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

• species, cyclopalladated intermediates, and products (Figure 1). The monitoring results confirmed the crucial role of TsOH and acetonitrile (MeCN) as additives in the catalytic bromination of the C–H bond in L1. The experimental results were supported by quantum-chemical calculations, which showed that

• yield of 30% after one hour of milling (Table 1, entry 10 and Figures S77–S81 in Supporting Information File 1). Interestingly, in the reactions of L4 and L5 with NIS, instead of the halogenation of the aromatic C–H bond, imidation of the aliphatic C–H bond was observed. Imides are among the most

• Supporting Information File 1). Compared to L1 [51], iodination of its para-halogenated derivatives resulted in lower yields of diiodinated products (Table 2, entries 9–12) since the activation/halogenation of the C–H bond occurs preferentially at the unsubstituted azobenzene phenyl ring [57]. The reactions

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• , directing groups are introduced to the substrates covalently to achieve site-selective C–H bond activation, which prospered greatly in the past decades [7][8][9]. Template regulation is also introduced to locate reactive centers in a noncovalent way through hydrogen bonding [10][11][12]. Even though

• cyclodextrin as the anchoring template. For example, cyclodextrin would fix the steroid substrate with a certain set of orientation, which exposes one certain C–H bond to the metalloporphyrin catalytic moiety and produces site-selective oxidized product. As shown in Figure 8, in this methodology, the steroid

• the end. Once the two parts were mixed in the reaction system, the two p-tert-butylphenyl groups of the substrate 27 were recognized by the β-cyclodextrin and anchored through the host–guest binding. At this stage, the steroid core exposed the 6-position C–H bond to the metalloporphyrin unit catalytic

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• regioselectivity. The mechanism and origins of selectivity in the iridium-catalyzed hydroacylation reaction has been examined at the M06/Def2TZVP level of theory. The catalytic cycle consists of three key steps including oxidative addition into the aldehyde C–H bond, insertion of the olefin into the iridium

• bonds [6][7][8][9][10][11][12][13]. Hydroacylation reactions, the formal addition of an aldehyde C–H bond across a C–C π-system, has emerged as a powerful, and highly atom-economic approach to synthesize ketones. As such, C–H functionalizations are inherently both environmentally benign and economically

• to react. Alternative bases (Table 1, entries 7–10) were tested; however, the reaction produced isomerized naphthol derivative 17 rather than the predicted addition product. These results indicate the formation of a phenoxoiridium(I) species assists in the oxidative addition of the C–H bond, as

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

• José G. Hernández,
• Karen J. Ardila-Fierro,
• Dajana Barišić and
• Hervé Geneste

Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20

• . To assist the metal-free amidation of the aromatic C–H bond in 5, we repeated the milling experiment at 40 °C using a heat gun to increase the temperature of the milling jar (see Supporting Information File 1, Figure S2) [42], which gave a mixture of 5 and 6 (ratio 85:15). The same experiment at 60

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• a reactive species, often used in catalytic amounts, capable of promoting a highly selective homolytic cleavage of the C–H bond that results in a carbon-centered radical [5][6]. Nitrogenated structures are easily oxidized under mild conditions into their radical or radical cation forms [7], being

• . Alemán and co-workers also published the use of a photogenerated DABCO radical cation in a distal β-carbonyl enantioselective C–H functionalization for the synthesis of pyrroline derivatives [26] (Figure 2d). The latter is, to the best of our knowledge, the only work reporting a direct substrate C–H bond

• compared to benzaldehyde (17, 55%). Higher amounts of aromatic aldehydes were required, probably due to the diminished hydricity of their C–H bond and side reactions under photochemical conditions (see Supporting Information File 1, Table S3 for details). Surprisingly, the very bulky trimethylacetaldehyde

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• authors believe this reaction likely proceeds with the σ-aryliron intermediate 42 cyclizing to give the η1-allyliron species 45. Isomerization of 45 would deliver the less-hindered isomer 48 (path i). The stereochemical outcome can be rationalized by the steric interactions of the iron residue and the C–H

• bond of the aromatic ring in 47. Capturing of the iron complex by the Grignard reagent 2, followed by reductive elimination would deliver the observed product 40. Alternatively, the iron species 45 may undergo direct anti-attack by the Grignard reagent (path ii) [76]. One final possibility is the

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• ]. Organocatalytic aryl C–H activation via a nonradical process represents an enormous challenge in organic synthesis, although the nucleophilic aromatic substitution with cleavage of the electrophilic aryl C–H bond has only recently been developed by transition-metal-catalyzed aryl C–H activation [57]. In the

