Multicomponent versus domino reactions: One-pot free-radical synthesis of β-amino-ethers and β-amino-alcohols

• Bianca Rossi,
• Nadia Pastori,
• Simona Prosperini and
• Carlo Punta

Beilstein J. Org. Chem. 2015, 11, 66–73, doi:10.3762/bjoc.11.10

• aldehyde or ketone, and a suitable source of nucleophilic radicals (Nu–H = formamide [24][25], methanol [26][27], ethers [28]), in the presence of titanium chlorides, and slowly dropping a solution of hydroperoxide (H2O2 or tert-butyl hydroperoxide (t-BuOOH)) into the reaction medium (Scheme 1). Aqueous

Cyclization–endoperoxidation cascade reactions of dienes mediated by a pyrylium photoredox catalyst

• Nathan J. Gesmundo and
• David A. Nicewicz

Beilstein J. Org. Chem. 2014, 10, 1272–1281, doi:10.3762/bjoc.10.128

• challenges. Classical approaches to the introduction of cyclic peroxides typically rely on cycloadditions of alkenes and dienes with singlet oxygen. However, ene processes can often compete, leading to complex mixtures of hydroperoxide adducts [1][6][7][8]. More recently, cyclization reactions of

• , to exclude the intervention of a singlet oxygen mechanism, we conducted the reaction in the presence of Rose Bengal. Under these conditions, we observed only 1O2 ene reactivity with the isoprenyl group (65% yield of hydroperoxide), underscoring the unique reactivity garnered by this catalyst system

• (see Supporting Information File 1 for hydroperoxide characterization). Suitable crystals of 3a provided X-ray confirmation of the endoperoxide structure (Figure 2). We invoke a mechanism similar to that proposed by Miyashi [12] and Yoon [15] in their respective transformations (Scheme 3). Following

An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

• Suresh Babu Meruva,
• Akula Raghunadh,
• Raghavendra Rao Kamaraju,
• U. K. Syam Kumar and
• P. K. Dubey

Beilstein J. Org. Chem. 2014, 10, 471–480, doi:10.3762/bjoc.10.45

• reaction with tryptamine in presence of NaI. The Schiff base on in situ oxidation with cumene hydroperoxide afforded an unstable oxaziridine derivative 15. Ring opening of the oxaziridine derivative 15 in presence of base afforded ketoiminol 16, which on iminol–amide tautomerism provided the required α

• N2 atmosphere and it was stirred for 1–2 h at 25–45 °C. Then cumene hydroperoxide (88% n-hexane solution, 3.73 g, 21.6 mmol) was added to the mixture over a period of five minutes (exothermic reaction), and it was further stirred for another 3–6 h at the same temperature. After completion of the

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• provides an efficient tool for introducing the hydroperoxide function. The reaction starts with the coordination of oxygen to the double bond followed by the formation of hydroperoxides presumably by a stepwise or concerted mechanism [229][230]. The oxidation of α,β-unsaturated ketones 1a–c by singlet

• oxygen affords 3-hydroxy-1,2-dioxolanes 3a–c via the formation of β-hydroperoxy ketones 2a–c (Scheme 1) [231]. Dioxolane 6 was synthesized in 36% yield by the reaction of oxygen with hydroperoxide 4 in the presence of di-tert-butyl peroxalate (DTBPO) followed by the treatment of the reaction mixture with

• obtained as the by-product (Scheme 15, Table 6) [249]. The desilylation of the initially formed silicon peroxide followed by cyclization of the hydroperoxide accompanied by the attack on the electrophilic center is another example of the use of the Isayama–Mukaiyama reaction for the synthesis of cyclic

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• stable and inexpensive electrophilic trifluoromethyl radical source to access trifluoromethyl-substituted alkenes [62]. Cinnamic acids were reacted with sodium trifluoromethanesulfinate and a catalytic amount of copper(II) sulfate in the presence of tert-butyl hydroperoxide (TBHP) as the radical

A protecting group-free synthesis of the Colorado potato beetle pheromone

• Zhongtao Wu,
• Manuel Jäger,
• Jeffrey Buter and
• Adriaan J. Minnaard

Beilstein J. Org. Chem. 2013, 9, 2374–2377, doi:10.3762/bjoc.9.273

• . For both reactions, however, varying enantioselectivities had been reported, so both substrates were studied. According to the published procedure, upon treatment of freshly distilled geraniol (Scheme 3) with tert-butyl hydroperoxide in the presence of D-(−)-diisopropyl tartrate (DIPT) and Ti(OiPr)4

