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

• motif allowed to access the corresponding product 3l in a higher yield. Notably, phosphate 2a with no substitution on the aromatic ring and on the nitrogen atom showed a good reactivity, furnishing the corresponding product 3a in the highest yield, possibly owing to not having steric hindrance. It

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

• , explaining the lowered yield. The reaction also required six equivalents and 72 h of reaction time to produce the product. ortho-Substituted anilines are interesting substrates as the product enables several possibilities for post-functionalization. Despite the inherent steric hindrance originating from the

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• alkanes were preferentially functionalized at the 2-position due to the less steric hindrance. In addition to alkanes, a variety of ethers and amines were also compatible and selectively functionalized at the α-heteroatom positions in moderate to good yields and excellent regioselectivity. Interestingly

Facile and innovative catalytic protocol for intramolecular Friedel–Crafts cyclization of Morita–Baylis–Hillman adducts: Synergistic combination of chiral (salen)chromium(III)/BF₃·OEt₂ catalysis

• Karthikeyan Soundararajan,
• Helen Ratna Monica Jeyarajan,
• Raju Subimol Kamarajapurathu and
• Karthik Krishna Kumar Ayyanoth

Beilstein J. Org. Chem. 2021, 17, 2186–2193, doi:10.3762/bjoc.17.140

• (15 mol %)/BF3·OEt2 (2.5 mol %) in 10 mL dichloromethane (Table 2). A series of indene derivatives were obtained from moderate to excellent yield (58–85%). The steric hindrance and electronic effect of electron-withdrawing substituents such as nitriles and methyl/ethyl esters did not significantly

• the Cr(salen)/BF3·OEt2 catalytic system (5m–r, Table 2). This could be an outcome of steric hindrance exerted by the substitutents at the arene moiety of the MBH adducts. Thereafter, to inspect the utility of the reaction for a gram-scale reaction, we endeavoured a model reaction using the optimized

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• (transformation of the vinyl group at C-6 was preferred, except for the reactions of isoxazoline (±)-4 with 7f and 7g), while all CM reactions of (±)-6 were completely regioselective (the vinyl group at C-6 was transformed first). This can be explained by steric hindrance: the substituent at C-3 on the

• . Some commercial Ru-based catalysts used in the current work. Synthesis of divinylated cyclopentane-fused isoxazolines [41]. Various fluorine-containing olefins used in the current work. Chemoselective CM reaction due to steric hindrance. Cross-metathesis of divinylated isoxazoline (±)-4 with

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

• diminished with the increasing length of the oligosaccharide, possibly due to steric hindrance [180]. The nucleophilic modulation strategy in combination with the O-6-Lev remote anchimeric assistance could further improve the stereoselectivity of the 1,2-cis glycosylations, leading to the synthesis of long

• acceptor to create a dendron-like structure. To overcome the high steric hindrance of both coupling partners, careful optimization of the LG and the reaction temperature was imperative [118][278][280][282]. A [31 + 30 + 30 + 30 + 30] fragment coupling allowed assembling a 151mer polymannoside 97, 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

• 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

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• were incubated without a transfection agent [110]. The β-configured ON variants resulted in a decrease in Tm towards their complementary RNA and DNA targets, which was ascribed to increased steric hindrance [109], although an improved triplex stability for the 2’-OMe RNA phosphoramidate variant was

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• formation of C–C bonds involving free radical species means that the new bond is formed at a reasonable distance from the carbon radical acceptor, thereby reducing the expected steric hindrance [74][75]. As mentioned above, a useful strategy for generating the desired tertiary carbon radicals is the use of

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

• 1,2,4-trisubsitituted tetralin 14ga was isolated as a 17:83 mixture of cis/trans isomers, but with 20% yield. The poor yield may be attributed to the enhanced steric hindrance. This cyclization methodology was also applicable to 2-(1-vinylnaphthalen-2-yl)acetaldehyde (13h), for which the reaction with

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• temperatures (Table 1, entries 1–3). This is likely due to the steric hindrance of the CF3-substituted quaternary carbon atom in substrate 1a. Therefore, the solvent was changed to H2SO4 (5%) in water (Table 1, entry 4) or glacial acetic acid (entry 5), and the reactions were performed at room temperature

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

• steric hindrance [1][14][44][45] (Scheme 5). Other contributions to the nucleophilic addition reactions to N-tert-butanesulfinyl imines were made by Yus and co-workers employing organozincates [46][47][48][49] and indium [50]. After this brief about the synthesis of enantiomerically pure N-tert

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

• oxidative Heck-type product. The authors stated that as a result of the coordination with PPh3, there is a steric hindrance disfavouring the β-hydride elimination [43]. Catalytic systems based on NHC ligands Historically, the second type of ligands used were N-heterocyclic carbenes (NHC). The first use was

