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

• oxidative addition, transmetallation, and reductive elimination processes. On the other hand, iron may act as a Lewis acid, activating carbon–carbon multiple bonds via π-binding or heteroatoms via σ-complexes. This can either generate the organoiron complex after nucleophilic attack or produce a carbocation

• is the termination of the reaction through the trapping of the reactive intermediate. Organoiron complexes have been shown to undergo electrophilic trapping with external species or proceed through cross-coupling eventually undergoing reductive elimination. Radical addition will typically conclude

• produce the pyrrolidinyl methyl radical 10 which may add to the iron center to form the Fe(III) complex 11. Reductive elimination would give rise to the final product, and transmetallation with a Grignard reagent regenerates the active Fe species. Alternatively, release of the aryl radical via ipso-attack

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• first step, vinyl triflate undergoes oxidative addition to give complex 4, which subsequently transmetalates with arylboronic acid to form palladium complex 5. In the case of Pd(PPh3)4, reductive elimination occurs to give enamide 2. However, using catalysts with very bulky ligands, such as Pd(dppf)Cl2

• causes the tautomerization of complex 5 [30] to zwitterionic carbene 6 which can now isomerize through the C–C bond rotation to the thermodynamically more stable palladium complex 7, followed by reductive elimination to enamide 3. A possible isomerization of enamides 2 or 3 in the presence of a catalyst

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

• , in path b (a rebound cycle), CuI* is trapped after a SET by the radical intermediate to generate a CuIII species, which undergoes ligand exchange with the nucleophile and reductive elimination to produce the target product and the regenerated CuI catalyst [37][38][40]. 2.2 Visible-light-mediated Cu(I

• to its triplet state CuICN*, in which the fluoroalkyl iodides were reduced to Rf• and I−. Subsequently, the radical Rf• attacks the alkene forming a new alkyl radical species. This radical species is then trapped by CuII(CN)n to generate a CuIII intermediate, which undergoes reductive elimination to

• resulting cyanoalkyl radical then adds to the alkene to form a new alkyl radical. This radical is captured by a high-valent CuIII complex, which undergoes a reductive elimination to give the target product (Scheme 12). In 2018, Reiser and co-worker [63] established a CuII-catalyzed oxo-azidation of vinyl

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• trapped by Cu(II) to deliver the Cu(III) species 12, which undergoes intramolecular annulation and reductive elimination to afford the desired product 8 and regenerate the Cu(I) catalyst. Path b: vinyl radical intermediate 11 is oxidized by Cu(II) to give the cationic vinyl species 14. Finally, the

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• manner as reductive elimination forms during the mercury removal process (Scheme 6). Mercury(II) salts had been effectively used to synthesize five-membered furanose derivatives with high stereoselectivity. Nicotra et al. developed Hg(OAc)2-mediated cyclization of hydroxy-alkene derivative 15 to form α-ᴅ

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• nickel(II) species 2-VI and radical species 2-IV forms a nickel(III) intermediate 2-VII, which undergoes a reductive elimination to afford the desired product 7 and the nickel(I) species 2-VIII. The SET reduction of 2-VIII by the iridium(II) species 2-III regenerates the nickel(0) catalyst 2-V and the

• nickel(III) intermediate 3-VI, which results in the cross-coupled product 7 upon reductive elimination. The SET event between the reduced photocatalyst 3-III and the nickel(0) species 3-IV regenerates both catalysts simultaneously. Further studies by the Doyle group established the α-oxy C(sp3)−H

• (III) species 4-IX, which undergoes reductive elimination to release the desired product 10a. Concurrently, Molander and co-workers also reported a related nickel-catalyzed arylation of α-heteroatom-substituted or benzylic C(sp3)‒H bonds by aryl bromides 3 at room temperature using an iridium

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• KI formed ferrous iodide, which reacts with indole to form the iron bis-indolide 107, followed by reaction with N,N-dimethylmethanethioamide to get the S atom inserted (108). A reductive elimination then generated the bis(indol-3-yl)sulfides 105 along with Fe0, which was re-oxidized by aerial oxygen

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• –H activation involving carbon–metal bond or a mechanism involving the usual metal-mediated coupling pathways comprising oxidative addition, transmetalation and reductive elimination steps, they are beyond the scope of this review and will not be extensively covered herein. Homogeneous and

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• elimination to produce 23C, whereby the addition of BPh3 presumably accelerates this process [65]. Subsequently, the manganese species participate in the catalytic cycle by yielding alkynylated product 25. However, the mechanism entailing oxidative addition, followed by reductive elimination could not be

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• bond of an alkyne into the Cu–triazole bond gives 64, which then undergoes syn-β-oxygen elimination to provide the target product. On the other hand, an oxidative addition and reductive elimination sequence can also generate the target product (Scheme 20) [50]. An immobilized copper complex has been

• . Finally, a reductive elimination takes place to give the corresponding final product and the catalyst for the next run [51]. A tandem Click/intramolecular sulfenylation procedure for the synthesis of sulfur-cycle-fused 1,2,3-triazoles 75 and 77 was described by Xu et al. The reaction was performed through

