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

• ; radical cyclization; radical fragmentation; spiro-indoles; Introduction Radical additions and cyclizations of ene-sulfonamides are useful reactions in a number of settings. The primary products of these reactions, α-sulfonamidoyl radicals, are often thought to undergo elimination reactions of sulfonyl

• ] = 0.01 M) led to complete conversion after 1 h of heating. Solvent evaporation and flash chromatography provided spiro-3,3'-biindoline 8 in 47% isolated yield. As with the formation of 5a–c in Scheme 1, an imine is presumably formed by aryl radical cyclization and then sulfonyl radical elimination, but

• mechanism aside, the take home message is N-sulfonylindoles undergo both radical cyclization and elimination; however, the resulting spirocyclic N-arylimines may be susceptible to further reduction to the amine depending on the carbon substituent of the imine. In contrast, related spirocyclic imines with N

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

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

• ). Molander and Harris developed the samarium(II) iodide-mediated cyclization of α,β-unsaturated esters and amides [167] (Scheme 20). Previous methods for the cyclization of alkyl halides and α,β-unsaturated carbonyl systems include: (1) tin-mediated radical cyclization [168] or (2) nucleophilc cyclization

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• reactions is presented and discussed in this review. Keywords: anodic cyclization; electrosynthesis; heterocycle; olefin coupling; organic electrochemistry; radical cyclization; Introduction The construction of heterocyclic cores undoubtedly represents a highly important discipline of organic synthesis

• electrochemical reaction leads to an Umpolung of the functional group with the lower redox potential, triggering the ring-closure reaction between a nucleophilic and an electrophilic site. Another possibility for an intramolecular ring closure is represented by electrochemically induced radical cyclization

• , recent efforts in electrochemical heterocycle synthesis can mostly be differentiated into anodic olefin coupling (section 1.1), radical cyclization (section 1.2), and trapping of anodically generated iminium/alkoxycarbenium ions (section 1.3). On the other hand, cycloadditions (section 2.1), sequential

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

• the reactivity of the diene with respect to its structure to better predict the mode of diene cation radical cyclization (5-exo vs 6-endo). Herein is reported an organocatalytic photoredox-mediated strategy for the endoperoxidation of 1,5-dienes using 3O2 to rapidly generate complex endoperoxide

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• coworker [200] found an intriguing example of a light mediated radical cyclization/arylvinylcyclopropane rearrangement. Subjecting cyclopropyl bromide 237 to an Ir-polypyridyl catalyst and visible light initiated the desired photoredox cascade forming a cyclopropylradical, which readily cyclized in an 5

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

• ) in AcOH/CH2Cl2 produced 3-hydroperoxy-6-(2-methoxyethoxy)-3,6-dimethyl-1,2-dioxane (286) (Scheme 80) [270]. 3.11. Other methods for the synthesis of 1,2-dioxanes The di(tert-butyl)peroxalate-initiated radical cyclization of unsaturated 2-(3-hydroperoxypropyl)-6,6-dimethylbicyclo[3.1.1]hept-2-ene

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

• light-mediated reductions such as reductive dehalogenation [47][48][49][50][51], reductive radical cyclization [52][53][54], reduction of activated ketones [49], and reduction of aromatic azides [55]. The third mode involves deprotonation of amine radical cation 2 to form α-amino radical 3, which is

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

• similar. The length of the forming bond is 2.30 Å and the angle of attack to the double bond is 108.2° in our treatment. These values are slightly different than the values used in the modeling based calculations of radical cyclization (2.34 Å and 105.8°) that were derived from values of the attack of

Copper(II)-salt-promoted oxidative ring-opening reactions of bicyclic cyclopropanol derivatives via radical pathways

• Eietsu Hasegawa,
• Minami Tateyama,
• Ryosuke Nagumo,
• Eiji Tayama and
• Hajime Iwamoto

Beilstein J. Org. Chem. 2013, 9, 1397–1406, doi:10.3762/bjoc.9.156

• hexenyl radical cyclization reactions [21], (Figure 1) [22][23][24][25][26][27][28][29][30]. For example, PET reactions of probe I with amines were observed to produce a spirocyclic ketone product while its reduction reaction induced by samarium diiodide (SmI2) gives rise to a cyclopropanol (left in

• suggest that a rapid equilibrium does indeed exist between isomeric radical intermediates 9 and 10 (Scheme 7) and that the thermodynamically less stable isomer 9 undergoes fast hexenyl-radical cyclization leading to the formation of 11 in reactions promoted by copper(II) carboxylates. On the other hand, a

• 22 and 23. However, competitive generation of 19 does not take place (Table 3, entry 4). Finally, reaction of 1c with Cu(OTf)2 leads to the formation of ring-expanded enone 20 and acetoamide 24 (Table 3, entry 5). As described above, observation of the occurrence of hexenyl-radical cyclization

A construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with carbon monoxide

• Mitsuhiro Ueda,
• Yoshitaka Uenoyama,
• Nozomi Terasoma,
• Shoko Doi,
• Shoji Kobayashi,
• Ilhyong Ryu and
• John A. Murphy

