A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• carboxylate substrate and [Ru(p-cymene)Cl2]2. Subsequently, the Ru complex coordinates with the aniline substrate, followed by C–H activation to form a six-membered Ru species. The final product is generated through reductive elimination, releasing Ru(0), which is then reoxidized on the anode to regenerate

• mechanism. Initially, C–H activation occurs, resulting in the formation of a cyclometalated Ir(III) intermediate. Ligand exchange with the alkyne substrate, followed by migratory insertion, leads to the formation of a seven-membered 18-electron Ir(III) complex. This complex then undergoes reductive

• elimination (RE) to produce an 18-electron Ir(I) complex. The Ir(I) complex is subsequently anodically oxidized back to an Ir(III) complex, with the concomitant elimination of the product. This protocol can be applied to the LSF and diversification of natural products, as demonstrated by the examples of

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• of the reductive elimination very slow, the intermediary Cu(III) species safely existed until the addition of D2O. Because the significant overlap of NMR peaks was observed due to the quite similar structure of 11a and 11a-D, quantitative analysis of the deuterium content of 11a-D was not possible

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• then undergoes a proton shift to provide intermediate B. Intermediate B collapses via reductive elimination to give nitrenium ion C, along with the release of iodobenzene and sulfamate. Finally, nucleophilic attack of the olefin moiety of C on the electrophilic nitrogen atom, followed by the

• migration and reductive elimination, along with the release of iodobenzene and sulfamic acid. Cyclization of protonated G takes place to afford the intermediate H. Finally, release of water and β-proton elimination produces the rearranged product 3a (Scheme 8). Conclusion In summary, we reported the

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• then reacted with a different isocyanide (R4–NC) in the presence of a palladium catalyst. The release of nitrogen from intermediates I resulted in nitrenes II, which in turn involved in the intramolecular transfer to yield species III. The carbodiimides IV, which were formed through reductive

• elimination of III, underwent intramolecular cyclization to deliver the desired products 85. The scope of reaction showed that higher yield (57–90%) of 85 were obtained when benzaldehydes 83 were equipped with electron-donating groups (R1) and when bulky groups, such as 1-adamantyl or t-Bu (R4), were

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• ] reacted a perfluorinated iodine(III) compound with XeF2 and postulated the formation of a (perfluoroalkyl)iodine(V) difluoride intermediate which underwent a reductive elimination to afford perfluorinated products (Scheme 2C). In 2019 Togni reported a safer route to a range of acyclic iodine(V) fluorides

• to a trans-configuration because of the bicyclic carbon skeleton. Trifluoroiodane 3, on the other hand, has both trans- and cis-configurations of the fluorine ligands which could play a key role in the reductive elimination step in the fluorination of phenylmagnesium bromide. Trifluoroiodane 3 also

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• pervasive in organic synthesis and can also be used to efficiently fluorinate benzylic C(sp3)–H bonds. The general blueprint for this transformation follows a metal insertion into the C(sp3)–H bond followed by C–F reductive elimination [11][22][38]. In 2006, Sanford and co-workers published a seminal and

• palladacycle intermediate, defining the stereochemical outcome. Subsequent oxidation to the Pd(IV)–F species, which triggered reductive elimination, afforded the fluorinated product. The non-innocent behaviour of the isobutyrylnitrile co-solvent aided in stabilising the palladacycle through occupying the

• was effective for the stereoselective fluorination of benzylic positions ortho to aldehyde substituents (Figure 9). The choice of a bulky amino, transient, directing group dictated the stereochemical outcome and promoted the C–F reductive elimination through an inner-sphere pathway. A competitive C–O

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• then extrude CO2 to generate the alkyl radical. Concurrently, Cu(II)–CN species are produced in the presence of cyanide anion through anodic oxidation. At this stage, Cu(II)–CN species are believed to capture alkyl radicals and the product would be readily generated via reductive elimination from the

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• final reductive elimination gives the desired alkene and Ni(I). The two catalytic cycles are finally completed by single-electron reduction of [Ni(I)] by [Ir(II)], which regenerates [Ni(0)] and ground-state [Ir(III)]. Cyclic oxalates readily form the corresponding alkyl radicals under iridium

