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

• 1b with p-nitrophenol (2d, DMF/H2O, 50–55 °C, 3 h) furnished product 8b (14% yield) along with phenoxyhydroxyketone 4k (78% isolated yield). Bromopropargylic alcohol 1c having a tert-butyl group reacted with phenol (2a) in DMF for 3 h to give phenoxyhydroxyketone 4l in only 34% yield, 5

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

• -methylnaphthol (17) to menadione (10) are quite similar to those employed for the oxidation of 2-methylnaphthalene (16) using H2O2, molecular oxygen, and tert-butyl hydroperoxide as oxidizing agents. Similar to the oxidation of compound 16, it is possible to oxidize 2-methylnaphthol (17) with H2O2 to produce

• the predominant path depends mainly on the dioxygen pressure and the solvent nature [73]. Another approach was reported by Zalomaeva and co-workers, which used an iron tetrasulfophthalocyanine (FePcS) supported catalyst (FePcS-SiO2) in combination with the oxidizing agent tert-butyl hydroperoxide for

• dichloromethane and tert-butyl hydroperoxide at 80 °C (Table 2, entry 12). Methylation of 1,4-naphthoquinone Another route to prepare menadione (10) involves the methylation of 1,4-naphthoquinone. Because of their electron-deficient character, quinones are highly reactive with nucleophilic radicals [75]. The most

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• -azidobenzaldehyde (1a), benzoic acid (2a) and tert-butyl isocyanide (3a) as the reactants (Scheme 2). When a mixture of 1a, 2a, and 3a in CH2Cl2 was stirred at room temperature for 48 h, the three-component Passerini reaction was carried out smoothly and the azide 4a (R = Ph) was finally obtained in 87% yield

• ). In cases when aliphatic isocyanates (compounds 8o–q, R3 = n-Bu, cyclohexyl and PhCH2) were used, 65–74% yields of the products were obtained. Even as the steric tert-butyl isocyanate was applied, the 3,4-dihydroquinazoline 8r was obtained in 42% yield, but when diphenylamine was used, no product was

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• -supported heterogeneous Fe(III) catalyst. Suggested catalytic cycle for the Sonogashira coupling using a silica-supported heterogeneous Fe(III) catalyst. Chemoselective iron-catalyzed cross coupling of 4-bromo-1-cyclohexen-1-yltrifluromethane sulfonate with (tert-butyl dimethylsilyl)ethynylmagnesium bromide

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• smoothly with ethyl, tert-butyl, and p-methoxybenzyl esters of malonamate to furnish the oxyaminated products in good yields and moderate to good enantioselectivities (4o–u). Pleasingly, the reactions carried out using m-methoxybenzyl and 3,4,5-trimethoxybenzyl esters of malonamate afforded the

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

• ]. Accordingly, we will be somewhat brief in the introduction to this treatment before discussing its application to a study of solvolyses taking place at the sulfur atom of sulfonyl chlorides. The original scale of solvent ionizing power (Y) values was based on a study of the solvolyses of tert-butyl chloride

• X), the moderate to weak nucleophilic participation with tert-butyl derivatives [35] can be avoided. The more reactive 3° compound is used to set up scales of Y values for the relatively poor leaving groups and the less reactive 2° compound is used for the relatively good leaving groups [25]. In the

• majority of solvolysis reactions, one also needs to evaluate the nucleophilic attack by the solvent which contributes modestly to the overall scheme for tert-butyl chloride solvolyses but appreciably for the solvolyses of methyl and primary alkyl halides. The original Grunwald–Winstein equation can be

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• exchange NMR experiments such as saturation transfer have been widely used in such cases (e.g., 1D selective NOESY). In this case, the 1H NMR spectrum of 4b revealed singlets of tert-butyl protons at δ 1.24 ppm (major rotamer) and δ 1.44 ppm (minor rotamer). When the signal at δ 1.44 ppm was irradiated

