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

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• selectivity, which is observed at the more electron-rich and the less sterically hindered position. Manganese-catalyzed late-stage C–H alkynylation Alkynes are invaluable intermediates in organic synthesis and are conventionally prepared via palladium-catalyzed cross-coupling reactions [62]. Moreover, they

2,4-Bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines: synthesis and photophysical properties

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli,
• Noureddine Chaaben,
• Kamel Alimi,
• Stefan Jopp and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 1629–1640, doi:10.3762/bjoc.17.115

• molecules have been examined. Additionally, theoretical studies based on density functional theory (DFT/B3LYP/6-31G(d)) were carried out. Keywords: alkynes; catalysis; cross-coupling; heterocycles; palladium; Introduction The development and design of small π-conjugated molecules have attracted increasing

• using 0.6 mol % of tetrakis(triphenylphosphine)palladium(0) and 1.2 mol % of copper iodide (Scheme 2, Table 1). The reaction proceeded chemoselectively at the two carbon–bromine bonds giving 2,4-bis(phenylethynyl)-9-chloro-5,6,7,8-tetrahydroacridine (4a). This result was not entirely predictable, as the

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

• [58]. Postfunctionalization by Pd- or Pd/Cu-catalyzed synthesis of fully decorated triazoles A palladium-catalyzed aminocarbonylation reaction of 5-iodo-1,2,3-triazoles to give 1,4,5-trisubstituted 1,2,3-triazole-5-carboxamides 119 was introduced by Schwab et al. in 2019. The 5-iodo-1,2,3-triazole 117

• -triazole-based phenol or alcohol coordinates to the Pd center to form complex 158. Then, the electrophilic palladation of the 1,2,3-triazole ring occurs to achieve Pd(II) intermediate 159. Isocyanide migrates to 159 to obtain the seven‐ or eight‐membered palladium cycle 160. The reductive elimination of

• '. The isocyanide is inserted into intermediate 158' to achieve intermediate 159'. A 1,2,3-triazole C–H bond activation occurs using palladium, which subsequently undergoes a reductive elimination process to afford final product 154. Likewise, the Pd(0) species is reformed for the next cycle [64]. The

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

• -substituted β-diketones 2a and 2b (61 and 70% yield, respectively). Notably, the unsaturated carbocycles expected from palladium β-hydride elimination were not observed, indicating that an oxidant was not required in the reaction medium to regenerate the Pd(II) species. Later, deuterium-labeling experiments

One-step synthesis of imidazoles from Asmic (anisylsulfanylmethyl isocyanide)

• Louis G. Mueller,
• Allen Chao,
• Embarek AlWedi and
• Fraser F. Fleming

Beilstein J. Org. Chem. 2021, 17, 1499–1502, doi:10.3762/bjoc.17.106

• to substituted imidazoles. Raney nickel hydrogenolysis was effective in interchanging the C4 anisylsulfanyl group for hydrogen (Scheme 3); attempted lithium–anisylsulfanyl exchange [19] or palladium- [22] or nickel- [23] anisylsulfanyl cross coupling was not successful. Raney nickel reduction of 7f

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• . Global deprotection of 32 using palladium-catalyzed hydrogenation conditions resulted in the formation of the targeted double-headed nucleoside 33 (Scheme 8) [33]. The double-headed nucleoside 33 was dimethoxytritylated, phosphitylated, and incorporated into duplex and its ability to recognize

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

• of 1,2-aminoalcohol 110 (90% yield, anti/syn 7:3, 78% ee). At the end of the Henry reaction an in-line plug of silica gel removes the catalyst before the second reduction step to prevent issues of chelation and palladium deactivation. Knoevenagel condensations are also of considerable interest to the

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• contribution for the palladium derivative 17. In the IP this is further demonstrated with a significant decrease in the A1g contribution of 17 giving the palladium derivative the lowest overall DIP contribution. This indicates that while there are minor differences within conformation of these porphyrins

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• proceeded with high levels of diastereocontrol. The resulting sulfonamide derivatives 95 were transformed into the target spiro compound 97 by performing successive desulfinylation and intramolecular palladium-catalyzed N-arylation. To rationalize the stereochemical course of the addition, DFT calculations

• the Re face of the imine with S configuration at the sulfur atom, through a chelated transition state. The reaction of chiral aldimine (SS)-104b with pentylmagnesium bromide gave compound 106 in 75% yield. Further successive N-desulfinylation, intramolecular palladium-catalyzed N-arylation, and final

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• configuration. Thioglycosides 22–31, 34 and 36 were then hydrolyzed into the corresponding hemiacetals 37–48 using treatment with NBS in acetone/water (Scheme 4). To obtain the target fluoro analogs, the hemiacetals 37–48 were debenzylated and their azide group converted to an acetamide. Although palladium

