Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• diaryliodonium salts in a cascade cyclization, the cyclization features a copper-catalyzed activation strategy involving the cleavage of the C–I bond and esterification. The resulting cascade of selective arylation/intramolecular cyclization facilitated the synthesis of 3,4-benzocoumarin derivatives. The

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

• General procedure for copper-catalyzed multicomponent reaction of β-amino esters Into a flask were added amines 1 (0.4 mmol), acids 3 (0.1 mmol), CuI (20 mol %), and CH3CN (2 mL). Then, the mixture was stirred at room temperature under a nitrogen atmosphere and t-BuONO (0.4 mmol) was added dropwise

• IKERBASQUE, Basque Foundation for Science, Alameda Urquijo 36-5, Plaza Bizkaia, 48011 Bilbao, Spain 10.3762/bjoc.20.21 Abstract An efficient multicomponent reaction of newly designed β-trifluoromethyl β-diazo esters, acetonitrile, and carboxylic acids via an interrupted esterification process under copper

• -catalyzed conditions has been developed, which affords various unsymmetrical β-trifluoromethyl N,N-diacyl-β-amino esters in good to excellent yields. The reaction features mild conditions, a wide scope of β-amino esters and carboxylic acids, and also applicability to large-scale synthesis, thus providing an

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

• (DBDAPs) is disclosed in this article through a palladium and copper-catalyzed amination (Buchwald–Hartwig (B–H) or Chan–Lam (C–L)) followed by a palladium-catalyzed intramolecular aminocarbonylation with Mo(CO)6 as CO surrogate (to avoid toxic CO handling) of readily available o-phenylenediamines and

• diverse dibenzodiazepinones via a copper-catalyzed C–N bond coupling between 2-halobenzoates and o-phenylenediamines leading to a key intermediate that undergoes an intramolecular N-acylation to afford the corresponding dibenzodiazepinone structure in high yields (Scheme 1b) [14]. Another innovative

• approach in the case of the synthesis 4a (47% vs 41%). Our mechanistic proposal is based on the information in previous reports by the groups of Bose [28], Watson [29], and Stahl [30]. Mechanistically, under basic conditions, the reaction is triggered by copper-catalyzed activation of o-phenylenediamine

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• -scale use. Therefore, novel bromination reagents and simple bromination approaches are still required to be established. Very recently, we reported a copper-catalyzed C5-bromination and difluoromethylation reaction of 8-aminoquinolines using ethyl bromodifluoroacetate as bifunctional reagent [30] and

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• wormlike nanoparticles. In rotaxanes, the utilization of metal–ligand bonding involving CuI is a common strategy for immobilizing a thread moiety within a macrocycle. However, the efficacy of such a bonding is compromised when catalysts are used in stoppering reactions, e.g., the copper-catalyzed azide

Selectivity control towards CO versus H₂ for photo-driven CO₂ reduction with a novel Co(II) catalyst

• Lisa-Lou Gracia,
• Philip Henkel,
• Olaf Fuhr and
• Claudia Bizzarri

Beilstein J. Org. Chem. 2023, 19, 1766–1775, doi:10.3762/bjoc.19.129

• complex obtainable via a straightforward synthesis, with improved solubility, concerning our previous Co(II) complexes [21]. Thus, the new Co(II) complex bears two 1-benzyl-4-(quinolin-2-yl)-1H-1,2,3-triazole (BzQuTr) units, that were obtained through a copper-catalyzed alkyne–azide cycloaddition (CuAAC

Lewis acid-promoted direct synthesis of isoxazole derivatives

• Dengxu Qiu,
• Chenhui Jiang,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2023, 19, 1562–1567, doi:10.3762/bjoc.19.113

• reported [16]. In 2015, Yang’s group [10][17] reported the copper-catalyzed conversion of methylarenes into isoxazole derivatives with KNO3 as the source of nitrile oxide (Scheme 1, reaction 1). In 2019, Deng’s group [18] developed a three-component synthesis method of isoxazole derivatives using TBN as

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

• functionalization of aryl C(sp2)–H bonds. FeCl3-catalyzed carbosulfenylation of unactivated alkenes. Copper-catalyzed electrophilic thiolation of organozinc halides. h-BN@Copper(II) nanomaterial catalyzed cross-coupling reaction of sulfoximines and N‑(arylthio)succinimide. AlCl3‑mediated cyclization and