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

• nitriles in moderate to good yields. Zhang and co-workers developed an efficient methodology for the synthesis of cyanated isoxazolines from the corresponding alkenyl oximes under mild reaction conditions (Scheme 25) [48]. The dual role of tert-butyl nitrite as oxidant and as a nitrogen source further

• catalyst. Synthesis of cyanated isoxazolines from alkenyl oximes catalyzed by [RuCl2(p-cymene)]2 in the presence of tert-butyl nitrite. Proposed mechanism for the synthesis of cyanated isoxazolines from alkenyl oximes. Oxidative cyanation of differently substituted alcohols. Cyanation of tertiary amines

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

• bond in the staple (cis and trans, respectively). Synthesis of SMC stapled axin CBD peptides. Reaction conditions: (a) Pd2(dba)3, sSPhos, KF, DME/EtOH/H2O 9:9:2, 120 °C, µwave, 30 min; (b) TFA/TIS/H2O 95:2.5:2.5, DTT, phenol, 2 × 2 h. B(OR)2 = B(OH)2, B(pin), pin = pinacolato, t-Bu = tert-butyl, Trt

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

• aromatic and cyano groups. The oxidation of species 80 would reduce the Fe catalyst back to its reduced form, while a tert-butyl alkoxide can furnish the final product through acid-base catalysis. In 2019, Li and co-workers investigated a three-component dialkylation of alkenes 82 with common alkanes 83

• a four-component radical dual difunctionalization and ordered assembly of two chemically distinct alkenes 114/115, aldehyde 65, and tert-butyl peroxide (Scheme 23) [108]. In order to selectively couple one alkene to another, without the formation of oligomers, the authors utilized the different

• and carbazates 117 (Scheme 24) [112][113]. Both protocols utilized a catalytic loading of FeCl2·4H2O mediated by tert-butyl hydroperoxide. The scopes of both reactions were broad and tolerated a variety of functional groups; however, both groups noted unsubstituted terminal alkenes and N

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• good yields (81–94% yields). It was noteworthy that p-QMs bearing functional groups, such as methyl, methoxy, tert-butyl, fluoro, chloro, bromo, and trifluoromethyl were well compatible under the optimal reaction conditions. The efficiency of this method was not affected by the pattern of substituents

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

• diastereomers by silica gel column chromatography and reaction with lead tetraacetate provided the key oxathiolane derivative 31. In 1995, Jin et al. [46] carried out the reaction of 1,4-dithiane-2,5-diol (3q) with glyoxylic acid (3g) hydrate at reflux temperature in tert-butyl methyl ether, which provided the

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

• ], CBr4 [22], or peroxides like tert-butyl hydroperoxide (TBHP) [35]. Other oxidative cyclizations have been developed starting from biarylglyoxylic acids (using Na2S2O8) [36], and even 2-methylbiphenyls and 2-(hydroxymethyl)biphenyls can be converted into fluorenones by means of TBHP oxidation [37]. In

• [22], and tert-butyl hydroperoxide [37] (TBHP). Formation of postulated intermediate aminofluorenes of type 5 could not be observed for any of the reactions performed during the initial screening process, and cyclization to the target compound fluorenone (3) was confirmed for only two of the substrate

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• conditions. The same set of β-silylenones was explored and an almost similar trend in reactivities, yields as well as enantioselectivities was observed. To probe the role of the β-silyl group, the reaction of tert-butyl-substituted enone 3o and nitromethane (2) was conducted under the standard reaction

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

• /mismatched combination of chirality, we employed both enantiomers of tert-butyl sulfinamide with the (S)-enantiomer of the pyrrolidine building block. The introduction of green chemistry principles into chemical transformations is an important goal toward sustainable production and manufacturing. Asymmetric

• of the catalysts in organocatalytic Michael addition and suggested the possibilities of further improvement in catalyst design. Experimental Synthesis of catalysts (S)-tert-Butyl 2-(aminomethyl)pyrrolidine-1-carboxylate (2) The solution of PPh3 (1.64 g, 6.3 mmol) and N-Boc-(S)-prolinol (1, 1.0 g, 5.0

