Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• and Discussion Methodology development In our work towards Rh-catalyzed homo-coupling reactions of benzyl halides, we observed that a similar rhodium–bis(benzyl) complex can also be formed from benzyl halide by using a Grignard reagent instead R2Zn in the presence of RhCl(PPh3)3 to subsequently give

• , so various alkyl halides to replace the benzyl halides were investigated in this reaction (Table 1). Allyl bromide, propargyl bromide, and carbon tetrabromide did not work well as shown in entries 1, 2, and 6 in Table 1. On the other hand, other alkyl halides gave the product in moderate to good

• benign synthetic applications [14][15][16][17][18]. We have successfully achieved various reactions using a Rh complex easily derived from dialkylzinc (R2Zn) and RhCl(PPh3)3 [19][20]. Additionally, in the related study, we also reported a new Rh-catalyzed C(sp3)–C(sp3) homo-coupling reaction of benzyl

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

• be employed in two variants modulated by light irradiation. This external switch can be used to selectively trigger side-chain or core halogenation. Keywords: aryl halides; benzyl halides; bromination; sustainability; Introduction Activation through halogens has become a key strategy in achieving

Beyond n-dopants for organic semiconductors: use of bibenzo[d]imidazoles in UV-promoted dehalogenation reactions of organic halides

• Kan Tang,
• Megan R. Brown,
• Chad Risko,
• Melissa K. Gish,
• Garry Rumbles,
• Phuc H. Pham,
• Oana R. Luca,
• Stephen Barlow and
• Seth R. Marder

Beilstein J. Org. Chem. 2023, 19, 1912–1922, doi:10.3762/bjoc.19.142

• dimers reduce halides that have reduction potentials less cathodic than ca. −2 V vs ferrocenium/ferrocene, especially under UV photoexcitation (using a 365 nm LED). In the case of benzyl halides, the products are bibenzyl derivatives, whereas aryl halides are reduced to the corresponding arenes. The

• several other benzyl halides (1b–e), an alkyl halide 2, and several aryl halides (3a–f). Again GC–MS was used to identify and quantify the products; the necessary authentic samples were mostly commercially available, but the R2 products from 1b and 1c were not, although well-known in the literature (for

• the main products are those in which the halide is replaced by a hydrogen atom. The more easily reduced benzyl halides examined (1b and 1c) are dehalogenated by (N-DMBI)2 in the dark, and with (N-DMBI)2 and UV irradiation are quantitatively dehalogenated in 2–6 h with the corresponding substituted

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

• , whereafter Buchwald–Hartwig amination afford the various diarylazepines. A three-component one-pot process allowed for a second in situ Buchwald–Hartwig amination of the diarylazepine with aryl or benzyl halides to give the respective N-aryl and N-benzylazepine derivatives 83 and 84 (Scheme 16). 3.2 Mizoroki

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

On the hydrolysis of diethyl 2-(perfluorophenyl)malonate

• Ilya V. Taydakov and
• Mikhail A. Kiskin

Beilstein J. Org. Chem. 2020, 16, 1863–1868, doi:10.3762/bjoc.16.153

• , hydrolysis of the ester with a mixture of HBr and AcOH gave 2-(perfluorophenyl)acetic acid in a good preparative yield of 63%. A significant advantage of this new approach to 2-(perfluorophenyl)acetic acid is that handling toxic substances such as cyanides and perfluorinated benzyl halides is avoided

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• cleavage of various benzyl halides 7.1 (I, Br, Cl). The radical is then intercepted by an H atom donor (Hantzsch ester), which delivers the corresponding toluene derivative 7.2. Other organic dyes can promote the reductive fragmentation of alkyl halides. For instance, König and Zeitler demonstrated that a

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• washed with acetonitrile and dried before being used in “click” reactions. CuI/AK (68) furnished the desired products of the reaction of phenacyl halides (with Me, Br, and Cl substituents), benzyl halides or methyl iodide, and phenylacetylene or propargyl alcohol as substrates using a catalytic amount of

