropylmethyl carbocation (C4H7+), which is generated in liquid SO2 medium, can undergo a rearrangement to form a cyclobutyl carbocation [68]. The latter can be trapped by a water molecule forming

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• products [1][2][3][4][5][6][7][8]. Prins and related cyclization reactions [9][10], hetero-Diels–Alder cyclization [11], cyclization onto epoxides [12], Petasis–Ferrier rearrangement [13], intramolecular oxa-Michael reactions [14], cyclization through oxidative C–H bond functionalization [15], ring-closing

• major drawbacks identified with the Prins cyclization are the racemization due to competing oxonia-Cope rearrangement and side-chain exchange. Willis and co-workers studied the reactivity of the Prins reaction of different aryl group-substituted homoallylic alcohols 18 with propanal in the presence of a

• substituent at the arene ring produced predominantly symmetric THP product 26 over the desired trisubstituted heterocycle 23. The mechanism of the reaction was further investigated using enantioenriched homoallylic alcohol (S)-18 with 89% ee, which favored 2-oxonia-Cope rearrangement to give THP 23 only in 14

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• electrostatic interaction between carboxylate and iminium moieties undergoes a nucleophilic attack by isocyanide to generate nitrilium ion B. The intramolecular acylation of B forms C followed by Mumm rearrangement results in the formation of the desired products 22. The intermediate D may exist in equilibrium

• Michael addition of aminouracil to intermediate C to give D. Finally, desired product 90 is formed by intramolecular cyclization of intermediate D and subsequent rearrangement of E. 6.2.2 Pyridopyrimidines: Zhang and co-workers [84] proposed a synthetic route for the construction of substituted

• potential rearrangement explained the regioselectivity during ring closure as depicted in Scheme 44. Theoretically, two regioisomeric pairs of adenine (115, A) and isoadenine are possible (C, D) (Scheme 44). However, using the multicomponent approach one product, 4-amino-7-arylimidazo[1,2-a][1,3,5]triazines

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• ), and E (3e) comprising the pyrrolo[2,3-c]quinoline skeleton [25]. As demonstrated in Scheme 1, Curtius rearrangement of carboxylic acid 4 resulted in the formation of isocyanate 5, which, upon electrocyclization furnished pyrrolo[2,3-c]quinoline 6. Intermediate 6 was subsequently transformed into

• prepared from an appropriate carboxylic acid through a Curtius rearrangement reaction (50–98% yield). Treatment of urea derivatives 19a–d with CBr4, PPh3, and Et3N afforded carbodiimides 20a–d in 64–75% yield. Compounds 21a–d were obtained in situ following the removal of the TIPS protecting group in 20a–d

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• reported. The sequence starts with a new tandem nucleophilic substitution/Brook rearrangement/single electron transfer-induced radical oxygenation furnishing orthogonally protected α,γ-dioxygenated N-allylamides with wide scope, mostly good yields, and partly good diastereo- and enantioselectivity for

• reactions providing functionalized pyrrolidones in high yields as diastereomeric mixtures. They converge to 3,4-trans-γ-lactams by base-mediated equilibration, which can be easily further diversified. Stereochemical models for both reaction types were developed. Keywords: Brook rearrangement; cyclization

• access to complex target molecules [74][75]. The principle is illustrated for a merger of nucleophilic opening of allylepoxides 1 with silylacetamides 2/Brook rearrangement [76][77][78] and oxygenation with TEMPO (3) leading to γ-(silyloxy)-α-(aminoxy)amides 5, which can be subsequently subjected to

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• open transannular bond (σ-homoaromatic structure) [79]. It was found that, as a rule, the [5,6]-open adducts formed initially can undergo rearrangement into [6,6]-closed isomers that are more thermodynamically stable. An alternative variant of [2 + 1] cycloadditions to the fullerene frame involves the

• C60 or b) possible formation of both isomers as a result of 1,3-dipolar cycloaddition of the diazo compound to the fullerene, followed by elimination of molecular nitrogen from the pyrazoline intermediate. Second, the rearrangement of [5,6]-open isomers into thermodynamically more stable [6,6]-closed

• chromatography (HPLC) (methanol/toluene as the eluent) to isolate a reddish-brown powder of methanofullerene 3 in 21% yield (Scheme 4). Similar to photolysis, the thermal rearrangement of kinetic products gives [6,6]-closed isomers that are thermodynamically more stable. After some time, the team of scientists