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

• tetrahydroimidazoles 72 based on intramolecular interception of the iminium ions by a tethered sulfonamide (71, Scheme 18) [86]. Ru(bpy)3Cl2 was employed as the photocatalyst with oxygen as the stoichiometric oxidant. The use of a base in an alcohol solvent, such as MeOH, was also the key to the success of this

• solvent. No external base was needed when the alcohol was the nucleophile. However, if the sulfonamide was the nucleophile, an external base such as t-BuOK was required presumably to increase the nucleophilicity of the sulfonamide. The Rueping group trapped the iminium ions using phosphites 76 to produce

Anodic coupling of carboxylic acids to electron-rich double bonds: A surprising non-Kolbe pathway to lactones

• Robert J. Perkins,
• Hai-Chao Xu,
• John M. Campbell and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2013, 9, 1630–1636, doi:10.3762/bjoc.9.186

• electron-rich olefin was coupled to one of two competing nucleophiles, a sulfonamide and an alcohol (5). When the oxidation was run with 2,6-lutidine as a base (not shown), the reaction led to the formation of a radical cation from the electron-rich olefin followed by trapping by the alcohol nucleophile to

• form product 9. No product from sulfonamide trapping (8) was observed. However, when the reaction was run under more basic conditions (0.5 equivalents of lithium methoxide) cyclic voltammetry data indicated that the oxidative cyclizations were initiated by the oxidation of sulfonamide anion. This led

• to initial formation of N-localized radical 6. Depending on the reaction conditions, the experiment favoured either a sulfonamide or alcohol based cyclization. Density functional theory (DFT) calculations suggested that sulfonamide based cyclizations proceed by addition of the N-localized radical to

Gold-catalyzed intermolecular hydroamination of allenes with sulfonamides

• Chen Zhang,
• Shao-Qiao Zhang,
• Hua-Jun Cai and
• Dong-Mei Cui

Beilstein J. Org. Chem. 2013, 9, 1045–1050, doi:10.3762/bjoc.9.117

• ; hydroamination; N-sulfonyl; selectivity; sulfonamide; Introduction Hydroamination of an N–H bond across a C–C unsaturated bond represents one of the most effective and atom-economical methods to prepare amine derivatives [1][2][3][4][5]. In the case of using allenes, this reaction can lead to allylamines, which

• 3e in 54 and 72% yields, respectively (Table 2, entries 4–5). Under the same reaction conditions, the hydroamination of aliphatic sulfonamides took place smoothly to afford the corresponding N-allylic sulfonamide 3f with 56% yield (Table 2, entry 6). We also used N-substituted sulfonamide 2g as the

• aliphatic allene 1e formed a 71:29 mixture of linear product (3ka) and branch product (3kb) under the same conditions (Table 3, entry 4). Furthermore, disubstituted allenes also worked well. Differentially 1,1-disubstituted allene 1f reacted with sulfonamide to afford trans-adducts 3l with high selectivity

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

• Reik Löser,
• Steffen Fischer,
• Achim Hiller,
• Martin Köckerling,
• Uta Funke,
• Aurélie Maisonial,
• Peter Brust and
• Jörg Steinbach

Beilstein J. Org. Chem. 2013, 9, 1002–1011, doi:10.3762/bjoc.9.115

• hydrolytic cleavage [15][16][17]. As an alternative to acyl-based prosthetic groups the 3-[18F]fluoropropanesulfonyl group introduced by Li et al. attracted our interest [18]. Labelling with radiofluorine by sulfonamide formation seems to be intriguing not only because of the inertness against the metabolic

• product 18. This compound was obtained in the form of crystals suitable for X-ray diffraction analysis. The molecular structure of 18 is shown in Figure 2A, confirming unambiguously its identity as N-(4-nitrophenyl)-3-fluoropropane-1-sulfonamide. Crystal data and structure refinement parameters are

• be also observed for the molecular structure of 18 in the crystal. This is indicated by the fact that the sum of the three valence angles around the sulfonamide nitrogen (C4–N1–S1, C4–N1–H1C, and S1–N1–H1C) is equal to 348(4)°, which is significantly less than 360° for trigonal planar geometry

