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

• -butyldiphenylsilyl chloride (TBDPSCl) for selective protection. The compound was further debenzoylated by ammonolysis, which gave compound 16. Compound 16 underwent oxidative cleavage using lead tetraacetate, and the intermediate aldehyde was oxidized to the carboxylic acid using sodium chlorite, which afforded acid

• provided the corresponding carboxylic acid, and further oxidative decarboxylation with lead tetraacetate and pyridine provided oxathiolane 20. Chu and co-workers [41][42] further established a more proficient system for the synthesis of (+)-BCH-189 (1a) from 1,6-thioanhydro-ᴅ-galactose (3d, Scheme 4

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• using authentic references) are the aldehyde 2l and, to a lesser extent, the carboxylic acid B, whereas formation of proposed intermediate aminofluorene 5 or other stable reaction intermediates was not observed. This suggests that benzylamine 2 is first oxidized by TBHP to aldehyde 2l prior to

• cyclization. From aldehyde 2l an acyl radical should subsequently be formed, for which cyclization reactions with heteroarenes and benzenoids are well documented [67][68]. Aldehyde 2l may also be further oxidized to give carboxylic acid B instead. With the oxidant of choice, aqueous TBHP, however, aldehyde 2l

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• bile acids, derivatives with altered hydrophobicity are being studied [12][13][14]. The tetrazole moiety can be found in many biologically active compounds, and monosubstituted tetrazole is being used in medicinal chemistry as a bioisostere of carboxylic acid [15] because it increases the lipophilicity

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

• ]. Likewise, Miyaji et al. reported an efficient method for the synthesis of 2-substituted indolines 79 via intramolecular aza-Michael addition of α,β-unsaturated carboxylic acid derivatives 77 in the presence of bifunctional thiourea organocatalysts (cat. 78) (Table 18). The product was obtained in moderate

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

•  9). In addition to perfluoroalkyl iodides, this protocol was further extended to alkyl halides, trifluoromethylthiolate, amines, cycloketone oxime esters, and carboxylic acid N-hydroxyphthalimide esters (NHPI). In 2018, Peters and Fu [57] explored the copper-catalyzed three-component coupling of

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• transformed into racemic tetrahydroisoquinoline-1-carboxylic acids [19], simple isoquinoline alkaloids [20], and (+)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid [21]. In this paper we report a straightforward synthesis of new strained tetracyclic tetrahydroisoquinoline derivatives

• cyclization reaction was easily performed by treatment of 6a with 20% HCl for 24 h to give dihydromethanodibenzoazocine-5-carboxylic acid (7a, Scheme 5) in 72% yield by extraction of the neutralized reaction mixture. Compound 7a was obtained in two simple steps from 3a with an overall yield of 67%. Then the

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

• had also performed experiments with different isoprenoid derivatives (carboxylic acid, ketones alcohols, and keto esters) to form different bicyclic products (Scheme 19). A Hg(II)-salt-promoted cyclization of amidal 56 was performed to synthesize optically active cyclic alanine derivatives 57 as 1:1

• catalytic Hg(II)-salt-induced cyclization. Yamamoto and co-workers published the intermolecular cyclization of alkynyl-carboxylic acid 153 to produce 6-membered morpholine type ring compound 154 and compound 155 [103]. The stereochemistry of the chiral amino acid was not conserved in the cyclized product

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

•  41) [124]. Here, dimethyl dicarbonate (DMDC) was the choice of activator to convert the carboxylic acid to a mixed anhydride in situ. In this protocol, the bisoxazoline-based chiral ligand 83 enabled the synthesis of α-amino ketones in high enantioselectivities under mild reaction conditions. Good

• yields were observed for carboxylic acid substrates 81 with different steric properties. Similarly, amine substrates 80 with diverse substitution patterns and functional groups were well tolerated to provide the desired products in optimal yields. The proposed mechanism involves the cleavage of the C(sp3

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• of the azulene was substituted by an aryl group. To achieve the synthesis of these polymers, 1,3-dibromo-2-arylazulenes 92–98, were first synthesized from azulene-1-carboxylic acid (84) in two steps as shown in Scheme 18A [39]. The treatment of dibromo monomers 96–98 with bis(trimethylstannyl

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

• for tryptophan metabolism in the human body. Thus, the inhibition of these enzymes may help in tumor immunotherapy [105][106][107]. Xu recently found indole-2-carboxylic acid derivatives as IDO1/TDO dual inhibitors. In their effort to synthesize the following bis(indol-4-yl)amine derivatives via a

