C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• -trifluoroacetophenone as an internal standard. ND = not detected. Optimization of the reaction conditions.a Supporting Information Supporting Information File 28: Full experimental procedures, characterization of products, details of mechanistic studies, and spectral data. Funding This work has been partially

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• isolating the low-boiling non-polar products. Mechanistic studies suggested that in situ-generated difluorocarbene reacts with the ketone oxygen, followed by intermolecular protonation/deprotonation. Although the process has still synthetic limitations, also acyclic ketones can now be converted into

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• rise to a series of differently substituted 1,4-enynes with monofluoroalkyl units in high yields and ee values (Scheme 18, 18a–i). The reaction effectively overcomes the drawbacks of low activity of tertiary carbon nucleophiles and instability of fluorinated compounds. Preliminary mechanistic studies

• vinyl allenylidene species. A series of differently substituted spiro-cyclic products can be obtained with high yields, regio- and stereoselectivities (Scheme 32, 30a–x). Preliminary mechanistic studies indicated that the reaction first undergoes a substitution at the α-position of yne-allylic ester

• ). Preliminary mechanistic studies have ruled out the 1,3-sigmatropic shift, indicating that the reaction proceeds through a nucleophilic substitution–annulation process of a reactive π-extended copper-allenylidene intermediate (Scheme 43). At the same time, Qi and Xu et al. [79] also realized the dearomative

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

• further emphasized its utility. Mechanistic studies have demonstrated that the key to this selective chemical conversion lies in the dual oxidation process at the anode. The authors suggest that anodic oxidation of the sulfide generates a sulfur radical cation intermediate, which reacts with water at the

• ]. This mild method proceeds with a broad range of unactivated alkenes, including natural products and pharmaceutical derivatives such as sulbactam acid and oxaprozin. Mechanistic studies revealed that the reaction was initiated by the electrochemical oxidation of iodide ions, generating iodine radicals

• group. Based on extensive mechanistic studies, they proposed the formation of a formal Ni(IV) complex during the process. Remarkably, nickel proved to be uniquely effective for this protocol, as other transition-metal catalysts based on Cu, Co, Pd, Ir, Ru, and Rh did not catalyze the reaction (Scheme 36

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

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

• position 1. This protocol involves the utilization of enaminones, hydrazine, and various aryl halides as substrates, resulting in the formation of 1,3-substituted pyrazoles 76 (Scheme 27) [105]. Mechanistic studies have indicated that in this domino reaction, the initial formation of 3-substituted

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• the methods for the preparation of HFO-1132 as well as reactions demonstrating the chemical behavior of this compound. From the reactions not included in this Review article, mechanistic studies on 1,2-difluoroethylene ozonolysis [77][103][104][105][106][107][108] and studies on the stability of

Electrochemical radical cation aza-Wacker cyclizations

• Sota Adachi and
• Yohei Okada

Beilstein J. Org. Chem. 2024, 20, 1900–1905, doi:10.3762/bjoc.20.165

• reactions rather than ionic ones, since five-membered pyrrolidine formation is preferred over six-membered piperidine formation. Further mechanistic studies of the electrochemical radical cation aza-Wacker cyclizations are underway in our laboratory. Experimental Electrochemical aza-Wacker cyclizations: The

• mmol), Bu4NOTf (0.1 M), TFA (1 equiv), CH3CN (0.4 mL), and 1,2-DCE (3.6 mL). Yields reported here are isolated yields. Mechanistic studies of aza-Wacker cyclization. A: Electrochemical (Bu4NOTf in CH3CN/1,2-DCE), B: non-electrochemical (LiClO4 in CH3NO2). Control studies for electrochemical aza-Wacker

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

• , in an undivided cell, at 2.3 V cell potential, 400 nm LEDs, for 12 hours. a2,4,6-Collidine (1.0 equiv) was used instead of BTMG. bPhen was used instead of BPhen. cDMF/CH3CN (1:15 v/v) was used as solvent. dReactions were run with 0.4 mmol LiClO4 instead of TBABF4. Mechanistic studies and proposed

• catalytic cycles. Reaction discovery and optimization.a Supporting Information Supporting Information File 18: Experimental procedures, mechanistic studies, analytical data and copies of NMR spectra. Funding We thank the National Natural Science Foundation of China (No. 22071252) and the Chinese Academy

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• 110 °C for 16 h), moderate to good yields of N-methylamines were produced (Scheme 15). The mechanistic studies suggested that the base activates the complex Mn3. The active catalyst dehydrogenates methanol into formaldehyde and converts nitroarenes to anilines via transfer hydrogenation. The latter

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• different amides, including dipeptides, under mild and operationally simple conditions in high yields. Mechanistic studies suggest that BT-SCF3 can generate acyl fluorides from carboxylic acids via two distinct pathways, which allows the deoxyfluorinating reagent to be employed in sub-stoichiometric amounts

• under mild and operationally simple conditions while peptide coupling between two amino acids could be efficiently conducted using the longer-chain perfluoroalkyl reagent BT-SC5F11. Mechanistic studies revealed that each equivalent of the benzothiazolium reagent can feasibly generate two equivalents of

