Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• difunctionalization of alkynes with various heteroatom and carbon nucleophiles [27][28][29][30][31][32][33][34]. Specifically, intermolecular trans-iodo(III)functionalization of alkynes has been achieved using oxygen nucleophiles such as alcohols [28][32], ethers [33], carboxylic acids [31], phosphate esters [31

• iodoazolation reaction, highlighting the unique utility of the iodine(III) electrophile in the present alkyne difunctionalization. With the standard conditions (Table 1, entry 1) in hand, we explored the scope of the three-component N-vinylation (Scheme 2). First, various azoles were subjected to the vinylation

• difunctionalization reaction to afford the product 4ag in 62% yield. While sluggish, trimethylsilylacetylene was selectively azolated at the terminal position (see 4ah), which could be rationalized by the better stabilization of a partial positive charge at this position by the β-silyl substituent. Finally, an

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

• electrophilic trapping of onium ylides generated from metal carbenes with nucleophiles, providing an ingenious difunctionalization strategy for diazo compounds to access structurally complex and diverse molecules (Scheme 1b, top) [28][29]. In recent years, radical-mediated MCRs with diazo compounds have become

• a highly emerging area of research and exhibit complementary reactivity to those well-developed carbene-mediated MCRs [30][31][32][33][34][35][36][37][38][39][40][41][42]. In the radical-mediated difunctionalization of alkenes, the carbon-centered radical species from a diazo compound can add to

• diverse alkenes followed by a diradical coupling or radical addition process to achieve the difunctionalization (Scheme 1b, middle) [32][33][34][35][36][37]. However, to the best of our knowledge, the methodology involving the addition of a carbon radical from a diazo compound onto the double bond of an

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

• the difunctionalization of styrenes [68] (Scheme 17B). The catalytic cycle for the styrene difunctionalization reaction is depicted in Scheme 18. First, EDA complex 88 consisting of RAE 58 and the PTH1 catalyst is formed. Under blue light irradiation, intra-complex SET leads to the formation of PTH

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

• reacted with thiosulfonates 70 and N-arylthiosuccinimides 1 as thiolating reagents. 1,2-Thiosulfonylethenes 71 were obtained via vicinal thiosulfonylation. However, in the case of 1,1-dithioethenes 69, germinal disulfenylation occurred. In addition, 1,2-difunctionalization of indole-derived 1,1

• . Co-catalyzed C2-sulfenylation and C2,C3-disulfenylation of indole derivatives. Plausible catalytic cycle for Co-catalyzed C2-sulfenylation and C2,C3-disulfenylation of indoles. C–H thioarylation of electron-rich arenes by iron(III) triflimide catalysis. Difunctionalization of alkynyl bromides with

• thiosulfonates and N-arylthio succinimides.· Suggested mechanism for difunctionalization of alkynyl bromides with thiosulfonates and N-arylthio succinimides. Synthesis of thioesters, acyl disulfides, ketones, and amides by N-thiohydroxy succinimide esters. Proposed mechanism for metal-catalyzed selective

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

• addition to alkenes and radical decarboxylation, with many of these being driven by light energy. RLT in alkene functionalization Outside of the realm of C–H activation, RLT has been leveraged to afford complex medicinal scaffolds in alkene difunctionalization. A recent example can be found in the merger

• paradigm with photocatalytic ATRA to enable the modular difunctionalization of alkenes under reagent control (Scheme 3). In Stephenson’s photocatalytic ATRA reports, the C–X bond in the product was proposed to be formed through both direct quenching of a transient alkyl radical by halogen atom transfer

• instead of the halide included in the alkyl halide reagent, limiting the ability to form different difunctionalization products. Taking inspiration from Groves’ bio-inspired manganese tetradentate manganese catalysts, we found we could instead functionalize the transient alkyl radical via RLT from a

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

• coupling partners to either propagate the reaction or to terminate the process. This review presents a comprehensive examination of domino reactions involving strained bicyclic alkenes. Rather than being exhaustive in the range of potential difunctionalization processes covered, the review will be limited

• difunctionalization of norbornene derivatives 15 with alkynes (Scheme 3) [35]. It was noted the reaction is amenable to both electron-donating groups (EDGs) and electron-withdrawing groups (EWGs); however, yields were diminished with increasing electron deficiency. Moreover, the use of the bulkier tert