• -assisted method was developed for the preparation of 1,2,3-triazole products, substituted at the 1- and 4-positions, from benzyl halides, sodium azide, and nonactivated alkynes in a mixture of water and ethanol using a Cu(I) complex supported on graphene oxide, 88 [81], and the synthesis of “click

• organic frameworks (CNOF, 90) for the preparation of 1,2,3-triazole derivatives substituted at the 1- and 4-positions under green reaction conditions [82]. The CNOF (90) worked well as catalyst for the Huisgen cycloaddition of benzyl azides and aromatic azides (generated from benzyl halides and diazonium

KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones

• Qiao Lin,
• Shiling Zhang and
• Bin Li

Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44

• -dihydrothiazole with benzyl halides under basic conditions is described for the first time. The method provides a convenient and practical pathway for the synthesis of versatile 2-aminoethyl acetates and N-substituted thiazolidinones with good functional group tolerance and selectivity. KOt-Bu not only plays an

• on our continuing interest in developing new transformation methodologies of oxazolines [25], herein, we report a simple KOt-Bu-promoted selective ring-opening N-alkylation of 2-methyl-2-oxazolines and 2-(methylthio)-4,5-dihydrothiazole with benzyl halides, leading to 2-aminoethyl acetates and N

• new and simple transition-metal-free selective ring-opening N-alkylation of 2-methyl-2-oxazoline or 2-(methylthio)-4,5-dihydrothiazole with benzyl halides and allyl halides under mild conditions. Various 2-aminoethyl acetates and N-substituted thiazolidinone derivatives were successfully isolated in

Reactions of 3-(p-substituted-phenyl)-5-chloromethyl-1,2,4-oxadiazoles with KCN leading to acetonitriles and alkanes via a non-reductive decyanation pathway

• Akın Sağırlı and
• Yaşar Dürüst

Beilstein J. Org. Chem. 2018, 14, 3011–3017, doi:10.3762/bjoc.14.280

• that are generally obtained by the reaction of benzyl halides with appropriate cyanating agents such as KCN [14], TMSCN [15], K4(Fe(CN)6 [16]. Deprotonation of the α-carbon (adjacent to nitrile) by strong bases, especially lithiated ones, resulted in an anionic species that easily undergoes a

One-pot synthesis of epoxides from benzyl alcohols and aldehydes

• Edwin Alfonzo,
• Jesse W. L. Mendoza and
• Aaron B. Beeler

Beilstein J. Org. Chem. 2018, 14, 2308–2312, doi:10.3762/bjoc.14.205

• ]. Despite these efforts, the synthesis of epoxides using this powerful transformation still often requires multiple steps due to the need to independently synthesize the sulfonium salt. Typically, the salt is synthesized from nucleophilic displacement of benzyl halides but the work by Aggarwal and co

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• triazole moiety (Scheme 37a) using benzyl halides, sodium azide and a terminal alkyne via an alumina-supported copper catalyst. Using 10 mol % of Cu/Al2O3, differently substituted phenyl acetylenes and aliphatic alkynes led to 70–96% yield of triazoles [152]. Phenyl boronic acids were also used to

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• competing Wurtz-type coupling, (i.e., the coupling of benzyllithiums with the starting benzyl halides); b) the nucleophilic attack of organolithium species to aldehyde or ketone carbonyl groups (Scheme 3). The authors reported that the extremely fast micromixing avoided undesired Wurtz-type coupling [21][22

Hydroquinone–pyrrole dyads with varied linkers

• Hao Huang,
• Christoffer Karlsson,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 89–96, doi:10.3762/bjoc.12.10

• utilized for C–C cross coupling of benzyl halides with heteroarylboronic acids. However, in contrast to its use for the synthesis of thiophene and furane derivatives, it has rarely been employed for the coupling of pyrrolylboronic acids with benzyl halides [13][14][15][16][17]. We applied the Suzuki

Recent developments in copper-catalyzed radical alkylations of electron-rich π-systems

