Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• styrenes (Scheme 14). Their preliminary investigation provided both C2 and C3-olefinated products, with the C2-selective product 69 as the major product (Scheme 14a). With the optimized conditions of Pd(OAc)2 (10 mol %), AgOAc (3 equiv), PivOH (2.5 equiv) in DMF, the method showed wide substrate scope and

• groups used Pd(OAc)2 as catalyst with 1,10-phenanthroline as ligand. The group of Yu used aryl halides 137 as coupling partner, whereas the group of Tan utilized aryl tosylates 142 as coupling partner (Scheme 26). The Yu group also applied the developed protocol for the synthesis of the drug molecule

Honeycomb reactor: a promising device for streamlining aerobic oxidation under continuous-flow conditions

• Masahiro Hosoya,
• Yusuke Saito and
• Yousuke Horiuchi

Beilstein J. Org. Chem. 2023, 19, 752–763, doi:10.3762/bjoc.19.55

• high potential for further optimization. Aerobic oxidation using transition metals instead of TEMPO was also investigated. Pd(OAc)2 (Table 1, entry 6) [42] and Cu(OAc)2 (Table 1, entry 7) [43], and Ni(OH)2 (Table 1, entry 8) [44] left the starting material 1a. Pd(OAc)2 led to moderate conversion, but

• Pd(OAc)2 did not dissolve in toluene even with pyridine. As a substitute for TEMPO, 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) was tried (Table 1, entries 9 and 10) [45]. Although the reactivity was improved compared with the TEMPO catalytic system in Table 1, entries 3–5, the DDQ catalytic system

Naphthalimide-phenothiazine dyads: effect of conformational flexibility and matching of the energy of the charge-transfer state and the localized triplet excited state on the thermally activated delayed fluorescence

• Kaiyue Ye,
• Liyuan Cao,
• Davita M. E. van Raamsdonk,
• Zhijia Wang,
• Jianzhang Zhao,
• Daniel Escudero and
• Denis Jacquemin

Beilstein J. Org. Chem. 2022, 18, 1435–1453, doi:10.3762/bjoc.18.149

• (468.0 mg, 1.209 mmol), phenothiazine (289.0 mg, 1.452 mmol), Pd(OAc)2 (49.2 mg, 0.219 mmol) and sodium tert-butoxide (760.0 mg, 7.908 mmol) were dissolved in dry toluene (22 mL). Then tri-tert-butylphosphine tetrafluoroborate (66.4 mg, 0.229 mmol) was added. The mixture was refluxed and stirred for 8 h

• , 20.81, 10.66; HRMS–MALDI (m/z): [M + H]+ calcd for C32H30N2O3S, 522.1977; found, 523.2050. Synthesis of NI-PTZ2 Compound NI-PTZ2 was synthesized in a manner similar to [21]. Under N2 atmosphere, compound 1 (190.0 mg, 0.409 mmol), phenothiazine (294.5 mg, 1.478 mmol), Pd(OAc)2 (36 mg, 0.160 mmol), and

• a manner similar to [21]. Under N2 atmosphere, compound 2 (51 mg, 0.110 mmol), phenothiazine (26.3 mg, 0.132 mmol), Pd(OAc)2 (4.5 mg, 0.020 mmol), and sodium tert-butoxide (69.1 mg, 0.720 mmol) were dissolved in dry toluene (3 mL). Then, tri-tert-butylphosphine tetrafluoroborate (6.1 mg, 0.021 mmol

Palladium-catalyzed solid-state borylation of aryl halides using mechanochemistry

• Koji Kubota,
• Emiru Baba,
• Tamae Seo,
• Tatsuo Ishiyama and
• Hajime Ito

Beilstein J. Org. Chem. 2022, 18, 855–862, doi:10.3762/bjoc.18.86

• Discussion Initially, we conducted an optimization study on the mechanochemical cross-coupling between 2-bromo-6-methoxynaphthalene (1a, 0.3 mmol) and bis(pinacolato)diboron (2, 1.2 equiv) in the presence of Pd(OAc)2 (2 mol %), KOAc (3.0 equiv), and H2O (60 μL) as a liquid additive [43][44][45] (Table 1

• mixture of 1 (0.30 mmol), 2 (0.36 mmol), KOAc (0.9 mmol), Pd(OAc)2 (0.006 mmol), t-Bu3·HBF4 (0.009 mmol), and H2O (60 μL) was milled in a 1.5 mL stainless-steel jar at 30 Hz using one stainless-steel ball that was 5 mm in diameter. The isolated yields are shown. The NMR yields are shown in parentheses

