Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• starting from indoles and o-dibromoarenes as substrates [59]. In this tandem reaction, various symmetrical bromoarenes were utilized to eliminate the problem with regioselectivity. Two tests by using 2-bromo-5-methoxyphenyl triflate and 2-bromo-4-methoxyphenyl triflate were performed to evaluate the

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• ) [95]. Xu et al. identified GjCCD4a from G. jasminoides. Through prokaryotic expression and in vitro characterization, GjCCD4a was found to cleave the 7,8-/7',8'-double bonds of lycopene (5), β-carotene (6), and zeaxanthin (7). Further investigation revealed that GjCCD4a originated from tandem

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• extension of this methodology. This study is aimed at the development of convenient protocols for the synthesis of new spiroheterocycles via tandem Rh(II)-catalyzed OH insertion/base-promoted cyclization using DAS and various OH substrates containing an activated multiple bond (propiolic and allenic acids

• alcohol followed by base-promoted cyclization. The procedures developed allow to obtain derivatives of such sought-after scaffolds in the field of medicinal chemistry as Δα,β-butenolides, tetrahydrofurans, and pyrans spiro-conjugated with a pyrrolidine ring. The tandem approach proposed is characterized

• earlier and the synthetic methodology investigated in this work. An initial example on Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazo compound 1a. Tandem Rh2(esp)2-catalyzed O–H insertion/base-promoted cyclization involving DAS 1 and various propiolic acids; PMP = 4-methoxyphenyl

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• -effects that it can cause in the more sensitive subgroups of patients. Specifically, when DIM was used in tandem with tamoxifen, the ratio between 2OHE1/16αOHE1 increased up to 229%, as well as the concentration of the sex hormone binding globulin (SHBG) that inhibits the growth of breast cancer cells [4

• is an intriguing solid support, since it is a low cost, commercially available and non-hazardous support, that can be employed in tandem with various traditional catalysts [70]. Some examples in literature are ZrOCl2·8H2O/SiO2 [71], P2O5/SiO2 [72], LiHSO4/SiO2 [73], (PhCH2PPh3)+Br−/SiO2 [74], H2SO4

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• aligned the individual units of the tandem repeat CBM13 domains, indicated by the N-terminal (34-158) and C-terminal units (162-286) and compared those to the domains of ricin (Figure 1b). R-type lectins have a characteristic Q-x-W structural motif close to their binding site, which is highly conserved

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

• ; multi-step reactions; multicomponent reactions; one-pot synthesis; organocatalysis; tandem reactions; transition-metal-catalysis; The synthesis of pharmaceutical ingredients, natural products, agrochemicals, ligand systems, and building blocks for materials science has reached a high level of

• stereocenters [7]. In the Review paper by Kisszékelyi and Šebesta, the diverse variety of chiral metal enolates obtained by asymmetric conjugate additions of organometallic reagents and the possibilities to engage metal enolates in tandem reactions with new electrophiles are presented [8]. A Perspective from X

• facile stereoselective tandem reaction based on the asymmetric conjugate addition of dialkylzinc reagents to unsaturated acylimidazoles, followed by trapping of the intermediate zinc enolate with carbocations [12]. A practical one-pot synthesis of fluorescent pyrazolo[3,4-b]pyridin-6-ones by reacting 5

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

•  3b). The expected three-component tandem reaction did not occur, and the target 4a was not observed with almost all of the starting amine 1a remaining. This result indicates the reaction proceeds through the diazo intermediate. According to the above experimental results and literature reports [39

• catalytic cycle. Finally, the acetimidic anhydride D undergoes a Mumm rearrangement to furnish the desired β-trifluoromethyl diacylamino ester 4a. The final goal of this work is the examination of the scale-up applicability of this three-component tandem reaction (Scheme 5). To our delight, the reaction

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• Tsvelikhovsky introduced an efficient synthetic strategy to construct diverse dibenzodiazepinones through a sequential methodology consisting of a B–H coupling between o-carbonylanilines and 1,2-dihaloarene derivatives providing access to key precursors that undergo a tandem amination–intramolecular cyclization

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

• Polytechnique, CNRS, Institut Polytechnique de Paris, F-91128 Palaiseau, France Sorbonne Université, CNRS, Laboratoire de Chimie Théorique, 75005 Paris, France 10.3762/bjoc.20.15 Abstract The Hock cleavage, which is compatible with tandem processes, was applied to the synthesis of 1-aryltetralines through a

• benzyl moiety on the substrate resulted in tandem Friedel–Crafts reactions to form the 1-aryltetraline products. These compounds share a close analogy to the cyclolignan natural products. Experimental observations and a DFT study support the involvement of an aldehyde intermediate during the Friedel

• –Crafts reactions, rather than an oxocarbenium. Keywords: 1-aryltetralines; Friedel–Crafts reaction; Hock rearrangement; oxidative cleavage; tandem reactions; Introduction The Hock cleavage [1] consists in the acid-catalyzed rearrangement of organic hydroperoxides, leading to the oxidative cleavage of a

Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• the structure of the prepared compounds. To explain the outcome of the tandem reaction of 3,3-diaminoacrylonitriles to heterocyclic azides, a tentative mechanism for the formation of 1,2,3-triazoles 3 from acrylonitriles 1 and azides 2 is shown in Scheme 3. Firstly, treatment with a base, leads to

• embryonic cells. Identification of the cause of the registered selective toxicity of the tested compounds requires further study. Conclusion Thus, we have introduced an effective base-catalyzed tandem reaction including a Cornforth-type rearrangement of 1-heteroaryl-1,2,3-triazole-4-carboximidamides and

• and elaboration of a novel tandem process, synthesis of starting building blocks and 21-st target compounds was made by chemistry team and founded by Russian Science Foundation, project number 23-13-00248. The study of cytotoxic effect of 7 compounds was financially supported by the Ministry of

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• -triazolines and their derivatives via tandem 1,2-addition/cyclization reactions between trifluoromethyl acylhydrazones and cyanamide [105] (Scheme 17b). Afterwards, Hu et al. developed a method for the N-arylation and N-alkylation of trifluoromethyl acylhydrazones with diaryliodonium salts and alkyl halides

A deep-red fluorophore based on naphthothiadiazole as emitter with hybridized local and charge transfer and ambipolar transporting properties for electroluminescent devices

• Suangsiri Arunlimsawat,
• Patteera Funchien,
• Pongsakorn Chasing,
• Atthapon Saenubol,
• Taweesak Sudyoadsuk and
• Vinich Promarak

Beilstein J. Org. Chem. 2023, 19, 1664–1676, doi:10.3762/bjoc.19.122

• performed using either a Bruker LC-Quadrupole-Time-of Flight tandem mass spectrometer or a Bruker Autoflex MALDI-TOF mass spectrometer. UV–vis spectra were recorded using a Perkin Elmer Lambda 1050 UV–vis–NIR spectrometer. Luminescence emission spectra and lifetimes were analyzed using an Edinburgh

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• protodemetalation to provide ultimately the 1,4-addition adduct. In the presence of carbonyl acceptors, aldol condensation occurs providing overall a tandem 1,4-addition–aldol process. When a tert-butanesulfinyl moiety is present on the nitrogen atom, these electrophilic substitution reactions occur with good

• levels of chiral induction, paving the way to enantioenriched β2-amino acids and β2,2-amino acids. Keywords: β-amino acids; tandem reactions; radical–polar crossover; tert-butanesulfinamide; zinc radical transfer; Introduction Dialkylzinc reagents react in aerobic medium with a range of α,β-unsaturated

• benefit from a similar effect, even though in this case, the direct formation of an intermediate enolate remains uncertain [11]. With this context in mind, we surmised that β-aminoenoates I could be suitable 1,4-acceptors (Scheme 2, bottom). We previously reported tandem reactions of such substrates

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• multifunctional catalytic system 142 incorporating ruthenium nanoparticles (RuNPS) and an NHC–Cu–Cl complex supported on silica (Scheme 56). The catalyst, Ru@SiO2–[Cu(NHC)] was successfully applied to a one-pot tandem A3 reaction of an aldehyde, alkyne, and secondary amine followed by hydrogenation of the

• the A3 reaction is catalyzed by the NHC–Cu complex while the selective hydrogenation is catalyzed by Ru(0) nanoparticles. The versatility of this tandem catalytic approach was established by using a wide range of substrates. Furthermore, the catalytic activity and selectivity remained fairly constant

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins

• Feng Chen,
• Xiu-Hua Xu,
• Zeng-Hao Chen,
• Yue Chen and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2023, 19, 1372–1378, doi:10.3762/bjoc.19.98

• the synthesis of trifluoromethyl aromatic acyloins. Maekawa’s group [24] developed a tandem reaction of the reductive coupling between arylaldehydes and ethyl trifluoroacetate in the presence of magnesium and chlorotrimethylsilane, followed by desilylation to produce the trifluoromethyl aromatic

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

• of ethers to obtain symmetric and asymmetric 1,1-bis-indolylmethane derivatives (Scheme 23) [84]. The reaction proceeds through the tandem oxidative coupling of the C–O bond and cleavage of the C–H bond. Fe plays a dual role in catalysing the C–C bond coupling and C–O bond cleavage as Lewis acid

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

• indicative of a carbocationic pathway are not observed, suggesting that RPC does not occur. Further, the inability of ATRA products to undergo SN2 with the added nucleophiles under our reaction conditions is inconsistent with a tandem ARTA/nucleophilic displacement alternative mechanism. Finally, a

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

• ’ conPET, this Review will also cover deviating variants such as neutral (acridine) radical conPET as well as polysulfide or ‘tandem’ photoredox catalysis that similarly rely on the absorption of two photons to access activated catalyst states that engage redox-inert substrates. Other two-photon processes