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

• elimination of ethylene. Further transmetalation between the complex 8 and another Grignard reagent gives Rh(III)–bis(aryl) complex 9. Finally, reductive elimination affords the desired homo-coupling product 3 and regenerates the Rh catalyst. We did not identify any cross-coupling products such as (2

• -bromoethyl)arenes or styrenes in this reaction. Unfortunately, we have not clarified the reason why a cross-coupling reaction did not proceed. At this stage, we speculate that the elimination rate of ethylene and reductive elimination rate of 3 might be fast in this reaction. Medicinal chemistry application

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• rise to either diaryl selenoxide via dehydration or diaryl monoselenide via reductive elimination by eliminating H2O2 [39]. Observation of m/z peaks for compound 8 clearly confirmed the formation of diaryl selenoxide in the reaction. Mechanism for the formation of oxamides The possible reaction

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

• reaction mechanism proceeds with an initial reduction of Pd(II) to Pd(0) followed by oxidative addition on the ArCH2–Cl bond to form the ArCH2–PdII–Cl complex. Then, insertion of CO, from TFBen, takes place followed by nucleophilic displacement and reductive elimination. The obtained compound undergoes

• reductive elimination and the generated Pd(0) species gets oxidated by the oxygen to the active Pd(II) species (Scheme 7). Synthesis of indoles by metal-catalyzed reductive cyclization reaction of organic nitro compounds with carbon monoxide as reductant In the last 60 years, the metal-catalyzed

• ). The proposed mechanism, shown in Scheme 34, suggested that the process proceeded through a Pd(0) catalysis proceeding through first an intramolecular Heck reaction, followed by CO insertion, N-cyclization (anilines) or O-cyclization (phenols) and final reductive elimination. Carbonylative

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• following mechanism (Scheme 30B): Initially, the terminal palladium species H, formed through the hydropalladation of terminal or internal alkenes (upon chain walking), coordinates to NCS via hydrogen bonding (I). Subsequent oxidation takes place to yield a Pd(IV) species (J), which then undergoes reductive

• elimination, resulting in a Pd(II) complex and the corresponding alkyl chloride K. Conclusion Despite being regarded as uninteresting museum chemistry for a considerable time, recent advancements in the hydrochlorination of alkenes have significantly expanded its applicability. Approximately three decades ago

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• would initially involve the addition of azide radicals to an alkene, generating a carbon-centered radical. Then, different trapping of this intermediate could be performed (Scheme 1B). First, C-centered radicals are known to recombine with metal-acetylides, in particular copper [27]. Reductive

• elimination of the organometallic intermediate would lead to the desired product (Scheme 1B, reaction 1). Unfortunately, this approach will not be compatible in the case of azidation since the copper, azides and alkynes present in the mixture are expected to undergo alkyne–azide cycloaddition reactions [28

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• cycle involves the oxidative addition of 1,8-dibromonaphthalene. Then, a concerted metalation–deprotonation of the arene, which usually occurs at the ortho-position of an activating group such as a fluorine or a chlorine atom, followed by reductive elimination, gives the corresponding intermediate 1

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• intermediacy of free radicals, indicating the involvement of the SET pathway (Scheme 21C). Eventually, reductive elimination of 113 afforded product 114 while regenerating the catalytic species 109. It is worth nothing that further transformations of NHPI esters under photoinduced Cu catalysis have been

• alkyl radical 12 is captured by intermediate 122, resulting in the formation of complex 123. At this point, the metal center has undergone a two-electron oxidation, making it well-suited for reductive elimination yielding the cross-coupling product 124. Under these catalytic conditions, various TM

• -coupling product 127 is then formed via reductive elimination of 126 which gives NiI intermediate 128. At this stage, it is proposed that the NiI complex 128 can participate in a SET event with another equivalent of substrate 10, generating another equivalent of radical 12, that propagates into the next

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

• energy barrier (ΔΔG = 0.9 kcal·mol−1). The formation of intermediate α-INT 3 and β-INT 3 was found endergonic by 9.3 and 7.6 kcal·mol−1, respectively. Subsequently, both site isomers of INT 3 can undergo reductive elimination with barriers of 6.9 and 9.4 kcal·mol−1 to deliver the corresponding

