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

• 184. Subsequently, oxidative coupling of the azide with the β-carbon atom of the 1-alkyltriazene gives the Ir–carbene intermediate 185. In continuation, intermediate 185 can be transferred to intermediate 186, leading to the triazole ligand being coordinated to the Ir center in 187. Finally, the

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• –Wadsworth–Emmons (HWE) reaction of carbonyl compounds with organophosphorus reagents containing carbene sources and the 1,2-rearrangement of alkylidene carbenes and related species, referred to as Fritsch–Buttenberg–Wiechell (FBW) rearrangement [8][9]. While alkynes are synthesized from carbonyl compounds

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

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• (by direct attack of a aryl oxide nucleophile or deprotonation and loss of chloride in a second carbene generation followed by a second phenoxide attack) would be substantially greater than an aryloxydifluoromethane such as 5, with milder conditions allowing us to avoid the undesired isomer 7

[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

• thermal addition of diazo compounds (the well-known carbene precursors), followed by N2 elimination. However, it occurs much more difficultly for diazo compounds than with singlet carbenes. This is due to the formation of a mixture of [5,6]-closed and [6,6]-open isomeric cyclic adducts. This phenomenon

• can be due to a number of reasons. First, two cyclopropanation mechanisms are equally likely in the thermal reaction of diazo compounds with C60 fullerene: a) preliminary carbene formation due to the thermal decomposition of diazo compounds, followed by synchronous addition to the double [6,6]-bond in

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• temperature (35 °C) but toxic CH2Cl2 solvent (Scheme 1). The reaction using second-generation N-heterocyclic carbene ligands was faster and preferably yielded cyclododecatriene. Larger cyclic butadienes may be used in the production of flame retardants, lubricants and specialty polymers [149][150]. 3.1.3

• electronic effect of the ligand [267]. A reaction mechanism for PLA depolymerisation was proposed, consisting of two consecutive first-order steps, in which Me-La production follows the formation of chain-end groups intermediates [265]. A zinc–N-heterocyclic carbene complex was used as catalysts for the

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• challenging [15][16], and this was also the case for (rac)-13, since we first obtained the incomplete triene intermediate (rac)-15 as a result of only ring-opening metathesis (ROM) mediated by the Fischer carbene complex [Ru]=CH–OAc [6], generated by the reaction of Zhan catalyst-1B (14) with vinyl acetate

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• -disubstituted pyrroles (minor products). The observed selectivities in the case of the reactions with aliphatic alkynes were high. Keywords: pyrrole; transannulation; rhodium carbene; triazole; Introduction Pyrroles are known to be important structural moieties appearing in natural products, synthetic drugs

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• dichlorophosphites followed by alcoholysis with hydroxy esters, the phosphinylation of hydroxy esters with phosphonochloridites followed by oxidation, and the carbene insertion of N-protected amino acids with 1-diazoalkylphosphonates. This review includes the synthesis of α-, β-, and γ-phosphonodepsipeptides and

• amino acids 206 to give the corresponding protected phosphonopeptides 207. After deprotection by hydrogenolysis and treatment with CF3CO2H, the phosphonodepsipeptides 208 were obtained (Scheme 38) [59]. Phosphonodepsipeptides with C-1-hydroxyalkylphosphonic acids are also accessible through carbene

• tetraacetate (Scheme 39) [60][61]. To develop novel bone-targeting prodrugs, a copper-catalyzed carbene insertion of tetraethyl diazomethyldiphosphonate (216) with N-Boc-protected amino acids 214 and 215 provided a simple method to synthesize phosphonodepsipeptides 217 and 218 containing a C-1

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

• difluorocyclopropane and its derivatives can be distinguished: carbene and non-carbene methods of cyclopropanation along with functional group transformations of existing cyclopropanes. The most popular route to prepare fluorocyclopropanes is to generate fluorine-containing carbenes (or carbenoids), which then react

• . The carbene-based methods typically give the highest yields when alkenes with electron-donating substituents are used. There are few examples in which the cyclopropanation by carbene methods of electron-deficient alkenes containing substituents with a large −M effect (for example, CO2R, COR, CN, SO2R

