Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• ethylenediamine monohydrochlorides were grinded with a half equivalent of 4-diethylamino (Et2N‒), 3,5-dichloro (Cl‒), or 3,5-di-tert-butyl (t-Bu‒) salicylaldehydes (blue moieties in Scheme 2) for 10 minutes. The synthesis of diamine monohydrochlorides and characterization data of mono-imine ammonium salts were

• ), half equivalent of 5-bromo (Br‒), 5-methyl, 4-diethylamino (Et2N‒), 3,5-dichloro (Cl‒), or 3,5-di-tert-butyl (t-Bu‒) salicylaldehydes (red moieties in Scheme 2), and trace methanol, followed by grinding for 20 minutes for the second reaction step to complete, monitored by TLC. A trace amount of

• between 1g (81%) and 1h (76%). Yields of 1d (79%), 1e (81%), and 1f (72%) were less than 1a‒c, caused by the steric hindrance of di-tert-butyl groups. In the aspect of characterization of salens, two singlets were shown at around 8 ppm in the 1H NMR spectrum, indicating two unsymmetrical imines. The broad

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• /z): [M + H]+ calcd 407.2377; found, 407.2359. (6R)-tert-Butyl 5-(diethoxyphosphoryloxy)-6-(2-((triisopropylsilyl)oxy)ethyl)-3,6-dihydro-2H-1,2-oxazine-2-carboxylate (10b): A solution of the enol phosphate 17 (420 mg, 1.03 mmol) in chloroform (1.8 mL) was added to a solution of the Wightman reagent 6

• ppm; HRMS (m/z): [M + Na]+ calcd 560.2779; found, 560.2775; [α]20D : +5.8 (c 1.0, CH2Cl2); ee: 8% (Whelk-O1, 1 mL/min, 95:5 hexane/EtOH, tr (R) = 14.9 min, tr (S) = 16.2 min). (6R)-tert-Butyl 5-oxo-6-(2-((triisopropylsilyl)oxy)ethyl)-1,2-oxazinane-2-carboxylate (11b): A solution of the cycloadduct 10b

• %). tert-Butyl (6R)-5-((E)-2-((2S,3S)-3-ethyl-6-oxo-3,6-dihydro-2H-pyran-2-yl)vinyl)-5-hydroxy-6-(2-((triisopropylsilyl)oxy)ethyl)-1,2-oxazinane-2-carboxylate (25): Data for 25: Rf: 0.10 (30% AcOEt/cyclohexane); 1H NMR (360 MHz, CDCl3) δ 6.97 (dd, J = 9.7, 5.5 Hz, 1H), 6.05 (d, J = 9.7 Hz, 1H), 5.95 (dd, J

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

•  1b). Alternatively, the oxidation of α-C–H of active methylene ketones generate α-carbon-centered radicals, thus providing another way to obtain thiazoles. Recently, Sun et al. reported a tert-butyl hydroperoxide/azodiisobutyronitrile-mediated synthesis of 2-aminothiazoles from active methylene

• presence of ᴅʟ-alanine (Table 1, entry 24). Under the optimized reaction conditions (entry 24, Table 1), the scope of the electrochemical reaction was studied using a series of active methylene ketones (Scheme 2). Various linear and branched alkyl acetoacetates including methyl, ethyl, tert-butyl, and amyl

• ethyl, n-propyl, isopropyl, n-butyl, tert-butyl and cyclohexyl moieties were also compatible with the optimized conditions, providing the corresponding 2-aminothiazoles in 24% to 65% yields (3g–l). As shown in Scheme 2, when the R1 group changed from alkyl to aryl, the target products could also be

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• thermodynamically controlled basic intramolecular aldol addition of compound 108 using the bulky amine base 2,6-di-tert-butyl-4-methylpyridine (DTBMP) led to epimerization of the methyl group and cyclization, giving preussochromone F (109) as single isolable diastereomer probably via transition state XII. The

From amines to (form)amides: a simple and successful mechanochemical approach

• Federico Casti,
• Rita Mocci and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 1210–1216, doi:10.3762/bjoc.18.126

• ). N-(1-Naphthyl)formamide (6) was obtained in satisfying yield, while the methyl and tert-butyl ester moieties affected the reaction outcome (Scheme 1, amides 7 and 8). Secondary amines were also tested under the developed conditions; N-methylaniline provided the desired product 9 in 39% yield, while

Thermally activated delayed fluorescence (TADF) emitters: sensing and boosting spin-flipping by aggregation

• Ashish Kumar Mazumdar,
• Gyana Prakash Nanda,
• Nisha Yadav,
• Upasana Deori,
• Upasha Acharyya,
• Bahadur Sk and
• Pachaiyappan Rajamalli

Beilstein J. Org. Chem. 2022, 18, 1177–1187, doi:10.3762/bjoc.18.122

• to the singlet state via RISC [17][27]. Heteroatom lone-pair electrons are sensitive to acid and, once protonated, to base, which would facilitate the tuning of optical properties in such media [21][22]. Herein, (4-(3,6-di-tert-butyl-9H-carbazol-9-yl)phenyl)(pyridin-4-yl)methanone (BPy-pTC) and (4-(9

