Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• [17]. Also, M2CO3-catalyzed (M = K or Cs) addition of phenols to bromoacetylenes produced bromovinyl phenyl ethers, which were converted into 4H-chromen-4-ones, benzo[b]furans, etc. [18][19][20][21]. The latter reaction attracted our attention and prompted us to explore the interaction of phenols and

• p-cresol (2f), p-metoxyphenol (2g) and eugenol (2i) decreased the yields of phenoxyhydroxyketones 4f,g, and i in comparison with phenol. Bromovinyl phenyl ethers 3 were not isolated. In DMF, diphenoxyketones 5b–g were obtained in almost all the cases, the reaction with nitrophenols 2d,e being the

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• hydroquinone ethers [87]. The combination of tert-butyl hydroperoxide and poly(bis-1,2-phenyl)diselenide was the one that showed the best result: 90% yield after 12 h reaction and recrystallization (Table 3, entry 3). Construction of the naphthoquinone ring In addition to the oxidation of naphthalene

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

• reactivity was observed for 2° and 3° alkyltrifluoroborates under the optimized conditions. The authors were able to improve the product yield by increasing the amount of TsCN and avoiding the use of additive (Scheme 18). A wide variety of functional groups such as esters, cyano, amides, ethers, ketones

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

• then account for the isolation of the acetylated analogue 9. The photochemical pathway described here represents a formal oxidative olefin cleavage of vinylogous nitroaryl-modified amides and ethers. The pathway adds to the diversity of photochemical pathways known for 2-nitrophenyl systems, and the

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• reaction with bromine (Scheme 1a) [37][38]. While the industrial demand for α-bromolactones has grown in recent years, the above-mentioned laboratory-level synthetic methods are not suitable for scale-up because LDA, TMSCl, and enol silyl ethers are sensitive to moisture and air, as well as being expensive

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

• 166 which is oxidized by Fe(III) to a carbocation species 167. Subsequent attack by the nitrile affords the nitrilium ion 168 which upon hydrolysis gives the final product 164. Oxime esters and ethers represent a widely used starting material for the generation of nitrogen-containing heterocycles. Due

Synthesis of a novel aminobenzene-containing hemicucurbituril and its fluorescence spectral properties with ions

• Qingkai Zeng,
• Qiumeng Long,
• Jihong Lu,
• Li Wang,
• Yuting You,
• Xiaoting Yuan,
• Qianjun Zhang,
• Qingmei Ge,
• Hang Cong and
• Mao Liu

Beilstein J. Org. Chem. 2021, 17, 2840–2847, doi:10.3762/bjoc.17.195

• Macrocycles with converging binding sites and functional groups hold a key position in supramolecular chemistry, which has been repeatedly confirmed by classic macrocyclic molecules, such as crown ethers, cyclodextrins, calixarenes, cucurbiturils and their homologues [1]. For the past decades, numerous

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• ethyl chloroformate/Et3N, followed by Wittig olefination with an ylide generated from (methoxymethyl)triphenylphosphonium chloride and LDA to give the enol ethers as E/Z mixtures. N-Phenethyl carbamates were obtained from benzaldehydes via Henry reaction with nitromethane, followed by zinc dust

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

• . Both TBS and SEM protecting groups were tolerated, as demonstrated by the syntheses of the fluorenones 10u and 10v (52 and 46% yields). As expected, the O-benzyl group was not tolerated, giving only trace amounts of product 10w, as benzyl ethers are well known to undergo side reactions with free

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

• a privileged structural motif central to many catalyst designs [12]. This fact stems from the success of diarylprolinol silyl ethers as chiral organocatalysts, which were independently introduced by Hayashi [13] and Jørgensen [14]. These compounds were used in a large number of stereoselective

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

• silyl ethers. Ooi et al. utilized an axially chiral organoaluminum Lewis acid catalyst (18) to convert a series of α,α-dialkyl-α-siloxyaldehydes 16 to α-siloxyketones 17 in high yields and >74% ee (Figure 5) [7]. This reaction is noteworthy for its tolerance of silyl protecting groups, which are

