Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• the past years are discussed. This review contains cycloaddition reactions, nucleophilic halogenation reactions, metal-free coupling reactions, formation of N-heterocyclic carbenes, and multicomponent reactions, mainly three-component reactions. The mentioned methodologies have been performed by

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• as ligands in organometallic catalysts [9] and as versatile organocatalysts [10] in a very wide range of organic reactions such as classical benzoin condensation, transesterification, acylation, Knoevenagel reaction, Claisen condensation etc. The electrochemical generation of carbenes from ILs avoids

• the use of strong bases and the formation of byproducts (dimers of carbenes and nitrogen dealkylation products), where the IL acts as NHC precursor, solvent, and supporting electrolyte, needing no additional chemicals in the electrolytic cell [11]. An added attraction of this approach is that unstable

• . Esterification of trans cinnamaldehyde Once the possibility of obtaining the Breslow intermediate was demonstrated, another typical reaction of N-heterocyclic carbenes was tested: the oxidative esterification of cinnamaldehyde in the presence of alcohols. To carry out these experiments three different alcohols

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• repertoire of chemical transformations that are amenable to organocatalysis [14]. Within the realm of covalent activation, chiral carbenes and phosphines are diverse and structurally rich groups of catalysts. The synthetic scope was greatly expanded by noncovalent activation via a range of proton-mediated

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• and enantiomeric excesses. On the other hand, N-heterocyclic carbenes and chiral pyrrolidine derivatives acting through covalent bond formation such as the iminium ions with the substrates have also been included. Wherever possible, a comparison has been made between the efficacies of various

• aza-MRs. However, the last three review articles are almost 10 years old and they do not cover the application of many important organocatalysts, such as thioureas and nitrogen heterocyclic carbenes (NHCs) used for the asymmetric aza-MRs. Furthermore, in the last review article [24], the application

• -2,3-dihydro-4-quinolones 99 were obtained in good yields of up to 95% and good ee (58–72%) (Table 22) [61]. 2. Covalent-bonding organocatalysis of aza-Michael reactions This category of organocatalysts includes N-heterocyclic carbenes and pyrrolidine derivatives. 2.1 Catalysis by N-heterocyclic

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• stereogenic centers. Review A plethora of highly effective small‐molecule organocatalysts have enriched the field of organic synthesis [27], including chiral proline derivatives, N‐heterocyclic carbenes, chiral thioureas and Brønsted acids as well as phase‐transfer catalysts (PTC), such as the quaternary

• ]coumarins are formed with good to excellent yields and enantioselectivities (Scheme 14). N-heterocyclic carbenes (NHC) have also been successfully used as organocatalysts, in particular, to obtain coumarin derivatives [47]. In this context, Yetra et al. reported a NHC catalyzed reaction of 2-bromoenals 46

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• prepared with nucleophilic catalysis using 10 mol % N-heterocyclic carbenes such as 1,3,4-triphenyl-4,5-dihydro-1H-1,2,4-triazol-5-ylidene or 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene. The polymerization was carried out at room temperature for 24 h and no solvent was used. The resulting reaction

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

• reactivity between geometric isomers, the formation of alkynes via the 1,2-rearrangement of free alkylidene carbenes is unlikely. To gain insight into the reaction mechanism, 13C-labeled sulfoxides [13C]-(E)-2e and [13C]-(Z)-2e were prepared from acetophenone-α-13C and HWE reagent (Scheme 6a), and each

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

• (phosphines, NHC-carbenes, bisoxazolines, pyridine-oxazolines, and miscellaneous) is used. Review Catalytic systems based on phosphine ligands A pioneering work on the enantioselective addition of boron-derived carbon nucleophiles to cyclic enones was published by the group of Miyaura et al. in 2005 [32

• oxidative Heck-type product. The authors stated that as a result of the coordination with PPh3, there is a steric hindrance disfavouring the β-hydride elimination [43]. Catalytic systems based on NHC ligands Historically, the second type of ligands used were N-heterocyclic carbenes (NHC). The first use was

• reported in a work Shi and co-workers in 2008 who studied the addition of arylboronic acids to 2-cyclohexenone catalysed by Pd complexes of axially chiral NHC carbenes with two other weakly coordinating ligands [44][45]. The complexes with acetates (PdL7a), trifluoroacetates (PdL7b), and diaquo complex

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

• phenols [14], our results suggest that sequential phenoxide ion attacks on intermediate carbenes (Scheme 7) was indeed the mechanism responsible for the production of compounds 4, 11 and 12. The bis(aryloxy)fluoromethane moiety had proven robust with respect to radical, brominative conditions as well as

[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

• synthetic organic chemists as it allows to obtain methanofullerenes, fullerenoaziridines, or fullerenooxyranes. These reactions can involve, for example, the addition of stabilized carbanions, carbenes, and nitrenes and can involve various reaction mechanisms. While in the early years of intense research on

• 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

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• -halopurines [41]. O-Alkylation of guanosine and inosine with Cu(I)-stabilized carbenes derived form α-diazocarbonyl compounds is also known [42]. Alkylation of 6-oxopurine derivatives under Mitsunobu conditions which usually proceeds with O-regioselectivity are mostly described for guanine derivatives [43][44

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

• with multiple bonds, resulting in cyclopropanation. One of the important properties of fluorine-containing carbenes and carbenoids is their electrophilicity, which is a result of the high electronegativity of fluorine. Also, fluorine has an +M effect which tends to reduce the reactivity of the carbenes

• alcohols, ethers, esters, and amines (121, Scheme 53) [103]. They proposed that an initial tin–lithium exchange was followed by a β-elimination of LiF to form the intermediate cyclopropenes 119. The ring opening of the latter then generated the vinylcarbenes 120. The carbenes 120 could then insert into 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