• . Substrate scope of liquid aryl bromides. Reaction conditions: a mixture of 1 (0.30 mmol), 2 (0.36 mmol), KOAc (0.9 mmol), Pd(OAc)2 (0.006 mmol), t-Bu3·HBF4 (0.009 mmol), and H2O (60 μL) was milled in a 1.5 mL stainless-steel jar at 30 Hz using one stainless-steel ball that was 5 mm in diameter. The isolated

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• protocol for the ortho-halogenation of acetanilide with NXS (X = Cl, Br, I) using Pd(OAc)2 as precatalyst in the presence of p-toluenesulfonic acid (TsOH) as an additive under solvent-free conditions [49]. Recently, Mal and Bera reported the utilization of NXS (X = Br, Cl) as bifunctional reagents for the

• azobenzene with NXS and Pd(OAc)2 as precatalyst in the presence of TsOH and MeCN as solid and liquid additives, respectively, led to the ortho-halogenated products relative to the azo group of the azobenzenes. In situ Raman monitoring of these reactions confirmed that the most favorable reaction pathway is

• electron-accepting substituents at the para position relative to the azo group: 4-chloroazobenzene (L6), 4-bromoazobenzene (L7), and 4-iodoazobenzene (L8) (Scheme 2 and Table 2). The synthetic protocols included milling the mixture of Ln/NXS/TsOH 1:1.2:0.5 equiv, 5 mol % Pd(OAc)2 precatalyst, and 15 µL

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• indole derivative 31 in 82% yield (Scheme 11) [22]. Being a kinetically very active catalyst, Rh2(OAc)4 favored the formation of the five-membered ring. On the other hand, employment of Pd(OAc)2-catalysis switched the regioselectivity of this C–H insertion reaction. More specifically, under Pd(OAc)2

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

• contrast, only very few reports deal with the oxidative cyclization of nitrogen-containing biaryl intermediates. Ravi Kumar and Satyanarayana mentioned two successful control reactions using 2-phenylbenzylamine and 2-iminomethylbiphenyl with 5 mol % Pd(OAc)2 and 2 equivalents Ag2O in acetic acid at 140 °C

• aldehyde (33%) being generated (Table 2, entry 11). Similar results were obtained when adding iodine to promote benzylic oxidation [56] (Table 2, entry 12). Finally, Pd(OAc)2 was added in hopes of improving the mediation of C–C bond formation [38] (Table 2, entry 13). Interestingly, here the yield of

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• product 3aa was preferentially formed (2aa/3aa, 29:71, Table 1, entry 6). Although other catalysts, such as Pd(acac)2, Pd(dba)2, and Pd(OAc)2(PPh3)2 showed good selectivity to inversion product 3aa, the products were formed in low yields (Table 1, entries 7–9). Further screening of the solvent and the

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

• found with Pd(OAc)2/bpy as the catalyst, N-methylacetamide as the solvent, and a temperature of 80 °C. Variously substituted indoles as well as esters of 118 (R = aryl, alkyl, vinyl) were generally well tolerated, but oxa- (X = O) and azo- (X = NR) cyclobutanes met with limited success. Alternative

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• sterically hindered 1-(2-bromophenyl)-1,2,3-triazole derivatives 130. The target compounds, triazolo[1,5-a]indolones 131, were then obtained from 130 in high yield using catalytic amounts of Pd(OAc)2 and PCy3, carbon monoxide, and potassium carbonate and with heating in toluene at 120 °C. The structure of

• ) tetrafluoroborate (138) in the presence of HBF4 and NaNO2 at 0 °C. Next, the nanoparticles were obtained from the reduction of Pd(OAc)2 and Cu(OAc)2 employing NaBH4 in the presence of diazonium salt [63]. A possible mechanism for the synthesis of polycyclic triazoles 142 was proposed by Sekar et al. as well [63

• functionalized tricyclic triazoles 152–154. It was proved that o‐azidophenols 148 react well with alkynes 149 using CuI in DMF at 120 °C and then, the resulting intermediates react with isocyanides using Pd(OAc)2 and an O2 atmosphere at 120 °C to produce the desired products (Scheme 42). o‐Azidophenols 148 were