• use of silica gel and montmorillonite K 10 as catalysts is that they function under neutral conditions, permitting the use of acid-sensitive groups, such as silyl ethers. For example, 101 was converted to 102 in 70% and 96% yield, respectively, with silica gel and montmorillonite K 10, but with

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• incorporated by its nucleophilic attack at a cationic intermediate, leading to terpene alcohols [5][6] or sometimes ethers [7][8]. Substrate ionisation by TPSs is achieved through binding of the diphosphate portion to a trinuclear Mg2+ cluster in the active site that is itself bound to two highly conserved

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

• α-lithio ethers, to give convergent access to allylic alcohols and allylic amines, respectively. The process can be considered as proceeding by selective strain-relieving attack (ring-opening) of the lithiated three-membered heterocycle by the lithio ether and then selective β-elimination of lithium

• stereoselectivity. However, neither isopropyl or neopentyl benzylic ethers 26 and 27 [23][24] led to a significant change in the E/Z ratio for cinnamylamine 23 (Scheme 11). Conclusion In summary, we report a new, convergent access to allylic alcohols and amines. The process proceeds by selective cross-coupling of α

• -lithio terminal epoxides or N-Bus-aziridines with α-lithio ethers. Where 1,2-disubstituted alkenes are generated the E/Z stereoselectivity is modest, and preliminary results suggest the size of the leaving group does not play a significant role. However, the geometry of alkene formation might be

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

• ‘path b' was followed. Cyclization involving allenes (>C=C=C<) Apart from alkenes/alkynes, there are also examples where cyclization takes place involving allene functionalities. Some of the examples are discussed below. Balasubramanian et al. reported the cyclization of aryl allenic ethers 113 on

• fused polycyclic ethers by the treatment of a catalytic amount of Hg(TFA)2 with suitable starting material was demonstrated by Tan et al. [89]. They had reported a Hg(II)-catalyzed intramolecular trans-etherification reaction of 2-hydroxy-1-(γ-methoxyallyl)tetrahydropyrans 118 and 120 to the

• vinylmercury intermediate (Scheme 55). For the synthesis of stereoselective tetrahydropyran derivatives 184, Hg(II)-catalyzed cyclization proved to be more effective than silver(I)-salt-mediated cyclization. It showed that methyl-substituted allenes undergo efficient cyclization to form polycyclic ethers under

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• methoxy group as a leaving group have been documented [16]. Our previous research, as shown in Scheme 1, indicated that exposure of the oxime ether 7 to UV radiation resulted in the formation of the phenanthridine 8. Attempts to synthesize the related oxime ethers from biaryl compounds 13a, 13c and 13e

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

• chiral contact-ion pair can be formed, which is necessary for the transfer of the chiral information to the product. As a consequence, most of the reported methods embracing enantioselective anion-binding catalysis rely on the use of nonpolar solvents such as ethers or aromatic compounds. Pioneering work

• ][75][76][77][78]. Nevertheless, the activation of α-chloro ethers via anion abstraction continued to be a foundation for anion-binding catalyst evolution. In fact, Jacobsen's group further refined the design of their tetradentate N–H-bond donor catalyst 80 by covalently linking it into the more rigid

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

• arylation of cyclic and acyclic ethers 9 with aryl chlorides 8 under photoredox nickel catalysis (Scheme 5) [56]. Here, aryl chlorides 8 serve as cross-coupling partners and the chlorine radical source, which rapidly abstracts an α-oxy C(sp3)−H of the ethers to form the key α-oxyalkyl radical intermediate

• photocatalyst, substoichiometric 4,4′-dimethoxybenzophenone (DMBP) additives, and visible light (Scheme 6) [57]. A variety of cyclic and acyclic ethers 9 reacted with (hetero)aryl bromides 3 under the mild reaction conditions to give the desired products 10 in moderate to good yields, however, with longer