Beilstein J. Org. Chem. 2013, 9, 1340–1345, doi:10.3762/bjoc.9.151

• Technology, 5-16-1 Ohmiya, Asahi-ku, Osaka 535-8585, Japan Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, UK 10.3762/bjoc.9.151 Abstract A straightforward synthesis of 4,4-spirocyclic indol γ-lactams by tandem radical cyclization of iodoaryl allyl

• ; iodoaryl allyl azides; tandem radical cyclization; Introduction 4,4-Spirocyclic oxindole γ-lactams containing a quaternary carbon center are key structures for the synthesis of biologically active natural products and the related analogues [1][2][3][4]. Therefore, the development of an efficient synthesis

• -spirocyclic oxindole γ-lactams by the cycloaddition of imines and succinic anhydrides [5]. Tandem radical cyclization can also provide a powerful tool for the construction of heterocycles [6][7][8][9][10][11][12]. One of us previously reported on the construction of spirocyclic pyrrolidinyl oxindoles by the

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

• -carbonyl radical that underwent radical cyclization to a terminal alkyne unit. The resulting vinyl radical attacked the silicon atom in an SHi manner to give dihydrosilole. The reaction preferentially formed trans isomers of bicyclosiloles with an approximately 7:3 to 9:1 selectivity. Keywords

• : bicyclodihydrosilole; free radical; radical cascade reaction; SHi reaction; tris(trimethylsilyl)silane; Introduction Radical cyclization occupies a unique position in organic synthesis because it is a useful reaction for the construction of cyclic molecules [1][2][3][4][5][6][7][8][9][10]. The radical cascade

• radical cyclization in a 5-exo-dig mode giving vinyl radical intermediate B, which is potentially reactive for attacking the silyl group in an SHi manner to give a Me3Si radical and 2. The process from B to 2 should be very rapid. Giese and co-workers have reported that the reaction rate for a similar SHi

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

• Brad M. Loertscher,
• Yu Zhang and
• Steven L. Castle

Beilstein J. Org. Chem. 2013, 9, 1179–1184, doi:10.3762/bjoc.9.132

• for synthesis. Herein, we provide an account of our studies directed toward the construction of this alkaloid. Specifically, we describe our efforts to prepare advanced intermediates that could be employed in the aforementioned pyridone annulation and tandem radical cyclization processes. In the

• functional-group manipulations. Based on the aforementioned model study [11], 7-exo–6-exo tandem radical cyclization of phenyl selenoester 4 was expected to produce ketone 3. Disassembly of the pyridone moiety of 4 according to our annulation protocol [14] revealed thioester 5 as a suitable precursor. We

Formal synthesis of (−)-agelastatin A: an iron(II)-mediated cyclization strategy

• Daisuke Shigeoka,
• Takuma Kamon and
• Takehiko Yoshimitsu

Beilstein J. Org. Chem. 2013, 9, 860–865, doi:10.3762/bjoc.9.99

• have developed a new approach to key compounds 5a/5b for (−)-agelastatin A (1) synthesis, which features the iron(II)-mediated radical cyclization of N-tosyloxycarbamate, a safe azidoformate surrogate. Although somewhat moderate chemical yields of the compounds were obtained in this study, the

Direct alkenylation of indolin-2-ones by 6-aryl-4-methylthio-2H-pyran-2-one-3-carbonitriles: a novel approach

• Sandeep Kumar,
• Ramendra Pratap,
• Abhinav Kumar,
• Brijesh Kumar,
• Vishnu K. Tandon and
• Vishnu Ji Ram

Beilstein J. Org. Chem. 2013, 9, 809–817, doi:10.3762/bjoc.9.92

• hydride-AIBN initiated radical cyclization [33][34]. In 2005, Player and co-workers reported a tandem Heck/Suzuki–Miyaura coupling process for the synthesis of (E)-3,3-(diaryl)oxindoles [35][36][37]. Recently, alkenylation of indolin-2-ones has been developed by palladium-catalyzed aromatic C–H activation

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• ]. As a result, Hoveyda’s zirconium-catalyzed reactions provided homobenzylmagnesium intermediates 4j, while Kambe’s titanium-catalyzed reactions afforded benzylmagnesium intermediates 4k. Kambe applied the titanocene-catalyzed reaction to a three-component coupling reaction involving a radical

• cyclization reaction (Scheme 44). Under Nakamura’s iron-catalyzed carbometalation reaction conditions (shown in Scheme 17), the reaction of oxabicyclic alkenes provided ring-opened product 4m through a carbomagnesiation/elimination pathway (Scheme 45, reaction 4l to 4m) [82]. In contrast, the use of the 1,2

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

• alkyl iodides in the presence of Me2Zn/O2 with β-(propargyloxy)enoates entails the intramolecular carbometallation of the pendant alkynes substituted by silyl, alkyl, aryl, alkenyl or amino groups by a 5-exo dig radical cyclization step [37][38]. Intermolecular carbozincation of terminal arylacetylenes