• product 19c, the latter was obtained in a greatly reduced yield, perhaps due to less ring strain providing a thermodynamic driving force. In 2013, Mannathan et al. discussed a Ni-catalyzed intermolecular three-component difunctionalization of oxabicyclic alkenes 1 with organoboronic acids 20 and alkynes

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

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• mainly as mediators of oxidative electron transfer (SET mechanism). For example, one-electron oxidative properties of triarylamine cation radicals were used for the vinylarene difunctionalization with the formation of thiadiazolidine 1,1-dioxides that can be further transformed to the corresponding 1,2

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

• with the reductive addition or difunctionalization of the π-system; however, it has been demonstrated the radical intermediate can go through a SET oxidation/elimination to recover the initiating π-functionality. In this review, Fe-catalyzed domino coupling reactions involving π-systems will be

• of the alkyl radical generating the cross-coupled product cannot be ruled out [57][60]. In 2020, Gutierrez and co-workers developed a Fe-catalyzed intra- and intermolecular difunctionalization of vinyl cyclopropanes 14 with alkyl bromides 13 and aryl Grignard reagents 2 (Scheme 4) [61]. Using

• generating a benzylic radical which can be oxidized by Ag(I) to afford the corresponding benzylic cation. Nucleophilic trapping with an amine will produce the final product. In the same year, Song and co-workers reported a dehydrogenative 1,2-difunctionalization of conjugated alkenes 107 with silanes 92 and

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

• thiocyanate to generate 4-alkyl/aryl-2-aminothiazoles. Mechanistic experiments demonstrated that the photocatalyst formed in situ from Cu(OAc)2 and ammonium thiocyanate promoted the intermolecular cyclization (Scheme 7). 3.2 Difunctionalization of alkenes The 1,2-difunctionalization of alkenes is a versatile

• strategy for the construction of complex molecules. The primary process involved in the 1,2-difunctionalization of alkenes catalyzed by copper complexes is an atom-transfer radical addition (ATRA). Copper complexes or copper-based photoredox-active complexes formed in situ serve as photocatalysts to

• with oxime esters. Oxo-azidation of vinyl arenes. Azidation/difunctionalization of vinyl arenes. Photoinitiated copper-catalyzed Sonogashira reaction. Alkyne functionalization reactions. Alkynylation of dihydroquinoxalin-2-ones with terminal alkynes. Decarboxylative alkynylation of redox-active esters

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

• regenerate the nickel(0) species 21-VI and the carboxylate product 21-IX. Olefin difunctionalization Nickel-catalyzed alkene 1,2-difunctionalization is considered as useful method for preparing complex molecules in a single-step reaction [137][138][139]. In this aspect, the groups by Kong [140] and Molander

• -acylsuccinimides. Proposed catalytic cycle for the photoredox nickel-catalyzed aldehyde C–H functionalization. Proposed mechanism for the photoredox carboxylation of methylbenzenes with CO2. Proposed catalytic cycle for the decatungstate photo-HAT and nickel catalysis enabled alkene difunctionalization. Proposed

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• yields and enantioselectivities when subjected to four sequential reactions mediated by a cooperative catalysis of a NHC organocatalyst with LiCl in the presence of DPQ as an oxidant, as shown in Scheme 17. Recently, Chen et al. used a NHC catalyst 59 in γ,δ-difunctionalization of coumarins 56 through an

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

• were found to be unreactive, probably due to steric hindrance. The one-pot difunctionalization of arenes involving a sequential C–O cleavage and C(sp2)–H activation mediated by chromium was recently reported by Luo and Zeng [124]. The reaction allows an ortho-directed diarylation of o

• reaction was kept at room temperature to avoid the difunctionalization, and the oxidant was added only in the second step. Following this route, six examples were obtained with moderate yields (56–70%, Scheme 16C). Although the use of chromium catalysis is still considered challenging due to the high

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• defined combinations of chiral epoxides and chiral amides. This represents a very rare example of an oxidative geminal C–C/C–O difunctionalization next to carbonyl groups. The resulting dioxygenated allylic amides are subsequently subjected to persistent radical effect-based 5-exo-trig radical cyclization

• -allylic 2-silylacetamides would provide an intermediate alkoxide from which the Brook rearrangement and subsequent oxygenation could proceed (Scheme 1C). This represents in the event a geminal C–C/C–O difunctionalization of amide 8 and results in the α,γ-dioxygenated N-allylic amides 9. Thermal radical

