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

• substoichiometric amounts afforded significantly decreased yields of 14aa (Table 1, entries 7 and 8). The relative cis- and trans-configuration of the C-2 hydroxy group and the C-4 aryl substituent (Figure 2) were assigned on the basis of 1H-1H COSY analysis. Firstly, the HSQC analysis was used to determine H3. The

• in the side chain. The further manipulation of the hydroxy group affording the PAT analogue demonstrated the synthetic potential for accessing medicinally useful derivatives. Parent structure of 2,4-disubstituted tetralins (1) and selected medicinally useful derivatives 2–4. The speculated

Co-crystallization of an organic solid and a tetraaryladamantane at room temperature

• Fabian Rami,
• Jan Nowak,
• Felix Krupp,
• Wolfgang Frey and
• Clemens Richert

Beilstein J. Org. Chem. 2021, 17, 1476–1480, doi:10.3762/bjoc.17.103

• monoclinic. The TEO/phenol asymmetric unit consists of three TEO and three phenol molecules, resulting in a molar ratio TEO/phenol of 1:1 (Figure 2b/d). In the crystals, the ethoxy group of one of the TAA molecules is disordered, and one phenol molecule exhibits a 120°-rotational disorder for its hydroxy

• group. But again, hydrogen bonds between phenol hydroxy groups and the alkoxy substituent of the crystallization chaperone can be resolved. So, in both co-crystal lattices, hydrogen bonding stabilizes the packing arrangement. For TDA/phenol, the host builds the crystal lattice with TDA molecules in

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

• phosphitylation at the secondary hydroxy group afforded the double-headed nucleoside monomer 19 (Scheme 5) [45]. The synthesized double-headed nucleoside 19 was introduced in oligonucleotides and its impact on the secondary nucleic acid structure was studied. It was revealed that the double-headed nucleoside 19

• the nucleobases with propargyl bromide in the presence of K2CO3. Nucleoside 94 was synthesized from thymidine (93) which was first tritylated at the C-5′ primary hydroxy position followed by acetylation at the C-3′ secondary hydroxy group [61]. Next, detritylation and tosylation of the protected

• nucleosides where an aromatic moiety or a nucleobase is attached at the C-5′ position of the nucleoside. The synthetic methodology started with the 5′-epoxide 97, which was synthesized from 3′-O-(tert-butyldimethylsilyl)thymidine in three steps, where the oxidation of the C-5′-hydroxy group followed by 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

• hydroxy group in the adducts, and β-elimination (Scheme 3a) [16]. The 1-bromovinyl p-tolyl sulfoxide 6 was prepared by the deprotonation of sulfoxide 8 with LDA followed by electrophilic bromination with 1,2-dibromo-1,1,2,2-tetrachloroethane. 1-Methoxyvinyl p-tolyl sulfoxide 7 was prepared by a Peterson

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

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

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

• biomedical applications due to their ability to inhibit the glycan and glycosaminoglycan biosynthesis [34][35][36][37]. The fluorine substituent has typically been introduced into these GlcNAc and GalNAc analogues using nucleophilic fluorination. The primary position (C6 hydroxy group) was fluorinated by

• (Scheme 3). Reaction of β-thiogalactosides possessing an unprotected C6 hydroxy group with DAST was accompanied by migration of the anomeric thio-aglycone to C6 [41][52] as shown for β-thiogalactoside β-17, which mostly delivered migration product 32 (Scheme 3, see also the synthesis of compound 24 in the

• ], deoxyfluorination of the C4-hydroxy group in compound 18 was expected to occur with inversion of configuration to give the desired galacto-configured 4-fluoro products. Accordingly, treatment of diol 18 with DAST resulted in deoxyfluorination of both hydroxy groups to yield trifluoro thiogalactosazide 34 (Scheme 3

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

• in excellent yields (89–94%) and enantioselectivities (95–99% ee; Table 3). It is worth mentioning that a free phenolic hydroxy group did not interfere with the Pd complex and did not affect the enantioselectivity of the reaction. The authors also demonstrated that the product mixture obtained after

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

• alcohols having unactivated and unsubstituted alkenes, whereas the substituent adjacent to the hydroxy group in the homoallylic alcohol controls the oxonia-Cope rearrangement (see 273a–c). The alkyl substituent favored the exclusive formation of crossed THP derivatives, whereas 2-oxonia-Cope rearrangement