• degree upon reaction with AcSH in pyridine and traces of O1 acetates were removed by chromatography or recrystallization. Palladium-catalyzed hydrogenolytic debenzylation of 49–58 then yielded the target fluoro analogs 61–70. To complete the series of fluorinated analogs for the purpose of comparing

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

• Sciences, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic 10.3762/bjoc.17.84 Abstract The transition metal (palladium)-catalysed asymmetric 1,4-addition of arylboronic acids to conjugated enones belong to the most important and emerging strategies

• reaction, however, palladium holds a special place in this area. There are several review articles partially covering this topic [25][26][27][28][29][30][31]. However, a comprehensive review is missing. In the following sections, we attempt to fill this gap. As a sorting criterion, the type of ligand

• with excellent yields and enantioselectivities (89–92%; 91–99% ee; Scheme 5) [8]. In 2007, the group of Ito described the application of ferrocenylphosphines for the palladium-catalysed addition of arylboronic acids to 2-cyclohexenone at various temperatures giving the products with high conversions

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• -position of an oxazoline or amide is selectively activated using a copper or palladium catalyst. Manganese is one of the most abundant and nontoxic transition metals found in the earth’s crust and its corresponding complexes and salts are useful in synthetic organic reactions [29][30][31][32][33][34][35

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• -dimethylaminopyridine (DMAP) as the base. Then, the palladium-catalyzed hydrogenation of compounds B1–21 in THF or EtOAc led to the hydroxy derivatives C1–21. It has been observed that a catalytic amount of triethylamine (TEA) in EtOAc enhances the rate of the hydrogenolysis of benzyl ethers. Compounds C1–21 were then

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• illustrated in Scheme 20 [105]. A methanofullerene variety 69 with a pincer ligand containing a disulfidoaryl moiety was synthesized from 3,5-bis(phenylsulfidomethyl)benzaldehyde hydrazone. In the presence of [Pd(CH3CN)4](BF4)2, the latter gives the corresponding palladium complex 70 (Scheme 21) [106]. A

• nitrophenylfullerenes 48 and 50. Synthesis of conjugate 52 of C60 with ethyl diazo(4-nitrophenyl)acetate. Synthesis of fluoride-containing phenylmethanofullerenes 53–56. Synthesis of “bucky ligands” 57–60. The synthetic route to methanofullerene-based palladium–bisaminoaryl complex 62. Synthesis of N-containing

• fullerene ligands 66–68. Synthesis of C60-attached SCS pincer–palladium(II) complex 70. Synthesis of spiro-linked C-glycosides of fullerenes 71 and 72. Synthesis of quinone-substituted methanofullerene derivatives 76–78. Synthesis of spiroannelated methanofullerenes 79–81. The synthetic route for

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

• Group, Faculty of Chemistry, University of Lodz, Pomorska 163/165, 90-236 Łódź, Poland 10.3762/bjoc.17.50 Abstract Amino- and polyaminophthalazinones were synthesized by the palladium‐catalyzed amination (alkyl- and arylamines, polyamines) of 4-bromophthalazinones in good yields. The coordinating

• quinazolinones [30][31] and taking into consideration the biological importance of aminophthalazine derivatives, we decided to apply the methodology based on the palladium-catalyzed C–N-bond formation (Buchwald–Hartwig-type reaction) as a convenient and effective approach for the synthesis of the new

• -bromobenzoate via palladium-catalyzed isocyanide insertion [32][33] (a method that is limited to tertiary-substituted isocyanides) or 2) the palladium or copper-catalyzed coupling of bromolactams with amines (a method that requires the usually lengthy synthesis of the bromoprecursors) [19][34]. Therefore, the

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• -catalyzed cycloaromatization (Scheme 3, route a and Scheme 4a). Treatment of 1,2-dibromobenzene (2a) with 3 in the presence of a palladium catalyst with SPhos afforded o-terphenyl derivative 4a bearing two acetal groups in 96% yield (Scheme 4a). The obtained bisacetal 4a successfully underwent

• subsequent cycloaromatization (Scheme 6a). Again, phenylboronic acid ester 3, used above in the synthesis of [5]- and [6]helicenes, was adopted as the coupling partner for 10. In the presence of a palladium catalyst, treatment of 3-bromobenzofuran (10a), 3-bromobenzothiophene (10b), and 3-bromo(N-tosyl

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• cleavage by the use of either palladium(II) oxide or Raney nickel as the catalyst (Scheme 66) [116]. Butylbenzene (152) and 2-fluoro-1-phenylbutane (153) were the main products, although the unsaturated intermediates 154 and 155 were also detected. The contribution of the fluorine substituents to the