• Kirk W. Shimkin and
• Donald A. Watson

Beilstein J. Org. Chem. 2015, 11, 2278–2288, doi:10.3762/bjoc.11.248

• optimizing the cross coupling of nitroalkanes and benzyl halides, it was clear that the nature of the ligand had a profound effect on the reaction. Various multi-dentate amine ligands, which are commonly used in ATR reactions, were not effective in the reaction, affording low yields of product and

• , evidence suggests that radical intermediates are involved in the bond forming step (Scheme 5). For instance, bibenzyl byproducts were observed in the cross-coupling of benzyl halides, suggesting a homodimerization of benzylic radicals. The reaction does not proceed in the presence of radical scavengers

• dihydrofurans could be easily converted into furans using DDQ in a one-pot process. In addition to α-bromo esters and ketones, Lei and co-workers have also recently shown that benzylic halides could undergo radical alkenylation via copper catalysis [39]. By exploiting the propensity of benzyl halides to form

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• the hydrogen transfer catalyzed by transition metal complexes. In these reactions, compounds with a double bond or a C–Hal bond act as oxidants (hydrogen acceptors). Examples of these reactions with aldehydes or primary alcohols as C–H reagents are given in Table 2. Crotononitrile, acetone, and benzyl

• halides were used as oxidants. Ruthenium, iridium, and palladium complexes acted as catalysts. In most cases, structurally simple alcohols, which are taken in a large excess relative to the CH-reagent, served as OH-reagents. The exception is a study [95], in which the coupling was accomplished using an

Cu-Mediated trifluoromethylation of benzyl, allyl and propargyl methanesulfonates with TMSCF₃

• Xueliang Jiang and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2013, 9, 2862–2865, doi:10.3762/bjoc.9.322

• -mediated trifluoroethylation of arylboronic acids [13][14] (Scheme 1a) and trifluoromethylation of benzyl halides [15][16][17][18][19][20][21] (Scheme 1b) are more convenient. Especially trifluoromethylations of benzyl bromides with a [CuCF3] species, which are generated from different precursors, are

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

• Kalicharan Chattopadhyay,
• Erik Fenster,
• Alexander J. Grenning and
• Jon A. Tunge

Beilstein J. Org. Chem. 2012, 8, 1200–1207, doi:10.3762/bjoc.8.133

• halomethylcoumarin and highly stabilized nucleophiles or amines [6][7][8][9][10][11][12][13][14][15]. Due to the sensitivity and toxicity of related benzyl halides, there has been interest in catalytically activating hydroxymethylarene and heteroarenes (e.g., benzyl alcohol derivatives) toward reactions with

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• , or styrenes, can be used instead of toxic benzyl halides. Additionally, only low catalyst loadings are needed to provide a wide range of products. Following a short introduction about the origin and classical definition of the Friedel–Crafts reaction, the review will describe the different

• . Review The FC alkylation with benzyl alcohols – An efficient approach to 1,1-diarylalkanes 1,1-Diarylalkanes are important building blocks for the synthesis of many pharmaceuticals, agro- and fine chemicals (Figure 2). Traditionally, 1,1-diarylalkanes have been prepared from benzyl halides under Friedel

Synthesis of phosphorothioates using thiophosphate salts

• Babak Kaboudin and
• Fatemeh Farjadian

Beilstein J. Org. Chem. 2006, 2, No. 4, doi:10.1186/1860-5397-2-4

• route to phosphorothioates via O,O'-dialkyl thiophosphate anion formation. Studies on the reaction of ambident nucleophile ammonium O,O'-diethyl thiophosphate with benzyl halides and tosylate in different solvents show that only S-alkylation is obtained. Reaction of this ambident nucleophile with

• on the reaction of ambident nucleophile ammonium O,O'-diethyl thiophosphate with benzyl halides and tosylate in different solvents show that only S-alkylation will be obtained as sole product. Reaction of this ambident nucleophile with benzoyl chloride (hard electrophilic center), gave the O