• represents an oxidative C–C/C–O difunctionalization at the α-position of the amides. With correct configuration combination of chiral epoxides 7 and chiral amides 8, 2,4-dioxygenated amides 9 can be obtained with good anti-diastereoselectivity and enantioselectivity. Dioxygenated amides 9 are convenient

Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes

• Xiaojuan Li,
• Qiang Zhang,
• Weigang Zhang,
• Jinzhu Ma,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49

• , Nanjing 210023, China School of pharmacy, Wannan Medical College, Wuhu, 241002, China 10.3762/bjoc.17.49 Abstract The difunctionalization of alkenes involving a trifluoromethylthio group (SCF3) for the conversion of versatile and readily available olefins into structurally more complex molecules has been

• . Keywords: alkenes; difunctionalization; metal-free; photoredox; trifluoromethylthiolation; Introduction The incorporation of fluorine atoms into drug molecules will significantly enhance the physical, chemical, and biological properties of the pharmaceuticals [1][2][3][4][5][6]. Modifying drug candidates

• ][16][17]. The vicinal difunctionalization of olefins to introduce two functional groups across a double bond has appeared as a powerful transformation to rapidly increase molecular complexity in synthetic chemistry with improved efficiency [18][19][20][21][22]. Various transition-metal-mediated

Silver-catalyzed synthesis of β-fluorovinylphosphonates by phosphonofluorination of aromatic alkynes

• Yajing Zhang,
• Qingshan Tian,
• Guozhu Zhang and
• Dayong Zhang

Beilstein J. Org. Chem. 2020, 16, 3086–3092, doi:10.3762/bjoc.16.258

• is the most rapid and convenient one (Scheme 1). Although studies on alkyne difunctionalization are ongoing [23], the successful attachment of a fluorine atom to the resulting alkene through transition metal catalysis remains a challenge. In particular, the phosphonofluorination of alkynes for the

• introduction of two strong electron-withdrawing groups into double bonds has not yet been reported. With our continuous interest in, and inspiration from the well-established transition metal-catalyzed radical difunctionalization of unsaturated carbon–carbon bonds, specifically the work of Li’s group and

• substrate scope and excellent functional group tolerance, this simple protocol may represent a general, one-step approach for the preparation of β-fluorophosphonate frameworks for the use in medicinal chemistry. Metal-catalyzed difunctionalization of unsaturated carbon–carbon bonds. Substrate scope for the

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

• cations and radical anions) Recently, the exploitation of alkenyl and aryl radical ions has emerged as a platform for the functionalization of small molecules. They appear as attractive intermediates for a direct alkene difunctionalization or arene C–H functionalization. In particular, radical cations are

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• witnessed. 1.1 ATRA reactions Atom transfer radical addition reactions are linchpin transformations in organic synthesis as they allow an easy difunctionalization of alkenes. Usually, these reactions require the use of a radical initiator or thermal activation to initiate the radical chain. Recently

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• group of Liang reported the difunctionalization of terminal styrenes and arylacetylene derivatives by introducing SeCF3 with the [(bpy)CuSeCF3]2 copper complex developed by the group of Weng and difluoroalkyl groups with ICF2CO2Et (Scheme 8) [25]. Only six examples were reported, with good yields

• heterocycles with [(bpy)CuSeCF3]2 by the group of Weng. Difunctionalization of terminal alkenes and alkynes with [(bpy)CuSeCF3]2 by the group of Liang. Synthesis of Me4NSeCF3. Oxidative trifluoromethylselenolation of terminal alkynes and boronic acid derivatives with Me4NSeCF3 by the group of Rueping

Synthesis and optoelectronic properties of benzoquinone-based donor–acceptor compounds

• Daniel R. Sutherland,
• Nidhi Sharma,
• Georgina M. Rosair,
• Ifor D. W. Samuel,
• Ai-Lan Lee and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2019, 15, 2914–2921, doi:10.3762/bjoc.15.285

• difunctionalization is dependent on the electronics of the substituent added to BQ) [14], 5 was instead furnished from the dibromo-functionalized BQ 1-Br2 using a double Suzuki coupling. As expected, much harsher conditions (100 °C) were required to achieve conversions under Pd(0) catalysis to produce 5 in 22% yield

α-Photooxygenation of chiral aldehydes with singlet oxygen

• Dominika J. Walaszek,
• Magdalena Jawiczuk,
• Jakub Durka,
• Olga Drapała and
• Dorota Gryko

