One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• the reported procedures [41], the Ugi-azide reaction of 2-bromobenzaldehyde (1a, 1 mmol), allylamine hydrochloride (2, 1 mmol), trimethylsilyl azide (3, 1 mmol) and tert-butyl isocyanide (4a, 1 mmol) in MeOH at 40 °C for 24 h afforded 1,5-DS-1H-T 5a in 92% yield after chromatography purification. Our

• mmol), trimethylsilyl azide (3, 1 mmol), and tert-butyl isocyanide (4a, 1 mmol) was stirred in MeOH at 40 °C for 24 h, and after the reaction was completed, the solvent was evaporated under vacuum to give crude Ugi adduct 5a which was used for the intramolecular Heck reaction without further

• . Experimental General procedure for the synthesis of Ugi-azide adduct 5a A solution of 2-bromobenzaldehyde 1 (1 mmol, 1 equiv), allylamine hydrochloride (2, 1 mmol, 1 equiv), trimethylsilyl azide (3, 1 mmol, 1 equiv) and tert-butyl isocyanide 4a (1 mmol, 1 equiv) in MeOH (5 mL) with Et3N (1.5 mmol) was heated

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• -workers, and was accessed over 8 steps from diene 161 (Scheme 17A) [51]. Diels–Alder reaction of diene 161 and di-tert-butyl azodicarboxylate (160) followed by palladium-assisted elimination of acetic acid gave diene 162. A sequence of 4π-electrocyclisation and electrophilic transcarbamation (to 163

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• 3au and 3av were produced in 34% and 39% yields, respectively, in which methoxy and tert-butyl groups were located in the para position to the hydroxy group (Table 2, entries 20 and 21). In the case of 3al, the mono-arylation of naphthol generated 3al’ in 20% isolated yield, which is the reason for

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• carbenium ions are highly energetic species which tend to react unselectively according to the reactivity–selectivity principle. In contrast, MH HAT produces relatively stable radicals which is demonstrated by, e.g., the strong difference of heat of formation of the tert-butyl radical and cation (Figure 7B

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• work [45], and will be only shortly described in a summarized form (Scheme 3). Styrene substituted with a tert-butyl at the para position afforded 4b in 78% yield. Using a styrene bearing a sterically hindered aryl afforded 4c in a similar yield. Homopropargylic azides possessing oxygen substituents

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• our hands, when we tried to reproduce the reaction between 2-aminopyridine (1a), benzaldehyde (2), and tert-butyl isocyanide (3a), following in detail the reported protocol using exactly the same reaction conditions, the reaction failed completely in 20 minutes (followed by TLC) and after 72 h only 46

• -Aminopyridine (1a), 4-nitrobenzaldehyde (2a), and tert-butyl isocyanide (3a) were chosen as model substrates and different conditions were screened (Table 1). Glycerol, a green and sustainable solvent, was tried first, but unfortunately, the expected intense orange solid product 4a was obtained in low yields

• -position gave moderate product yields (4c and 4d). Furthermore, cyclohexyl isocyanide gave higher yields compared to tert-butyl isocyanide. Ortho-substituted aromatic aldehydes were very efficient, regardless the type of substituents used, and good to excellent yields (74–99%) of products 4k–r were

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• tweezers with tert-butyl groups positioned farther from the salphen via alkyne spacers were synthesized [42]. While, like in the parent tweezers 12, no intercalation of aromatic guests was observed in the closed form, strong intramolecular and intermolecular Pt–Pt bonds were achieved in the solid state

• ]. In the neutral state, the tweezers 34 adopt an anti-conformation because of steric hindrance between the N–H and the tert-butyl groups. Again, the N–H proton of the indole can bind to anions through hydrogen bonds and causes the system to adopt a cis-conformation, closing the tweezers. This closed

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• amounts of water (Table 3, entries 12–14) [39]. The same decelerating effect of water in MeOH solvent was seen with [JPhosAu(NCCH3)]SbF6 (5) (Table 3, entries 15–17). Substrate effect The rate of hydroamination to cyclized 3a–c was measured for three substrates, tert-butylurea 1a, tert-butyl carbamate 1b

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• hydrogen atom to terminate the radical reaction. The proposed mechanism of the hydroalkylation cascade is depicted in Scheme 13B. Upon excitation of complex 59 with blue light, intra-complex SET takes place from the HE to the NHPI ester, leading to the formation of tert-butyl radical 64 and radical cation

• isonicotinate tert-butyl ester) in C(sp2)-borylation methods under photochemical and thermal conditions, respectively [65][66]. The activation of NHPI esters through EDA complex formation is also possible by employing a catalytic donor species, which enables a range of redox neutral transformations. In 2019