• Difluorocarbene methods with non-metal sources Difluorocarbene chemistry was first reported by Doering in 1954 [12]. The lone electron pairs on the fluorine substituents interact with the carbene center, making the structure stabilized [13]. Difluorocyclopropanes 4 were synthesized from the reaction of

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

• synthesis of (±)-hirsutene (14) used an alkylidene carbene as source of TMM diyl in the intramolecular [3 + 2] cycloaddition [24] (Scheme 1D). Heating of epoxyaziridinyl imine 32 produced tricyclic compound 36 in 57% yield as a single product. The authors proposed that heating of epoxyaziridinyl imine 32

• generates alkylidene carbene 33. Transformation of 33 to TMM diyl 35 enables an intramolecular [3 + 2] cycloaddition to give the desired tricyclic product 36. Trimethylenemethane (TMM) cycloaddition An intramolecular trimethylenemethane diyl [3 + 2] cycloaddition was reported by Berson [28] and Little [14

• ] independently in the late 1970s, which was used to prepare (±)-hirsutene (14) in 1981 [22] (Scheme 1A). In 2003, Lee and co-workers disclosed an intramolecular trimethylenemethane diyl [3 + 2] cycloaddition with a linear alkylidene carbene as diyl source and was applied in the synthesis of linearly fused

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• synthesis inhibitor (Figure 1) [10][11][12]. In addition, compounds with this structure were investigated as photoluminescent sensors [13] and have been employed to generate pincer and heterocyclic carbene ligands for transition metal catalysis [14][15]. A lot of efforts have been dedicated to the

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• 100 in good yields and enantioselectivities (21 examples for THCs, up to 98:2 er and 10 examples for THIQs, up to 98:2 er). N-Heterocyclic carbene catalysis N-Heterocyclic carbene (NHC) catalysis was first used in combination with photoredox catalysis by Rovis in 2012. They showed that iminium ions

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

• the chemistry of the sumanene and its congeners, quite recently the same group has also prepared sumanene-based carbene 60 starting from monosumanenone 38 by reacting it with hydrazine hydrate to provide the corresponding hydrazone 58 which on further oxidation with MnO2 followed by irradiation using

• an LED lamp at ca. 365 nm for 1 min in 2-methyltetrahydrofuran (mTHF) at 77 K gave 60 (Scheme 13) [45]. It was noticed from both experimental as well as theoretical studies that the ground state of the prepared carbene 60 is a triplet which was confirmed by ESR as well as density functional theory

• (DFT) calculations. As we are aware that if the carbene formed is a singlet then a C–H bond inserted product is predominating whereas if the dimer is the major product along with the minor C–H bond inserted product then the triplet carbene is generated. During their study, they obtained the C–H

Isolation and structure determination of a tetrameric sulfonyl dilithio methandiide in solution based on crystal structure analysis and ⁶Li/¹³C NMR spectroscopic data

• Jürgen Vollhardt,
• Hans Jörg Lindner and
• Hans-Joachim Gais

Beilstein J. Org. Chem. 2020, 16, 2057–2063, doi:10.3762/bjoc.16.172

• of 2 with carbon and metal-based electrophiles revealed a high synthetic potential, allowing, for example, the synthesis of carbo- and heterocycles [4][6], and transition-metal carbene complexes [1][2], carrying the synthetically versatile sulfonyl group [7][8]. Dilithio methandiides 2 are accessible

Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation–cyclization cascade mediated by K₂S₂O₈

• Qiang Liu,
• Weibang Lu,
• Guanqun Xie and
• Xiaoxia Wang

Beilstein J. Org. Chem. 2020, 16, 1974–1982, doi:10.3762/bjoc.16.164

• sciences over the last few years [1][4][5]. In general, chroman-4-one derivatives could be obtained via a polarity reversal strategy enabled by the N-heterocyclic carbene (NHC)-catalyzed intramolecular Stetter reaction [6][7][8]. Besides, chroman-4-one derivatives were also constructed via intramolecular