Preparation and ring-opening reactions of N-diphenylphosphinyl vinyl aziridines

• Ashley N. Jarvis,
• Andrew B. McLaren,
• Helen M. I. Osborn and
• Joseph Sweeney

Beilstein J. Org. Chem. 2013, 9, 852–859, doi:10.3762/bjoc.9.98

• ]. However, a key limitation to the synthetic application of aziridines in general is the nature of the N-substituent: most synthetic routes to aziridines deliver N-sulfonylated products, and the cleavage of the sulfonamide bond is often challenging. Perhaps for this reason, and despite the plethora of

Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

• Sushil K. Maurya,
• Mark Dow,
• Stuart Warriner and
• Adam Nelson

Beilstein J. Org. Chem. 2013, 9, 775–785, doi:10.3762/bjoc.9.88

• with methyl chloroformate and DMAP. The allylic carbonate 15 underwent efficient asymmetric allylic amination [20] with o-nitrophenylsulfonamide as the nucleophile to give the allylic sulfonamide 17 in 66% yield; in addition, the linear product 16 was also obtained in 7% yield. Desilylation of 17 (→ 18

Regio- and stereoselective carbometallation reactions of N-alkynylamides and sulfonamides

• Yury Minko,
• Morgane Pasco,
• Helena Chechik and
• Ilan Marek

Beilstein J. Org. Chem. 2013, 9, 526–532, doi:10.3762/bjoc.9.57

• give 3c (Table 1, entry 3). Although N-heterosubstituted alkynes were used in all cases, the α-isomer is regioselectively obtained, as confirmed by 1H NMR analysis of the crude reaction mixture after hydrolysis, through an intramolecular chelation between the N-sulfonamide moiety and the organocopper

Facile synthesis of benzothiadiazine 1,1-dioxides, a precursor of RSV inhibitors, by tandem amidation/intramolecular aza-Wittig reaction

• Krishna C. Majumdar and
• Sintu Ganai

Beilstein J. Org. Chem. 2013, 9, 503–509, doi:10.3762/bjoc.9.54

• chloride followed by the reaction with appropriate amines to give the requisite 2-azido-N-substituted benzenesulfonamides 10a–i. The sulfonamide 10b was reacted with ethyl carbonochloridate to afford the corresponding amide derivative 9b required for our study. Initially, we turned our attention to the

• heating the sulfonamide 10b with ethyl carbonochloridate, Et3N and PPh3 in DCB at 135 °C for 6 h, which gave the cyclized product 13b in 78% yield (Table 2, entry 1). The base Et3N was then replaced by Cs2CO3 or K2CO3, but no better result was obtained (Table 2, entries 2 and 3). Only DIPEA gave 69% yield

• SO2NH2 by the reaction of nucleophilic sulfonamide 10 with ethyl carbonochloridate in the presence of Et3N to form the intermediates 9, which may then undergo intramolecular aza-Wittig reaction via the formation of iminophosphorane intermediate I. We isolated iminophosphorane intermediate 12b from the

Iridium-catalyzed intramolecular [4 + 2] cycloadditions of alkynyl halides

• Andrew Tigchelaar and
• William Tam

Beilstein J. Org. Chem. 2012, 8, 1765–1770, doi:10.3762/bjoc.8.201

• ). Deprotonation of 8 with sodium hydride, followed by trapping with propargyl bromide provided 9 in 60% yield, and a Mitsunobu reaction between 8 and sulfonamide 10 (prepared as per reference [47]) provided 11 in 74% yield. Bromination of 9 and 11 provided diene-tethered alkynyl halides 1c (57%) and 1e (83

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

• Marcus Frings,
• Isabelle Thomé and
• Carsten Bolm

Beilstein J. Org. Chem. 2012, 8, 1443–1451, doi:10.3762/bjoc.8.164

• thiourea or sulfonamide unit, and the second relates to the activation of the alcohol by the basic nitrogen of the amine. Which effect dominates in the case of (S)-3 – a carbonyl activation by a single hydrogen bond or an enhancement of the alcohol activity by the weakly basic sulfoximine nitrogen

