Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities

• Meifang Wu,
• Xiangdong Su,
• Yichuang Wu,
• Yuanjing Luo,
• Ying Guo and
• Yongbo Xue

Beilstein J. Org. Chem. 2022, 18, 200–207, doi:10.3762/bjoc.18.23

• ], hirsutrin (5) [13], genkwanin 5-O-β-ᴅ-primeveroside (6) [14], (7S,8R)-5-methoxydehydrodiconiferyl alcohol 4-O-β-ᴅ-glucopyranoside (7) [15], 9'-methoxydehydrodiconiferyl alcohol 4-O-β-ᴅ-glucopyranoside (8) [16], dehydrodiconiferyl alcohol-4-O-β-ᴅ-glucopyranoside (9) [17], (+)-pinoresinol (10) [18], 4,4

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• decided to take advantage of an asymmetric chelate enolate Claisen rearrangement, which should allow the stereoselective generation of the unusual amino acid, depending on the configuration of the chiral allylic alcohol used [41][42]. If a peptide Claisen rearrangement [43][44][45] is carried out with a

• approach, 1 was mono-O-allylated to 2 under similar conditions reported previously for monobenzylation (Scheme 3) [50]. Iodination (3) and subsequent elimination of the iodide with zinc dust gave allylic alcohol 4 as a single enantiomer, which was esterified with Boc-protected glycine to allyl ester 5

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• steps as shown in Scheme 3. First, reduction of commercially available indole-2-carboxylate with lithium aluminum hydride in dry tetrahydrofuran gave (1H-indole-2-yl)methanol (10) in 89% yield. The obtained alcohol was exposed to benzoyl chloride and triethylamine to furnish benzoate 11, which was

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• transition metal ions due to the presence of abundant amino and alcohol groups in the structure [18]. Because of this chelating character, as well as due to the hydrophilicity, unique three-dimensional structure, and mechanical properties, chitosan has several catalytic applications [19][20]. In this work

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• ] studied the solvolysis of 2,4,6-trimethylbenzenesulfonyl chloride in a mixture of water with acetone, acetonitrile, dioxane, ethanol or methanol in terms of rates of reaction and also product selectivities for the binary hydroxylic solvents, where both of the components (usually water plus an alcohol

• only solvent-ionizing power. Shallow maxima observed when selectivity values (S, indicating the extent of product formation involving replacement of the chloride by the alkoxy group from an alcohol molecule reactive to replacement by the hydroxy group of a water molecule) could be due to two reaction

• channels varying in importance as the solvent composition is varied [43][44][45] but, as was shortly thereafter pointed out by Bentley and co-workers [46][47][48], the ratio will be influenced by a general base catalysis by a second alcohol or water molecule to the nucleophilic attack by the first alcohol

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• afforded the products in excellent yields. The authors also conducted various experimental and theoretical studies to analyze the reaction mechanism. The proposed mechanism begins with the oxidative dehydrogenation of the alcohol to afford the aldehyde which undergoes condensation with ammonia to give the

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• deuterated carbons. The NOESY-based assignment of the diastereotopic hydrogens at these carbons for the unlabelled compound then allows to conclude on the absolute configuration of alcohol 3. A second set of experiments made use of (R)- and (S)-(1-13C,1-2H)IPP [20] that were enzymatically converted with

• three Me groups, four olefinic carbons (two quarternary, one CH and one CH2), and a tertiary alcohol, suggesting the structure of an oxidised (dehydrogenated) bicyclic sesquiterpene alcohol (Figure 4). The 1H,1H-COSY spectrum revealed one large contiguous spin system C-2-3-4(15)-5-6-7-8-9. HMBC

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• by side chain cross-linking of bromotryptophan and an organoboron moiety. Bromotryptophans are accessible by enzymatic bromination utilising cross-linked enzyme aggregates (combiCLEAs) containing an FAD-dependent tryptophan halogenase, a flavin reductase and an alcohol dehydrogenase [73][74]. For

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• . C–O cleavage, Figure 1A) through H-atom abstraction from a photoexcited intermediate, which produces an oxonium-type intermediate (in brackets). Hydrolysis of this intermediate then affords an alcohol product. Recently [16][17], we demonstrated that vinylogous analogues of this mechanism (Figure 1B

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

• EWGs and EDGs on the phenyl ring were amenable to the reaction; however, the yield was dramatically reduced with electron-deficient N-substituents. Substitution of the alcohol partner was well-tolerated though sterically demanding functionality lowered its reactivity. On the basis of the experimental

• results, the authors proposed a catalytic cycle (Scheme 12). First, the hydroperoxide, in the presence of an Fe(II) species, generates an Fe(III) intermediate and the alkoxy radical which can oxidize the incoming alcohol 67 to an aldehyde 70. Another equivalent of hydroxy radical, either generated under

• solvent-tuned [129]. In neat CH2Cl2, the reaction produced the expected β-trichloromethyl alkyl azide; however, the reaction was chemoselective for diazidation when tert-butanol was used as co-solvent. The authors hypothesized the presence of the alcohol suppresses the polar-unmatched HAT process from