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

• derivatives to withstand solid-phase conditions, inevitably laying the groundwork for GNA solid-phase synthesis [98]. Using the glycidol approach, Zhang et al. synthesized 18-mer oligonucleotides containing GNA-T monomers [99]. Starting from (R)-glycidol, the free hydroxy group is tritylated. The resulting

• acids (ANA) are analogs of RNA where the hydroxy group at C2' is inverted (Figure 1G). In fluoroarabino nucleic acids (FANA) this C2' hydroxy group is replaced by fluorine. Arabino- and fluoroarabino nucleosides have demonstrated anticancer and antiviral activities (as reviewed in [173]). β-ᴅ

• DNA and RNA, with the nucleobase positioned at the C2' position in an axial orientation mimicking the C3'-endo (north) sugar puckering of furanose nucleosides [221]. MNA and AtNA possess an additional hydroxy group at the C3' position in the R and S configurations, respectively [219][220]. HNA was

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• %, respectively) with excellent stereoselectivity (E/Z = 95:5–99:1). Terminal alkylalkynes with chloro (2d), cyano (2e), and ester (2g) groups provided the corresponding adducts 3d, 3e, and 3g in 33%, 41%, and 54% yields, respectively (E/Z = 94:6–100:0). In sharp contrast, the presence of a hydroxy group

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

• malononitrile produced isatylidene malononitrile derivative A. This intermediate A undergoes Michael addition with tetronic acid to afford an intermediate B. Ultimately, the cycloaddition of the hydroxy group to the cyano group afforded the desired product 53 via C. Meanwhile, Nepali and co-workers [58

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• methoxycarbonylpyridazine 4a reacted with 5 equivalents of Zn in acetic acid at room temperature overnight the corresponding pyrrole 10aa was obtained. When using 10 equivalents of Zn instead of 5 equivalents, hydroxypyrrole 10ab was formed, in which the carbonyl group was also reduced to the hydroxy group. Then

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

• yield improved, however, still an amino derivative as side product was observed. The addition of CH2Cl2 with ethyl acetate proved helpful in increasing the yield and the NMR of the crude product 8 was acceptable to use it for further reaction without purification. The hydroxy group in 8 was then

Stereoselective syntheses of 3-aminocyclooctanetriols and halocyclooctanetriols

• Emine Salamci and
• Yunus Zozik

Beilstein J. Org. Chem. 2021, 17, 705–710, doi:10.3762/bjoc.17.59

• are reported. Reduction of cyclooctene endoperoxide, obtained by photooxygenation of cis,cis-1,3-cyclooctadiene, with zinc yielded a cyclooctene diol followed by acetylation of the hydroxy group, which gave dioldiacetate by OsO4/NMO oxidation. The cyclooctane dioldiacetate prepared was converted to

• with sodium azide of the corresponding cyclic sulfate intermediate 9, which contains the only stereocentre. The cyclic sulfate 9 could be synthesized from diacetatediol 7 [33]. For this purpose, the reduction of the endoperoxide 5 with zinc followed by acetylation of the hydroxy group and OsO4/NMO

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

• alkene units furnished 4-isopropenylpyrrolidones 12g,k in very good yields as mixtures of inseparable diastereomers (Table 3, entries 7 and 11); no alkoxyamine-containing products were isolated. Lactam 12h with a defined hydroxy group configuration in the side chain at C3 of the lactam as well as

• pyrrolidones 12i–k bearing configurationally defined 1-arylethyl groups at the amide nitrogen and the hydroxy group in the C3 side chain were obtained as inseparable mixtures of four diastereomers (Table 3, entries 8–11). The two possible trans-diastereomers predominated with moderate selectivity. These

• the convex face of the bicyclic system. Amide 9p with an enantiomerically enriched cyclohex-2-enyl substituent cyclized with exclusive diastereoselectivity and only two diastereomers 12pA differing in the orientation of the hydroxy group were obtained in high yield. The radical coupling with TEMPO

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

• , based on the activation of the C=O bond by the IL Lewis acid cation and of the hydroxy group in EG by the IL anion (Scheme 6). The IL catalysts could be easily separated by distillation and reused up to six times with no significant efficiency drop. Catalytic glycolysis by heterogenised, metallated

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• 1,2-diols. Starting with a compound already possessing a hydroxy group at the position C11, only hydroxylation at C9 is needed. Commercially available corticosteroid cortisol already possesses a hydroxy group at the position C11, and therefore only hydroxylation at C9 is needed, making cortisol (1) an

