Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• aromatic [14][15] and heteroaromatic [16][17] SF5 compounds have become readily available and many applications have been described [18][19], the chemistry of aliphatic analogs is still underdeveloped [20]. Generally, the incorporation of SF5 groups into aliphatic positions is based on radical addition of

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• acid-catalyzed reaction of phenols and propynoic acids [22] and the (−)-riboflavin-catalyzed photochemical reaction of cinnamic acids [23] were reported recently. Moreover, the use of radical cyclization for the construction of the coumarin skeleton has become widespread. Examples include the radical

• addition–cyclization reactions of aryl 2-alkynoates with RC(=O)CO2H/AgNO3(cat.)/K2S2O8 at 60 °C [24], with Cu(OAc)2/1-trifluoromethyl-3,3-dimethyl-1,2-benziodoxole (Togni reagent) at 60 °C [25], with R2P(=O)H/Ag2CO3(cat.)/Mg(NO3)2 at 100 °C [26], with BrCF2CO2Et/fac-Ir(ppy)3(cat.) under irradiation at rt

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• radical anion then deprotonates the thiyl radical cation. Subsequent addition to the alkene yields the anti-Markovnikov radical intermediate. Radical addition to dioxygen leads finally to the β-ketosulfide, which subsequently is oxidized by the in situ generated hydrogen peroxide radical to the respective

• . Radical addition to the alkyne leads to the anti-Markovnikov adduct via the more stable secondary radical intermediate. As alkyne 2-methyl-3-butyn-2-ol was selected, which is easily prepared from acetylene and acetone on large scale and the respective thiol–yne adducts can be converted into valuable

• as oxidant. Based on radical trapping experiments, the authors suggest that the reaction might proceed via a radical addition pathway. Wang et al. developed a 9-mesityl-10-methylacridinium tetrafluoroborate (Acr+-Mes BF4−) catalyzed radical thiol–ene reaction with broad scope (Scheme 12) [42]. Both

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• moderate to excellent yields. Interestingly, performing the reaction on 1,1-disubstituted alkenes did not impact the yield significantly, while 1,2-disubstituted alkenes provided slightly less satisfying results. Chlorotrifluoromethylation reactions can also be included in cascade radical addition

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• radical from CF3SO2Na with extrusion of SO2. Then, CF3• underwent a radical addition to the alkene to form the radical 29, which was trapped by the aryldiazonium salt to give the radical cation 30. Finally, 30 was reduced by [Ru(bpy)3]2+* to end up with the product 31 (Scheme 13). The

Palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides

• Tao Fan,
• Wei-Dong Meng and
• Xingang Zhang

Beilstein J. Org. Chem. 2017, 13, 2610–2616, doi:10.3762/bjoc.13.258

• , developing efficient methods for the synthesis of such valuable structures has received less attention [10][11][12][13][14][15]. Commonly, fluoroalkylated alkenes can be prepared through fluoroalkyl radical addition of alkynes via an atom transfer pathway [16][17] or cross-coupling of alkenyl halides with

Synthesis of 1,3-cis-disubstituted sterically encumbered imidazolidinone organocatalysts

• Jan Wallbaum and
• Daniel B. Werz

Beilstein J. Org. Chem. 2017, 13, 2577–2583, doi:10.3762/bjoc.13.254

• –Crafts alkylation [23] and in combination with photoredox catalysis (Scheme 1a) [24]. The enantioselective α-alkylation was achieved by merging the common photoredox catalyst Ru(bpy)3Cl2 with imidazolidinone catalyst 3a·TfOH, controlling the stereochemistry of the radical addition via an intermediate

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• . [45], who developed a micro-channelled cell for synthesis and monitoring (MICCS) (Figure 8) and this was integrated into a 500 MHz NMR instrument. The system was used to elucidate the mechanism of the radical addition to an oxime ether with triethylborane (Scheme 1). The use of the NMR micro flow cell

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• (Scheme 2) [15][16][17]. A Mg-(bis)oxazoline complex serves as both a Lewis acid for the activation of α-substituted acrylates 6 towards radical addition and as a chiral template for an enantioselective hydrogen atom transfer from Bu3SnH to the α-ester radical intermediate. The authors found that the

Cascade alkylarylation of substituted N-allylbenzamides for the construction of dihydroisoquinolin-1(2H)-ones and isoquinoline-1,3(2H,4H)-diones