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

• ring (especially with functional groups) is annulation of the latter moiety to the quinazoline ring. Thus, a series of 1,5-disubstituted pyrroloquinazolines 3 were obtained by a three-component Sonogashira-type coupling of 2-chloro-4-substituted quinazolines 4, propargylic alcohol, and secondary amines

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• tetrasubstituted allenes with aryl substituents, the asymmetric synthesis of these scaffolds has received much attention. In 2020, Lu and co-workers carried out the enantioselective dehydrative γ-arylation of α-indolyl-α-trifluoromethylpropargyl alcohol 105 and 1-naphthol (106) or 2-naphthol (107) catalyzed by

• indole ring of the propargyl alcohol, the yield decreases, which could be due to steric effects. Since the chiral phosphoric acid catalysts can interact with these groups via double hydrogen bonds, control studies have shown that the free OH on naphthol/phenol and the NH groups on the α-indolyl-α

• -trifluoromethylpropargyl alcohol are very important for the reaction. Li and co-workers developed a chiral phosphoric acid-catalyzed asymmetric remote 1,8-conjugate addition of thiazolones 111 and azlactones 112 to propargyl alcohols 110 for the synthesis of the chiral allenes 113 and 114, respectively. In the presence of

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

• was prepared from ᴅ-mannose (3c) by protecting the primary alcohol with a tosyl group, followed by protection of the four hydroxy groups by acetylation. Further, bromo-substituted sugar compound 10 was obtained by a bromination reaction of the anomeric acetyl group. 1,6-Thioanhydro-β-mannose

• into a primary alcohol with sodium borohydride affords compound 23. The protection of the hydroxy group of compound 23 was carried out by TBDPSCl in the presence of imidazole and N,N-dimethylformamide (DMF) as solvent, and deprotection of the benzoyl group by ammonolysis provides silylated compound 24

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

•  1, entries 7 and 8). The primary alcohol 2k and aldehyde 2l, both bearing oxygen-containing functional groups instead of nitrogen adjacent to the reactive center, gave 26% and 25% of the target compound 3 under these conditions, respectively (Table 1, entries 11 and 12). The TBHP-mediated

• cyclization of primary alcohols like 2k has been successfully utilized in the synthesis of fluorenones and azafluorenones [37], however, the authors used TBHP in n-decane. We repeated the reaction for primary amine 2a, primary alcohol 2k, as well as aldehyde 2l with TBHP in n-decane and obtained fluorenone (3

• fluorenone (3) in a TBHP-mediated cyclization of alcohol 2k under otherwise very similar reaction conditions in previously published research [37]. The reaction was also performed under alkaline conditions (addition of KOH), however, the yield of fluorenone (20%) decreased significantly in favor of more

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

• ratio of 86:14 and high enantiomeric purity of 95:5 er for the major diastereomer (Table 1, entry 1). Using chloroform/isopropyl alcohol 9:1 as the solvent mixture afforded after 120 hours, aldehyde 10a in 45% yield with 83:17 dr and 97:3 er (Table 1, entry 2). The Michael addition in methanol catalyzed

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

• features the 1,2-shift of an alkyl or aryl group. In the process, the hydroxy group is converted to a carbonyl and the aldehyde/ketone or imine is converted to an alcohol or amine. Such α-ketol/α-iminol rearrangements are used in a wide variety of synthetic applications including asymmetric synthesis

• rearrangements utilizes asymmetric induction arising from the chiral alcohol. When the ketol’s carbonyl is located at the α position to an amide, as in β-hydroxy-α-ketoamide 21, the difluoroalkoxyborane intermediate 22 that results from BF3-promoted α-ketol rearrangement can be isolated chromatographically

• with diverse biological activities [17]. The key step first involved the rhodium carbenoid-mediated OH insertion/Claisen rearrangement following complexation of diazoester 56 and allylic alcohol 57 to produce intermediate 58 (Figure 13). Addition of BF3·OEt2 to the reaction mixture then catalyzed the α

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• . Common cryogel compositions include natural polymers such as gelatin and chitosan, and synthetic acrylamide-based polymers and poly(vinyl alcohol) (PVA) [12][13][14]. The reader is directed to a recent review by Thakor and co-workers which discusses cryogel synthesis in greater depth [15]. 2. Cryogel

• buffered saline (PBS) from composite cryogels. Lima et al. presented an interesting partnership of cryogels with ceramics for a DDS [96]. Polyvinyl alcohol and polyacrylic acid were used as the precursor to the cryogel, and integrated within the ceramic. They produced a layer-by-layer structure by adding

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

• the copper-catalyzed oxidative coupling of alkynes, nucleophiles (e.g., phenols 25 and 28; amines 24, 27, 29, and 32; 2-hydrazinylpyridine 26; alkyne 33; and alcohol 30), and oxidants (benzoquinone or O2). Based on the literature and mechanistic experiments [72][73], the reaction is initiated by the

• -CuII superoxo complexes A. Under light irradiation, complex A produces the excited-state ligand-CuII superoxo complex A*, which undergoes coordination with the aliphatic alcohol to form complex B. The latter initiates the oxidation reaction and transfers a hydrogen atom from α-C(sp3)–H of the alcohol