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• Minnaard group reported a protocol for the addition of boronic acids to enones [37]. At first, they tested the combination of Pd(OAc)2 with triflic acid (TfOH) to obtain a Pd(II) complex with a weakly coordinating anion that is necessary for a fast Pd–C bond cleavage and thus avoiding the undesired β

• underwent addition of phenylboronic acid (Scheme 4). The complex L2/Pd(OAc)2 was used to obtain the product with excellent enantioselectivity (95% ee) but only poor yield (12%) (Scheme 4) [38]. A catalytic system based on L2/Pd(OAc)2 was recently used by Khatua et al. for the synthesis of ar-macrocarpenes

• the reaction (Scheme 6) [40]. A different approach using microwave irradiation was explored by the group of Toma et al. [41]. After an initial tuning of the reaction conditions of a catalytic system based on Pd(OAc)2/2,2’-bipy several optically pure phosphoramidite and diphosphine ligands in

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• then examined the conditions reported by Orito and co-workers [30]. Gratifyingly, the treatment of 22c with Pd(OAc)2, Cu(OAc)2, and K2CO3 afforded the cyclized product 23 in 34% yield. The focus subsequently shifted to the total synthesis of trigonoine B (1) (Scheme 5). The key starting material, 2

• -iodo-5-methoxyaniline (24), was synthesized according to the procedure previously reported by Wetzel and co-workers [31]. The Suzuki–Miyaura coupling of 2-iodoaniline derivative 24 and pyrrole-3-boronic acid pinacol ester 13 was carried out in the presence of Pd(OAc)2 and SPhos, followed by the

• and desilylation, the electrocyclization of 29a proceeded smoothly to afford the desired 4-aminopyrroloquinoline 30a in 68% yield. Subsequently, the cycloamination of 30a in the presence of Pd(OAc)2, Cu(OAc)2, and K2CO3 gave tetrahydroquinoline 31 in 25% yield. However, although attempts were made to

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• . Previously, we have observed that the coupling system involving Xantphos/Pd(OAc)2 (used in the ratio of 15 mol %/15 mol % or 30 mol %/30 mol %) and t-BuOK or DIPEA in 1,4-dioxane as the solvent was effective for the C–N or C–S bond formation [30][31][35]. Unfortunately, it turned out, that the application of

• Xantphos/Pd(OAc)2/t-BuOK and our standard procedure [30][35], in which the amine is added after the lactam 3a, for the initial experiments ended with failure. In most cases, regardless of the used catalytic system (Pd source: Pd(OAc)2, Pd2(dba)3, ligand: DPEPhos, DavePhos, BINAP), solvent (1,4-dioxane

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• , K2CO3, DMF/acetone 1:2, 80 °C, 43 h (98%). Final steps in the synthesis of biaryl 1. Conditions: h) Pd(OAc)2, SPhos, Cs2CO3, dioxane/H2O 7:1, 70 °C, 18 h, (R = TBS: 98%, containing non-separable impurities; R = Bn: 89%) ; i) R = Bn: Pd/C (10%), H2, THF, 8 bar, 24 h, 40 °C (88%). NMR data of natural and

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• ), DIPEA, DMF, 60 °C, 16 h, 44–71% 32a–h); d) TFA, rt, 30 min. for Boc protected amines (32b,c); e) Pd(OAc)2, TES, DCM/MeOH, rt, 16 h for Cbz protected amines. Selected results from conditions’ screening for pyridin-2-(1H)-one formation (7). Validation of library conditions.a Selected results from

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• common organic solvents, they first tried the esterification reaction with soluble monoiodosumanene 79 using Pd(OAc)2 under CO atmosphere and obtained the desired sumanene methyl ester in very low yield. Surprisingly, when they used hexabromosumanene 94 under similar reaction conditions, no product

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• Scheme 10. Very recently, the groups of Nimura and Arisawa reported the synthesis of a phenyl C-glucoside derivative of spliceostatin beginning from ᴅ-glucal (Scheme 12) [35]. A Heck coupling of the tris(trimethylsilyl) ether of 74 with phenylboronic acid in the presence of Pd(OAc)2 and benzoquinone (BQ

Synergy between supported ionic liquid-like phases and immobilized palladium N-heterocyclic carbene–phosphine complexes for the Negishi reaction under flow conditions

• Edgar Peris,
• Raúl Porcar,
• María Macia,
• Jesús Alcázar,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2020, 16, 1924–1935, doi:10.3762/bjoc.16.159

