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

• procedure, an aryl amine, a ketone, and a cyclic ether or an alcohol molecule are assembled in a one-pot synthesis by nucleophilic radical addition of ketyl radicals to ketimines generated in situ. The reaction occurs under mild conditions by mediation of the TiCl4/Zn/t-BuOOH system, leading to the

• : aminoalcohols; free-radical addition; imine; multicomponent reaction; titanium salts; Introduction Multicomponent reactions (MCRs) represent a green approach towards the synthesis of polyfunctionalized molecules by promoting multiple bond-forming mechanisms in a one-pot synthesis [1][2][3][4][5][6][7

• our ongoing investigation of the role of titanium salts in mediating selective radical transformations [13][14], we have developed new, simple protocols for the synthesis of complex organic compounds through nucleophilic radical addition to imines generated in situ [15]. Several recent contributions

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• carbohydroxylation reaction and postulated intermediate 18 [18]. A radical addition and electron transfer reaction of N-acyliminium ions generated electrosynthetically [19]. Catalytic indirect anodic fluorodesulfurization reaction [37]. Micromixing effects on yield 92% vs 36% and ratio of alkylation products [43

Investigations of thiol-modified phenol derivatives for the use in thiol–ene photopolymerizations

• Sebastian Reinelt,
• Monir Tabatabai,
• Urs Karl Fischer,
• Norbert Moszner,
• Andreas Utterodt and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 1733–1740, doi:10.3762/bjoc.10.180

• the performance of more hydrophobic ester-free thiol-modified bis- and trisphenol derivatives in thiol–ene photopolymerizations. For this, six different thiol-modified bis- and trisphenol derivatives exhibiting four to six thiol groups are synthesized via the radical addition of thioacetic acid to

• synthesis of the phenol-based thiols (10a,b, 14a–c, 17) was accomplished by the radical addition of thioacetic acid to suitable allyl-modified precursors as depicted in Scheme 1 and Scheme 2. For the synthesis of 10a and 10b the well-established hydroxymethylation of bisphenol A was the starting point of

• etherification, which was conducted in analogy to a procedure described in literature [40], as demonstrated in Scheme 2. Bisphenol A, bisphenol S and the trisphenol derivative 1,1,1-tris(4-hydroxyphenyl)ethane were chosen as basic structures. Subsequently, the successful radical addition of thioacetic acid (8

Postsynthetic functionalization of glycodendrons at the focal point

• Thisbe K. Lindhorst and
• Katharina Elsner

Beilstein J. Org. Chem. 2014, 10, 1482–1487, doi:10.3762/bjoc.10.152

• expected in case of the glycodendrons 3–9. However, the so-called “thiol-ene” reaction [10] gave reliable results with both bivalent and tetravalent glycodendrons. The radical addition of mercaptododecane to either 3 or 7, employing AIBN as radical starter, led to the amphiphilic thioethers 12 and 13

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• -adduct. The stereoselectivity of the method determines the conformation at the newly formed chiral centers. The hydrophosphination typically proceeds via thermal [68][69], radical, acidic [70][71][72] or basic [73][74] initiation. Radical addition of secondary phosphines to alkenes can be accomplished by

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• unit. Representative synthetic reactions of fullerene C60 (2) include cyclopropanation [29][30], [3 + 2] cycloaddition [31][32], [4 + 2] cycloaddition [33], nucleophilic addition [34], and radical addition reactions [35]. Two of the earliest and most widely used reactions, the Bingel–Hirsch reaction

Visible-light-induced, Ir-catalyzed reactions of N-methyl-N-((trimethylsilyl)methyl)aniline with cyclic α,β-unsaturated carbonyl compounds

• Dominik Lenhart and
• Thorsten Bach

Beilstein J. Org. Chem. 2014, 10, 890–896, doi:10.3762/bjoc.10.86

• major reaction products were obtained in combined yields of 30–67%. One product resulted from aminomethyl radical addition, the other product was a tricyclic compound, which is likely formed by attack of the intermediately formed α-carbonyl radical at the phenyl ring. For five-membered α,β-unsaturated

• 2 [38] and of N-methyl-N-((trimethylsilyl)methyl)aniline (5) to 2-cyclohexenone (6) [41]. Ir-catalyzed formation of tricyclic product 10 by a domino radical addition reaction to α,β-unsaturated lactone 9. Ir-catalyzed addition reactions of N-methyl-N-((trimethylsilyl)methyl)aniline (5) to 5,6