• processes with PEC are limited to the use of recirculated flow or batch (vide infra). As another alternative to organic photocatalysts, the Polyzos group presented a tandem photocatalytic sequence applying [IrIII(ppy)2(dtbbpy)]PF6 ([Ir1]+) in combination with Et3N to accumulate the energy of two visible

• conditions. In 2020, the Polyzos group also demonstrated the carbonylative amidation of aryl halides in continuous flow with the in situ-generated [Ir2]0 (Figure 19A) [79]. This multi-photon tandem photocatalysis protocol provides an elegant alternative to established classical procedures for condensing

Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• the results of our study of this tandem reaction. Results and Discussion Initially, we synthesized the key imine 3a by refluxing a solution of the starting 2-(5-methylfuran-2-yl)ethylamine (1a) and commercially available benzaldehyde (2a) in absolute CH3CN for one hour in a quantitative yield. To our

• optimized reaction conditions, in addition to the desired tetrahydrofuro[3,2-c]pyridine (4h), led to the major formation of the corresponding 1,4-diketone 5h. This unexpected formation of 3-(2-oxopropyl)piperidin-4-one (5h) led us to the idea that the tandem sequence Pictet–Spengler cyclization/furan acid

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• 10.3762/bjoc.19.65 Abstract We present here a stereoselective tandem reaction based on the asymmetric conjugate addition of dialkylzinc reagents to unsaturated acylimidazoles followed by trapping of the intermediate zinc enolate with carbocations. The use of a chiral NHC ligand provides chiral zinc

• a tandem reaction comprising the Cu–NHC-catalyzed addition of dialkylzinc reagents to enoyl imidazoles followed by a trapping reaction with various onium compounds (Scheme 1). In this work we show the development of this methodology and its application to a range of acylimidazoles and carbocations

• , Table 1, entry 3). The addition of two equivalents of tropylium NTf2 led to a decrease of the diastereoselectivity (Table 1, entry 4). In the next tandem reaction, 1.1 equiv of tropylium bistriflimide (2a) were added to the reaction mixture every hour until the full conversion of the starting

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

• synthesis of synthetically useful N-arylsulfonylimines from N-(arylsulfonyl)benzylamines using K2S2O8 in the presence of pyridine as a base is reported herein. In addition, a “one-pot” tandem synthesis of pharmaceutically relevant N-heterocycles by the reaction of N-arylsulfonylimines, generated in situ

• deliver N-arylsulfonylimines under mild reaction conditions is highly desirable. Previously, we reported a tandem oxidative intramolecular cyclization of N-aryl(benzyl)amines, having an internal nucleophile substituted at the ortho-position in the aniline ring, to nitrogen heterocycles using potassium

• approach, a gram-scale synthesis and a “one-pot” tandem synthesis of pharmaceutically relevant N-heterocycles by the reaction of in situ-generated N-arylsulfonylimines with various ortho-substituted anilines were also developed. The mechanism of the oxidation is believed to occur via hydrogen atom

Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• , Zaporizhzhya National University, Zhukovsky str., 66, Zaporizhzhya, 69600, Ukraine 10.3762/bjoc.19.53 Abstract Peptidomimetics with a substituted imidazo[1,2-a]pyridine fragment were synthesized by a tandem of Groebke–Blackburn–Bienaymé and Ugi reactions. The target products contain substituted imidazo[1,2-a

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

• the enol carboxylate and subsequent 1,2 radical rearrangement and decarboxylation. Moderate to good yields of dibenzo[b,f]oxepine carboxylates 25 were achieved (63–85%). Stopka et al. [46] reported on tandem C–H functionalisation and ring expansion as an alternative to the Wagner–Meerwin rearrangement

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• . Short information on applications in total synthesis is also given. Keywords: asymmetric catalysis; conjugate addition; electrophile; enolate; tandem reaction; Introduction The formation of complex chiral molecules is a crucial task of organic synthesis that enables the synthesis of pharmaceuticals

• , crop-protecting agents, or advanced materials. Their syntheses often involve numerous reaction steps requiring laborious isolation and intermediate product purification steps. An important strategy for improving syntheses’ effectiveness is the concept of domino reactions, cascade, or tandem reactions

• Following the seminal work of Feringa in 1997 [21], the tandem asymmetric organozinc conjugate addition followed by subsequent aldol reaction was scarcely applied in the last decade. Welker and Woodward studied the reaction of zinc enolates 2 with chiral acetals 3 (Scheme 2) [22]. The Lewis acid (TiCl4 or

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

• shed light on future directions for further development in this field. Keywords: bicyclic alkenes; cascade; catalysis; domino; transition-metal-catalyzed; Introduction A well-orchestrated sequence of events – cascade, also known as domino, tandem, and sequential reactions, constitutes a fascinating

• phenanthridinones produced, the authors were able to quickly afford novel fagaronine 117j and nitidine 117k derivatives. Rhodium-catalyzed reactions In 2002, the Lautens laboratory reported a tandem cyclization of arylboronate esters 118 with a variety of bicyclic alkenes 15 using a water-soluble Rh-catalytic