Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• have provided innovative strategies, substrates in all of these reaction systems are generally limited to benzylic, α-amino-, and α-oxy aliphatic acids, presumably due to the necessity of stabilized radical intermediates for the following radical cyanation step. We and others have recently demonstrated

• investigated (Figure 2). Arylacetic acids with relatively stable benzylic radicals as the corresponding intermediates have been proved to be suitable substrates to the reaction, providing the desired decarboxylative cyanation products with generally good yields (2–18). To show the synthetic potential of this

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• were determined by detailed analysis of their NMR spectral data. In particular, 1H NMR spectrum of the representative compound 4aa shows two characteristic signals at δ = 4.16 (singlet) and 3.89 (singlet) that correspond to the two groups of benzylic protons, respectively. Two peaks at δ = 3.77

• -cyclohexenone. This is further supported by the 13C NMR spectrum, which contains two peaks at δ = 38.4 and 47.7 indicating the two types of benzylic carbons. The NMR data of known compound 4ab were also in good correlation with previously reported data [19]. The synthetic practicability of the protocol was

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• benzylic residues differed depending on the benzylic residue's functional groups and the pyrazole substitution pattern. For starting materials 15a and 15d, an excess of product 17 was usually observed. With the ester-functionalized triazene 15c and m-substituted benzylic reagents, regioisomer 18 was the

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• alcohols and benzylic alcohols delivered fruitful results. However, the reaction of benzyl alcohols was found to proceed within shorter reaction times and much higher yields compared to aliphatic alcohols. This process presumably involves a Cannizzaro reaction during the conversion of the benzyl alcohols

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• -mediated deoxygenative trifluoromethylation technique worked with both benzylic and unactivated thiocarbonates. The proposed mechanism starts with the homolysis of (bpy)Cu(III)(CF3)3 by blue-light irradiation, which produces CF3 radicals and (bpy)Cu(II)(CF3)2. Subsequently, the interaction between the CF3

• directly activated via photoredox catalysis. In 2018, Doyle and co-workers [54] documented a catalytic method for the deoxygenation of benzylic alcohols to toluenes, utilizing phosphines and photoredox catalyst under visible-light irradiation (Scheme 18). In this method, they were able to synthesize

• (i.e., 62e–h, 30–82%) of the corresponding hydrocarbons. m-Substitution also provided a good product yield (i.e., 62i and 62j, 67 and 68%). Additionally, electron-rich benzylic alcohols yielded the product in a lower yield (i.e., 62k and 62l, 53 and 59%) compared to 62a. This was due to the generation

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• undergo cyclization reactions under mild conditions. In case of 1,3-diphenylacetone (4a) some activation of the methylene group is observed as well, because of benzylic stabilization. Dianions of 1,3-dicarbonyl compounds follow a different regioselectivity as compared to simple monoanions [6][7][8][9][10

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• according to well-established protocols [71][72][73][74]. The β-ketoesters were obtained employing a sequence of two reactions, the formation of the benzylic alcohol derivative, through a Reformatsky reaction using In(0), followed by a pyridinium chlorochromate (PCC) oxidation, giving the β-ketoesters 7a–g

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• hydride. In 2018, the Milstein group demonstrated a partial hydrogen-borrowing reaction with a manganese-pincer complex by coupling alcohols and hydrazine to form N-substituted hydrazones. Benzylic and aliphatic alcohols were studied with hydrazine using Mn(t-Bu-PNN)(CO)2Br (Mn5, 3 mol %) and a catalytic

• amount of t-BuOK (5 mol %) at 110 °C [38]. Benzylic alcohols bearing electron-donating and withdrawing groups afforded 65–92% yields of the product within 24 h (Scheme 7). However, aliphatic alcohols such as 1-hexanol and 1-octanol required 36 h to give the corresponding products with 77% and 65% yields

• optimized with 5 mol % of Mn1 and 10 mol % of K2CO3 in xylene at high temperature (150 °C) for 24 h afforded the desired N-alkylated sulfonamide compounds [40]. A wide range of aryl and alkyl sulfonamides were alkylated with various benzylic and aliphatic alcohols, providing good to excellent yields (Scheme

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• desired reactivity. Substitution of a hydrogen atom with a halogen atom within an organic skeleton significantly increases the electrophilicity of the linked carbon centre, enhancing concerted (SN2) as well as carbenium ion-mediated (SN1) substitutions, common – for instance – on benzylic positions

• ] resulting in easier recyclability. Light irradiation often significantly influences the selectivity of halogenation processes. Photolytic cleavage of molecular halogens gives rise to radicals that are known to favour benzylic functionalisation [17]. Conversely, the same molecular halogens exhibit prominent