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

• , the dissociation of the M–NHC produces Pd intermediates from which metal clusters and MNPs can be readily formed while the carbene can react through C−NHC or H−NHC coupling. The presence of onium salts significantly contributes to the stabilization of both Pd clusters and PdNPs [40]. Thus, a

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• reaction of internal alkynes with a difluorodiazoethane reagent, offering efficient access to a broad range of enantioenriched difluoromethylated cyclopropenes with almost quantitative yields and up to 97% ee [82]. This asymmetric carbene transfer reaction was performed using chiral RhII complexes, more

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach

• Rhys A. Lippa,
• John A. Murphy and
• Tim N. Barrett

Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134

• the exact mechanism is not known, it may involve a reactive carbene intermediate formed by α-elimination of the phosphonate as described in previous reports [23]. Alternatively, a base-promoted autoxidation of phosphonate 7 in the presence of trace amounts of oxygen, followed by olefination may be

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• Alyn T. Davies Mark D. Greenhalgh Alexandra M. Z. Slawin Andrew D. Smith EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, United Kingdom 10.3762/bjoc.16.129 Abstract The N-heterocyclic carbene (NHC)-catalyzed formal [2 + 2] cycloaddition between α

• moderate to good yield as a single diastereoisomer. Keywords: enantioselective catalysis; formal [2 + 2] cycloaddition; N-heterocyclic carbene; ring opening; trifluoromethyl group; Introduction The trifluoromethyl unit holds a prominent and privileged position within organic chemistry [1][2][3][4][5][6

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• combined with a solution-phase reagent, including: (1) copper(I) oxide to produce N-heterocyclic carbene–Cu(I) complexes for use as catalysts [13]; (2) proline to perform proline-based catalytic reactions [14]; (3) zinc powder to produce organozinc halides in tandem with Negishi couplings [15]; (4) zinc

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• reminiscent of the entatic state model. The proposed mechanism (Scheme 12) involves the insertion of a nitrene or carbene group to the copper complex 22 to form intermediate 23. Subsequent alkene insertion yields species 25 and the group-transfer product (21a,h–j,n,o, 26a–g and 27a–o) is released upon ring

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• that enyne metatheses are atom economical processes driven by the enthalpic stability of the conjugated diene products. Depending on the steric requirements of the transition metal carbene and of the starting enyne, the intramolecular reaction can proceed either via ene–yne or yne–ene pathways to yield

• catalyzed by Grubbs 2nd generation Ru-carbene, these intermediates then led to the tricyclic sesquiterpenoid-like scaffolds I–VIII (Scheme 4), as suitable precursors for the synthesis of artemisinin and its analogs (1a–c). After selecting the optimal tricyclic intermediate, the installation of the bridged

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• undergoing proto-demetallation afforded the final product 46 (Scheme 11B). Initially, the reaction was limited to the generation of racemic products. Ultimately, optimization using McQuade’s six membered N-heterocyclic carbene (NHC) L2 [37] in combination with CuCl led to conditions applicable to different

• forming allylic silanes, only Z-isomers were obtained [75]. In furthering Zhou’s initial report [76], Ollevier and co-workers [77] recently described carbene insertions, starting with 229, into Si–H bonds, leading to a wide variety of silylated products [18]. The original work by Zhou included asymmetric

• , including both diazoesters and diazoketones as carbene precursors. After the impressive report from Dow Corning on the hydrosilylation of alkenes in 2013 [78], recently, the Buchwald group extended this chemistry to the asymmetric hydrosilylation of alkenes [79]. They used nonracemic ligand (S,S)-Ph-BPE

Synthesis of organic liquid crystals containing selectively fluorinated cyclopropanes

• Zeguo Fang,
• Nawaf Al-Maharik,
• Peer Kirsch,
• Matthias Bremer,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2020, 16, 674–680, doi:10.3762/bjoc.16.65

• illustrated in Scheme 1. Difluorocyclopropane 8 can be directly prepared through a [2 + 1] carbene cycloaddition reaction. Thus, treatment of 12 with trimethyl(trifluoromethyl)silane (TMSCF3) and sodium iodide under refluxing conditions [13][14] gave the corresponding product 8 in one step and a 55% yield