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• electrophilic attack takes place at the more reactive angular position of the aromatic ring, but in case of a substantial steric hindrance, the linear isomer is formed (Scheme 27). Later, this SEAr reactivity was used for the synthesis of pyrroloquinazoline from 5-aminoindole [63]. Contrary to the one-pot

• described above in the dedicated section. However, there are a few counter examples where the addition of the amine took place on the cyano group first: by using trimethylsilylamines [74], activation of the thiomethyl group by Cu(I) [75], or in case of consequent steric hindrance in the vicinity 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

• formation of the expected N-benzylaminodiol either at room temperature or under reflux conditions, probably due to the strong steric hindrance of the bicyclic system and the hydroxymethyl group. The 1H NMR spectroscopic measurements in CDCl3 clearly showed that the crude product was a five-component

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

• 1-O-methyl glucoside α-S9 as a glycosyl donor, we have demonstrated that methoxide can act as a mediocre leaving group in liquid SO2 (Scheme S1, Supporting Information File 1). Other limitations for the glycosylation with mannosyl fluoride α-1a include steric hindrance and the presence of a Lewis

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

• yield from 69% to 84% over the conventional protocol as observed during the study. The explored mechanism in Scheme 16 indicates an in situ anti-azomethine ylide (A) generation (between isatin and primary amine) favored due to steric hindrance in syn-ylide. The crucial step determines the route via

• 115, could be only obtained. The regioisomer A being less stable due to steric hindrance between the amino and the aryl group rearranges to give desired product 115. The mechanism involved in the formation of intermediate B is similar to the mechanism proposed for amino-1,3,5-triazine ring

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• additives at 50 °C and under irradiation with light (Scheme 32). The reaction is compatible with phenyl substituents with high steric hindrance, indicating that steric effects of the aryl moiety in the migrating styrenyl group do not play a major role. In 2018, You and colleagues [19] reported the discovery

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• ) bearing pseudoaxially oriented OTs group suffers from only limited steric crowding (1,3-diaxial interaction). In the case of dimedone 2d, the two bulky methyl groups impart greater steric hindrance (1,3-diaxial interaction) to the incoming nucleophile in the event of pseudoaxial approach leading to

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

• reaction of 16a with CBr4, PPh3, and Et3N. Using the same procedure, carbodiimide 17b was then synthesized in 58% yield starting from aniline 14 via urea 16b. Then, the electrocyclization of 17b was attempted, but the cyclization did not proceed at all. As possible reason we considered a steric hindrance

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• blood circulation times by allowing them to evade immune detection. PEGs often play a key role in the design of the ligands as a spacer between the nanocarrier surface and the lipid. PEGs have, however, some shortcomings, such as a broad molecular weight distribution, large steric hindrance, and the

• proposed for the preparation of functional drug carriers for clinical applications [25][28][29]. In order to alleviate the steric hindrance effect of PEG chains, a novel spacer consisting of alternating serine–glycine sequences (SG)n was introduced between the ligand and lipid within the molecular

• step by washing. The human epidermal growth factor receptor-2 (HER2)-targeting KCCYSL peptide–(SG)n–lipids in which the (SG)n (n = 3, 5, 7) sequence was used as a spacer allowed the reduction of the steric hindrance when compared to the conventional PEG2000 spacer [28]. Liposomes containing these

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• the bisacetal precursor 4b bearing a 1,8-diphenylnaphthalene framework in 45% yield despite high steric hindrance (Scheme 4b). Then, [6]helicene (1b) was obtained in 92% yield via cycloaromatization in the presence of 15 mol % of TfOH. It was noted that the gram-scale synthesis for both [5]- and [6

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• change of the pH value from pH 7.0 to pH 5.0 leads to an addition of one hydroxy group. This means that the number of possible hydrogen bonds increases from four at pH 7.0 to five at pH 5.0. Yet, the added hydroxy group is in a position where steric hindrance can play a major role. Furthermore, Flavy and

Facile preparation and conversion of 4,4,4-trifluorobut-2-yn-1-ones to aromatic and heteroaromatic compounds

• Takashi Yamazaki,
• Yoh Nakajima,
• Minato Iida and
• Tomoko Kawasaki-Takasuka

Beilstein J. Org. Chem. 2021, 17, 132–138, doi:10.3762/bjoc.17.14

• slowdown of the reaction rate when tert-butylamine was employed, which was considered to be a reflection of the sensitivity of ynones 2 towards steric hindrance. Because appropriate conditions for the initial Michael addition reactions were thus determined, further conversion to the benzene derivative 4aa