• -dihydro-2H-pyran-2-one (12). Ir-catalyzed addition reactions of N-methyl-N-((trimethylsilyl)methyl)aniline (5) to 2-cyclopentenone (15). Ir-catalyzed formation of tricyclic products 19 by a domino radical addition reaction to α,β-unsaturated lactams 18. Ir-catalyzed addition reactions of N-methyl-N

End-group-functionalized poly(N,N-diethylacrylamide) via free-radical chain transfer polymerization: Influence of sulfur oxidation and cyclodextrin on self-organization and cloud points in water

• Sebastian Reinelt,
• Daniel Steinke and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 680–691, doi:10.3762/bjoc.10.61

• allyl bromide (2) and subsequent radical addition of ethanethioic S-acid (4) yielded the corresponding thioesters S-(3-(4-(1,1-dimethylethan-1-yl)phenoxy)propyl) ethanthioate (5a) and S-(3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propyl) ethanthioate (5b). The thioester functions were hydrolyzed to obtain

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• selectively can be enhanced dramatically by the use of continuous flow microreactor devices. Daikin Industries, Ltd. developed the flow microreactor synthesis of fluorinated epoxides. In the first step (radical addition of perfluoroalkyl iodides to unsaturated alcohols), there is a problem concerning 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

• ring opening to release the ring strain while producing a distonic ion 149 with a primary radical. Distonic ion 149 is added via a Giese-type radical addition to an alkene, yielding a more stable distonic ion 151 with a secondary radical. Intramolecular addition of the secondary radical to the iminium

Continuous flow photocyclization of stilbenes – scalable synthesis of functionalized phenanthrenes and helicenes

• Quentin Lefebvre,
• Marc Jentsch and
• Magnus Rueping

Beilstein J. Org. Chem. 2013, 9, 1883–1890, doi:10.3762/bjoc.9.221

• derivatives. We choose stilbenes with bromide and methyl substituents, as the latter can be used in subsequent oxidation, deprotonation, and radical addition reactions, whereas the former opens access to various functional groups via lithium-halogen exchange or cross-coupling chemistry. Methoxy groups were

Flow Giese reaction using cyanoborohydride as a radical mediator

• Takahide Fukuyama,
• Takuji Kawamoto,
• Mikako Kobayashi and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2013, 9, 1791–1796, doi:10.3762/bjoc.9.208

• reductive radical addition reaction, better known as the Giese reaction, was historically carried out most by using tributyltin hydride as the radical mediator [8][9]. Recently borane derivatives such as borohydride reagents [10][11][12][13] or NHC-boranes [14][15][16][17][18] can be used in simple radical

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

• Andreas Gansäuer,
• Meriam Seddiqzai,
• Tobias Dahmen,
• Rebecca Sure and
• Stefan Grimme

Beilstein J. Org. Chem. 2013, 9, 1620–1629, doi:10.3762/bjoc.9.185

• und Theoretische Chemie der Rheinischen-Friedrich-Wilhelms-Universität Bonn, Beringstraße 4, D-53115 Bonn, Germany 10.3762/bjoc.9.185 Abstract The intramolecular radical addition to aniline derivatives was investigated by DFT calculations. The computational methods were benchmarked by comparing the

• was therefore employed in further calculations. Corrections for intramolecular London dispersion and solvation effects in the quantum chemical treatment are essential to obtain consistent and accurate theoretical data. For the investigated radical addition reaction it turned out that the polarity of

• ][7][8] proceeding via catalysis in single electron steps (for experimental results see Scheme 1) [9][10]. The C–C bond forming step of the catalytic cycle is an intramolecular alkyl radical addition to substituted anilines. Even though only rarely used, reaction sequences employing such steps in an

Stability of SG1 nitroxide towards unprotected sugar and lithium salts: a preamble to cellulose modification by nitroxide-mediated graft polymerization

• Guillaume Moreira,
• Laurence Charles,
• Mohamed Major,
• Florence Vacandio,
• Yohann Guillaneuf,
• Catherine Lefay and
• Didier Gigmes