• Ping Qian,
• Bingnan Du,
• Wei Jiao,
• Haibo Mei,
• Jianlin Han and
• Yi Pan

Beilstein J. Org. Chem. 2016, 12, 301–308, doi:10.3762/bjoc.12.32

• cross-dehydrogenative coupling (CDC) reactions of alkanes, which were reported by Li and other groups [11][12][13][14][15]. Recently, several types of reactions with alkanes as substrates have been developed, such as the Minisci reaction with heteroarenes [16][17], radical addition to unsaturated bonds

• [18][19], decarboxylative alkenylation of cycloalkanes with aryl vinylic carboxylic acids [20][21], trifluoromethylthiolation [22], thiolation [23][24], alkenylation [25][26], dehydrogenation−olefination and esterification [27][28], radical addition/1,2-aryl migration [29], cascade alkylation

• final study of this reaction was the investigation of the mechanism. Firstly, a substrate (8a) bearing a hydrogen atom at the nitrogen was tried for the current system. The cyclohexane radical addition product 9aa’, instead of a cyclization product, was observed with 35% yield (Scheme 5a). This result

Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes

• Norbert Vida,
• Jiří Václavík and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 110–116, doi:10.3762/bjoc.12.12

• for a more widespread use of SF5 compounds are low accessibility of basic building blocks and the lack of understanding of their chemical behavior. Lack of availability of SF5 compounds is particularly evident in aliphatics where radical addition of expensive and toxic SF5Cl to unsaturated compounds

Copper-catalyzed aminooxygenation of styrenes with N-fluorobenzenesulfonimide and N-hydroxyphthalimide derivatives

• Yan Li,
• Xue Zhou,
• Guangfan Zheng and
• Qian Zhang

Beilstein J. Org. Chem. 2015, 11, 2721–2726, doi:10.3762/bjoc.11.293

• addition and a nucleophilic oxygen attack [35]. Very recently, Studer and co-workers presented an aminooxygenation of alkenes with N-fluorobenzenesulfonimide (NFSI) and sodium 2,2,6,6-tetramethylpiperidine-1-olate (TEMPONa) via nitrogen-centred radical addition to the alkene followed by trapping of 2,2,6,6

• , the oxidation of Cu(I) with NFSI provided F–Cu(III)–N complex I, which could transform into a copper(II)-stabilized benzenesulfonimide radical II through a redox isomerization equilibrium. Next, the intermolecular radical addition of II to styrene 1g took place, producing benzylic radical III and Cu

• aminooxygenation reaction of alkenes with phthalimide and (diacetoxyiodo)benzene through cis-aminopalladation and SN2 C–O bond formation [34]. In 2013, Zhu and co-workers described an n-Bu4NI-catalyzed aminooxygenation of inactive alkenes with benzotriazole and water which underwent a nitrogen-centred radical

Recent developments in copper-catalyzed radical alkylations of electron-rich π-systems

• Kirk W. Shimkin and
• Donald A. Watson

Beilstein J. Org. Chem. 2015, 11, 2278–2288, doi:10.3762/bjoc.11.248

• alkenes and alkynes One of the burgeoning areas of copper-catalyzed cross-coupling chemistry is the alkenylation of alkyl halide substrates. This transformation is achieved via formation of a transient radical, addition to a π-system (an alkene or an alkyne), followed by elimination or reincorporation of

• the observed product (Scheme 9). While the reaction conditions are similar to those utilized in atom transfer radical addition and polymerization reactions, the use of excess amine was critical for a robust alkenylation reaction and to avoid atom transfer and polymerization products. Various electron

• the alkyl bromide coupling partner was changed to an α-bromo keto ester, the radical addition is followed by a tautomerization/cyclization event that provides dihydrofurans in excellent yields [38]. The radical formation/addition events proceed largely in the same manner as the aforementioned

Aerobic addition of secondary phosphine oxides to vinyl sulfides: a shortcut to 1-hydroxy-2-(organosulfanyl)ethyl(diorganyl)phosphine oxides

• Svetlana F. Malysheva,
• Alexander V. Artem’ev,
• Nina K. Gusarova,
• Nataliya A. Belogorlova,
• Alexander I. Albanov,
• C. W. Liu and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2015, 11, 1985–1990, doi:10.3762/bjoc.11.214

• the P(O)H species to molecular oxygen has been reported for example for Ph2P(O)H [30]. Then, the radical addition of A to vinyl sulfide, proceeding in an anti-Markovnikov manner, takes place. Subsequently, a 1,2-intramolecular transfer of an H atom within the radical adduct B (from PCH2 group to