• the literature [32]. (S)-tert-Butyl 2-(isothiocyanatomethyl)pyrrolidine-1-carboxylate (3a) The solution of Et3N (0.13 g, 1.3 mmol) and (S)-tert-butyl 2-(aminomethyl)pyrrolidine-1-carboxylate (2, 0.08 g, 0.4 mmol) in dry THF (4 mL) was cooled in an ice–water bath and next it was added dropwise into

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• well as tert-butyl as precursors for the silica gel-mediated cyclization reaction to form pyrrolizine products. The bromomethyl ketones required for the initial sulfide contraction were either purchased from commercial suppliers or prepared from the corresponding methyl ketones by reported procedures

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

• of compounds 14a–f can be found in Supporting Information File 1. UV cyclization of oxime ester derivatives: general procedure A quartz UV reactor was charged with oxime ester and tert-butyl alcohol (5 mL) and the solution was degassed for 30 min. The solution was then subjected to UV irradiation

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• therefore greatly benefit our procedure. The in situ formation of the aryldiazonium salt from the corresponding aniline and tert-butyl nitrite in methanol and subsequent exposure to green light in the presence of 2,5-dichlorobenzoquinone (1) proved to generate the desired product in yields that were similar

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• investigating the behaviour of different alkylating agents (Table 2). Reactions with alkylating agents with increased steric demand provided products in higher ee (compare Table 2, entries 1, 2 and 3); with 3,5-bis(tert-butyl)benzyl bromide allowing the isolation of oxindole 10Ac in 92% yield and 84% ee. The

• -alkylated with bromo ester 13. The formed product (i.e., 14) was first amidated and then cyclised using benzylamine 11 to generate spirooxindole 15 in 54% yield and 94% ee. Chlorination with NCS, followed by tert-butyl ester cleavage in TFA/CH2Cl2 provided the final bioactive compound 6 in 93% ee

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

• -amino C(sp3)–H bonds using di-tert-butyl peroxide (DTBP) or dicumyl peroxide (DCP) as the methyl source under mild conditions [93]. Based on the substrate structure and peroxide choice, the authors developed four sets of reaction conditions (Scheme 29) [93]. In these reaction conditions, photocatalyst

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

• protocol (Scheme 7). The synthesis of the key building blocks 2-aminoazulene (24), 2-amino-6-bromoazulene (26), and its corresponding carbamate, tert-butyl N-(6-bromoazulen-2-yl)carbamate (27), used in their synthesis is presented in Scheme 7A. The carbamate 27 was subjected to a Buchwald–Hartwig reaction

• of directly connected 4,7-polyazulenes 18–20. Synthesis of (A) tert-butyl N-(6-bromoazulen-2-yl)carbamate (27), (B) dimeric aminoazulene 29, and (C) poly[2,6-aminoazulene] 31. Synthesis of poly{1,3-bis[2-(3-alkylthienyl)]azulene} 33–38. Synthesis of polymer ruthenium complexes 40–43. Synthesis of 4,7

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

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

• was described by Sun et al. [46]. In this method, the catalyst (DHQ)2PYR 42 reacts with tert-butyl 2-bromoacetate, and then an ylide is formed by the base Cs2CO3. After a conjugated addition of this intermediate to the coumarin 43 followed by nucleophilic substitution, the corresponding cyclopropa[c

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• observed > 99% N-1 regioselectivity for 3-carboxymethyl, 3-tert-butyl, 3-COMe, and 3-carboxamide indazoles. Further extension of this optimized (NaH in THF) protocol to various C-3, -4, -5, -6, and -7 substituted indazoles has highlighted the impact of steric and electronic effects on N-1/N-2 regioisomeric

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

• usually mediated by V(V) and V(IV)-oxo-peroxo complexes, which are produced in situ from vanadium-oxo and dioxo precatalysts in the presence of oxidants, such as H2O2, O2, and tert-butyl hydroperoxide (TBHP) [76][77][78][79][80][81][82]. Inorganic acids and chelating and non-chelating carboxylic acids