Beilstein J. Org. Chem. 2013, 9, 1589–1600, doi:10.3762/bjoc.9.181

• of elaboration of this alkoxyamine has already been described elsewhere [28]. Briefly, the synthesis of the cello-SG1 alkoxyamine is performed in two steps: (i) acroylation of one hydroxy function of cellobiose to graft one acrylate function, (ii) intermolecular 1,2-radical addition (1,2-IRA) of the

Mechanistic studies on the CAN-mediated intramolecular cyclization of δ-aryl-β-dicarbonyl compounds

• Brian M. Casey,
• Dhandapani V. Sadasivam and
• Robert A. Flowers II

Beilstein J. Org. Chem. 2013, 9, 1472–1479, doi:10.3762/bjoc.9.167

• initial rotational transition structure TS1a’ has a barrier of 2.5 kcal/mol, and the corresponding radical intermediate 2a’ is 0.6 kcal/mol above 1a’. For the radical addition to the aromatic ring, the energy barrier is 15.8 kcal/mol, and the product cyclohexadienyl radical 3a’ is 8.8 kcal/mol higher in

• position, path A is followed. Intramolecular cyclization of 7 occurs through radical addition to the aromatic ring forming intermediate 8. As demonstrated by the oxidation of substrate 1j, intramolecular cyclization of this radical occurs at the more electron-rich carbon atom of the δ-aryl rings. A second

Diastereoselective radical addition to γ-alkyl-α-methylene-γ-butyrolactams and the synthesis of a chiral pyroglutamic acid derivative

• Tomoko Yajima,
• Eriko Yoshida and
• Masako Hamano

Beilstein J. Org. Chem. 2013, 9, 1432–1436, doi:10.3762/bjoc.9.161

• ][7][8] and no reports on radical addition. We have already investigated diastereoselective alkyl radical additions to α-methylene-γ-phenyl- γ-lactam and reported that the N-unsubstituted lactam yields cis-α,γ-disubstituted lactams using (Me3Si)3SiH under UV irradiation, whereas the reactions of N

• , because N-pivaloyl gave high trans-selectivity of γ-phenyl substrate, yielded the chiral radical substrate 10. The trans-selective ethyl radical addition proceeded, yielding 11 with high diastereoselectivity, as we previously reported [9]. The trans-isomer was isolated by silica-gel column chromatography

• synthesize chiral pyroglutamic acid derivatives starting from (S)-phenylglycinol. Chelation of 5a and 5d. Radical addition to α-methylene-γ-phenyl-γ-butyrolactams. Synthesis of chiral substrate 10. Synthesis of chiral 4-butyl-L-pyroglutamic acid 13. Radical addition to 1 under non-chelating conditions

Preparation of optically active bicyclodihydrosiloles by a radical cascade reaction

• Koichiro Miyazaki,
• Yu Yamane,
• Ryuichiro Yo,
• Hidemitsu Uno and
• Akio Kamimura

Beilstein J. Org. Chem. 2013, 9, 1326–1332, doi:10.3762/bjoc.9.149

• reaction, radical addition–cyclization cascade followed by intramolecular radical substitution (SHi) occurred in one-pot to give optically active bicyclostannolanes in good yields [15]. We are interested in whether such a cascade SHi process might occur with other radical species. We have found that a

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

• selective oxidation of organic substrates. Radical addition of aldehydes and analogues to alkenes. NHPI/AIBN-promoted aerobic oxidation of 2,6-diisopropylnaphthalene. NHPI/AIBN-promoted aerobic oxidation of CHB. NMBHA/MeOAMVN promoted aerobic oxidation of PUFA. Alkene dioxygenation by means of N-aryl

Homolytic substitution at phosphorus for C–P bond formation in organic synthesis

• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 1269–1277, doi:10.3762/bjoc.9.143

• literature [19][20][21]. This review deals with two transformations, radical phosphination by addition across unsaturated C–C bonds and substitution of organic halides. Review Radical addition of phosphination agents Stannylphosphines of the type R3Sn–PR’2 are known to undergo radical addition to carbon

• reported that diphenyl(trimethylstannyl)phosphine reacts not only with terminal alkynes but also with internal alkynes and allenes (Scheme 4) [24][25]. It is noteworthy that the regioselectivity of the radical addition to propynamide is opposite to that of the relevant ionic Michael addition. Considering