• presence of a chiral phosphoric acid, the azo group has recently been revealed to be a useful moiety that may efficiently activate an aromatic ring for formal nucleophilic aromatic substitution, resulting in the cleavage of the aryl C–H bond and direct arylation of the nucleophile [58]. In 2018, Tan and co

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• exchange was observed at the ortho-position of 1a with 3.0 equivalents of CD3CO2D under standard conditions (Scheme 5a). Furthermore, a larger value of kinetic isotope effect (KIE = 2.4) was detected (Scheme 5b). These results indicated that the cleavage of C–H bond was most likely involved in the rate

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• involved in the HAT process of benzylic C‒H bond using DMBP as co-catalyst to deliver benzylic radical species 9-IX (Figure 9) [71]. The benzylic radical 9-IX intercepted with the nickel catalytic cycle to result in the desired products 26. The photoredox nickel-catalyzed arylation of α-amino C(sp3)–H

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• by treatment with PCC/Celite in dichloromethane (DCM). Finally, treatment with a catalytic amount of CF3SO3H provided the corresponding anthracenes 30a–c in good yields (57–75%) [40]. Metal-catalyzed C–H bond activation In 2016, Hong’s group developed a synthetic strategy to generate substituted

• converted to the substituted anthracenes 109 and 110 by varying the acidic workup procedures. In addition, they prepared 9-chloro-10-phenylanthracene (112) in good yield (87%) through diol 111 [59]. Synthesis of substituted benzo[a]anthracene and dibenzoanthracene derivatives Metal-catalyzed C–H bond

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• synthetic methodologies is the C–H bond activation process that enables a straightforward access to several important and innovative compounds [14][15][16][17][18]. In the last few years, metals such as ruthenium [19][20][21], rhodium [22][23][24], palladium [25][26][27], and iridium [28][29][30] have been

• widely applied as catalysts for this matter, including in the synthesis of bioactive substances. Although catalysts based on these metals, are known to be efficient in C–H bond activation reactions affording the products in good yields and mild conditions, they are also known to be usually expensive

• isosteviol derivate furnished a useful and versatile oxathiazinane (46). The betulinic acid-derived sulfamate ester preferentially underwent amination at the γ primary C–H bond of the equatorial C23 methyl group with high site- and diastereoselectivity to furnish the oxathiazinane derivative in 76% yield

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

• is also oxidized to Mn(III)/L–N3. Azide radical addition to Mn(II)/L to form Mn(III)/L–N3 was considered as a possible route. Concurrently, the photocatalyst is irradiated by blue LED light to induce hydrogen atom transfer (HAT) at the C–H bond of substrate 12, generating alkyl radicals and enabling

• , citalopram (17b), an antidepressant, was also reacted under amination conditions involving HBF4, affording product 19b in good yield and excellent diastereoselectivity (dr > 20:1). Other multiple benzylic C–H bond-containing molecules, including a dopamine receptor agonist analogue 17c as well as derivatives

• , metallonitrene intermediate 18A is formed from the reaction of catalyst 18 with iminoiodinane, which is subsequently transformed to Mn–imido complex 18B via conversion of substrate 17 into a temporary benzylic radical species, wherein C–H bond cleavage is proposed to be the rate-determining step (inter- and

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

• . Later, carboxylate-ligand-assisted C–H bond activation takes place through a concerted metalation–deprotonation transformation to produce the next intermediate. Finally, the corresponding product 142 is formed by a reductive elimination process, along with the regeneration of the active catalytic

• '. 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

• −Miyaura cross-coupling produced a series of 5-aryl-4-ethynyl triazoles 136 in the presence of Pd(PPh3)4 as catalyst and K3PO4 as base in 1,4-dioxane as solvent at 100 °C (Scheme 39) [62]. A paper by Sekar et al. described the synthesis of polycyclic triazoles 142 through a domino alkyne insertion and C–H

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• prove instrumental for the further diversification of the thus obtained 3-methyleneisoindolin-1-ones 3da–ka. For substrates bearing two potential reactive sites, the annulation selectively took place at the less congested ortho-C−H bond (see 3la and 3ma). Moreover, the challenging isonicotinic acid

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

• [18][19][20][21]. In the presence of a Brønsted acid source, the alkylmetal bond can be transformed into a C–H bond to afford a hydrofunctionalized olefin product (Scheme 1) [22]. The relevance of the formation of new C(sp3)–C(sp3) bonds has led to great efforts to enable the use of carbon

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• turn, this next abstracts hydrogen at C-3, regenerating the carrier and continuing the cycle. The C–H bond at position 3 of Guareschi imides is unusually weak. Hydrogen abstraction by an alkyl radical and formation of a hydrocarbon C–H bond is strongly exothermic (calculated enthalpy change: ≈20 kcal