Hybrid super electron donors – preparation and reactivity

• Jean Garnier,
• Douglas W. Thomson,
• Shengze Zhou,
• Phillip I. Jolly,
• Leonard E. A. Berlouis and
• John A. Murphy

Beilstein J. Org. Chem. 2012, 8, 994–1002, doi:10.3762/bjoc.8.112

• mixture of 32 [35], the product of aryl radical cyclization, (74%), together with recovered 30 (6%) and deiodinated but uncyclised product 31 (12%). This is the first observation of efficient aryl radical generation at room temperature from a super-electron-donor. For comparison, less than 1% yield of 32

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

• was required to perform the radical cyclization of this cyclohexenyl trichloroacetamide, presumably due to the unfavorable disposition of the trichloromethyl unit and the endocyclic double bond in the most stable rotamer of the amido group [11]. Hence, this preliminary experiment allowed us to

• that adding a benzyl or tosyl group to the amide functionality of compound 5 facilitated its radical cyclization mediated by complex 3. Replacing the trichloroacetamide moiety with the corresponding tribromoacetamide unit was also found to enhance the Kharasch reactivity [11]. Thus, we synthesized four

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• base generates the styrene 107 and oxalic acid. 4.2. Vedejs. Anionic Michael addition This strategy is very similar to Ziegler’s preceding approach since both share the same method for forming the C3–N4 bond and aim at constructing the C1–C9a bond. But while Ziegler uses a tandem radical cyclization

• developments have been reported on this series of compounds. 4.4. Jones. Radical cyclization A radical cyclization was used by the Jones group for the formation of smaller rings via a 5-exo-dig radical cyclization. Bromoalkyne 118 was chosen to construct pyrrolo[1,2-a]indole 119. The reaction was initiated

• ) [114]. 5.4. Parson. Radical cyclization The development of novel cascade (or domino) radical reactions is an active area of current research, and one approach to the mitomycin ring system focused on the application of 1-6-hydrogen atom transfer to create a pyrrolidinone radical, which could then

Reduction of arenediazonium salts by tetrakis(dimethylamino)ethylene (TDAE): Efficient formation of products derived from aryl radicals

• Mohan Mahesh,
• John A. Murphy,
• Franck LeStrat and
• Hans Peter Wessel

Beilstein J. Org. Chem. 2009, 5, No. 1, doi:10.3762/bjoc.5.1

• )]. We expected that the aryl radical 53a generated by the reduction of arenediazonium salt 49a by TDAE would undergo 5-exo-trig radical cyclization onto the vinyl bromide to afford the alkyl radical intermediate 54a, from which Br• would be eliminated to afford the exocyclic alkene 50a (Scheme 6). Such

• electron donor. Additionally, we have described the utility of the aryl radicals in the construction of indolines and indoles by intramolecular radical cyclization of aryl radicals onto appropriately placed alkenes bearing terminal radical leaving groups. The presence of a suitable radical leaving group

• like a sulfide, sulfoxide or sulfone is necessary for the self-termination of the 5-exo-trig radical cyclization reactions to avoid competing intermolecular radical side-reactions. The TDAE-mediated radical-based addition-elimination route for the construction of indole ring systems warranted anhydrous

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

Sordarin, an antifungal agent with a unique mode of action

• Huan Liang

Beilstein J. Org. Chem. 2008, 4, No. 31, doi:10.3762/bjoc.4.31

• believed to involve single-electron oxidation of the cyclopropanol, fragmentation of a transient radical cation, and diastereoselective radical cyclization. In the enantioselective synthesis, this transformation was more efficiently achieved by treatment of enantioenriched 41b with the AgNO3-ammonium

• persulfate-pyridine system [32]. The ensuing Ag(I) catalyzed oxidative radical cyclization proceeded in 85% yield. Racemic ketone 43 underwent regio- and stereoselective allylation under Corey-Enders conditions to provide olefin 44, which was subjected to Lemieux-Johnson cleavage to corresponding aldehyde

Do α-acyloxy and α-alkoxycarbonyloxy radicals fragment to form acyl and alkoxycarbonyl radicals?

• Dennis P. Curran and
• Tiffany R. Turner

Beilstein J. Org. Chem. 2006, 2, No. 10, doi:10.1186/1860-5397-2-10

• us to suggest that some radicals in the Wille cascade progress to products by oxidation or group transfer rather than β-fragmentation. Results and Discussion We choose to generate the candidate radicals for fragmentation by a radical cyclization rather than by a standard atom or group abstraction

• radical cyclization of enol ether 11a with tributyltin hydride (0.1 M) followed by chromatographic purification provided 14a in 95% yield as an inseparable 1:2 mixture of exo and endo isomers. Likewise, cyclization of enol ester 11b provided a 1:2 mixture of 14b-exo and 14b-endo in 68% isolated yield. The

• concentrations, complete conversion of 11b was observed and reduced product 14b was formed in good yield. None of the directly reduced product 18b was observed even at the highest concentration, indicating that the intermediate radical cyclization is fast (kC > 106 s-1). Negligible amounts of ketone 15 (≤ 2