• 3β-hydroxykemp-7(8)-en-6-one (7) features a palladium-catalyzed intermolecular [3 + 2] cycloaddition to generate tricycle 28 [23]. (C) A stereospecific phosphine-catalyzed [3 + 2] cycloaddition completes the synthesis of (±)-hirsutene (14) [25]. (D) Linear alkylidene carbenes involved TMM [3 + 2

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

• cross-coupling; NHC complex; palladium; supported ionic liquid; Introduction N-heterocyclic carbenes (NHCs) are known as efficient coordination ligands for different types of metals. The main feature of NHC complexes is their structural tunability [1]. Thus, their catalytic efficiency can be easily

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• -haloalkyl)thiiranes with various nucleophiles, nucleophilic ring expansion of thiiranes with sulfur ylides, and the electrophilic ring expansion of thiiranes with carbenes generated from sulfur ylides under the catalysis of transition-metal catalysts. 4.1.1 Synthesis via nucleophilic ring expansion of 2-(1

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

• applications in various synthetic fields by utilizing the ability of copper to sustain mono- and bielectronic elementary steps. Further to the development of well-defined copper complexes with classical ligands such as phosphines and N-heterocyclic carbenes, a new and fast-expanding area of research is

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

• reorganization [45][46]. This process may follow an intra- or intermolecular course (Scheme 1, A or B). The reaction is promoted by an array of metathesis catalytic systems, particularly derived from Mo, W, or Ru carbenes or it is induced by specific conventional transition-metal salts. It should be pointed out

Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

• Shohei Mimura,
• Sho Mizushima,
• Yohei Shimizu and
• Masaya Sawamura

Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50

• chiral p-tol-BINAP/copper catalyst established the excellent utility of chiral bisphosphine ligands for this type of reaction [4]. Surprisingly, however, chiral ligands based on N-heterocyclic carbenes (NHCs) [12] have not been applied to the conjugate reduction of α,β-unsaturated carbonyl compounds

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• steps, the lithiation and the introduction of the phosphine were performed at low temperature (−70 °C), compound 81 was obtained in 63% yield [80]. In both instances, the other isomer was present in minute quantities and could be separated by recrystallization. Hybrid phosphine N-heterocyclic carbenes

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

• Sara Peeters,
• Linn Neerbye Berntsen,
• Pål Rongved and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2019, 15, 2156–2160, doi:10.3762/bjoc.15.212

• : catalysis; cyclopropanation; indole; norfloxacin quinoline; quinolone; Rh(II); ring expansion; Introduction The development and use of metal carbenes occupy a central part in the field of the C–H functionalization [1]. Among the metal carbenes, the transient Rh carbenes, usually made by Rh-catalyzed

• carbene transfer reaction typically give N–H, C–H (at C3) and double N–H/C–H insertion products. The presence of electron-withdrawing groups on the indole nitrogen makes it possible to cyclopropanate the indole C2–C3 double bond and isolate indoline cyclopropanes. We recently discovered that Rh carbenes

• derived from ethyl α-halodiazoacetates (X-EDA) react readily with unprotected indoles to form ethyl 3-carboxyquinoline structures (Scheme 1) [15]. The Rh carbenes derived from X-EDAs stand out from the three other types of classified carbenoids with respect to chemoselectivity in reactions with indoles

Attempted synthesis of a meta-metalated calix[4]arene

• Christopher D. Jurisch and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2019, 15, 1996–2002, doi:10.3762/bjoc.15.195

• whether stable meta-metalated calix[4]arenes could be formed, isolated and used. For this, our attention turned to the work of Albrecht and co-workers on mesoionic carbenes (MICs) [18][19][20][21][22], particularly the fact that 1,4-diphenyl-substituted 1,2,3-triazol-5-ylideneruthenium(II), iridium(III

The cyclopropylcarbinyl route to γ-silyl carbocations

• Xavier Creary

Beilstein J. Org. Chem. 2019, 15, 1769–1780, doi:10.3762/bjoc.15.170

• ], which have also been termed ”percaudal” interactions [56]. Certain carbenes can also be stabilized in a similar fashion [60][61]. Thus substrates of type 10 solvolyze in protic solvents with large rate enhancements (anchimeric assistance) to generate carbocations 11 as reactive intermediates (Scheme 3

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• yield [70]. In certain cases, sulfur can be trapped by in situ generated carbenes to afford O-thiocarbamates [71][72]. Thioureas and S-thiocarbamates are also accessible through multicomponent reactions starting from isocyanides and sulfur [73][74][75]. The cumbersome synthesis of isothiocyanates from

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• ; nucleophilic carbenes; sulfur transfer reaction; Introduction Imidazole N-oxides constitute a practically valuable class of five-membered aromatic N-heterocycles [1][2][3][4][5]. The subclass of 2-unsubstituted imidazole N-oxides 1 with diverse substituents located at N(1), C(4), and C(5) is of special

• -tetramethylcyclobutane-1,3-dione. Imidazolium salts are of special importance as they are widely used as ionic liquids or precursors of imidazole-based nucleophilic carbenes (imidazol-2-ylidenes). For example, deprotonation of 1,3-diadamantylimidazolium chloride led to the first stable imidazol-2-ylidene (the so-called

• ) at 137.0 and 120.2 ppm, respectively. Unfortunately, attempted syntheses of analogous, symmetric 1,3-dialkoxyimidazolium bromides, derived from diacetyl or 1,2-diphenylethane-1,2-dione, using the same protocol, were unsuccessful. Nucleophilic carbenes are known to undergo conversion into imidazole-2