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

• difficult and resulted in a moderate yield of 12 (41%) due to insufficient differences in the Rf values of compound 12 and the by-product 2,3-dimethoxybenzyl alcohol (not shown), formed through the hydrolysis of 13 (Scheme 8). In this situation N-(2,3-dimethoxybenzyl)veratrylamine 10 was chosen as the

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• amination occurred selectively at the ortho position to the N-quinolinyl amides with acceptable yields (3f–l). Notably, free alcohol was also compatible with this protocol, exclusively giving the mono-aminated product in 73% yield (3m) without the observation of any competitive alkoxylation product [38][57

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• results presented in Table 1 revealed that NIR-light-triggered click reactions produced the corresponding products with slightly higher yields favored by the higher penetration of NIR light to the reaction media containing heterogeneously dispersed BPNs. Compared with propargyl alcohol (Alk-1) and

• when the components are light sensitive at short wavelength region and spatial control is required. Experimental Materials Red phosphorus (98.9%), tin (99.5%), and tin(IV) iodide (95%) were purchased from Alfa Aesar. Ethyl alcohol (absolute) was obtained from Sigma-Aldrich. Dimethyl sulfoxide (DMSO

• ) was purchased from Merck. All chemicals and solvents were used as received without further purification for synthesis of black phosphorus. Benzyl bromide (Merck), phenylacetylene (Sigma), propargylamine (Sigma), propargyl alcohol (Sigma), d-dimethyl sulfoxide, (DMSO-d6, Merck), N,N,N’,N’’,N

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

• pyrrole derivatives: i) Knorr reaction: the condensation of α-aminoketones or α-amino esters in the presence of zinc powder and sodium acetate; ii) Paal–Knorr reaction: the condensation of 1,4-dicarbonyl compounds and amines, catalyzed by formic acid in anhydrous alcohol; iii) Hantzsch reaction: the

• -aryl-substituted pyrroles 55 in moderate to good yield. In addition, the method could tolerate a wide range of functional groups, such as phenolic hydroxy, aryl bromide, ester, terminal olefin, aryl chloride, and silyl-protected alcohol moieties. Furthermore, both aromatic and aliphatic nitriles

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• commercially available (E)-p-methoxycinnamic acid (17). The vital intermediate 16 is expected from cyclopropyl epoxy alcohol 18, which in turn can be prepared from allylic alcohol 19 via the Furukawa-modified Simmons–Smith cyclopropanation and VO-mediated epoxidation. Acetylfuran (20) is chosen as the six

• -carbon precursor for the synthesis. The forward synthesis transformed 2-acetylfuran (20) to its corresponding alcohol 21 through an asymmetric transfer hydrogenation catalyzed by a ruthenium complex (0.5 mol %) in 98% yield with 95% ee (Scheme 2). The azeotropic mixture of HCO2H/Et3N 5:2 was employed as

• the hydrogen source. Following protection of the alcohol moiety with PMBCl, ether 22 was realized in 93% yield. Afterwards, this species was transformed into the γ-keto α,β-unsaturated aldehyde 23 through an NBS-assisted furan oxidation procedure in moderate yield (65%). The keto functionality was

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• . This led to the desired allylic alcohol 6 (38%), likely via the selective (ring strain-relieving) 1,2-metalate rearrangement outlined in Scheme 2 (2→3, X = O, LG = OMe), then preferential β-elimination [7][8] of lithium methoxide rather than dilithium oxide. However, also isolated was dodecanal (50

• %), which arises from hydrolysis during work-up of the enamine that is formed from trapping of the lithiated epoxide by LTMP [9][10]. Omitting LTMP gave a significantly improved yield of the allylic alcohol 6 (79%, using BuLi and stannane 4 (3 equiv each)). This latter result suggests that

• -carbon homologation of an epoxide to an allylic alcohol (cf Scheme 3) can also be achieved using excess dimethylsulfonium methylide [12][13], although non-terminal alkenes have not been shown to be directly accessible by higher homologation. To examine the latter in the context of the current chemistry

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

• –halide complex compound 3 (Scheme 1). Review Cyclization reactions involving stoichiometric amounts of Hg(II) salts Cyclization involving alkenes (>C=C<) In 1900 and 1901, the Sand and Biilmann group had first reported the Hg(II)-mediated cyclization of allyl alcohol using Hg(II) nitrate (Hg(NO3)2) in

• selectivity of α-stereochemistry was primarily due to the strong directing effect of the neighboring benzyl ether group with the Hg(OAc)2. When cyclic mercuric halide 8 was treated with NaBH4 and oxygen (O2) in DMF oxidative demercuration takes place to give alcohol 10 in quantitative yield (Scheme 4). The

• positions of the starting material. It had been cited in many publications that the stereoselectivity of products formed due to Hg(II)-salt-mediated cyclization reactions of alkene-alcohol derivatives depends on several factors: the nature of the Hg(II) salts [46], the starting materials [47], and the