4,6-Diaryl-5,5-difluoro-1,3-dioxanes as chiral dopants for liquid crystal compositions

• Maurice Médebielle,
• Peer Kirsch,
• Jérémy Merad,
• Carolina von Essen,
• Clemens Kühn and
• Andreas Ruhl

Beilstein J. Org. Chem. 2024, 20, 2940–2945, doi:10.3762/bjoc.20.246

• found in some natural products [34] with some fluorinated analogues [35][36], this motif is rarely found in LCs [37][38][39]. Based on these observations and literature data, we embarked in the synthesis and evaluation of enantiomerically pure acetals derived from anti-2,2-difluoro-1,3-diols as

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• trichloroacetimidate failed, due to competing formation of orthoester-like amide acetals during the reaction with 1b. We then focused our work on an alternative synthetic approach (vide infra). In 2021, Pfretzschner and Unverzagt reported the application of our methodology to the synthesis of indigo-N-glucoside 7c

• (Scheme 4) [20]. The reaction of 1b with 3,4,6-tri-O-acetyl-2-O-benzoyl-α-ᴅ-glucosyl trichloroacetimidate (6a) afforded indigo-N-glycoside 7a. The benzoyl group located at OH-2 seemed to be unreactive enough to avoid formation of orthoester-like amide acetals during the N-glycosylation with 1b. Oxidative

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• anhydride, the intermediately formed hemiacetal underwent acetylation, leading to N,O-acetals 1. In this method, an acid amide can be used as an amine masked with an acyl group. Subsequent elimination of acetic acid occurred to afford 2 in situ upon treatment with a base, enabling nucleophilic addition with

• -acetals 1 and alkynes 3 to determine the substrate scope of this protocol (Table 2). This reaction was effective with alkyl- and silyl-substituted alkynes 3b–d, yielding the corresponding adducts 4b–d, respectively (Table 2, entries 1–3). A significant advantage of this method is the high modifiability of

• amount of ammonium acetate and extending the reaction time (Table 4, entries 2 and 3). Conclusion N,O-Acetals 1, derived from DEMO and acid amides, reacted with lithium acetylide to afford the corresponding adduct 4 through highly electrophilic NAIs. The N-acyl and alkynyl groups could be modified using

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• of the substrate. The formed radical reacts with t-BuOOH to produce the corresponding ketone, with tert-butanol as a byproduct (Scheme 7). A closely related transformation was developed by Cheng and Xu in 2020 for the electrooxidation of methylarenes to aromatic acetals [15]. With this method

• , several structurally diverse aromatic acetals have been synthesized. Dehydroabietic and norcholanoic acid derivatives have been effectively modified using the developed protocol. The reaction is reported to involve the oxidation of the benzene core, followed by electron transfer to the radical cation, and

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• [39] developed a direct, highly enantioselective three-component reaction between aromatic acetals, BocNH2, and various 2-monosubstituted or 2,3-disubstituted allyltrimethylsilanes in the presence of 10 mol % of triethylsilyl triflate (TESOTf) and 10 mol % of the chiral bifunctional thiourea catalyst

• give the desired product 99 after 72 h returning hemiaminal (Scheme 21). Alkyl acetals, such as cyclohexyl carboxaldehyde acetal reacted sluggishly with low yield and selectivity (<10% yield, 43–50% ee), possibly due to their inability to participate in π–π interactions. In general, the π-stacking

• interaction between the catalyst and the aryl group of the substrate in the enantio-determining step appears to affect the scope. Other problematic substrates included (Z)-α-methylcinnamyl and (Z)-α-bromocinnamyl acetals giving the respective products with lower ee. Despite some phenyl substrates with 3

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• enantioselective formation of N,S-acetals catalysed by CPAs. To represent the catalysts, the authors developed the average steric occupancy (ASO) descriptors, a representation inspired by CoMFA [104][105][106], which recently also was applied in the selectivity prediction of aldehydes to nitroalkenes [68]. In ASO

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• Haifeng Yu Wanting Zhang Xuejing Cui Zida Liu Xifu Zhang Xiaobo Zhao College of Chemistry, Baicheng Normal University, Baicheng, Jilin 137000, China 10.3762/bjoc.20.190 Abstract An eco-friendly selective hydrolysis of chain α-oxo ketene N,S-acetals in water for the switchable synthesis of β-keto