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• radical D which is then trapped by TsCl to produce the corresponding alkyl chloride E. Detailed mechanistic studies on a related reaction were recently reported by Shenvi and co-workes [84]. These studies alternatively suggest that intermediate C could also be the result not of a non-simultaneous addition

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• amine and the traces amount of water in this reaction system may serve as proton sources for the formation of hybrid α-ester alkylpalladium radical. On the basis of above mechanistic studies and previous reports [47][48][49][50][52][58], the following plausible mechanisms are proposed for the palladium

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

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• and unsymmetrical N,N'-substituted alkyl- and arylindigos with tunable thermal half-lives (follow-up mechanistic studies in 2022) 2018: first report on photochromic monoarylated indigos Synthesis of indigo derivatives Indigo (Ind) is one of the oldest organic molecules, which has been used as a dye

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

• photoredox radical reactions are relatively scarce [52], representing an unexplored area that requires further investigation. Developing asymmetric methodologies in this domain holds great promise for future exploration. Last but not the least, conducting detailed mechanistic studies on iodide/phosphine

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• gem-difluoroalkenes with organic azides in morpholine as a solvent to construct fully decorated morpholine-substituted 1,2,3-triazoles. Mechanistic studies revealed the formation of an addition–elimination intermediate of morpholine and gem-difluoroalkenes prior to the triazolization reaction via two

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

• pyrrolines 62 were obtained by changing the reaction solvent to MeCN. Also, organic fluorophore compounds such as benzothienopyrrole and bis-thiolated boron dipyrromethene can be achieved from 3-thiolated pyrroles. Mechanistic studies showed that the oxidative species HNO and HCHO were generated through a

• conversion of 1-I to 2-II was confirmed by mechanistic studies due to the stability of the benzyl carbocation, followed by 6-endo-dig cyclization. In this method, toxic transition metal catalysts, oxidants, or bases are not used, which made it economically and environmentally reliable. In 2023, Gao et al

• is no need to use a metal catalyst, base, or additive. N-(Sulfenyl)succinimide/phthalimide acted as an active electrophilic sulfur source, acted in the reaction mechanisms. However, mechanistic studies need further exploration to define a valid reaction pathway. Therefore, we believe that the use of

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

• form new C–Cl bonds in the presence of transient alkyl radicals, with mechanistic studies implicating homolytic abstraction of a chlorine ligand from the intermediate copper complex. Outside of the substitution products which could be generated from the RLT pathway, alkyl radicals could also undergo an

• simplified manganese salen complex I, allowing for the identity of the carbon–heteroatom bond to be controlled based on added nucleophile and enabling C–Cl, C–N, and C–S bonds to be formed directly while completely suppressing traditional ATRA products [9]. In mechanistic studies, rearrangement products

• adventitious discovery of nitrate functioning as a mild and selective oxidant in RLT catalytic systems presents many opportunities for future method development and are avidly pursuing this area of research. Outlook After scant exploration following its elucidation in early mechanistic studies of bioinorganic

Unravelling a trichloroacetic acid-catalyzed cascade access to benzo[f]chromeno[2,3-h]quinoxalinoporphyrins

• Chandra Sekhar Tekuri,
• Pargat Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2023, 19, 1216–1224, doi:10.3762/bjoc.19.89

• , copper(II) benzo[f]quinoxalinoporphyrin 17 for the mechanistic studies. On photophysical evaluation, the newly synthesized porphyrins displayed significant red-shifted absorption and emission as compared to simple meso-tetraarylporphyrins due to the extended π-electronic conjugation. Hence, the present

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• quenching study (Scheme 3F), expressed that the photoredox reaction started with the reductive generation of a malonyl radical from bromomalonate by interaction with the photocatalyst. Analyzing all the observations from the above mechanistic studies, we propose a plausible mechanism involving sequential

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

• their control experiments and literature mechanistic studies (Chegondi et al.) [84], the role of the base (LiOt-Bu) was considered. Following the Cu-catalyzed conjugate addition of B2pin2, the Michael cyclization is facilitated by the transmetalation of stoichiometric Li base with the Cu enolate (Scheme

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

• -trifluoromethyl substituent forming the ketone product in <10% yield. While substitution of the norbornene was tolerated, both EWGs and EDGs hindered the reaction. Upon several mechanistic studies, the authors proposed the catalytic cycle begins with the oxidative addition of the active Ni(0) catalyst to imide 27

• typically problematic in C–H activation reactions. Through mechanistic studies, the authors proposed the rate limiting step for this reaction is the C–H cleavage. In 2015, Miura and co-workers reported the Rh-catalyzed domino dehydrative naphthylation of oxabenzonorbornadienes 30 with arylphosphine

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

• isolated in 70% yield. Mechanistic studies indicated that the C–H bond activation event was the rate-limiting step and the authors suggested a similar mechanism to the one depicted in Scheme 20: formation of a palladacycle thanks to a concerted metalation deprotonation (CMD) process followed by oxidation

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• -depth mechanistic studies were so far reported regarding the reactivity of the enol phosphate electrophiles (Scheme 3 and Scheme 4, and Table 2, entry 4). Phosphate free anions released at each catalytic cycle could act either as NMP or alkoxides, that is, as ligands to the magnesium cations, or as