Electrogenerated base-promoted cyclopropanation using alkyl 2-chloroacetates

• Kouichi Matsumoto,
• Yuta Hayashi,
• Kengo Hamasaki,
• Mizuki Matsuse,
• Hiyono Suzuki,
• Keiji Nishiwaki and
• Norihito Kawashita

Beilstein J. Org. Chem. 2022, 18, 1116–1122, doi:10.3762/bjoc.18.114

• compound 6 in <24% and <26% yields, respectively (Table 3, entries 3 and 4). n-Propyl 2-chloroacetate (9), with the longer alkyl chain, and tert-butyl 2-chloroacetate (11), with the bulky alkyl group, produced 10 and 12 in <22% and <31% yields, respectively (Table 3, entries 5 and 6). The reaction of 13

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• transformation was investigated as shown in Scheme 2. Various 1-arylethanol derivatives were firstly examined. Substrates bearing p-methyl (1b) or p-tert-butyl (1c) groups afforded the desired products 2b and 2c in moderate yields. Halogen substituents such as fluorine (1d) and chlorine (1e) atoms were tolerated

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• performed a detailed investigation on the dearomatizing anionic cyclization of diphenyl-N-alkyl-N-benzylphosphinamides 107, 116, and 119 by treatment with sec-butyllithium and protonation with various alcohols (MeOH, iPrOH, t-BuOH), phenols (PhOH, 2-tert-butyl-4-methylphenol, and 2,6-di(tert-butyl)-4

• -dihydrobenzo[c][1,2]azaphosphole 1-oxide (210) was synthesized in low yields of 20–43% with diastereomeric ratios of 10:1 to >20:1 from (R)-1-tert-butyl-1,1-diphenyl-N-(1-phenylethyl)silanamine (204) via the treatment with butyllithium followed by double displacement with four different phosphorus

• )acetates 247 in moderate yields of 53–71% with diastereomeric ratios of 1:1.7 to 1:3. The synthetic strategy is more versatile (Scheme 39) [60]. [3 + 2] Annulation via formations of both C–C and P–N bonds After oxidation with K3Fe(CN)6, diphenyl 3,5-di(tert-butyl)-4-hydroxybenzylphosphonate (248) was

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• ], tert-butyl/α,α-gem-dimethyl [29], or fluorinated groups [30] will preferentially form cis-amides (Figure 1A). Peptoid helicity modulation has also been investigated through specific placement of chiral and achiral monomers [31][32]. Comparatively fewer N-functional monomers capable of promoting trans

• -methylhydrazine as a submonomer was adopted in this work (Figure 2). Benzyl bromoacetate, rather than tert-butyl bromoacetate, successfully used in the past for the synthesis of peptoids in solution [22], was chosen as the starting substrate to ensure orthogonality of the C-terminal protecting group with respect

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• be extracted from grapefruits or prepared by, e.g., oxidation of (+)-valencene (7) (using toxic di-tert-butyl chromates), which is isolated from the essential oil of oranges [9]. In 2014, Neuenschwander and Jensen reported a flow setup for the catalyst and solvent-free oxidation of (+)-valencene (7

Substituent effect on TADF properties of 2-modified 4,6-bis(3,6-di-tert-butyl-9-carbazolyl)-5-methylpyrimidines

• Irina Fiodorova,
• Tomas Serevičius,
• Rokas Skaisgiris,
• Saulius Juršėnas and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 497–507, doi:10.3762/bjoc.18.52

• achieving efficient deep-blue emission, we were interested to study the influence of substituents in position 2 of the pyrimidine ring on the TADF properties of pyrimidine–carbazole emitters. For this purpose, we performed the synthesis of novel 4,6-bis(3,6-di-tert-butyl-9H-carbazol-9-yl)pyrimidines

• -withdrawing groups, namely cyano, bromo or sulfonyl groups were introduced directly or through a phenylene bridge into position 2 of the pyrimidine ring. Results and Discussion Synthesis Due to the versatile reactivity of a methylthio group in the pyrimidine nucleus [34][35] we used 4,6-bis(3,6-di-tert-butyl

• (I) 3-methylsalicylate (CuMeSal), and Cs2CO3 as a catalyst system furnished the corresponding 2-substituted pyrimidines 2a–d. For the introduction of cyano and 4-(tert-butyl)phenylthio groups into position 2 of the pyrimidine, the conversion of the methylthio group to the better leaving

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• product in 65% yield with 68% ee (8al). The reactions for S-benzyl and S-ethyl substrates became sluggish and afforded the products in 34–48% yields in 96 h with very low selectivity (8am and 8an). For the S-tert-butyl substrate, only trace conversion was observed. Macrocyclic effect and catalytic

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• chiral alkyl groups we considered tert-butyl, ʟ-menthyl, and (−)-bornyl in this study. Results and Discussion The aldehydes 15–20 were prepared by analogous methods, which were described previously [12][13]. The starting ʟ-menthyl (7) and (−)-bornyl chloroformate (8) were obtained according to the

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