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

• limitation of the photoinduced palladium-catalyzed carboamination reactions and the radical-mediated difunctionalization of alkenes with diazo compounds. We envisioned an interesting MCR strategy with mild conditions to access unsaturated γ- and ε-AA derivatives via a π-allyl Pd radical-polar crossover

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

• photocatalytic radical-mediated dearomatization, with H2O serving as the nucleophile [54] (Scheme 9A). Despite the presence of H2O in the reaction, the reduction of 38 to its corresponding radical anion 39 could occur without the need for hydrogen-bonding (Scheme 9B). Cyclic voltammetry measurements of NHPI

• example, the NHPI ester derived from pivalic acid 58 and Hantzsch ester HE form EDA complex 59 which participates in radical mediated hydroalkylation reactions [60][61] (Scheme 13A). In the presence of electron deficient olefin 60, classic Giese-type addition takes place under photocatalyst-free

• form product 132 or by the in-situ-generated tetrachlorophthalimyl anion (–TCPhth) affording product 105. Stoichiometric reductants can facilitate certain radical-mediated transformations that involve NHPI esters, even without the presence of metal catalysts. Larionov and Sun have independently

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

• electron-deficient position of the pyridine ring in complex B to obtain pyridine radical C, which aromatizes through tert-butoxyl radical-mediated extraction of hydrogen to afford the desired 2-substituted pyridine and regenerate Sc(OTf)3. In 2019, Liu et al. first reported an enantioselective CDC 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

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• a TEMPO-trapped adduct (4) was detected by HRMS (Scheme 4a). Moreover, the radical-mediated ring-opening product 3am could be obtained with 66% yield in a radical clock experiment when redox-active ester 5 was engaged to react with acrylamide 1a under standard conditions (Scheme 4b). Finally, it

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• [98][99][100]. Preliminary biological screening indicates that members of this class are able to overcome multidrug resistance in vincristine resistant cells [98][99][100]. To access the common scaffold 188, the group relied on an intramolecular gold-photocatalyzed radical-mediated cyclization of an α

• meroterpenoids (Lou). Divergent synthesis of crinipellins by radical-mediated Dowd–Backwith rearrangement (Xie and Ding). Divergent total synthesis of Galbulimima alkaloids (Shenvi). Divergent synthesis of eburnane alkaloids (Qin). Divergent synthesis of Aspidosperma alkaloids (Boger). Photoredox based synthesis

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

• amine nucleophiles [139]. Following an iminyl radical-mediated intramolecular 1,5-cyclization, the subsequent alkyl radical could propagate across carbon monoxide, eventually terminating with an alkyl or aryl amine. In the following year, the Li group described an interesting radical cyclization of β,γ

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

• cycle involving the generation of methyl radicals via β-scission of a tertiary radical which in turn was generated from trimethyl orthoformate by a photogenerated chlorine radical-mediated HAT process (Figure 14) [92]. Recently, Stahl devised a photoredox nickel-catalyzed methylation of benzylic and α

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• “Guareschi 1897 reaction”, is one of the most unusual reactions in organic chemistry, involving the radical-mediated paradoxical aerobic generation of hydrocarbons in near-neutral water solution. A discussion of the mechanism of this amazing reaction, the only metal-free process that generates hydrocarbons

• so-called “1897 reaction” is not well known [7], despite that the unique mechanistic aspects make it one of the most unusual reactions in organic chemistry, involving the paradoxical radical-mediated aerobic generation of hydrocarbons in water under only slightly basic conditions [8]. Also

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• Nazarov cyclization with the strong silylating agent Me3Si+ B(OTf)4− to afford the corresponding 2-fluorocyclopentenone derivatives, e.g., compound 124 (Scheme 54) [37][90]. Radical-mediated ring-opening reaction: The photochemical iodine atom-transfer ring opening of 1,1-difluoro-2-(1-iodoalkyl

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• ) catalyst and subsequent base-promoted epimerization produced meloscine (158) in 83% yield. In 2017, Yang and co-workers disclosed the synthesis of (−)-pavidolide B (166) by using a thiyl-radical-mediated [3 + 2] annulation reaction to create four contiguous stereocenters on tricycle 162 in one step [71][72

• -cation equivalent in [3 + 2] cycloaddition in the synthesis of (±)-cuparene (13) [69]. The recent advances of [3 + 2] annulation in natural product synthesis. (A) The preparation of meloscine (158) features a cascade radical annulation of divinylcyclopropane [70]. (B) Thiyl-radical-mediated [3 + 2

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• alkanes provided an efficient protocol for the synthesis of alkanes from carboxylic acid substrates previously inaccessible through other methods. The mechanism of this reaction is similar to the previously proposed mechanism in Scheme 19. Isomerization reactions Thiyl radical-mediated isomerizations of C

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

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

• heteroarylated to give the desired dehalogenated products 13.3 or arylheteroarenes 13.4. Other organic dyes, such as dicyanoanthracene (OD5) and rhodamine 6G (OD14), have been successfully used in similar conPET strategies for the aryl radical-mediated derivatization of aryl bromides [82][83]. A similar double