• and the alkyne 73 or 76 using a base. This subsequently cyclized with the azide 73 to afford the triazole cuprate intermediate 79. Finally, the resulting intermediate proceeds through an oxidative addition and reductive elimination sequence to give the final product, followed by the next cycle (Scheme

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• carboxylate-assisted C−H cleavage to deliver copper(II) intermediate A. Next, the copper(III) carboxylate species B is generated. Thereafter, a facile base-assisted ligand exchange is followed by reductive elimination to afford the alkynylated benzamide D. Finally, the desired isoindolone 3 is formed via an

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• . Addition of the alkyl radical formed in the first step adds to D, followed by a reductive elimination step then affords the cross-coupling product. The enantioconvergent cross-coupling developed by Fu was restricted to the use of “activated” halides, such as the α-halocarbonyl compounds 83 (Scheme 32), and

• was based on the interception of tertiary alkyl radicals (B) from a hydrogen atom transfer process involving olefins by a low valent Ni complex (F), generating an alkyl–Ni complex (C) that, upon an oxidative addition to alkyl halides, gives the Ni(III) complex (D) (Scheme 34). After a reductive

• elimination step, a branched cross-coupling product was observed, and the Ni(I) species formed was reduced to generate the catalytically active Ni(0) species (F). The same authors then employed a catalytic system composed of Mn(III)tris(dipivaloylmethane) and phenylsilane in the MHAT cycle and Ni(II)bis

Palladium nanoparticles supported on chitin-based nanomaterials as heterogeneous catalysts for the Heck coupling reaction

• Tony Jin,
• Malickah Hicks,
• Davis Kurdyla,
• Sabahudin Hrapovic,
• Edmond Lam and
• Audrey Moores

Beilstein J. Org. Chem. 2020, 16, 2477–2483, doi:10.3762/bjoc.16.201

• ChsNC in the +2 oxidation state (Figure 3). These results align with our previous work where ChsNCs tend to stabilize Au in the +1 oxidation state as opposed to metallic Au. Since the Heck coupling primarily follows a classic oxidative addition/reductive elimination pathway with Pd(0) being the active

Catalytic trifluoromethylation of iodoarenes by use of 2-trifluoromethylated benzimidazoline as trifluoromethylating reagent

• Tatsuhiro Uchikura,
• Nanami Kamiyama,
• Taisuke Ishikawa and
• Takahiko Akiyama

Beilstein J. Org. Chem. 2020, 16, 2442–2447, doi:10.3762/bjoc.16.198

• (I)–CF3 species, generated through the reaction of benzimidazoline 2 with CuI under basic conditions, underwent an oxidative addition reaction with the aryl iodide to generate a Cu(III) complex. A subsequent reductive elimination furnished the trifluoromethylarene and Cu(I). Because an electron

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Synergy between supported ionic liquid-like phases and immobilized palladium N-heterocyclic carbene–phosphine complexes for the Negishi reaction under flow conditions

• Edgar Peris,
• Raúl Porcar,
• María Macia,
• Jesús Alcázar,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2020, 16, 1924–1935, doi:10.3762/bjoc.16.159

• authors, Pd–NHC complexes can evolve through two different pathways towards the formation of a catalytically active cocktail of Pd species. In the first one, a reductive elimination takes place from the Pd(II) intermediate with the concomitant release of NHC-containing byproducts. In the second pathway

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• reaction media in order to transfer electrons from the low-valent metal complex formed in situ after reductive elimination of the product (Figure 4, right). In this way, the metalacyclic intermediate is reoxidized while the photosensitizer is reduced, thus completing the C–H activation catalytic cycle. By

• that both, the excited Ir photocatalyst and the superoxide anion generated during the transformation, were able to oxidize the low-valent Pd(0) species resulting from the reductive elimination (Figure 6). Under such dual catalysis protocol, various oxidant-sensitive functional groups were tolerated

• ). A similar catalytic cycle than the one reported by Rueping was hence proposed for the C–H activation step. Nevertheless, the authors surmised that an alternative pathway via a Pd(III)/Pd(I) catalytic system could also be envisioned. In this scenario, the reductive elimination from a Pd(III

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• stereochemical outcome of the overall process. A carbon monoxide ligand then undergoes migratory insertion into one of the Co–C bonds in cobaltacycle V, followed by reductive elimination to release the final product (Scheme 3). As mentioned above, the regiochemistry of this transformation is, in most cases

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

• the C(sp3) radical, which is intercepted by an organometallic intermediate, obtained by the oxidative addition of a nickel catalyst to the (hetero)aryl bromide 5.2. The desired (hetero)arene product 5.3 is obtained after the reductive elimination of the nickel complex. In this method, the reduced

• tetrahydrofuran (8.1), giving access to the key C(sp3) radical. The nickel catalyst, after an oxidative addition with the aryl bromide 8.2 and intercepting the alkyl radical species, gave the radical cross-coupling product 8.3 upon a reductive elimination. Other diaryl ketone dyes, such as 9-fluorenone, have been