• good yields and with high (Z)-selectivity. The proposed mechanism involved the oxidative addition of the distal C–C bond to palladium, followed by a nucleophilic attack at the less hindered carbon atom of a 2-fluorinated palladium–π-allyl complex. Other examples of Pd-catalyzed ring-oрening reactions

• reaction of 2-(2,2-difluorocyclopropyl)naphthalene (167) with sodium arylsulfinates 168 under palladium catalysis afforded the 2-fluoroallylic sulfones 166 in moderate to good yields with (Z)-selectivity. This method showed a good compatibility with a broad range of substrates and substituents. As

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• , and related compounds. Some of them are catalyzed by expensive transition metals, such as gold, iridium, palladium, and titanium. More recently, the selective formation of C–S bonds using 1,3-dicarbonyl compounds, followed by a C–C bond cleavage has emerged as a versatile and less expensive protocol

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

• -3,5-dimethoxybenzene, where the longest linear sequence consists of five steps. The key reaction was a palladium-catalyzed Suzuki coupling of an aromatic boronate with a brominated resorcin derivative. Keywords: biaryls; boronates; mycotoxins; polyketides; Suzuki coupling; Introduction 5’-Methoxy-6

• a 73% yield. The Suzuki coupling of boronate 6a and aryl bromide 9a using palladium acetate and cesium carbonate in the presence of the ligand SPhos [25] yielded biaryl 10a with virtually quantitative yield (98%, Scheme 4). Unfortunately, the removal of non-identified byproducts and of 9a (which had

• protection to the bis(benzyl ether) 5b using standard conditions (Scheme 2) [27]. The preparation of boronate 6b applying the conditions used for the silylated substrate 6a (vide supra) led to a mediocre 44% yield, but the utilization of a palladium-catalyzed borylation with bis(pinacolato)diboron afforded

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

• goal of creating a rapid, 3-step route requiring a single preparative LC–MS purification at the end of the sequence (Figure 1). Results and Discussion Exploration of the C-3 amide vector: formation of the pyridine-2-(1H)-one motif by palladium catalysis We decided to validate the route by preparing

• . Finally, we turned out attention to transition metal-catalyzed formation of phenols from aryl halides [5]. After another round of screening, we successfully applied palladium-catalyzed conditions discovered by the Buchwald group [6], using KOH as the nucleophile and X-Phos as the ligand, to afford 7 in 83

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• mixture of (Z,E)/(E,E)-36a, respectively). Aldehyde 35 was then converted into dibromide 37 using PPh3/CBr4 followed by stereoselective palladium-catalyzed monoreduction according to the literature available protocol [41] to give vinyl bromide 38 in 76% yield (Z/E as 99:1 mixture). Iodide 15a [42] was

•  19). For the synthesis of inthomycin B ((+)-2), a Suzuki coupling reaction between (E,E)-128 and (Z)-(+)-130a was performed in the presence of palladium(II) acetate, triphenylphosphine, and aqueous sodium carbonate to give (E,E,Z)-triene (+)-131 selectively in 64% yield. Treatment of triene (+)-131

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• diastereoisomeric mixture, converted to ketone (±)-37 via methylene derivative (±)-36, in 63% over two steps (Scheme 5). Ketone (±)-37 was converted to alkenyl triflate (±)-38 after treatment with LDA at −78 °C, followed by the Comins reagent [47]. (±)-38 was subjected to palladium-catalyzed hydrogenation

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• was prepared via the palladium-catalyzed reduction of the corresponding phosphate 17 [54]. Iodination and Sonogashira coupling, followed by acetylation led to the formation of the desired enynyl acetate 20. This compound was treated with 5 mol % Ph3PAuCl/AgSbF6 in DCM, and after 6 h, this afforded the

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• ] cycloaddition through diyl trapping with an olefin [14][15] and Trost’s palladium-catalyzed trimethylenemethane cycloaddition [16], which allows the preparation of five-membered carbocycles, have been emerged since the 1970s. Thereafter, many novel and important all-carbon [3 + 2] cycloaddition reactions, such

• ] cycloaddition to give fused tricycle 25 in 85% yield. The synthesis of the hydroxykempenone 3β-hydroxykemp-7(8)-en-6-one (7) features Trost’s palladium-catalyzed trimethylenemethane [3 + 2] cycloaddition [27] and was reported by Paquette and co-workers in 1992 [23] (Scheme 1B). Catalytic TMM [3 + 2

• -mediated conjugated addition of methyllithium to enone 59 in the presence of boron trifluoride ether [34][35] produced desired ketone 60 in 75% yield. The resultant ketone 60 was converted to waihoensene (16) in two steps. Palladium-catalyzed carboxylative trimethylenemethane cycloaddition In 1986, Trost