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

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• bonds did not have a significant impact on the outcome of the reaction. It should be noted that this methodology afforded the products with a high regioselectivity, and no incorporation of the SCF3 moiety on the benzylic or at the C5 position of the quinoline part of the directing group was observed

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• of an ether linker on the pyrazine ring, with a two methylene unit chain length between the heterocyclic core and benzylic substituent, improved the potency of these compounds [16]. Hence, scaffolds 1–3 were then converted into a series of ether-linked triazolopyrazines with phenethyl alcohol or

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• resulted in the formation of insoluble intermediary iodoarenes. Derivatizing the benzylic position was done by employing secondary benzyl alcohols. These are well soluble and lead to an about 10-times shortened Friedel–Crafts step at 0 °C for the conversion of 3g. Longer times only resulted in the

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• further oxidized, and thus producing the respective benzylic cation. Intramolecular cyclization in the cationic position under participation of the methyl ester function provided the core for (+)-grandilodine C (191) and (+)-lapidilectine B (192), while allylation of the benzylic position allowed

• quenchers (e.g., PhSSPh) to the reaction mixture. When monosubstitution of the aryl group is present, the formed radical cation, the product of the photooxidation of the cinnamyl ether, readily cyclizes to cyclobutene radical cation 217. The latter cleaves the benzylic C–C bond to produce the 1,4-radical

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• HFIP. The regioselective amination of benzylic positions in alkylarenes [82] and ethers [83] directed by steric effects was achieved by the development of sterically hindered “bowl-shaped” imide-N-oxyl radical precursors (Scheme 7). The presented example with a sterically hindered N-hydroxyimide

• -hydroxybenzimidazole core has several modification sites that allow one to control the properties of the catalyst over a wide range. The authors demonstrated the high efficiency of N-hydroxybenzimidazole catalysts in the benzylic CH-amination with diethyl azodicarboxylate and the CH-fluorination of aldehydes with

• photoredox-catalyst or electrochemically on an anode. An example of the photochemical aerobic benzylic CH-oxidation employing a heterogeneous photoredox catalyst, nanosized TiO2, was demonstrated by our group [85] (Scheme 9). Mixing of NHPI and TiO2 leads to the emergence of visible light absorbance

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• hydroxy group were positioned at C-3 and C-4 of the aromatic ring, respectively, based on NMR chemical shift data comparison with related marine natural products [19]. The E configuration for the oxime in 1 was assigned by the diagnostic carbon chemical shifts of the benzylic methylene (C-7, δC 27.8) [21

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• of benzaldehyde led to the formation of adduct 14 (in 75% yield), which arose from the addition of a benzyl carbanion 17 to benzaldehyde. The generation of such a nucleophile strongly suggests the formation of pentavalent silicon intermediate 15 [27], which then produced a (stabilized) benzylic

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• through steric and electronic interactions involving peptoid amides and nearby side chains [17][18]. For example, N-substituted monomers bearing benzylic-type Nα-chiral groups including the phenylethyl [19][20][21], naphthylethyl [17][22][23][24], and triazolium groups [25][26][27], alkyl ammonium [28

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• cyclopropanes, Li and co-workers treated compound 36 with triflic acid (TfOH) in refluxing HFIP (Scheme 13) [24]. The reaction afforded compound 37 in 82% through the regioselective intramolecular ring-opening of the cyclopropane ring at the benzylic carbon atom. Very recently, our group has reported the

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• The substrate scope and the generality of the reaction under the optimized conditions were explored through the synthesis of various products using differently substituted primary amines 1, cinnamaldehydes 3, and dialkyl but-2-ynedioates 2. Aromatic, aliphatic, benzylic, and various other types of

Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

• Yelong Lei and
• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6

• heating, diazo esters 1 undergo a Wolff rearrangement to generate ethoxycarbonylketenes A by loss of nitrogen. The nucleophilic attack of 2-arylaziridine 2 on the ketene moiety produces zwitterionic intermediates B, in which the aziridinium is opened to form the benzylic carbocation stabilized through the

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• of other metals such as Au, Pt, Pd, Rh, Ag, and Fe and found that they were less efficient compared to Ru. The benzylic alcohols showed higher reactivity than aliphatic alcohols towards this methodology. Moreover, this protocol worked well for differently substituted heterocyclic alcohols and

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• -nitroaryl compounds. Various 2-nitrobenzyl derivatives are used to photocage heteroatom functional groups, including alcohols, amines, carboxylic acids, and phosphates [11]. Typical photochemical pathways result in cleavage of a benzylic C–X bond following initial benzylic H-atom abstraction [11][13]. In

• contrast, photorelease systems based on C–C or C=C bond photocleavage are quite rare [14][15]. We recently reported a vinylogous analogue of this photo-deprotection process, which allowed photocleavage of alkenyl sp2 C–X bonds, rather than benzylic sp3 C–X cleavage [16][17]. We now report that further