Beilstein J. Org. Chem. 2019, 15, 2076–2084, doi:10.3762/bjoc.15.205

• substituents into an aldehydes’ structure. Interestingly, to the best of our knowledge, there are no reports on ‘one-pot’ reactions leading to difunctionalization at both α and β-positions. To this end, in subsequent experiments, we attempted to merge two photochemical processes: β-benzylation (according to

• ). Photochemical difunctionalization of cinnamaldehyde (12) at the β and α-positions. Supporting Information Supporting Information File 416: Photochemical equipment, experiments for the optimization of the one-pot procedure, analytical data for 7, 8, 10, 11, HPLC chromatograms, and NMR spectra. Acknowledgements

Vicinal difunctionalization of alkenes by four-component radical cascade reaction of xanthogenates, alkenes, CO, and sulfonyl oxime ethers

• Shuhei Sumino,
• Takahide Fukuyama,
• Mika Sasano,
• Ilhyong Ryu,
• Antoine Jacquet,
• Frédéric Robert and
• Yannick Landais

Beilstein J. Org. Chem. 2019, 15, 1822–1828, doi:10.3762/bjoc.15.176

• difunctionalization of alkenes by four-component radical cascade reaction using xanthogenate 1, alkenes 2, CO, and sulfonyl oxime ethers 3 leading to 5a–l. Reaction conditions: 1 (0.4 mmol), 2 (4 mmol), CO (130 atm), 3 (0.5 mmol), DTBHN (30 mol %), (Bu3Sn)2 (0.8 mmol), DCE (8 mL), 45 °C, 16 h. Proposed radical chain

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• , Hungary Institute of Nanoscience and Nanotechnology National Center for Scientific Research “Demokritos”, Patr. Gregoriou E & 27 Neapoleos str., Aghia Paraskevi Attikis 15341, Greece 10.3762/bjoc.15.66 Abstract The regioselective difunctionalization of cyclodextrins (CDs) leading to derivatives amenable

• to further transformations is a daunting task due to challenging purification and unambiguous characterization of the obtained regioisomers with similar physicochemical properties. The primary-side homo-difunctionalization of β-CD can lead to three regioisomers, while the hetero-difunctionalization

• can generate three pairs of pseudoenantiomers. Previously, approaches with several synthetic steps, expensive reagents, high purification demands and low yields of the products have been employed. Herein we present direct, short and efficient primary-side difunctionalization strategies featuring

Tandem copper and photoredox catalysis in photocatalytic alkene difunctionalization reactions

• Nicholas L. Reed,
• Madeline I. Herman,
• Vladimir P. Miltchev and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2019, 15, 351–356, doi:10.3762/bjoc.15.30

• Nicholas L. Reed Madeline I. Herman Vladimir P. Miltchev Tehshik P. Yoon Department of Chemistry, University of Wisconsin–Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States 10.3762/bjoc.15.30 Abstract Oxidative alkene difunctionalization reactions are important in synthetic

• that are not accessible from the native reactivity of the organoradical intermediates by themselves. Our laboratory is interested in the design of photochemical strategies for oxidative functionalization reactions [15][16]. We recently described [17] a new approach to alkene difunctionalization that

• ) complex. We describe herein the results of this investigation, which has led to the identification of a tandem photoredox copper(II) catalytic system for the net-oxidative difunctionalization of alkenes. Results and Discussion A range of mild oxidants can oxidize copper(I) to copper(II), and the use of

Hypervalent iodine compounds for anti-Markovnikov-type iodo-oxyimidation of vinylarenes

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Mikhail A. Syroeshkin,
• Alexander A. Korlyukov,
• Pavel V. Dorovatovskii,
• Yan V. Zubavichus,
• Gennady I. Nikishin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2018, 14, 2146–2155, doi:10.3762/bjoc.14.188

• syntheses. In the row of organohalides, iodides are the most reactive and versatile reagents for the following transformations [60]. One of the purposes of our work was to introduce iodine in the process of difunctionalization of styrenes with imide-N-oxyl radicals. Iodine atom in the product can act as a

• styrene (1a, purple), NHPI (2a, red), I2 (blue) and PhI(OAc)2 (green) in 0.1 M n-Bu4NBF4/MeCN at a scan rate of 100 mV/s on a working glassy-carbon electrode. Difunctionalization of double C=C bond with the formation of C–O and C–I bonds. Iodo-oxyimidation of styrenes 1a–k with preparation of products 3aa