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• products [1][2][3][4][5][6][7][8]. Prins and related cyclization reactions [9][10], hetero-Diels–Alder cyclization [11], cyclization onto epoxides [12], Petasis–Ferrier rearrangement [13], intramolecular oxa-Michael reactions [14], cyclization through oxidative C–H bond functionalization [15], ring-closing

• enantioselectivity varied with the polarity of the solvent. The optimization study disclosed that the enantioselectivity increases with the decrease of the polarity of the solvent (Scheme 68). Yu and co-workers reported a novel segment-coupling Prins cyclization involving sequential benzylic/allylic C–H bond

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• complexes are the simplest and most rapid way. In this review, the focus lies on cyclization reactions, C–C-, C–S-, C–B-, C–N-, C–P-, C–O-, and C–H bond formation, primarily summarizing the chemical reaction step involving the EDA complex (Table 1) as well as the underlying mechanisms that have appeared

• reactions, C–C-, C–S-, C–B-, C–N-, C–P-, C–O-, and C–H bond formations. The absence of transitional-metal catalysts and photosensitizers is the most profound feature of EDA-complex- mediated reactions in most cases. On the other hand, the reaction conditions are mild, and light is utilized as the only

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• , while the remaining C–H bond in Flp acquires an enhanced positive charge due to the electron-withdrawing effect of fluorine. Based on these considerations, a fluoroproline–aromatic-system interaction has been previously utilized in the engineering of a few peptide therapeutics [44][45]. 2.3

Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride

• Beatrice Lansbergen,
• Catherine S. Meister and
• Michael C. McLeod

Beilstein J. Org. Chem. 2021, 17, 404–409, doi:10.3762/bjoc.17.36

• trichloride; dichloroalkenes; Friedel–Crafts alkylation; rearrangement; trifluoroalkanes; Introduction 1,1-Dichloro-1-alkenes are valuable synthetic intermediates and have been employed in Pd-mediated cross couplings of one or both chlorine atoms [1][2][3][4][5][6][7], carbonylation reactions [8], and C–H

• bond alkynylations of heteroarenes [9]. The 1,1-dichloro-1-alkenyl moiety is found in a number of pyrethroid insecticides including permethrin and marine natural products such as caracolamide A [10] (Figure 1). 1,1-Dichloro-1-alkenes 2 are commonly prepared from the corresponding aldehydes 1 in one

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• to be developed [14]. The formation of new C–C bonds through direct C–H bond functionalization in organic chemistry is attractive [15]. Such methodologies are omnipresent and facilitate sustainable organic transformations for the synthesis of complex natural products and pharmaceuticals. In the past

• years, C−H bond functionalization catalyzed by transition metals received a strong emphasis, and other different catalytic systems have also been encouraged [16][17][18][19][20]. Huang and co-workers first realized the addition of alkylazaarenes directly to unsaturated bonds via C(sp3)–H

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• such as potassium tert-butoxide or sodium hydride resulted in no formation of the desired product 3a because 2a was decomposed under the harsh reaction conditions (Table 1, entries 2 and 3). Thus we opted to employ another substrate 2b bearing a phenylthio group which polarizes the α-C–H bond to lead

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

• (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

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• catalysis and photochemistry. Where transition metal catalysis provides one strategy for C–H bond activation, transition-metal-free photochemical C–H fluorination can provide a complementary selectivity via a radical mechanism that proceeds under milder conditions than thermal radical activation methods

• ][51][52][53][54][55][56][57]. Accordingly, the reactivity and selectivity correlate with the homolytic C–H bond dissociation enthalpy and polarity matching principles [58][59][60][61][62][63][64]. One of the advantages of polarity matching is that it enables C(sp3)–H bond activations that are not

• –H bond is matched to the HAT catalyst. For example, an electrophilic radical abstracts H atoms selectively from the most electron-rich or “hydridic” C–H bond [65]. 1.1.3 Importance of visible light and visible-light photosensitization in synthesis: Unlike many other traditional energy resources

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

• last decade particular attention has been focused on two modern fields, C–H bond activation, and visible-light-induced photocatalysis. Couplings through C–H bond activation involve the use of non-prefunctionalized substrates that are directly converted into more complex molecules, without the need of a

• catalyst, able to insert selectively into one specific C–H bond. Accordingly, not only waste generation was significantly reduced, but also new retrosynthetic connections were envisioned, allowing the conception of more straightforward synthetic protocols [15][16][17][18][19][20]. Besides, the formation of

• these two activation modes. The advantages of the dual catalytic systems over traditional monocatalyzed approaches is also discussed, thus illustrating their sustainable character. Review Visible-light-mediated photocatalysis as a sustainable reoxidation strategy In the context of traditional C–H bond