• acceptors 18.2 to afford the desired ketone 18.3. Recently, the Melchiorre group reported a carbamoyl radical-mediated metallaphotoredox synthesis of arylamides (Scheme 19) [91]. In this protocol, excited-state 4CzIPN (OD6) oxidizes a 4-carbamoyl-1,4-dihydropyridine 19.1, which then fragments, releasing the

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

• ]. Benzaldehyde (8) was tested as an alternative to tertiary amines, which are commonly employed in radical-mediated reactions due to their ability to bind to atmospheric oxygen, which inhibits such reactions. The quinoxalines 32 were used as the prime photoinitiators, and the reaction was placed in a

Room-temperature Pd/Ag direct arylation enabled by a radical pathway

• Amy L. Mayhugh and
• Christine K. Luscombe

Beilstein J. Org. Chem. 2020, 16, 384–390, doi:10.3762/bjoc.16.36

• -temperature, Pd/Ag-catalyzed direct arylation systems are radical-mediated. This is in contrast to the commonly proposed two-electron mechanisms for direct arylation and appears to extend to other substrates such as benzo[b]thiophene and pentafluorobenzene. Keywords: direct arylation; indole; palladium

• studies are needed to conclusively indicate a radical mechanism, the trap experiments and room-temperature reactivity indicate that a radical-mediated mechanism similar to the indole direct arylation may be governing the observed reactivity. Conclusion In conclusion, in the midst of investigating room

• iodobenzene. Moreover, other substrates such as benzo[b]thiophene and pentafluorobenzene appear to undergo a radical-mediated Pd/Ag room-temperature direct arylation. This is a useful insight for advancing the direct arylation knowledge base, and serves as inspiration for designing new polymerization systems

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• 2011, Nagib and MacMillan reported the synthesis of a broad scope of trifluoromethylated products via a radical-mediated methodology using photoredox catalyst 13 (Scheme 13) [113]. In comparison to other reported methods that used harsher reaction conditions, they carried out the reaction using

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

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

• , alkenes, CO, and sulfonyl oxime ethers, can proceed under radical mediated conditions, using hexabutylditin as a radical chain carrier, to give the corresponding keto-oximes in moderate yields. A variety of functional groups are tolerated under the high CO pressure and temperature conditions. Among

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• thiyl-radical-mediated reactions have been extensively investigated for the preparation of carbohydrate derivatives [20] and some dithioether phospholipid and glycolipid analogues [21][22], no examples were reported for the synthesis of n-alkyl thioglycosides by using thiol–ene coupling [18][19]. In

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• synthesis of 1-naphthaldehydes 25 under mild conditions via a radical-mediated ring-opening and intramolecular cyclization of MCPs 23 with organic selenium reagents 24 (Scheme 8) [59]. In this reaction, the MCPs with electron-withdrawing groups gave lower yields than that with electron-donating groups

• radical intermediate 76. The intermediate 77, produced by the intramolecular cyclization of intermediate 76, reactes with diphenyl diselenide 73 to form the target product 74 via homolytic substitution (SH). In 2013, Ryu and co-workers developed the bromine radical-mediated ring-opening and alkylation of

• (path IV in Scheme 17). In 2016, Xu’s group exploited the fluoroalkyl (RF) radical-mediated ring-opening of MCPs 1 for the synthesis of fluorinated homoallylic compounds (80 and 81, Scheme 18) [96]. In this reaction system, the radical reaction of MCPs 1 with RF-X (X = Br, I) furnished homoallylic

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• electrochemical reduction. In addition, the corrin-ring of the B12 derivatives is tolerant to free radicals, as described above. Thus, alkylated complexes have been used for radical-mediated organic synthesis such as halide coupling, alkene coupling, and addition to double bonds [7][26][27]. In particular, the Co

• , and Irdfppy system was used for radical-mediated isomerization reactions. Visible-light irradiation of diethyl 2-bromomethyl-2-phenylmalonate produced the phenyl-migrated product (Scheme 10) [104]. The product distribution highly depended on the solvents. The yield of phenyl-migrated products relative

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• -radical mediated “click” process with diverse applications in small molecule and polymer synthesis and has been reviewed [74][75][76]. The importance of the thiol-ene reaction in the synthesis of β-hydroxy sulfides is exemplified by the work of Scanlan and co-workers as shown in Scheme 41 [77][78

Chlorination of phenylallene derivatives with 1-chloro-1,2-benziodoxol-3-one: synthesis of vicinal-dichlorides and chlorodienes

• Zhensheng Zhao and
• Graham K. Murphy

Beilstein J. Org. Chem. 2018, 14, 796–802, doi:10.3762/bjoc.14.67

• pathways. For example, Liu and co-workers used Togni’s benziodoxolone reagent [35] in a radical-mediated vicinal 2,3-difunctionalization of allenes, which proceeded via CF3-radical adduct A (Scheme 1a) [36]. In contrast, Muñiz reported that with PhI(NTs2)2, an oxidative amination occurred via cation B