• absorption spectra of PTH1 was observed, suggesting the formation of a charge transfer complex of the type 88 [68] (Scheme 17A). tert-Butyl radical (64), along with additional 2° and 3° alkyl radicals, resulting from these EDA complexes were harnessed in C(sp3)-heteroatom bond forming reactions [69], and in

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• condensation and Schiff base formation, which is then cyclized [12][16]. The reaction of 1 with arylamines 2a is performed in toluene solution in the presence of a catalytic amount of p-toluenesulfonic acid. This readily affords 6,8-di-tert-butyl-N-aryl-3H-phenoxazin-3-imines 3 but proceeds smoothly only with

• highly basic amines (Scheme 1) [6]. The choice for one of the other two possible reaction pathways (nucleophilic additions to either the C(1) or C(2) center) critically depends on the electrophilicity. Figure 1 shows the distribution of electronic density in 6,8-di-tert-butyl-3H-phenoxazin-3-one (1

• ). This is also the basic compound used in the transformations that are studied in this work due to the high kinetic stability and good solubility ensured by the tert-butyl groups. The largest positive charge of the C(1)–C(2)–C(3) segment is concentrated at the C(2) atom. The charge at the other

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• structure induced by the embedded heteropine ring. By way of example, the solubility of SeO-doped seco-HBC 29c is more than 100-fold higher than pristine HBC carrying four tert-butyl groups in both dichloromethane and ethanol. Ring contraction was next attempted on the series of heteropines synthesized

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• side reactions was carried out with benzyl 3-amino-4,4,4-trifluorobutanoate (1a) and benzoic acid (3a) as model substrates. The initial reaction of amine 1a and acid 3a in acetonitrile in the presence of diazotization reagent tert-butyl nitrite with CuI (10 mol %) as catalysts for 2.5 h at room

• bring any improvement on the reaction outcome (Table 1, entries 6 and 7). Further optimization of the reaction conditions focused on the variation of the amounts of amine 1a and tert-butyl nitrite (Table 1, entries 8–12). Considering the instability of the diazo structure generated from amine 1a, we

• increased the amount of amine 1a and tert-butyl nitrite to 4 equivalents. Pleasingly, the yield of product 4a was further increased to 74% (Table 1, entry 12). Furthermore, we optimized the reaction time and found that shortening the reaction time resulted in a decreased yield (Table 1, entry 13

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• steric hinderance of Hantzsch ester raised (Table 2, entries 1–3) and switching from ethyl to tert-butyl esters the desired product was obtained in excellent yield and enantioselectivity (Table 2, entry 3). Subsequently, we investigated the effect of the amounts of HE-t-Bu and chiral phosphoric acid on

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• could potentially after deprotonation be reacted with electrophiles as previously established [29] for the parent structure [30] without tert-butyl substituents. UV–vis absorption spectroscopy UV–vis absorption spectra of the known compound 4 [14] and new compounds 9–12 and 15 are depicted in Figure 3

• bulkiness of the TIPS groups along with the tert-butyl groups in compound 26 prevent these interactions, while for compound 29, the lack of π–π interactions can be ascribed to the methylene bridges as the hydrogens along with the tert-butyl groups prevent good overlap of the π-systems. Table 3 lists the

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• University of Technology, Stremayrgasse 9, 8010 Graz, Austria 10.3762/bjoc.20.6 Abstract The reactions of 2,4-di-tert-butyl-6-(diphenylphosphino)phenol and various Michael acceptors (acrylonitrile, acrylamide, methyl vinyl ketone, several acrylates, methyl vinyl sulfone) yield the respective phosphonium

• with several Michael acceptors [34]. In this work we present the formation of stable zwitterions from the reaction of 2,4-di-tert-butyl-6-(diphenylphosphino)phenol (1) and a variety of different Michael acceptors and disclose kinetic investigations on the zwitterion formation with carbonyl and non

• similar phosphonium salt 2,4-di-tert-butyl-6-(triphenylphosphonium)phenolate features this particular signal at 6.27 ppm (4JHH = 2.7 Hz, 3JPH = 14.4 Hz [30]). In the 13C NMR spectra, the chemical shifts of the carbon atoms in positions 1 and 6 of the phenolate unit are particularly noteworthy. In the

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• excess to compensate for the possible formation of sodium O-tert-butyl xanthate [72][73][74]. We reasoned that these conditions should favor a quantitative deprotonation of the starting triazolium salts and the concomitant trapping of the free carbenes by CS2 prior to their potential decomposition

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• fullerenes act as anion–π catalyst without additional activating groups, usually a tethered base to inject a negative charge into the substrate directly on top of the catalytic π surface [69]. The tert-butyl esters in Bingel fullerene 31 serve only to improve solubility and are not expected to participate in

Aromatic systems with two and three pyridine-2,6-dicarbazolyl-3,5-dicarbonitrile fragments as electron-transporting organic semiconductors exhibiting long-lived emissions