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

• (1a), followed by the oxygen-promoted insertion of the phenylboronic acid coupling partner 7 to deliver intermediate II that undergoes reductive elimination to give diarylamine 3a along with regeneration of the copper catalyst (Scheme 5). Then, a palladium-promoted oxidative addition of the C–Br bond

• takes places to deliver palladium species III. Then the insertion of CO that is released by Mo(CO)6, should afford intermediate IV that undergoes a base-promoted intramolecular cyclization via nucleophilic attack of the amine [31]. Finally, the dibenzodiazepinone 4a would be obtained through reductive

• elimination of the palladium catalyst. Conclusion In summary, we have reported two one-pot pathways and two step-wise pathways to access dibenzodiazepinone (DBDAP) derivatives via copper-catalyzed Chan–Lam amination/carbonylative cyclization and Buchwald–Hartwig amination/carbonylative cyclization and their

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• facilitated by the process of photoexcited radical decarboxylation. On the other hand, the copper catalytic cycle involved the capture of alkyl radicals by the copper complex B, the activation of heteroatom-containing substrates 30 by a base-mediated proton transfer, and the subsequent reductive elimination

• process. This reductive elimination led to the formation of C(sp3)–X (X = O or N) cross-coupling products 31. Cyclization Radical-involved selective C–H functionalizations [25][26], particularly annulation reactions [26], have emerged as highly effective and powerful techniques in synthesis, possessing

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

• intermediate III. Reductive elimination of Pd from III gave product 5 and species IV. Finaly, Pd(II) species were reproduced by ligand exchange to restart the next cycle (Scheme 4). In 2014, Fu and co-workers described a facile method for the C–H thiolation of phenols 7 with 1-(substituted phenylthio

• activated the N–S bond in II, which reacted with I to obtain IV, followed by C–S reductive elimination to give the thiolated product 30 or 31. On the other hand, the interaction of I with Cu(OAc)2 activated the N–S bond in III to afford IV, which was subjected to C–N reductive elimination to deliver the

• reductive elimination to yield ketone 78. In the acylthiolation cycle, the azaphilic ZnCl2 activated NTSE 1’’’ via N–Zn coordination to facilitate the leaving ability of succinimide. Then, nucleophilic substitution of arylmagnesium bromide 75 to intermediate IV provided thioester 79. In 2022, Gao and co

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

• activation to generate an aryl–Cu–NHC species. This is followed by the reaction with NHC–Pd to produce an Ar–Pd(NHC)Cl intermediate through the oxidative addition to Pd(0)NHC. Finally, transmetallation of [(It-Bu)Cu(Ar)] with [(SIPr)Pd(Ar)Cl] followed by reductive elimination leads to biaryl product. No

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

• pivalic anhydride as activator to afford Ni(II) intermediate F. Subsequently, trapping of the alkyl radical C generates high-valent Ni(III) intermediate G, which undergoes facile reductive elimination to furnish the final coupling product 3 and Ni(I) intermediate H. The single-electron transfer (SET

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

• functionalization via the canonical organometallic steps of oxidative addition/reductive elimination was ruled out via catalytic reaction of the macrocyclic Groves-type porphyrin catalyst V, a species that is unable to accommodate the mutual cis-orientation of ligands for metal-centered reductive elimination. 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

• literature to-date has shown that the vast majority of reactions follow the reductive elimination pathway to produce 4. However, a clear exception to this is in reactions with nucleophilic fluoride or [18F]fluoride, which reductively eliminate to exclusively generate fluoroarenes (e.g., 5). The rationale for

• reductive elimination of iodobenzene to give 11 (Figure 5, left). This was also the pathway subsequently suggested by Gallos et al. [116] for the synthesis of 13/14 from 12. In 2003, Hadjiarapoglou further investigated the intermolecular reaction between 8 and cyclopentene under thermal, metal-free

• , they believed that the reaction was likely initiated by either single electron transfer between the reagents (not shown), or by electrophilic addition of the olefin onto the ylide, forming intermediate adduct 17. This was followed by formation of iodocycle 18, from which reductive elimination of

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