• the oxidative addition of the nickel(0) catalyst 6-VI to aryl bromide 3b. The photochemical nickel catalysis is not limited to an α-oxy C(sp3)‒H arylation of ethers. MacMillan and co-workers disclosed a method for the selective direct α-arylation of alcohols 18 using photoredox, HAT, and nickel triple

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

• -substituted amines 15, 18, and 20 [43]. Taking aniline as the pivotal moiety, it was coupled with isomeric bromoindoles 14 and 16 for the synthesis of the targeted products (Scheme 3b). Ethers Hongtao and co-workers also studied the electroluminescence properties of the 3,3’-bis(indolyl) ether derivatives 23

• ability of the products. Up to >80% inhibition of the amyloid-β peptide aggregates were achieved with these compounds, with the highest activity found for the 4-N-methylpiperidyl derivative. Ethers The synthesis of the bis(indol-6-yl) ether 175 was performed by Chai in 2017. Their protocol used a Cu(OAc)2

• indolyl amines through Buchwald–Hartwig cross coupling. Synthesis of 3,3’-bis(indolyl) ethers. C–H silylation of indoles. n-BuLi-mediated syntheses of bis(indol-3-yl)silanes. Acid-catalyzed syntheses of bis(indol-3-yl)silanes and mechanisms. B(C6F5)3 and Al(C6F5)3-catalyzed syntheses of bis(indol-3-yl

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

• the selectivity of olefin bonds during a CM reaction [38][39][40][41][42][43]. Investigations of various types of olefins in CM, such as substituted and functionalized styrenes, unsaturated tertiary alcohols, olefins with quaternary carbon centers, acrylates, allyl ethers or allyl acetates gave a

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

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

• alkyl enol ethers as the allylic counterpart [120]. In the field of C–H activation studies, not many examples have been described in the literature so far, especially towards the synthesis of biologically active compounds. However, an interesting example of a C(sp2)–H activation reaction promoted by Cr

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• -handle, their fluorinating power was low. They could fluorinate only reactive carbanions, but not aromatics, olefins, vinyl acetates, trimethylsilyl or alkyl enol ethers, and so on. Soon after (1986), Schwartz and co-worker reported the stereospecific synthesis of alkenyl fluorides with N-fluoro-N-tert

• , olefins, silyl enol ethers, vinyl acetates, sulfides and so on, under mild conditions with high selectivity and yields [29][30][31][32]. All these reactions could be carried out routinely using standard glassware in normal laboratory environments and without any specialist training. Some interesting

•  30). NFSI is a stable and non-hygroscopic crystalline solid with a mp of 114–116 °C. NFSI was shown to fluorinate a variety of nucleophiles. As seen in Scheme 31, trimethylsilyl enol ethers, enolate anions of ketones and esters, and aryl- and vinyllithiums were fluorinated with NFSI in moderate to

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

• hampered the development of more general catalytic hydrofunctionalization methodologies until Widenhoefer’s work in 2001 [25]. Based on previous works that had demonstrated the addition of stabilized carbanions [26][27] and enol silyl ethers [28] to olefins under stoichiometric Pd catalysis, the authors

• hydroalkylation reactions of less activated substrates [31]. Later studies demonstrated that the true reason for the reaction success was not the putative in situ formation of silyl enol ethers but the HCl formation due to TMSCl hydrolysis. The HCl catalyzed the formation of the enolic form responsible for the

• also tolerable to functional groups, such as silyl ethers (52a), carbamates (52b), and heterocycles (52c), present in the olefin moiety. The initial mechanism proposed by the authors begins with the formation of Fe(III) hydride species (A), followed by hydrogen atom transfer to the olefin in a

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• + 2]-cycloadduct 10b undergoes spontaneous elimination of MeOH, yielding the aromatized product 9d. A similar mechanistic scenario was observed and discussed previously for the reactions of trifluoroacetonitrile imines 7 with enol ethers used as dipolarophiles [27]. An additional experiment deserves a

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