• Karolis Leitonas,
• Brigita Vigante,
• Dmytro Volyniuk,
• Audrius Bucinskas,
• Pavels Dimitrijevs,
• Sindija Lapcinska,
• Pavel Arsenyan and
• Juozas Vidas Grazulevicius

Beilstein J. Org. Chem. 2023, 19, 1867–1880, doi:10.3762/bjoc.19.139

• )-4-(4-bromophenyl)pyridine-3,5-carbonitrile (4) was obtained by the interaction of 3,6-di-tert-butyl-9H-carbazole with compound 3 in THF/DMF solution. The ethynylphenyl-substituted pyridine 5 was synthesized by Sonogashira coupling of 4 with ethynyltrimethylsilane in the presence of PdCl2(PPh3)2 and

• steady-state luminescence spectroscopy. Meanwhile, time-resolved spectroscopy at different temperatures was used to investigate the nature of long-lived emissions of 6–9 as it was previously done for the reference compound 2,6-bis(3,6-di-tert-butyl-9H-carbazol-9-yl)-4-(4-fluorophenyl)pyridine-3,5

• transfer from the donor to the acceptor. The absorption spectrum of REF is included in Figure 2a for comparison. Compounds 6–9 are characterized by similar absorption bands also caused by electron transfer from the 3,6-di-tert-butyl-9H-carbazole units to the pyridine-3,5-dicarbonitrile moiety. The number

Quinoxaline derivatives as attractive electron-transporting materials

• Zeeshan Abid,
• Liaqat Ali,
• Sughra Gulzar,
• Faiza Wahad,
• Raja Shahid Ashraf and
• Christian B. Nielsen

Beilstein J. Org. Chem. 2023, 19, 1694–1712, doi:10.3762/bjoc.19.124

• study raises a concern regarding the performance of dyes with tert-butyl substituted DPQ acceptors, either containing benzene (Qx74) or thiophene (Qx75) as a π-conjugation linker and their benzotriazole analogue. While the incorporation of the Qx enhances the interaction between the donor and acceptor

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• acrylates, under milder conditions [37][38][39]. Grimaldi et al. [40] achieved NMP of styrene and n-butyl acrylate using SG1-type nitroxide radical (N-tert-butyl-N-(1-diethylphosphono-2,2-dimethylpropyl)nitroxide). Compared with TEMPO, SG1 was considered that it initiated the truly “living”/controlled

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• started exploring the substrate scope around the gem-difluoroalkene handle. As shown in Figure 2, electron-donating groups in the para-position, for instance, methyl (3a), tert-butyl (3b), and methoxy (3c) were tolerated affording the products in 40–70% yields. Also electron-withdrawing groups, such as

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• . Importantly, the protocol was found to be similarly applicable with enoates 8b (Table 3, entry 6) and 8c (entry 7) having tert-butyl and benzyl ester groups, which, as the methyl ester unit, are typical in the context of amino acid synthesis. ZnBu2 was also amenable to 1,4-addition (Table 3, entry 8), but not

•  5). Product (RS)-14b (85:15 dr), i.e., a mixture of two enantiomerically pure diastereomers, was obtained from (RS)-tert-butylsulfinamide upon allylation with tert-butyl α-(bromomethyl)acrylate followed by 1,4-addition with Et2Zn. It was then converted into the known β2-amino acid 17 by TFA-promoted

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• 1H-tetrazole to produce the trialkyl phosphite 8.3 that was oxidized with tert-butyl hydroperoxide to produce phosphate 8.4. Then, β-elimination of the cyanoethyl protecting group produced PAF with a global yield of 70%. The limit of this method arises from the instability of the precursor 8.1 for

• polyunsaturated analogues, the reaction started with the metalation of tert-butyl methyl ether according to the conditions reported by Corey and Eckrich [140], followed by the nucleophilic addition on unsaturated or polyunsaturated aldehyde to produce, as an example, 31.5. Then, the alkylation of the secondary

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• benzothiazole, in which benzothiazole compounds have higher reactivity and regioselectivity than thiazole. In 2014, Lei et al. successfully realized the copper-catalyzed oxidative alkenylation of simple ethers to construct allyl ethers in the presence of di-tert-butyl peroxide and KI (Scheme 10) [60]. The

• in combination with di-tert-butyl peroxide (DTBP) as an oxidant enables the CDC of the C(sp3)–H bond in the α-position to oxygen of various ethers with the active methylene C(sp3)–H bond in 1,3-diketones (Scheme 17) [78]. This method can generate various functionalized molecules and is expected to

• 2010, Schnürch et al. utilized Fe(NO3)3 as the catalyst and TBHP (tert-butyl hydroperoxide) as the oxidant to realize the CDC of C(sp3)–H/C(sp2)–H bonds under solvent-free conditions (Scheme 21) [82]. However, the desired coupling products were obtained in low to moderate yields. The C–H oxidative