• and subsequent oxidative cleavage of the intermediate 17,20,21-trihydroxy side chain with NaIO4 in 99% total yield (Scheme 2) [27]. The C11 hydroxy group was protected with acetic anhydride in the presence of a base, resulting in C11-protected product 3 in 93% yield. Performing the same reaction under

• been shown before [29]. A positive control experiment with the same batch of KSH-expressing E. coli cells using cortisol (1) as a substrate yielded C9-hydroxylated product 5. From the results, we can also conclude that a protected C11 hydroxy group decreases the effectiveness of enzymatic

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• ferulate to the primary hydroxy group of α‐ʟ‐arabinofuranosides. Moreover, a novel feruloylated 4-nitrocatechol-1-yl-substituted butanetriol analog, containing a cleavable hydroxylated linker, was also synthesized in 32% overall yield in 3 steps (convergent synthesis). The latter route combined the

• chromogenic 5-O-feruloylated α-ʟ-arabinofuranosides 1a and 1b is usually achieved using a multistep pathway that involves trapping the furanose conformation, anomeric activation, glycosidation, regioselective deprotection of the primary hydroxy group, feruloylation, and final deprotection to yield the target

• the primary hydroxy group compare favorably with the previously reported overall yield (46 and 47%, respectively, in three steps) [15][16][17][29], which relate to the selective enzymatic O-5-deacetylation and esterification of the primary hydroxy group and a final deprotection of the 2,3-O-acetyl

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

• addition of a fifth hydroxy group, more binding sites become available for the association with the poly(allylamine), leading to an increase in assembly size: More multivalent small molecules bind to the polyelectrolyte, interconnecting more polyelectrolyte molecules into larger aggregates. At the same

• 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

• . The main difference is the first binding step ranging down to l = 0.5 (up to a molar ratio of 0.022) for pH 5.0, that is, farer than for pH 7.0. At pH 5.0 Flavy exists in the B form, which has one more hydroxy group. Thus, more binding groups that may attach to the polyelectrolyte are available and

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane

• Yukiko Karuo,
• Ayaka Kametani,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2021, 17, 89–96, doi:10.3762/bjoc.17.9

• , without byproduct formation from a Michael reaction (Table 2, entry 14). When o-aminophenol (1p) was used as the substrate, the coupling reaction occurred on the hydroxy group exclusively to give 2p (Table 2, entry 15). To show the synthetic advantages of the obtained gem-difluoro ethers 2, we examined

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• prepared stereoselectively from propargyl alcohol following the literature procedure, and the free hydroxy group was then protected as its TBDMS ether to produce 39 in 99% yield. The metal–halogen exchange of 39 followed by the Bu3SnCl quench in Et2O gave the desired stannane 40 in excellent yield (90

• expected alcohol (−)-140 was obtained in 93% ee and 72% yield. Compound (−)-140 was further transformed to the corresponding Mosher's esters and their NMR and X-ray crystallographic data were well-matched with the (R)-stereostructure of (−)-140 [77][78]. The hydroxy group of (−)-140 was protected as

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• %, and 92% yield, respectively (Table 2, entries 9–11). 4-Acetamidobenzaldehyde (2l) also reacted but provided a low product yield of 22% 3l (Table 2, entry 12). Starting materials with a para- and ortho-hydroxy group provided the corresponding alkenylpyridine products 4m and 4n in 58% and 34% yield

Chemical constituents of Chaenomeles sinensis twigs and their biological activity

• Joon Min Cha,
• Dong Hyun Kim,
• Lalita Subedi,
• Zahra Khan,
• Sang Un Choi,
• Sun Yeou Kim and
• Chung Sub Kim

Beilstein J. Org. Chem. 2020, 16, 3078–3085, doi:10.3762/bjoc.16.257

• downfield-shifted NMR resonances at H-2 [δC 4.24 for 1; δC 2.30 and 2.09 for 13] and C-2 [δC 87.8 for 1; δC 48.4 for 13] suggesting the presence of a hydroxy group at C-2 in compound 1. This initial proposal was supported by the HMBC correlations of H-4 and H-11 with C-2 and H-2 with C-3 (Figure 2A). The

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• quaternary carbon stereocenters in 86% yield. Reduction of aldehyde 119 and subsequent transesterification produced a lactone (not shown). It was exposed to SeO2 to install the allylic hydroxy group to give 120 in 65% yield. Upon catalytic hydrogenation of 120, alcohol 121 was formed. This alcohol 120 was