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

• of imidazolium salt 109 (R1 = iBu) resulted in the highest level of stereoinduction for the conjugate addition of EtMgBr to 3-methylcyclohexenone. 2.2.2 Reaction with organoaluminum reagents: Hoveyda and co-workers [60] investigated the NHC–copper-catalyzed asymmetric conjugate addition of alkyl- and

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

• azide was combined with a subsequent copper-catalyzed (3 + 2) cycloaddition with terminal alkynes. This one-pot process was developed with a simple model alkyne, but then applied to more complex alkynes bearing enantiopure 1,2-oxazinyl substituents. Hence, the precursor compounds 1,2-, 1,3- or 1,4-bis

• discovery of the copper-catalyzed alkyne azide (3 + 2) cycloaddition (CuAAC) [3][4], has dramatically changed the approaches to many problems in chemistry, supramolecular chemistry, materials science, biological chemistry and related fields (selected reviews: [5][6][7][8][9][10][11][12][13][14][15

• situ are possible [23]. Later, examples were published showing that these methods are also compatible with the conditions of CuAAC. The earliest case was probably published by Fokin et al. [24][25], one of the inventors of the original copper-catalyzed (3 + 2) cycloaddition. Many examples of

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

• reactions. Although the range of substrates for different C–H nucleophiles remains restricted, in recent years, copper-catalyzed oxidative coupling reactions between different C–H nucleophiles have been established. There are several common valence changes of copper in the catalytic process [44][45][46][47

• benzothiazole, in which benzothiazole compounds have higher reactivity and regioselectivity than thiazole. In 2014, Lei et al. successfully realized the copper-catalyzed oxidative alkenylation of simple ethers to construct allyl ethers in the presence of di-tert-butyl peroxide and KI (Scheme 10) [60]. The

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• their rhodium- and copper-catalyzed reactions (Scheme 2c) [116]. These results were in stark contrast to those observed for the ylide’s diazo counterparts, which did not react without a catalyst, and which gave the opposite diastereoselectivity with copper and rhodium. Inspired by ionic pathways

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• bond formation. However, these methods suffer from limitations such as moisture sensitivity, the requirement of specific ligands, and the use of expensive palladium catalysts [17]. Also, Chan Lam, Evans, and other research groups have developed copper-catalyzed C–N bond formation reactions by careful

• tuning of the ligand and base combinations [18][19]. Thereafter, copper-catalyzed C–N bond-formation reactions have experienced unprecedented development due to mild reaction conditions and the low cost of copper salts [20][21][22]. On the other hand, hypervalent iodine reagents serve as versatile tools

• temperature. However, the reaction was sluggish and resulted in only 52% yield after 48 hours (Table 1, entry 15). With the optimal reaction conditions in hand, we focused our attention on evaluating the scope and limitations of copper-catalyzed N-arylation using iodonium ylide 2 of variably substituted

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• at 60 °C (Scheme 15). Among the different solvents used to optimize the reaction conditions, H2O turned out to be a better and greener solvent compared to other organic solvents (e.g., MeCN, C6H6, CH2Cl2, THF, EtOH, EtOAc). Deng et al. [69] brilliantly described an expedient copper-catalyzed Clauson

• synthesis and proposed mechanism of N-substituted pyrroles 29. Magnetic nanoparticle-supported antimony catalyst used in the synthesis of N-substituted pyrroles 31. Iron(III) chloride-catalyzed synthesis of N-substituted pyrroles 33. Copper-catalyzed Clauson–Kaas synthesis and mechanism of pyrroles 35. β-CD

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

• and 163 through a two-fold C–H activation under palladium catalysis. Silver carbonate and 2,6-lutidine were found to be an effective base and ligand, respectively, for providing the desired products 164 and 165 in good yields (Scheme 31). In 2015, an economic route for copper-catalyzed biaryl coupling

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

• -workers explored the copper-catalyzed asymmetric conjugate borylation of β-substituted cyclic enones using chiral bisphosphine ligand L21 [77]. Other than the oxidation and hydrolysis of the produced enantiomerically enriched tertiary boronates, in one example, they have demonstrated the utilization of

• diastereocontrol originates from the preferred E/Z enolate geometry during the transition state. Interestingly, using t-BuOH instead of iPrOH resulted in exceptionally better results for some substrates with different ring sizes. In 2015, the group of Feringa investigated the copper-catalyzed conjugate borylation