• , tert-butyl hydroperoxide, CH2Cl2, 4 Å MS, –10 to –23 °C, 2 h, 93%, 94:6 er; b) HClO4 (70%), THF/water, rt, 30 min, 94%; c) 0.5 mol % 2, p-benzoquinone, CH3CN/water, rt, overnight, 91%. Synthesis starting from nerol. Reagents and conditions: a) L-(+)-diisopropyl tartrate, Ti(OiPr)4, tert-butyl

• hydroperoxide, CH2Cl2, 4 Å MS, −10 to −23 °C, 2 h, 89%, 87:13 er; b) HClO4 (70%), THF/H2O, rt, 30 min, 92%. Supporting Information Supporting Information File 490: Experimental and spectroscopic details for 1, 3 and 4, and determination of the ee of 3 and 4. Acknowledgements This work was supported by the

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• dark after 4 h irradiation. This observation supports the formation of hydroperoxide intermediate 21. Tan and coworkers employed a cocatalyst system composed of the organic dye Rose Bengal and graphite oxide (GO) for α-cyanation of N-aryltetrahydroisoquinolines (Scheme 7) [70]. The use of GO as

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• using a route analogous to one reported by Smith [38]. Allylation of 24 with (+)-B-allyldiisopinocampheylborane generated the alcohol 25 in high yield and enantioselectivity. Directed epoxidation using VO(acac)2 and tert-butyl hydroperoxide was initially performed in order to furnish 27 directly

Re₂O₇-catalyzed reaction of hemiacetals and aldehydes with O-, S-, and C-nucleophiles

• Wantanee Sittiwong,
• Michael W. Richardson,
• Charles E. Schiaffo,
• Thomas J. Fisher and
• Patrick H. Dussault

Beilstein J. Org. Chem. 2013, 9, 1526–1532, doi:10.3762/bjoc.9.174

• , tetrahydropyranol 4a and the O-t-butyldimethylsilyl ether of the latter (4b). While good yields of acetals were obtained from the reaction with primary or secondary alcohols, or t-butyl hydroperoxide, acetalization with phenol proceeded in poor yield. Attempted acetalizations of 2,3,4,6-tetrabenzylglucose, the

• hydroperoxide (which would presumably lead to heterolytic fragmentation) and activation of the peroxide C–O was clearly disfavored relative to activation of the alkoxide C–O bond. Rapid alkoxide metathesis was also observed in the presence of a strong Brønsted acid. Our observations suggest that the seeming

Metal-free aerobic oxidations mediated by N-hydroxyphthalimide. A concise review

• Lucio Melone and
• Carlo Punta

Beilstein J. Org. Chem. 2013, 9, 1296–1310, doi:10.3762/bjoc.9.146

• hydroperoxide intermediate, prolonging the free-radical chain [39][40][41]. The NHPI-activation by AQ has been also adopted by other research groups. Li and co-workers applied the NHPI/AQ system to promote the metal and solvent-free oxidation of α-isophorone to ketoisophorone, preventing the isomerization

• desired hydroperoxide in 28% yield with 84% of selectivity. Similarly, ethylbenzene was oxidized to the corresponding hydroperoxide with a lower yield (13%), but a higher selectivity (91%), by operating at the same temperature with 2% NHPI, 2% acetaldehyde, and with a volume ratio ethylbenzene/CH3CN of 1

• described above led to the formation of acetophenone as the major product of ethylbenzene oxidation. A different result was achieved by Fierro et al. who, in the same year, reported the ethylbenzene oxidation to its hydroperoxide by operating in the presence of NHPI (or other NHIs, i.e., N

Copper-catalyzed aerobic aliphatic C–H oxygenation with hydroperoxides

• Pei Chui Too,
• Ya Lin Tnay and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2013, 9, 1217–1225, doi:10.3762/bjoc.9.138

• (Scheme 2b). Findings We commenced our investigation with the Cu-catalyzed aerobic reactions of hydroperoxide 1a in the presence of Et3N as a terminal reductant [15] to keep lower valent Cu(I) species in the reaction mixture (Table 1). As expected, when 1a was treated with Cu(OAc)2 (20 mol %) in the

• 4a were described in Scheme 3. Single-electron reduction of the starting Cu(OAc)2 by Et3N forms the Cu(I) species, which reduces hydroperoxide 1a to give O-radical I along with the generation of the Cu(II) species. 1,5-H-Radical shift of O-radical I generates C-radical II, which is trapped by