• corresponding Pd–NHC complexes 4a and 4b (Scheme 1) were obtained by treatment of the supported imidazolium species with Pd(OAc)2 in the presence of a base. The amount of immobilized NHC ligand was determined by elemental analysis, while the palladium loaded on the polymer was determined by ICP analyses (see

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• photocatalyst Ru(bpy)3Cl2·6H2O and Pd(OAc)2 promoted the formation of the coupling products in high yields when the reaction was irradiated with visible light. This new procedure exhibited a good functional group tolerance and turned out to be compatible with a wide range of DGs, including amides, pyrazoles

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• Pd(OAc)2 (5 mol %), was involved in the design of an efficient annulation between benzamides and in situ-generated arynes. The process occurred under oxygen saturated atmosphere at room temperature, likewise offering a straightforward access to the phenanthridone backbone [93]. Conclusion

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• the two mechanisms of Pd-catalysed C–H activation reaction considered in this study. Comparison of the published experimental results with the computational predictions for the Pd(OAc)2-catalysed reactions.a Predicting C–H activation bond for heteroaromatic compounds.a A comparison of the published

• experimental results with the computational predictions for the Pd(OAc)2-catalysed reactions.a A mechanism threshold tested based on the literature examples.a Supporting Information Supporting Information File 96: Comutational details, comparison of data, mechanistic threshold, Cartesian coordinates and

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• . Since the known procedures for the syntheses of oxazoles are rather harsh and usually involve higher temperature [Pd(OAc)2, toluene, AcOH, 100 °C, 24 h [41] and/or the presence of Lewis acids (FeCl3, ACN (24 h, 80 °C) or 1,2-DCE (2 h, 80 °C), DCM (24 h, 45 °C) [40]], we envisioned that the present

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• using 10 mol % of Pd(OAc)2 or 10 mol % of PdCl2 with 20 mol % of PPh3 as a ligand and 2 equiv of K2CO3 in MeCN at 80 °C for 10 h without additive to give 6-exo-cyclized product 9a in 32% and 18% yields, respectively (Table 1, entries 1 and 2). Addition of NaOAc increased the yield of 9a to 71% (Table 1

• the amount of Pd(OAc)2 to 5 mol % or the reaction temperature to 40 °C gave lower product yields (Table 1, entries 8 and 10). Double the amount of Pd(OAc)2 to 20 mol% gave 9a in 79% yield, just 1% increase than that of using 10 mol % of catalyst (Table 1, entry 9). Besides K2CO3, other bases including

• Na2CO3, Cs2CO3 and Et3N were also used for the Heck reaction, but none of them improved the product yield (Table 1, entries 12–14). A base-free control reaction gave 9a in 10% yield (Table 1, entry 15). Thus, the optimized conditions for the Heck reaction was to use 10 mol % of Pd(OAc)2, 20 mol % of PPh3

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• reaction of 4-((Z)-arylidene)-2-(E)-styryl-5(4H)-oxazolones 2 with Pd(OAc)2 resulted in ortho-palladation and the formation of a dinuclear open-book complexes 3 with carboxylate bridges, where the Pd atom is C^N bonded to the oxazolone. In 3 the two exocyclic C=C bonds of the oxazolone are in a face-to

• oxazolones 2 promoted by Pd(OAc)2, which shows multiple possibilities (Figure 2b). Treatment of the oxazolones 2a–j with Pd(OAc)2 (1:1 molar ratio) in CF3CO2H as solvent under reflux for 2 h resulted in the formation of the dinuclear complexes 3a–f and 3h–j, as shown in Scheme 1. In the case of oxazolone 2g

• . The new (Z)-4-arylidene-2-(E)-styryl-5(4H)-oxazolones 2 react with Pd(OAc)2 through a C–H bond activation reaction to give the dinuclear ‘open-book’ ortho-palladated complexes [Pd2(μ-O2CCF3)2(C^N-oxa))2] 3 with bridging carboxylate ligands. Despite the presence in 2 of different functional groups and

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• catalytic system showed that the ligand-free PdCl2 was the most effective catalyst (Table 1, entry 14). Other catalysts such as Pd(PPh3)4, Pd/C or Pd(OAc)2 provided inferior results (Table 1, entries 11–13). We then examined the reaction of 2a with 1.5 equiv of a variety of arylboronic acids. Using the