• of a benzylic hydrogen atom from the substrate by Br•, to give HBr and a structure-stabilised carbon-centred radical, which may react with Br2 to give the brominated product, thus regenerating Br• that is able to sustain the chain process. In the absence of light (left side of Figure 1), the reaction

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• 18 containing an exocyclic alkene was subjected to the reaction conditions, a mixture of benzylic chlorides (20) was formed in low yields, and trace amounts of the allylic chloride 19 was also isolated, the materials differentiated on the basis of the coupling of the acetal H5 with the respective

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• benzylic carbocation [42], in our case no product was observed. Since β-substituted styrenes can be involved in the transformation it is possible that the azide radicals can react either with the vinylic product formed in the reaction or with the starting vinyl-BF3K. Simple aryl-BF3K 12 only afforded 14

• to styrene would generate intermediate I-1. Oxidation of the benzylic radical (E1/2ox = +0.37 V vs SCE for the corresponding radical without the azide) [61] by the previously formed Ru(bpy)3+ (E1/2 [RuIII/RuII] = +1.29 V vs SCE) [53] regenerates the ground state photocatalyst and forms carbocation I

• -2. Finally, nucleophilic addition of the alkynyl-trifluoroborate onto the benzylic carbocation would afford homopropargylic azide 4 [45]. Conclusion In summary, an azido-alkynylation of styrenes to access homopropargylic azides was developed. The reaction was initially investigated using EBX

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• nucleophilic substitution of benzylic bromides with sodium azide and a subsequent copper(I)-catalyzed double click reaction in one pot [17]. In summary, these contributions by renowned experts demonstrate the broad diversity of impressive catalytic domino, tandem, and one-pot processes towards many valuable

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• dianion 7 forms (resonance form 7b will prevail in this case, Figure 1), it will be inactive to attack by nucleophiles. The behavior of acenaphthene 5 could be clarified further using its naphthalene analog 3, which lacks benzylic CH2 protons, but there is no information in the literature about its

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• reaction is possible upon elimination of the resulting benzylic alcohol on D, allowing another arylation forming E [18]. This complex sequence of transformations is herein applied to the synthesis of 1-aryltetralines, analogues of cyclolignan natural products having important medicinal applications [19][20

• reactions. Highly nucleophilic arenes like 1,3,5-trimethoxybenzene react easily under mild conditions and result in a stabilized benzylic cation in acidic conditions, allowing a second intramolecular Friedel–Crafts reaction involving the aryl substituent of the substrate. These reactions are favored by π

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• as a sulfenylating source gave the target product in 93% yield. Knochel and co-workers found that copper acetate can catalyze the cross-coupling reaction between (hetero)aryl, alkyl and benzylic zinc halides 36 with N-thiophthalimides 14 (Scheme 18) [55]. Various metal catalysts, including CrCl2

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• Hans-Ulrich Reissig Fei Yu Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, D-14195 Berlin, Germany Asymchem Boston Corporation, 10 Gill Street, Woburn, Massachusetts, 01801, USA 10.3762/bjoc.19.101 Abstract The nucleophilic substitution of benzylic bromides with sodium

• aminopyrans [54], should be converted into divalent compounds via coupling of the terminal propynyl group with benzylic biazides. Since biazides are potentially explosive [22] it was very desirable to avoid their isolation and to generate these reactive species in situ from the corresponding benzylic halides

• possible, that the N-benzyl group attached to the 1,2,3-triazole moiety is partially removed under these conditions and/or that even the C–O bond connecting the 1,2,3-triazole part with the aminopyran part is reductively cleaved since this bond also has benzylic character. In earlier investigations with

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• benzylic ethers occurs at room temperature in the presence of Cu(OTf)2/InCl3 as catalysts and DDQ as oxidant (Scheme 3) [51]. By this route, a series of 2-alkoxymalonate diester derivatives was synthesized through direct CDC reaction. The mechanism study showed that the first step of the catalytic cycle

• involves a hydride abstraction from the benzylic site of isochroman to generate a cationic species A, whereas the malonate is activated by the In/Cu catalyst (B). Subsequently, the coupling of the two intermediates yields the desired product and regenerates the catalyst. Alternatively, In(III) may be

• the substrate achieved the activation of the C(sp2)–H bond. Other non-noble metal-catalyzed reactions In 2013, Liu et al. reported that MnO2 could catalyze the CDC of the benzylic C(sp3)–H bond in benzyl ethers with α-carbonyl C(sp3)–H bonds in the presence of air at room temperature (Scheme 33) [98

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• potential of RLT reactions to be rapid and efficient. In both cases, benzylic carboxylic acids were most amenable as substrates, with alkyl carboxylic acids such as adamantane and dicyclohexylmethane providing fluorinated aliphatic products in low to moderate yields. Asymmetric RLT catalysis has also been