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

• Hanmo Zhang,
• E. Ben Hay,
• Stephen J. Geib and
• Dennis P. Curran

Beilstein J. Org. Chem. 2015, 11, 1649–1655, doi:10.3762/bjoc.11.181

• 6 and 9 that the imine 14 is reduced by radical hydrostannation to give 16 via 15. Finally, protodestannylation of 16 provides isolated product 8. Imine 11 with the ester substituent on C2 is formed by a similar sequence of reactions as 14. However, tin radical addition to 11 produces a captodative

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• probably involved the coupling of the initial aminium radical cation with the radical anion formed by SET to the furanone substrate [46]. An interesting further convolution was observed in the TiO2 and ZnS promoted SCPC reactions of N,N-dimethylaniline (10) with furanone 6. A tandem radical addition

Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application to the synthesis of SF₅-substituted phenylboronic esters and iodobenzenes

• George Iakobson,
• Junyi Du,
• Alexandra M. Z. Slawin and
• Petr Beier

Beilstein J. Org. Chem. 2015, 11, 1494–1502, doi:10.3762/bjoc.11.162

• interest in this functional group. Synthetic methods towards aliphatic SF5-containing compounds are based on free radical addition of SF5Cl or SF5Br to unsaturated compounds [7][8][9], whereas aromatic derivatives are available either by the Umemoto’s two-step synthesis from diaryl disulfides or

Intermolecular addition reactions of N-alkyl-N-chlorosulfonamides to unsaturated compounds

• Gerold Heuger and
• Richard Göttlich

Beilstein J. Org. Chem. 2015, 11, 1226–1234, doi:10.3762/bjoc.11.136

• derivatives like Chloramine-T to alkenes have been described by Sharpless [28][29], Komatsu [30][31][32] and Dodd [33]. In these examples the nitrogen center carries no substituents, which limits the scope of the reactions. In our own studies we wanted to develop a radical addition, using amidyl radicals with

• -aromatic alkenes. Addition to non-aromatic alkenes As expected non-aromatic alkenes are less good substrates for the radical addition of amidyl radicals and the yields of addition products of 2a decreased significantly (Table 3). A conjugated diene like cyclooctadiene (Table 3, entry 4) and a terminal

• HCl after the radical addition due to the high reaction temperature, the formation of regioisomers of 12 and especially the formation of 13 can be explained by a halonium-ion transfer to the alkene. This could produce an chloro-substituted alkene 14, which in a second step would undergo radical

Adsorption mechanism and valency of catechol-functionalized hyperbranched polyglycerols

• Stefanie Krysiak,
• Qiang Wei,
• Klaus Rischka,
• Andreas Hartwig,
• Rainer Haag and
• Thorsten Hugel

Beilstein J. Org. Chem. 2015, 11, 828–836, doi:10.3762/bjoc.11.92

• reduced state [5][9]. The byssal plaque also shows strong cohesion through crosslinks. The cysteins can crosslink with DOPA and the oxidized DOPA (semiquinones) can crosslink via radical addition. Furthermore, crosslinking by iron chelate complexes of DOPA improves cohesion [10]. The adhesion of a single

Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals

• Henok H. Kinfe,
• Fanuel M. Mebrahtu,
• Mandlenkosi M. Manana,
• Kagiso Madumo and
• Mokela S. Sokamisa

Beilstein J. Org. Chem. 2015, 11, 583–588, doi:10.3762/bjoc.11.64

• the regioselective ring opening of 1,2-cyclopropanated carbohydrates and the radical addition reaction of glycals [11][12][13][14][15]. Although the synthetic methodologies developed for the synthesis of C-glycosides and 2-C-branched sugars are extensively studied, the synthesis of 1,2-cis-2-C

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• few previous reports of this reaction [221][222][223], Sibi and co-workers reported some of the first examples of the 1,4-radical addition to α,β-unsaturated N-alkenoyloxazolidinones using a substoichiometric amount of a chiral Lewis acid [224][225] (Scheme 28). The authors were only able to decrease

Copper-catalyzed cascade reactions of α,β-unsaturated esters with keto esters

• Zhengning Li,
• Chongnian Wang and
• Zengchang Li

Beilstein J. Org. Chem. 2015, 11, 213–218, doi:10.3762/bjoc.11.23

• diastereoselectivity. As expected, a cyclic β-halo-α,β unsaturated aldehyde substrate led to the respective tricyclic lactone, the core structure of strigolactone [12]. Bertrand synthesized β-carboxylic acid-γ-lactones in high yields but with low diastereoselectivity via a dialkylzinc-mediated radical addition to the

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