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

• . 1,2-Adducts could be produced fluently with diazo substrates containing alkyl-substituted esters. Benzyl- (6r, 57%), cyclobutanemethyl- (6s, 81%), methoxyethyl- (6t, 66%), and adamantyl- (6u, 82%) substituted diazo esters underwent this photoinitiated radical reaction well. The donor/acceptor

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

• fragmentation of 8 affords a radical species 9 in a constructive step towards initiating the radical reaction, a principal competing step is back-electron transfer (BET) to return the closed shell starting materials (Scheme 2B). A recent study showed comparable rates for fragmentation (8 ± 5 × 105 s−1) and BET

• hydrogen atom to terminate the radical reaction. The proposed mechanism of the hydroalkylation cascade is depicted in Scheme 13B. Upon excitation of complex 59 with blue light, intra-complex SET takes place from the HE to the NHPI ester, leading to the formation of tert-butyl radical 64 and radical cation

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

• review, we primarily focus on summarizing the recent advancements in inexpensive and readily available iodide/phosphine-mediated photoredox radical transformations. Keywords: annulation; decarboxylative; iodide/phosphine; photocatalytic; radical reaction; Introduction Over the past few decades

Lewis acid-promoted direct synthesis of isoxazole derivatives

• Dengxu Qiu,
• Chenhui Jiang,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2023, 19, 1562–1567, doi:10.3762/bjoc.19.113

• that the reaction is not a free radical reaction. Based on the control experiments and previous literature [21], we propose the following possible mechanism, which is shown in Scheme 5. Aluminum trichloride reacts with sodium nitrite to form an intermediate aluminum complex A, which is further

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

• and regenerates the tert-butoxyl radical to complete the entire catalytic cycle. The formation of hydrogen bonds between the oxygen of the carbonyl group and the hydrogen of the 2,2,2-trifluoroethanol (TFE) reduces the activation energy of the radical reaction and improves the coupling efficiency. In

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

• radical reaction [87]. Indeed, when ʟ-tyrosine methyl ester (154), 1,4-cyclohexanedione monoethylene acetal (155), and dehydroalanine derivative 156 were allowed to react in the presence of TFA, molecular sieves, 1 mol % of fac-Ir(ppy)3, and Hantzsch ester under blue LED irradiation at 40 W, this resulted

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• ] could be simplified by in situ generation of the catalyst. Moreover, in the debromination of norbornene imide 11, the expected Diels−Alder adduct with furan was not obtained, but compound 12 incorporating a tetrahydrofuran ring at position 2, presumably by radical reaction (Figure 2) [19][20]. We

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• the amidyl radical precursor under air is reported. A possible mechanism is proposed that proceeds via a radical reaction in the presence of CuBr and triethyl phosphite. Keywords: amination; copper; N-hydroxyphthalimides; radical reactions; triethyl phosphite; Introduction Practical methods for

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• supramolecular containers applied for a radical reaction involving external radical initiators with dynamic hosts. Later, this group reported another highly site-selective radical monoreduction of dihalides by trialkylsilanes (R3SiH) using the similar strategy [63]. A very intriguing site-selective catalytic

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

• the synthesis of 1-azaspiro[4.5]decanes 77 (Scheme 13) [89]. The reaction was amenable to both EWGs and EDGs; however, substitution at the ortho-position of the cinnamamide lowered the product yield. Mechanistic experiments suggest the reaction proceeds through a radical reaction. Moreover, kinetic

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

• bonds in less sterically congested environments. A mixture of diastereomers (1:1 ratio) resulted from the azidation of estrone acetate (14e), strongly supporting a radical reaction pathway. Based on their additional mechanistic experiments, the authors suggested that the oxidation of the Mn(III) species

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• compound N-Ac-1a gives deacetylated product 3a. The use of 1,1'-azobis(cyclohexanecarbonitrile) or Et3B as radical reaction initiators instead of AIBN was unsuccessful. Therefore, the reaction conditions for the free-radical cyclization of salt 1a were further optimized by variation of the mediator

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

• for all dioxygenated amides 9 the stereocenter at the alkoxyamine unit will be destroyed in the subsequent radical reaction, the low diastereoselectivity at that center is not of concern. In contrast, in the reactions of silylamides 8e–g bearing enantiomerically pure 1-arylethyl substituents with

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• desired homotropane. Ikeda synthesis – 2002 Ikeda et al. prepared azabicycle (±)-42, a protected form of (±)-euphococcinine (2) [45]. The author’s method focused on the radical reaction of 2-(but-3-ynyl)piperidine (±)-34 mediated by Bu3SnH. This "6-exo-dig" cyclization occurred in a regioselective way to

Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation–cyclization cascade mediated by K₂S₂O₈

• Qiang Liu,
• Weibang Lu,
• Guanqun Xie and
• Xiaoxia Wang

Beilstein J. Org. Chem. 2020, 16, 1974–1982, doi:10.3762/bjoc.16.164

• , we successfully separated a small amount of byproduct 4 which was identified by NMR spectroscopy. These experiments clearly support a phosphorus-centered radical reaction pathway. It has been reported that phosphorus-centered radicals could be generated from phosphine oxides in the presence of

Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles

• Ming-Xi Bi,
• Shuai Liu,
• Yangen Huang,
• Xiu-Hua Xu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2020, 16, 657–662, doi:10.3762/bjoc.16.62

• involved in these transformations. Keywords: cyclization; indole derivatives; oxidation; radical reaction; trifluoromethylthiolation; Introduction The trifluoromethylthio (SCF3) group could significantly improve the lipophilicity of organic molecules as shown by its high Hansch constant (π = 1.44 for

Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons

• Goki Hirata,
• Yu Yamane,
• Naoya Tsubaki,
• Reina Hara and
• Takashi Nishikata

Beilstein J. Org. Chem. 2020, 16, 502–508, doi:10.3762/bjoc.16.45

• radical reaction [36]. Both cases were helpful in our development of the current Cu-catalyzed cascade C–H cyclization system. After careful optimization, we found that CuI, 1,10-Phen, Cy2NMe as a base, and 1,4-dioxane were effective for obtaining the best yields of products 5 (Figure 2). In this

• could suggest new aspects of alkyne transformations in a copper catalyzed alkyl radical reaction system. Substrate scope of 1 and 2. aConducted at 80 °C for 24 h in MeCN with CuBr (10 mol %), 1,10-Phen (20 mol %), Cs2CO3 (4.0 equiv), NaI (2.0 equiv), 1 (3.0 equiv) and 2 (1.0 equiv). Yields were

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• manner of a radical reaction [27][28][29]. Starting with alcohol 12b, a putative precursor of the alkaloid kuanoniamine A (3), the three described cyclization methodologies were tested starting directly from alcohol 12b as well as from ketone 21, obtained by oxidation of 12b. The intramolecular biaryl

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

• reaction using xanthogenates, alkenes, and sulfonyl oxime ethers (Scheme 1, reaction 1) [21][22]. The reaction proceeds efficiently to provide good yields of α-alkoxyimino esters, potential precursors of lactams, lactones and β-keto esters. Since the three-component radical reaction involving alkyl halides

• and two radical C1 synthons, CO and sulfonyl oxime ethers, is known to be feasible [23][24][25], we were tempted to explore a novel class of four-component radical reaction [26][27][28] incorporating a xanthogenate, an alkene, CO, and a sulfonyl oxime ether (Scheme 1, reaction 2). This paper reports

• mechanism. Concept: Alkene difuctionalization by four-component radical reaction using xanthates, alkenes, CO and sulfonyl oxime ethers. Four-component coupling reaction of ethyl 2-((ethoxycarbonothioyl)thio)acetate (1a), 1-octene (2a), CO, and sulfonyl oxime ether 3a under radical conditionsa. Supporting

Insertion of [1.1.1]propellane into aromatic disulfides

• Robin M. Bär,
• Gregor Heinrich,
• Martin Nieger,
• Olaf Fuhr and
• Stefan Bräse

Beilstein J. Org. Chem. 2019, 15, 1172–1180, doi:10.3762/bjoc.15.114

• , but has never been thoroughly investigated. In this study, we show that an UV initiated radical reaction can be used to synthesize symmetrically and unsymmetrically substituted BCP sulfides by reaction of [1.1.1]propellane (1) with disulfides. Depending on the ratio of 1 to the disulfide, only the BCP

• same for all reactions with yields of around 35% for 6 and between 8–15% for 11. The yield of 11a could be increased to 20% by using a ratio of 3:1 (Table 1, entry 4). The radical reaction as proposed in Scheme 3 should lead to higher yields of 11 with an increasing amount of 1. As the kinetically

Photochemical generation of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical from caged nitroxides by near-infrared two-photon irradiation and its cytocidal effect on lung cancer cells

• Ayato Yamada,
• Manabu Abe,
• Yoshinobu Nishimura,
• Shoji Ishizaka,
• Masashi Namba,
• Taku Nakashima,
• Kiyofumi Shimoji and
• Noboru Hattori

Beilstein J. Org. Chem. 2019, 15, 863–873, doi:10.3762/bjoc.15.84

• -iodo-4-nitrobenzene (3) [68]. The TEMPO moiety was introduced at the benzylic position of 5a and 5b using the copper-catalyzed radical reaction in the presence of tert-butyl hydroperoxide (TBHP) to afford 2a and 2b in 38% and 52% yield, respectively [69]. The caged TEMPOs 2a and 2b were thermally

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• energy of N–H bonds, which may be beneficial to N-centered radical formation. However, due to the characteristics of the radical reaction, the resulting cycloaddition product mixtures have a low diastereoisomeric ratio, which increases the difficulty of separation and limits applications. In view of this

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

• several decades [39][40][41][42]. The free radical reaction was applied in a range of organic transformations because of its unique advantages such as excellent reactivity, mild conditions, functional group tolerance, and atom economy. A series of radicals, such as carbon, Se, CF3, halogen, S and N

• (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

• halides in excellent yields (path VII in Scheme 18). Similarly, the radical reaction of MCPs 1 with the RFTMS/CsF/PhI(OAc)2 gave homoallylic acohol esters in moderate to good yields (path VI in Scheme 18). Oxidative radical ring-opening and cyclization of cyclopropyl olefins In 2016, Li’s group reported a

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

• vicinal-dichlorination of phenylallenes; however, no such chlorination reaction has yet been achieved [29][30][31][32][33][34]. Recent reports of reactions between hypervalent iodine reagents and phenylallenes have highlighted the possible product outcomes achievable through ionic and radical reaction

One-pot synthesis of block-copolyrotaxanes through controlled rotaxa-polymerization

• Jessica Hilschmann,
• Gerhard Wenz and
• Gergely Kali

Beilstein J. Org. Chem. 2017, 13, 1310–1315, doi:10.3762/bjoc.13.127

• [26][27][28] including dienes [29]. This approach drastically widens the range of suitable hydrophobic polymeric axes, to all monomers being complexed in CD or hydrophilic CD derivatives. Up to now, rotaxa-polymerization was only performed via free radical reaction without control of the polymer chain