• , considerable polymerization takes place unless substrates or olefinic products are reasonably inert. Yorimitsu and Oshima reported radical addition of a P–S bond across alkyne by using diphenyl(organosulfanyl)phosphine (Table 4) [35]. The addition proceeds mainly in an anti fashion to afford the adducts

Cascade radical reaction of substrates with a carbon–carbon triple bond as a radical acceptor

• Hideto Miyabe,
• Ryuta Asada and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2013, 9, 1148–1155, doi:10.3762/bjoc.9.128

• hydroxamate ester as a chiral Lewis acid coordination moiety was first shown in an intermolecular reaction involving a radical addition and sequential allylation processes. Next, the effect of hydroxamate ester was studied in the cascade addition–cyclization–trapping reaction of substrates with a carbon

• 2002 that hydroxamic acid derivatives are useful achiral templates in enantioselective Diels–Alder reactions [69][70]. To study the effect of hydroxamate ester as an achiral template in the intermolecular radical reaction, our experiments began with the investigation of cascade radical addition

• substrates and the stereochemistry of cyclization. Substrates for testing the cascade transformation. E/Z-selectivity of 9Aa–Ca. Model for the enantioselective reaction. Effect of hydroxamate ester on intermolecular C–C bond-forming reactions. Cascade radical addition–cyclization–trapping reaction of 5 and

Interplay of ortho- with spiro-cyclisation during iminyl radical closures onto arenes and heteroarenes

• Roy T. McBurney and
• John C. Walton

Beilstein J. Org. Chem. 2013, 9, 1083–1092, doi:10.3762/bjoc.9.120

• system necessarily occurs. The most commonly encountered type is C-centred radical addition (often an aryl radical) to an aromatic or heteroaromatic ring ortho to the point of attachment of the tether. In Pschorr and related processes re-aromatisation follows with production of phenanthrene-type

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• tedious by more traditional routes. The possibility of iterating the radical addition allows for a convergent and highly modular assembly of complex scaffolds. The three successive additions outlined in Scheme 8 and leading to 37 illustrate nicely this approach [25]. One xanthate, 36, and three different

• strategy for creating complexity from simple starting materials. In this approach, the radical sequence brings together the functional groups necessary for the ionic transformation. One example is the sequence that follows the radical addition of xanthate 61 to an alkene depicted in Scheme 12. Exposure of

• the ready formation of bicyclic compound 72 [33]. The use of a phosphonate-containing alkene allows the assembly of numerous polycyclic structures by combining the radical addition of a ketone-bearing xanthate with an intramolecular Horner–Wadsworth–Emmons condensation. This strategy is highlighted in

Radical zinc-atom-transfer-based carbozincation of haloalkynes with dialkylzincs

• Fabrice Chemla,
• Florian Dulong,
• Franck Ferreira and
• Alejandro Pérez-Luna

Beilstein J. Org. Chem. 2013, 9, 236–245, doi:10.3762/bjoc.9.28

• )enoates bearing pendant haloalkynes would be ideally suited (Scheme 1). On the one hand it would provide a means to control totally the regioselectivity of the radical addition to the haloalkyne, and on the other hand the envisioned zinc atom transfer to an α-halo vinylic radical should be favorable as a

Highly selective synthesis of (E)-alkenyl-(pentafluorosulfanyl)benzenes through Horner–Wadsworth–Emmons reaction

• George Iakobson and
• Petr Beier

Beilstein J. Org. Chem. 2012, 8, 1185–1190, doi:10.3762/bjoc.8.131

• chemical stability, high electronegativity and strong lipophilic character [2][3][4][5][6][7]. The availability of SF5-containing compounds is very limited. Aliphatic SF5-containing compounds are available through free-radical addition of toxic and expensive SF5Cl to unsaturated compounds [8][9], and

Tandem catalysis of ring-closing metathesis/atom transfer radical reactions with homobimetallic ruthenium–arene complexes

• Yannick Borguet,
• Xavier Sauvage,
• Guillermo Zaragoza,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2010, 6, 1167–1173, doi:10.3762/bjoc.6.133

• compound was first reported in 2005 by Severin et al. who successfully used it as a catalyst for atom transfer radical addition (ATRA) and cyclization (ATRC) reactions [4][5]. In 2007, we further extended its application field to the related process of atom transfer radical polymerization (ATRP) [2