Asymmetric organocatalytic decarboxylative Mannich reaction using β-keto acids: A new protocol for the synthesis of chiral β-amino ketones

• Chunhui Jiang,
• Fangrui Zhong and
• Yixin Lu

Beilstein J. Org. Chem. 2012, 8, 1279–1283, doi:10.3762/bjoc.8.144

• , entry 1). Quinine-derived sulfonamide [40], β-isocupreidine (β-ICD) [41][42] and biscinchona alkaloid (DHQ)2AQN were all found to be poor catalysts (Table 1, entries 2–4). On the other hand, cinchona alkaloid derived bifunctional thiourea tertiary amine catalysts afforded much improved results (Table 1

Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors

• Chao Che,
• Song Li,
• Bo Yang,
• Shengchang Xin,
• Zhixiong Yu,
• Taofeng Shao,
• Chuanye Tao,
• Shuo Lin and
• Zhen Yang

Beilstein J. Org. Chem. 2012, 8, 841–849, doi:10.3762/bjoc.8.94

• [39][40]. It is noteworthy that some polar groups, including amino, hydroxy and sulfonamide, could not tolerate the conditions of Higa cyclization, and had to be introduced through transformation reactions after the N-acylation step. As depicted in Scheme 3, NH2-derivative 7m was prepared from the NO2

Synthetic approaches to multifunctional indenes

• Neus Mesquida,
• Sara López-Pérez,
• Immaculada Dinarès and
• Ermitas Alcalde

Beilstein J. Org. Chem. 2011, 7, 1739–1744, doi:10.3762/bjoc.7.204

• as the most suitable way of functionalizing the 5-position of the indene, e.g., by changing the aryl(heteroaryl) structural motif of a sulfonamide moiety (Scheme 1). This route proceeded in three steps, and allowed the representative (3-indenyl)acetic acids 4 to be conveniently prepared from

Continuous-flow enantioselective α-aminoxylation of aldehydes catalyzed by a polystyrene-immobilized hydroxyproline

• Xacobe C. Cambeiro,
• Rafael Martín-Rapún,
• Pedro O. Miranda,
• Sonia Sayalero,
• Esther Alza,
• Patricia Llanes and
• Miquel A. Pericàs

Beilstein J. Org. Chem. 2011, 7, 1486–1493, doi:10.3762/bjoc.7.172

• ], binaphthyl-derived amines [22][23][24], pyrrolidin-2-yl-tetrazoles [25][26][27][28], thiaproline [29], 2-aminomethylpyrrolidine sulfonamide [30] and sulfonylcarboxamide [31], have been successfully used to promote the reaction. As a matter of fact, the rapid development of the methodology for the asymmetric

Amine-linked diglycosides: Synthesis facilitated by the enhanced reactivity of allylic electrophiles, and glycosidase inhibition assays

• Ian Cumpstey,
• Jens Frigell,
• Elias Pershagen,
• Tashfeen Akhtar,
• Elena Moreno-Clavijo,
• Inmaculada Robina,
• Dominic S. Alonzi and
• Terry D. Butters

Beilstein J. Org. Chem. 2011, 7, 1115–1123, doi:10.3762/bjoc.7.128

• unsaturated glycoside 4 to be achieved; phosphomolybdic acid [32] gave the product (α:β, 8:1) in 63% yield. Deacetylation of 4 and regioselective silylation of the primary alcohol gave the threo allylic alcohol 2. The sulfonamide nucleophiles 6, 7 and 9 were prepared from the corresponding amines 5 [33] and 8

• [34], as described previously [6], with only one equivalent of the sulfonylating agent so as to avoid bis-sulfonamide formation. Mixing equimolar equivalents of the erythro allylic alcohol 1 and the glucose-6-nosylamide 6 with DIAD and triphenylphosphine resulted in a smooth coupling reaction to give