• thioesters and β-keto amides is reported. In refluxing water, the hydrolysis reactions of α-oxo ketene N,S-acetals in the presence of 1.0 equiv of dodecylbenzenesulfonic acid effectively afforded β-keto thioesters in excellent yield, while β-keto amides were successfully obtained in excellent yield when the

• N,S-acetals; β-keto amide; β-keto thioester; dodecylbenzenesulfonic acid; hydrolysis; Introduction In the past decades, the application of easily available and stable α-oxo ketene N,S-acetals as significant synthons has received more and more attention in organic synthesis due to their unique

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• -unsaturated ketones 98 are S,S-ketene acetals capable of undergoing Liebeskind–Srogl coupling with boronic acids and phenylhydrazine in a consecutive three-component reaction to give pyrazoles 99 (Scheme 35) [118]. Beltrán-Rodil et al. used a similar strategy to synthesize 1,3,5-substituted pyrazoles 101 by

• (hetero)aryl iodides gives rise to 3-arylalkynyl acetals 142. Since 3-arylpropynals are sensitive to oligo- and polymerization, it proved useful to perform acetal deprotection and cyclization with hydrazine hydrate in a one-pot procedure to give 3-substituted pyrazoles 141 (Scheme 48) [151]. Given that

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• sodium methoxide in an undivided cell, three main products (namely benzophenone dimethyl acetals 133, diphenylmethyl methyl ethers 134 and diphenylmethanes 135) were obtained, the ratio of which was influenced by the electrode materials, the temperature and the amount of sodium methoxide. The range of

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• control of the current [32][33][34]. Early studies on the electrochemical oxidation of phenols revealed that the oxidation passes through a phenoxonium ion and forms acetals in methanol but quinones in the presence of water [35][36][37]. However, the reaction is sometimes accompanied by the formation of

• acetals. However, the methoxylated products from electrochemical oxidation of chrysen-1-ol (3b) and chrysen-6-ol (3d) rapidly hydrolysed to quinones during purification and could not be isolated. The attempted electrochemical oxidation of naphthalene-1-ol (1b) was unsuccessful; only small traces of

• multiple products were formed. The lability of the acetals prompted us to submit the crude intermediate directly to hydrolysis without prior isolation (Table 4). As mentioned above, having an aqueous reaction mixture in the electrochemical oxidation will give reduced yields. The overall yield of 9b from 6b

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• (entries 1–7, Table 1). Similarly to what was observed by Yu and co-workers for the intramolecular cyclization of alkynyl aldehyde acetals [28][29], it was found that the use of FeCl3 provided the better result in terms of overall yield (entry 3, Table 1). Moreover, the choice of iron(III) seemed to have

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• Heck adducts (methyl N,O-acetals) were efficiently converted into several arylated γ-lactams by a simple oxidation procedure (Jones oxidation). To demonstrate the applicability of the strategy, two of the chiral aryl-lactams were further derivatized to provide the selective phosphodiesterase-4

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• olefinic oxindoles to replace maleimides, the reactions gave spiro[indoline-tetrahydropyrrolothiazole] products 30 in 55–70% with greater than 4:1 dr [76]. The reaction mechanism suggests that the reaction of cysteine with arylaldehydes gives N,S-acetals 27 which convert to AMYs 28 after decarboxlyation

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• Following the seminal work of Feringa in 1997 [21], the tandem asymmetric organozinc conjugate addition followed by subsequent aldol reaction was scarcely applied in the last decade. Welker and Woodward studied the reaction of zinc enolates 2 with chiral acetals 3 (Scheme 2) [22]. The Lewis acid (TiCl4 or

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• gallium hydride, Goicoechea showed the catalytic hydroboration of ketones and CO2 with HBpin. This was also proposed to proceed by carbonyl reduction and Ga‒O/B‒H exchange (Scheme 24c) [116]. Schneider has shown that a mixture of Ga0, AgOTf, and 18-crown-6 catalysed the allylation of acetals, ketals, or

• ) methoxide (102) underwent Ga‒O/B‒C exchange with allyl-Bpin 103 to give MeOBpin and an allylic gallium(I) species 104, which reacted with the oxocarbenium 103 to give the allylic ether 105 and regenerate the GaI catalyst 99 (Scheme 25). Using allenylBpin, the selective propargylation of acetals was also

• , acetals, aminals, and alkyl ethers (Scheme 26) [119][120][121]. The proposed mechanism was analogous to the GaI catalysis by Schneider, with an In‒O/B‒C exchange proposed to drive catalytic turnover. Nakazawa reported an iron–indium cooperative catalytic system for the hydroboration of nitriles with HBpin