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

• final ring-opened adduct 37. Copper-catalyzed reactions In 2009, Pineschi and co-workers explored the Cu-catalyzed rearrangement/allylic alkylation of 2,3-diazabicyclo[2.2.1]heptenes 47 with Grignard reagents 48 (Scheme 8) [41]. The reaction is thought to proceed via the Lewis acid-catalyzed [3,4

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

• catalysts for such functionalization. In 2013, the group of Daugulis described the copper-catalyzed ortho-2,2,2-trifluoroethoxylation of a 3-trifluoromethylated benzamide derived from 8-aminoquinoline, giving the corresponding product in 73% yield [149]. The group of Baidya showed that the dehydrogenative

Synthesis and reactivity of azole-based iodazinium salts

• Thomas J. Kuczmera,
• Annalena Dietz,
• Andreas Boelke and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 317–324, doi:10.3762/bjoc.19.27

• to iodide and bromide were performed giving the salts 10a and 10b in excellent yields [27]. A copper-catalyzed iodination gave the diiodinated product 11 in quantitative yield [42]. Finally, N-methylation of 5aa was performed, to yield the dicationic salt 5av in 56% yield without decomposition of the

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• -butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine on polystyrene) which is valuable for reaction scale-ups [75] is used. Alternatively, a CuAAc (copper-catalyzed azide–alkyne cycloaddition) reaction has been demonstrated where the copper catalyst is supported on an Amberlist A-21 resin

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• reductively closed using SmI2. The synthesis of fragment 25 began with commercially available cyclohexenone (21), which underwent a copper-catalyzed vicinal difunctionalization with vinylmagnesium bromide and DMPU and trapping using methyl cyanoformate, leading to the formation of ketoester 22 (Scheme 4

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• in Scheme 1 speaks for the unusual facility with which the intramolecular azide–alkyne click reaction took place. Normally, intermolecular click reactions are copper-catalyzed [17][18][19][20]. Intramolecular positioning of the click reaction partners may eliminate the need for the metal-based

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• reports found in the literature suffer from the requirement of hazardous intermediates and harsh reaction conditions. Here, we report a new six-step synthesis for c1G base, starting from 6-iodo-1-deazapurine. The key transformations are copper catalyzed C–O-bond formation followed by site-specific

• intermediates. Here, we present a new tactic for the syntheses of 1-deazaguanine and 1-deazahypoxanthine stimulated by a recently published route of our research group for the corresponding nucleosides [16][17], employing the same key reaction, namely the copper-catalyzed coupling of an aryl iodide with benzyl

• 3,4-dihydropyran in dimethylformamide to obtain the corresponding tetrahydropyranyl-protected amine 17. Subsequently, a copper-catalyzed C–O bond formation at C6 using benzyl alcohol in the presence of caesium carbonate, copper(I) iodide, and 1,10-phenanthroline furnished benzyl ether 18 in excellent

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• enantioselective catalyst. On the other hand, their successful completions attest to the inexpensive and scalable requirements we had set. Indole scaffolds The synthesis of racemic tryptophol CPA 1 is shown in Scheme 2. Commercially available tryptophol (5, 225 $/mol) was N-arylated into 6 via copper-catalyzed

• -catalyzed hydrophosphinylation [45]. The key heterocyclization of 11 into 12 was accomplished using silver-promoted homolytic aromatic substitution [46], which was superior to our own manganese methodology (43% yield) [36]. Copper-catalyzed arylation [34] of 12 with iodobenzene and 4-nitroiodobenzene gave

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

• requirement for copper prompted us to test copper-catalyzed C(sp2)–C(sp3) cross-coupling reactions, as reported by Takeda et al., to achieve allylation reactions of benzyldimethyl(alkenyl)silanes [36]. Treatment of 4c with methallyl chloride in the presence of TBAF⋅(t-BuOH)4 (2.4 equiv), CuI (1.5 equiv), and

• approaches were contemplated for this purpose. Activation by alkoxides of the C3–SiEt3 or C3–SiMe2t-Bu bonds was ineffective. Conversely, treatment of the C3-benzyldimethylsilyl-appended derivatives with tetrabutylammonium fluoride led to cyclic siloxanes, which revealed to be competent donors for copper

• -catalyzed cross-coupling reactions, such as arylation reactions catalyzed by Pd2(dba)3/CuI, as well as allylation and methylation reactions catalyzed by CuI⋅PPh3. C3-Benzyldimethylsilyl-appended furfurals are thus introduced as versatile platforms, providing a modular access to 3-substituted 2-furyl