• of recent interest, with exciting preliminary decarboxylative azidation results obtained under thermal conditions by Hongli Bao and co-workers [44]. An asymmetric iron (NON) pincer catalyst IV was employed to decarboxylate benzylic peroxyesters and form enantiomerically enriched benzylic azides. An

• ) azide complex, reducing the iron catalyst back to the starting Fe(II) state. Organic azides can be formed in moderate to high enantioselectivity using this approach; however, the scope is largely limited to benzylic products, a result in line with Groves’ finding that benzylic acid substrates perform

Selective and scalable oxygenation of heteroatoms using the elements of nature: air, water, and light

• Damiano Diprima,
• Hannes Gemoets,
• Stefano Bonciolini and
• Koen Van Aken

Beilstein J. Org. Chem. 2023, 19, 1146–1154, doi:10.3762/bjoc.19.82

• in only 20 minutes. Scope Based on the obtained knowledge to optimize the reaction conditions, a variety of sulfides were tested. As shown in Scheme 3, the anticipated products were obtained in good to excellent yields with a few exceptions (2v–z). In general, heteroatoms at the benzylic position (2a

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• -Tribromopyrimidine (6a), whose core pyrimidine structure can be found in many biologically active compounds, could be sequentially substituted with 1,3,5-trimethoxybenzene and N-methylpyrrole to give 8a. The protocol also enabled the selective reductive dehalogenation at the benzylic position of 9a with green light

Linker, loading, and reaction scale influence automated glycan assembly

• Marlene C. S. Dal Colle,
• Manuel G. Ricardo,
• Nives Hribernik,
• José Danglad-Flores,
• Peter H. Seeberger and
• Martina Delbianco

Beilstein J. Org. Chem. 2023, 19, 1015–1020, doi:10.3762/bjoc.19.77

• ] and L2 [3] are based on the o-nitrobenzyl scaffold [23][24] and expose a hydroxy group that serves as glycosyl acceptor in the first AGA cycle (Figure 1B). While L1 displays a flexible aliphatic chain terminating with a primary alcohol, L2 carries a secondary benzylic alcohol. Upon irradiation with UV

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• selectively targeted by photoredox catalysis to enable unprecedented modification of the amino acid. In this context, it is worth mentioning that the single-electron oxidation of the indole moiety in tryptophan provides the radical cation, which enables selective C-radical generation at the weaker benzylic

• intramolecular decarboxylative cyclization with the formation of the 3,4-fused indole carbocycle rings (Figure 1b,c). In detail, the photocatalytic strategy for accessing the two C(sp3) radicals of DMAT derivatives envision the formation of a relatively stabilized allylic-benzylic carbon-centered radical by

• Hz, 1H)], strongly indicating that this product is not the desired structure 6’ but the eight-membered cycloalkene structure 6, shown in Scheme 2. Based on these results and previous reports on the benzylic and allylic C–H bond functionalization enabled by metallaphotoredox catalysis [86], we propose

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

• cationic Zr complexes provided good transformations, probably due to good accessibility of the coordination site and an increased Lewis acidity of the metal center. The authors also demonstrated that this catalytic system also catalyzes the alkylation of benzylic C–H bonds (C(sp3)–H) of various

• dialkylpyridines with alkenes. It is to be noted that the ligands’ backbones were found to be crucial for the regioselectivity of the addition to benzylic C(sp3)–H bonds, as N-arylamine-bridged bis(phenolato) Zr complexes provided branched products whereas N-alkylamine-bridged bis(phenolato) Zr complexes provided

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• single electron transfer (SET), is proposed to be involved in the plausible reaction mechanism. Keywords: arylsulfonylimine; benzylic oxidation; benzyl sulfonamide; K2S2O8; sulfate radical anion; Introduction Among various imine compounds [1], N-arylsulfonylimines are perhaps the most prominent due to

• -dehydrative reaction of aldehydes with isocyanate analogs ([3] and references therein) (Scheme 1b) and an oxidative reaction of primary benzylic alcohols with sulfonamides or chloramine-T ([3] and references therein), and although they are elegant, they use substrates that are not readily accessible or toxic

• were used as the substrates in this reaction, N-arylimines were not isolated. Rather, an amide, in some cases, was isolated via oxidation of the benzylic methylene to a carbonyl group [14]. In the quest of a new method for the synthesis of N-arylsulfonylimines, we questioned ourselves whether N

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• , prepared by benzylic bromination of the methyl substituents of 132 and 133 (Scheme 29). 5 1,4-Michael addition Narita et al. [72] reported their total synthesis of bauhinoxepine J (139), a quinone dihydrobenzoxepine derivative, by means of a base-promoted intramolecular etherification (Scheme 30). 6