• corresponding pyridinium and the desired carbamoyl radical. The latter can be intercepted by an organonickel species resulting from the oxidative addition of the nickel catalyst to the aryl bromides 19.2. The arylamides 19.3 are obtained following a reductive elimination, and the resulting Ni(I) species is

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• -diaminotruxillic bis-amino acids. The reaction of the cyclobutanes 4 with CO (1 atm) in MeOH/NCMe results in the ring opening of the oxazolone group, methoxycarbonylation of the Pd–C bonds, reductive elimination, and finally release of the 1,3-diaminotruxillic bis-amino esters 5 as single isomers (ε-isomer). The

• cyclobutanes 4 and reductive elimination. UV–vis spectra of 2 and 3: absorption maxima (λmax, nm). Supporting Information Supporting Information File 319: Complete experimental section; copies of NMR spectra of 2 and 3. Supporting Information File 320: Copies on NMR spectra of compounds 4 and 5

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• aminopalladation/reductive elimination. Keywords: alkynylanilines; arylboronic acids; indoles; isoquinolinones; palladium; Introduction The isoquinolinone nucleus is a key constituent of many natural products [1][2][3] and pharmaceuticals [4][5][6]. Substituted isoquinolinones have been found in biologically

• chemical and physical properties of the products. Furthermore, over the years, we have reported a general methodology for the Pd-catalyzed synthesis of 3-substituted indoles, now referred to as the “Cacchi reaction” [34], through an aminopalladation/reductive elimination sequence starting from 2

• halides [38], α-iodoenones [39], or by transmetalation of a Pd(II) species with boronic acids [33]. In this context, we decided to explore the use of substrates 2 in the reaction with 2-alkynyltrifluoroacetanilides 5 through a sequential cyclocarbopalladation/aminopalladation/reductive elimination process

Synthesis and anticancer activity of bis(2-arylimidazo[1,2-a]pyridin-3-yl) selenides and diselenides: the copper-catalyzed tandem C–H selenation of 2-arylimidazo[1,2-a]pyridine with selenium

• Mio Matsumura,
• Tsutomu Takahashi,
• Hikari Yamauchi,
• Shunsuke Sakuma,
• Yukako Hayashi,
• Tadashi Hyodo,
• Tohru Obata,
• Kentaro Yamaguchi,
• Yasuyuki Fujiwara and
• Shuji Yasuike

Beilstein J. Org. Chem. 2020, 16, 1075–1083, doi:10.3762/bjoc.16.94

• the diselenide 2. On the other hand, in the presence of excess imidazopyridine, the oxidative addition of imidazopyridine 1 to B, followed by the aromatization of C leads to the intermediate D. The intermediate D undergoes a reductive elimination to give the selenide 3, with the generation of Cu(I

• -position to form the intermediate C and the selenide anion F. The intermediate C undergoes a reductive elimination and aromatization to give the selenide 3 and Cu(I). Moreover, the Cu-mediated electrophilic addition of 3 and selenium affords G, which aromatizes to form E and then probably undergoes a

• reductive elimination to afford the diselenide 2. The anticancer activity of the novel synthesized bis(2-arylimidazo[1,2-a]pyridin-3-yl) diselenides 2 and selenides 3 was evaluated in human cervical cancer HeLa cells (Figure 5). At 25 µM, each compound significantly decreased the cell viability compared to

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• presence of the nickel catalyst and a base via a typical oxidative addition, insertion, and reductive elimination sequence to afford the desired product (Scheme 29). In the absence of K2HPO4, only traces of the desired product were detected. Other known photosensitizers, such as acetone (4), acetophenone

• formed reacts with an acyl radical 175 to give the nickel(III) complex 178, which could then undergo a reductive elimination reaction to furnish the desired ground state benzophenone product 172. The nickel(0) catalyst can then be regenerated by SET (Scheme 41). However, they suggested that the first

Synthesis of C₇₀-fragment buckybowls bearing alkoxy substituents

• Yumi Yakiyama,
• Shota Hishikawa and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2020, 16, 681–690, doi:10.3762/bjoc.16.66

• is formed. Two competitive processes, the reductive elimination from B to give the product 5b, and the 1,5-palladium migration from A to C through B, might exist, and from C, after the bond rotation, the intermediate D would form to afford the isomer 5c. The selectivity of these two processes are

Copper-catalyzed O-alkenylation of phosphonates

• Nuria Vázquez-Galiñanes,
• Mariña Andón-Rodríguez,
• Patricia Gómez-Roibás and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2020, 16, 611–615, doi:10.3762/bjoc.16.56

• groups, and final reductive elimination would form the new C(sp2)–O bond, providing an acyclic enol phosphonate with concomitant regeneration of the Cu(I) catalyst (Scheme 1b). Herein we report the successful realization of such a copper-catalyzed oxygen-alkenylation strategy and show that a range of