• residue (Figure 1C, step, i + iv → ii) [18][19][20]. Subsequent investigations validated the use of photoreactive boronic acids as an approach to reversible backbone N–H modification via photocleavage of an alkenyl C–N bond [16][17]. Traditional 2-nitroaryl groups allow cleavage of benzylic C–X bonds (e.g

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

• . Notably, the reaction did not proceed in the dark or in the absence of the photosensitizer at 30 °C; further, the reaction generated the desired product in lower yield at 120 °C. The scope was broad and tolerated a wide array of 1,3-keto esters and 1,3-diketones, as well as both benzylic and aliphatic C

• generating a benzylic radical which can be oxidized by Ag(I) to afford the corresponding benzylic cation. Nucleophilic trapping with an amine will produce the final product. In the same year, Song and co-workers reported a dehydrogenative 1,2-difunctionalization of conjugated alkenes 107 with silanes 92 and

• radical across the alkene to afford the benzylic radical. Oxidation of the corresponding radical affords the benzylic carbocation which is attacked by the indole nucleophile. The authors applied the reaction methodology to pyrrole as a substrate; however, only one example was given in a 50% yield. Further

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• results of its corresponding nickel(II) [18] and palladium(II) [19][20] complexes with the analogous tests obtained in the case of having a benzylic substituent at the same position. Also, DFT calculations are run in order to study the conformational analysis of the synthetized complexes. Results and

Synthesis of new pyrazolo[1,2,3]triazines by cyclative cleavage of pyrazolyltriazenes

• Nicolai Wippert,
• Martin Nieger,
• Claudine Herlan,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2021, 17, 2773–2780, doi:10.3762/bjoc.17.187

• [3,4-d][1,2,3]triazine compounds 5 (Scheme 4). The successful cyclizations gave the desired pyrazolo[3,4-d][1,2,3]triazines 5 in moderate to good yields. Not all cyclization products were air-stable. While compounds 5a–d with a benzylic side chain in R1'' were stable, a full characterization was

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• developed convenient access to phenolic benzyltetrahydroisoquinolines opens the possibility for flexible late stage etherification with various aromatic, benzylic and related residues for a comprehensive investigation of the chemical space around this pharmacophoric backbone. Experimental Materials and

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• give imines, iminium salts, aldehydes and other, in some cases dimeric products [49]. Here, oxidation of the benzylic amino moiety should lead either to iminium ions (or N-acyl iminium ions) 4a as strong electrophiles or to stabilized radicals 4b which could undergo cyclization to give the fluorenone

• backbone. Expected 9-aminofluorene intermediates 5 were envisaged to undergo subsequent oxidation by the same oxidant to hopefully provide the fluorenones 3 in a domino reaction. Results and Discussion After comprehensive literature search for successful oxidations of benzylic C–N bonds we tested a variety

• of oxidizing agents, oxidizing systems, and radical initiators on a set of model molecules 2 (see Table 1) in a preliminary screening for suitable oxidants for the intramolecular ring-closure reaction. The set of model molecules 2 bears different benzylic N-containing functional groups, including

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• functionalization reactions Benzylic or α-amino C–H groups and even the stable C(sp3)–H group were functionalized through the corresponding benzylic radical, α-amino radical, or alkyl radical. In 2016, Greaney and co-workers [92] investigated the direct C–H azidation with benzylic C–H compounds 47 and the Zhdankin

• reagent. After investigating a range of reaction parameters, copper salts and visible light were found to be necessary for the transformation. The reaction is highly selective for the benzylic position. In the same year, Bissember’s group [93] reported a copper-photocatalyzed α-amino C–H functionalization

• between N-heteroarenes 69 and redox-active esters 68. In 2018, Gong and co-workers [43] used benzyltrifluoroborates 71 as a benzylic radical source for the visible-light-induced alkylation of imines 70. In the catalytic system, chiral ligands initiated benzylic radical formation and governed the

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• allylic functionalization of 2-alkylazaarenes. Due to the high pKa value of alkyl azaarenes, the functionalization of benzylic C(sp3)–H was challengeable and pre-activation of the benzylic proton with suitable Lewis acids was often required prior to deprotonation of the alkyl chain by a stoichiometric

• our studies on a direct benzylic allylic reaction of 2-alkylpyridines with MBH carbonates as allylic precursors under base- and catalyst-free conditions. As depicted in Scheme 2, we envisioned that the MBH carbonate 2 can undergo the SN2’ reaction with the nucleophilic 2-picoline 1a, giving the

• pyridinium cation intermediate A. The in situ generated tert-butoxide anion has enough basicity to deprotonate of the activated benzylic proton of intermediate A and generates the anion B1, which can be tautomerized into more stable enamine intermediate B2. Finally, the intermediates B1 or B2 occur an