• conditions that had failed to give coupling reactions between a primary alcohol and a sulfonamide at a secondary carbohydrate position, or a secondary alcohol and a sulfonamide at a primary carbohydrate position, in our earlier study [6]. Coupling of this threo alcohol 2 with sulfonamide nucleophiles (6, 7

Intramolecular hydroamination of alkynic sulfonamides catalyzed by a gold–triethynylphosphine complex: Construction of azepine frameworks by 7-exo-dig cyclization

• Hideto Ito,
• Tomoya Harada,
• Hirohisa Ohmiya and
• Masaya Sawamura

Beilstein J. Org. Chem. 2011, 7, 951–959, doi:10.3762/bjoc.7.106

• linker chain of the alkynic N-tosylsulfonamide 4a (Table 3). The introduction of the substituents at the α or β positions relative to the alkyne moiety caused a significant decrease in the reactivity, but the cyclization of the substituted alkynic sulfonamide 4g–l proceeded smoothly, with 2.5–5.0 mol

• -dig cyclization in good yields (Table 3, entries 4–6). Among the cyclization products (5a–l) described above, only the β,β-diphenyl-substituted sulfonamide 5k was contaminated with a small amount of exomethylene product 6k (Table 3, entry 5). It should be noted that the geminal disubstitution in 4j–l

• reaction time and product yield. The reaction of N-tosylbenzamide 4n with L1 afforded the benzene-fused ε-caprolactam 6n within an exomethylene structure in 97% yield in an isomerically pure form (vide infra for discussion) (Table 4, entry 3). Sulfonamide 4o, with a cyclohexane-fused linker, also

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• method to construct synthetically useful four-membered carbocycles. Ye et al. reported a new type of gold(I)-catalyzed ring expansion of an non-activated alkynylcyclopropane/sulfonamide to obtain (E)-2-alkylidenecyclobutanamines [73]. For example, treatment of alkynylcyclopropane 159 with TsNH2 and 5 mol

• by the AuCl3/AgSbF6 catalyst and ionization of the starting material, which causes intramolecular nucleophilic addition of the sulfonamide unit to the allylic cation moiety and construction of a 1,2-dihydroquinoline. Our group also discovered that a regioselective hydroamidation of 2-(1-alkynyl

Synthesis of novel 5-alkyl/aryl/heteroaryl substituted diethyl 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates by aziridine ring expansion of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters

• Satish S. More,
• T. Krishna Mohan,
• Y. Sateesh Kumar,
• U. K. Syam Kumar and
• Navin B. Patel

Beilstein J. Org. Chem. 2011, 7, 831–838, doi:10.3762/bjoc.7.95

• ], pyrrolines [10][11][12][13][14], imidazolidinones [15], β-lactams [16][17][18] and azepines [19][20][21]. There is ample evidence in the literature to confirm that the syntheses and applications of the N-acyl, N-sulfonamide or N-benzyl protected C-vinylaziridines are of considerable interest in organic

Synthetic applications of gold-catalyzed ring expansions

• David Garayalde and
• Cristina Nevado

Beilstein J. Org. Chem. 2011, 7, 767–780, doi:10.3762/bjoc.7.87

• and trapping of the carbocation by the sulfonamide. Subsequent intramolecular hydroamination gave the pyrrolidine products. 1.3 Oxiranes As an oxophilic Lewis acid, gold can activate epoxides towards the attack of nucleophiles. A good example is the AuCl3 catalyzed ring opening of aryl alkyl epoxide

When cyclopropenes meet gold catalysts

• Frédéric Miege,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2011, 7, 717–734, doi:10.3762/bjoc.7.82

• yield (99%) and with high diastereoselectivity (dr > 96:4) by gold-catalyzed cycloisomerization of the N-allyl sulfonamide 70 (Scheme 28) [25]. The success of the gold-catalyzed cycloisomerization of cyclopropene-enes, proceeding with intramolecular cyclopropanation of the olefin, lies in the