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• . Another advantage inherent to this class of reagents is their easy purification by a classical acid/base work-up thanks to the presence of the carboxylic acid moiety, even if they could also be purified by standard chromatography on silica gel. They have thus been used in a variety of reactions, the most

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

• addition of cyclic 1,3‐dicarbonyl compounds, including 4-hydroxycoumarins 1, to α,β‐unsaturated enones 2 (Scheme 1). This versatile Michael reaction afforded (S)-warfarin (3a) and other Michael adducts 3 in high yields and good enantiomeric excess (ee), using (4S,5S)-4,5-diphenylimidazolidine-2-carboxylic

• 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

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

• 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

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

• , tetrazole (Figure 1b). As an established bioisostere for a carboxylic acid, tetrazole has found significant application within medicinal chemistry [12]. The aromatic tetrazole ring is considered a non-classical bioisostere, differing in size and number of atoms to the carboxylic acid. The functional group

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

• terms of overall redox transformation, the reaction formally “hydrolyses” a ketone into a hydrocarbon and a carboxylic acid, and the mechanism remained a black box for over a century, being eventually clarified only in 2007 by a team of British and Russian chemists [8]. One important starting

Photoinduced post-modification of graphitic carbon nitride-embedded hydrogels: synthesis of 'hydrophobic hydrogels' and pore substructuring

• Cansu Esen and
• Baris Kumru

Beilstein J. Org. Chem. 2021, 17, 1323–1334, doi:10.3762/bjoc.17.92

• acrylic monomers possessing different functional groups were explicitly confirmed via FTIR (Figure 4). Regarding the polyacrylic acid-based system (PAA), the broadened signal from 2730 cm−1 to 3703 cm−1 and sharp signal at 3303 cm−1 corresponds to O–H stretching of the carboxylic acid group. The peak

• appearing at 1723 cm−1 can be attributed to asymmetric C=O group stretching vibrations of carboxylic acid groups on PAA chains. The polyacrylamide-based (PAAM) pore substructure spectrum is exhibiting the typical –NH stretching vibrations at 3420 cm−1 and the band at 1656 cm−1 is corresponding to the strong

• due to amine groups' protonation on the polymer backbone via electrostatic attraction, and it responded to monovalent electrolyte with a higher ESR. With the increased pH, HGCM-PAA eventuated with enhanced ESR results arising from the dissociation of carboxylic acid groups. Swelling in saltwater

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

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• synthesize the nucleoside dimer phosphoramidite with the appropriate amide linkage, which can then be introduced into the strand by solid-phase synthesis. These dimers are synthesized by using an amide coupling reagent to condense a 3'-carboxylic acid nucleoside with a 5'-amine nucleoside, where the

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

• ] tailored a microwave-assisted multicomponent reaction for fast and efficient generation of diastereoselective dibenzo[c,e]azepinones. The protocol utilized substituted 2'-formylbiphenyl-2-carboxylic acid 19, benzylamines 20, and isocyanides 21 in TFE and Na2SO4 as drying agent for the construction of

• -proliferative activity against tumor cell lines leading to the discovery of new lead compounds (Scheme 6). A tentative mechanism in Scheme 7 depicts the formation of iminium ion A from the reaction between 19 and 20 after the intramolecular protonation by carboxylic acid. The A conformer stabilized by

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• )chloromethane via a published protocol for radical chlorination of an acetal due to the presence of vulnerable benzylic methyl groups proximate to the acetal [10]. We then synthesized carboxylic acid 9, from which we anticipated creating an aryloxylchlorofluoromethane (10, X = Cl, Scheme 4) via

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

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• derivative B22 which was treated with tetrabutylammonium fluoride (TBAF) in THF to obtain the hydroxy derivative C22. Compound C22 was converted to the sodium salt of A22 by using the procedure described for derivative A1. Analogously, compound A23 was prepared starting from 4-aminothiazole-2-carboxylic acid

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• ). Ugi product 6aaa (first letter – isocyanide code, second letter – amine code, third – carboxylic acid code) was the first to isolate in our trials and its structure was confirmed by X-ray analysis (Figure 3) in addition to mass spectrometry, elemental analysis, 1H and 13C NMR data. Compound 6

[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

• with a covalently attached fullerene molecule [86]. To this end, adduct 13 was obtained from 4-(tert-butoxycarbonyl)phenyldiazomethane and fullerene. Subsequent acid hydrolysis of the protective ester group quantitatively gave a derivative of carboxylic acid 14, a versatile synthon for the synthesis of