• hydroperoxide deliver 1,4-diol 3a. In the absence of molecular O2 (under a N2 atmosphere, Table 1, entry 15), the resulting C-radical I is oxidized by the Cu(II) species to give carbocation VI [19], which is trapped by the intramolecular hydroxy group to give 4a. We next explored the substrate scope of the

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• indole, furan, and benzofuran rings (Scheme 2) [48]. Working with indole and methyl acrylates in the presence of Pd(OAc)2 and 1,4-benzoquinone in catalytic quantity with tert-butyl hydroperoxide as oxidant, 3-alkenyl-substituted products were obtained. The synthetic value of the direct catalytic C–H

Conserved and species-specific oxylipin pathways in the wound-activated chemical defense of the noninvasive red alga Gracilaria chilensis and the invasive Gracilaria vermiculophylla

• Martin Rempt,
• Florian Weinberger,
• Katharina Grosser and
• Georg Pohnert

Beilstein J. Org. Chem. 2012, 8, 283–289, doi:10.3762/bjoc.8.30

• transformation of arachidonic acid to an 8-hydroperoxide, followed by reduction and elimination of water along with isomerization of the double bonds, could then provide the substrate for lactonization. Since 5 and 6 were configurationally unstable during purification, subsequent isomerizations may lead to the

Triple-channel microreactor for biphasic gas–liquid reactions: Photosensitized oxygenations

• Ram Awatar Maurya,
• Chan Pil Park and
• Dong-Pyo Kim

Beilstein J. Org. Chem. 2011, 7, 1158–1163, doi:10.3762/bjoc.7.134

• efficiency of the triple-channel microreactor. The product of this reaction is an allyl hydroperoxide alcohol that is used in the synthesis of artemisinin-derived antimalarial 1,2,4-trioxanes [48]. The reaction in the triple-channel and in batch was carried out as aforementioned with methylene blue as

Aromatic and heterocyclic perfluoroalkyl sulfides. Methods of preparation

• Vladimir N. Boiko

Beilstein J. Org. Chem. 2010, 6, 880–921, doi:10.3762/bjoc.6.88

Synthesis of spiroannulated and 3-arylated 1,2,4-trioxanes from mesitylol and methyl 4-hydroxytiglate by photooxygenation and peroxyacetalization

• Axel G. Griesbeck,
• Lars-Oliver Höinck and
• Jörg M. Neudörfl

Beilstein J. Org. Chem. 2010, 6, No. 61, doi:10.3762/bjoc.6.61

• our work on bis-peroxide synthesis from bifunctional ketones [22], we have also studied the peroxyacetalization of the allylic hydroperoxide 7 with the bifunctional cyclohexane-1,4-dione (CHD, Scheme 2). In this case, one equivalent of the diketone gave the monoadduct 9c in 20% yield. The products

• spectroscopic methods and by X-ray structure determination. Experimental Synthesis of the 4-fluorophenyl derivative 10b: A solution of 290 mg (2.0 mmol) of the hydroperoxide 4 (prepared from methyl 4-hydroxytiglate (3) by the method described in [10]) and 220 mg (2.0 mmol) of 4-fluorobenzaldehyde in 40 ml of

• and relevant bonds; structure of artemether (AM). Singlet oxygen ene reaction of methyl 4-hydroxytiglate (3) and mesitylol (6) under solid-phase conditions. 1,2,4-trioxane 9c and bis-trioxane 8a,b formation from the bifunctional cyclohexa-1,4-dione. BF3-catalyzed acetalization of hydroperoxide 4 with

The Elbs and Boyland- Sims peroxydisulfate oxidations

• E. J. Behrman

Beilstein J. Org. Chem. 2006, 2, No. 22, doi:10.1186/1860-5397-2-22

• , although they obtained evidence for a peroxide, isolated only phenol (in substantial yield). Heller and Weiler [18] investigated a more stable analog, namely p-nitrophenyl hydroperoxide formed by ipso displacement of a nitro group from p-dinitrobenzene by the hydrogen peroxide anion.p-Nitrophenyl

• hydroperoxide forms p-nitrophenol on decomposition. Similarly, Malykhin and Shteingarts found naphthols as products from the reaction of potassium peroxide with several nitronaphthalenes. [19] These findings are then consistent with the hypothesis that aryl hydroperoxides formed by reaction of arylphenoxide