• , underwent nucleophilic attack by the cyclopropene in a 5-exo-dig manner followed by ring-opening. A subsequent Friedel–Crafts cyclization allowed the formation of the indene subunit (Equation 1, Scheme 32). Sulfonamide 91 contains a 1,7-enyne subunit and its gold-catalyzed cycloisomerization delivered

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• yields (Scheme 9). However, in sumatriptan the indole product resulting from the Fischer synthesis can still react further which leads to the formation of by-products and significantly reduced yields. One way to minimise this was to protect the nitrogen of the sulfonamide group prior to indole formation

• and decarboxylation then affords sumatriptan [14]. All the reported methods for the synthesis of sumatriptan begin with the sulfonamide group already present on the aromatic ring and several routes are possible to introduce this functional group. The scalable route to the sulfonamides inevitably

• formaldehyde as by-products [15]. Another possible approach is based on the direct displacement of a benzylic chloride by sodium sulfite and subsequent sulfonamide formation as shown in Scheme 13 [16]. A more recent method utilises a palladium-catalysed Negishi coupling to access a diverse library of benzylic

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• sulfonamide derivatives 12 by reducing the nitro group to an amino group by catalytic hydrogenation followed by treatment with an arylsulfonyl chloride (Scheme 4). Alternatively, 5-aminopyrazoles 17 containing a cyclohexylmethyl- or phenylmethyl- sulfonamido group at position-3 were prepared by treating β

• cyanoacetaldehyde (7) with hydrazines. Synthesis of 5-aminopyrazoles and their sulfonamide derivatives. Synthesis of 5-aminopyrazoles, containing a cyclohexylmethyl- or phenylmethyl- sulfonamido group at position-3. Regioselective synthesis of 3-amino-2-alkyl (or aryl) thieno[3,4-c]pyrazoles 19. Solid supported

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

• , C6F5SSCF3, CF3I as well as (CF3S)2 with (CF3)2S suggesting the following reaction mechanism (Scheme 53). N-Trifluoromethyl-N-nitrosobenzene sulfonamide has been used as a source of CF3• radicals. This reagent (obtained by reaction of CF3NO, NH2OH and benzenesulfonic acid chloride) reacts with organic

Recent advances in carbocupration of α-heterosubstituted alkynes

• Ahmad Basheer and
• Ilan Marek

Beilstein J. Org. Chem. 2010, 6, No. 77, doi:10.3762/bjoc.6.77

• the stoichiometric version, the reaction proceeds smoothly for the addition of alkyl and phenyl substituents but the yield is much lower for the addition of methyl (30% yield, not indicated in Scheme 11). Even when phenylethynylarene sulfonamide 25 is used as starting material, a single regioisomer 26

• centers. Carbocupration of alkynyl sulfonamide. Tandem carbocupration-sigmatropic rearrangement. Silylcupration of alkynyl sulfonamides. Carbocupration of P-substituted alkynes. Carbocupration of alkynylphosphonates. Carbocupration of thioalkynes. Tandem carbocupration-1,2-metalate rearrangement

Anion receptors containing thiazine-1,1-dioxide heterocycles as hydrogen bond donors

• Hong-Bo Wang,
• James A. Wisner and
• Michael C. Jennings

Beilstein J. Org. Chem. 2010, 6, No. 50, doi:10.3762/bjoc.6.50

• potential hydrogen bond donor strength with anionic guests. Alternatively, the possibility of deprotonation in some specific systems by basic anions such as carboxylates or fluoride can be employed as an indicator for these species. Regardless, the incorporation of sulfonamide functional groups has

• typically been realized synthetically by sulfonylation of an amine to form a sulfonamide product. This approach is somewhat limited, from a design perspective, in that the majority of examples to date consist of sulfonamides derived from a few commercially available starting materials such as

• heterocycle can be viewed as a cyclic, vinylogous sulfonamide that presents a different spatial, conformational and electronic relationship between the sulfonyl and NH subunits than that of a typical sulfonamide function (Figure 1B). It is a simple matter to access many such derivatives with this framework