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

• (Figure 3). Chemical approaches Modified sugar rings containing a sulfur heteroatom at C-3' are found in medicinal chemistry. The reaction between oxygen-containing substrates (such as aldehydes or acetals) and sulfur sources (such as thiols or sulfenyl compounds) is one of the most important methods to

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

• tetrahydroisoquinoline derivatives, 7,12-dihydro-6,12-methanodibenzo[c,f]-azocine-5-carboxylic acids by three component Petasis reaction with the use of aminoacetaldehyde acetals bearing substituted benzyl groups as the amine components followed by Pomeranz–Fritsch double cyclization reaction. By applying this method

• the intramolecular Friedel–Crafts double cyclization reaction and N,N-dibenzylaminoacetaldehyde dialkyl acetals [12][14][15][16] in the Pomeranz–Fritsch-type double cyclization reaction. There is also one example of employing p-quinol acetates as substrates for the synthesis of these compounds [17

• Petasis three-component reaction followed by the Pomeranz–Fritsch–Bobbitt cyclization. The Petasis reaction between boronic acids, carbonyl derivatives, and amines, leading to the formation of amino acids and the Pomeranz–Fritsch–Bobbitt cyclization of amino acetals, leading to the construction of C-1

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

• frameworks from various tosylanilinoallyl acetals. 4H-Chromene derivatives were also synthesized starting from phenol derivatives (Scheme 38). Cyclization involving alkynes (-C≡C-) Marson et al. had developed the synthesis of substituted furans 133a–c promoted by catalytic use of Hg(II) salt through

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• ion pair with the chloride of the N-acyl(iso)quinolinium intermediate II. Hence, the reaction would follow a SN1-type mechanism via anion-binding catalysis. In Jacobsen’s report, the acylating agent 2,2,2-trichloroethyl chloroformate (TrocCl) and nucleophilic silyl ketene acetals were employed to

• ][75][76]. For this purpose, based on their initial findings in 2008 [38], the enantioselective addition of silyl ketene acetals to racemic 1-chloroisochromane (73) was more closely examined (Scheme 16) [73][74][75][76]. In this type of reaction, thiourea catalyst 76 actively engages in the ionization

• enantioselectivity, but the catalyst itself accommodates the anion by adopting a helical conformation upon complexation (Scheme 18a) [84][85][86]. Initial studies proved these systems highly effective for the enantioselective Reissert reaction of quinolines with silyl ketene acetals [22], which could be later

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

• cyclic ketene acetals [277]. This copolymer also showed a well-controllable reversible UCST behavior in aqueous solutions. In 2020, Zhao et al. reported that by incorporating azobenzene functionalities into polyacrylamide copolymers, the responsive UCST behavior was furthermore tuneable via light

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

• -unsaturated acetals 164 in the presence of electron-rich olefins using Ce(NO3)3 and SDS in water [74]. The mechanism of the reaction is shown in Scheme 39, which plausibly proceeded through trapping of oxocarbenium ion 166 in a chair-like transition state. The stability of the acetal under these reaction

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

• , fluoromethylene acetals. In the course of preparing synthetic samples of trace impurities in the herbicide pyroxasulfone, we were confronted with the problem of generating a bis(aryloxy)fluoromethane. Our intended route to structure 1 (Scheme 1) required the oxidation of bis-thioether 2, derived in turn from

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• nitriles, amides, amide acetals, and imidoesters [1][2][3][5][11][14] or from their independently prepared 3-chloromethylidene- [4][9][15][16][17], 3-hydroxymethylidene- or 3-(alkoxymethylidene)oxindoles [2][5][6][18][19][20] and the appropriate amines. Recently, original methods involving the construction

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

• )indole (10c) with 3 afforded the corresponding acetals 11a–c with 3-phenylbenzoheterole structures in 92%, 80%, and 93% yields, respectively. Acetals 11a–c successfully underwent TfOH-catalyzed cycloaromatization in HFIP to afford oxa-, thia-, and aza[4]helicenes 9a–c in 96%, 88%, and 93% yields

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• -difluorocyclopropyl acetals 110 to form 2-aryl-3-fluorofurans 112 (Scheme 50) [99]. The reaction could proceed either via the intermediacy of the gem-difluorocyclopropyl ketone 111 (path a) or by the direct rearrangement of the protonated acetal (path b). Recently, the group of Amii has reported the conversion of 1