Synthesis of phosphoramidites of isoGNA, an isomer of glycerol nucleic acid

• Keunsoo Kim,
• Venkateshwarlu Punna,
• Phaneendrasai Karri and
• Ramanarayanan Krishnamurthy

Beilstein J. Org. Chem. 2014, 10, 2131–2138, doi:10.3762/bjoc.10.220

• for the introduction of the canonical nucleobases by a SN2 displacement reaction. At this point, we chose the Mitsunobu reaction (Scheme 1), which has been widely employed [16]. The reaction with the N3-benzoyl protected thymine delivered 5 in good yield. However, the reaction with N6-benzoyladenine

• proved problematic and no product was detected. Therefore, in the adenine case, we tried a direct SN2 reaction of N6-benzoyladenine with tosyl derivative 6, which was only moderately successful (30% yield of 7). Unexpectedly, in both the thymine and adenine cases, the subsequent debenzylation reaction

• protecting group approach. We silylated 1 to afford 8 whose ketal was deprotected followed by tritylation to give the derivative 10, which is expected to be suited for the introduction of nucleobases by an SN2 reaction (Scheme 2). Once again, the Mitsunobu reaction with thymine proceeded smoothly. However

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• -RC reaction between the α,β-unsaturated imine and the enolate, followed by an SN2 reaction. 2.14 Annulations through double-Michael additions The bisphosphine-catalyzed double-Michael addition of dinucleophiles to electron-deficient alkynes provides an efficient approach for the synthesis of

A new charge-tagged proline-based organocatalyst for mechanistic studies using electrospray mass spectrometry

• J. Alexander Willms,
• Rita Beel,
• Martin L. Schmidt,
• Christian Mundt and
• Marianne Engeser

Beilstein J. Org. Chem. 2014, 10, 2027–2037, doi:10.3762/bjoc.10.211

• ). An SN2 reaction with 5 [55] led to 8. We abandoned our initial shorter synthetic route based on a Mitsunobu reaction leading from 6 directly to 8 due to severe purification difficulties. Compound 8 could be charge-tagged to 9 using ethyl bromide. Finally, the free catalyst 1 was obtained by acidic

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• mechanisms were proposed, namely reaction of the carboxylate at the phosphorus center (equivalent to pathway a in Scheme 3) or a SN2’ reaction at the N3 atom (equivalent to pathway b in Scheme 3) [34]. Experiments with [18O]-labeled benzoate indicated that conversion of carboxylic acids to the acyl HOBt

• displacement of the leaving group by attack at the N1 or by a SN2’-type of process by reaction at the N3 of the triazolyl moiety. The mechanistic analyses were conducted by a combination of 31P{1H}, [18O]-labeling, and other chemical experiments. The reaction of phenol with Bt-OTs yielded only the phenyl

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

One-pot stereoselective synthesis of α,β-differentiated diamino esters via the sequence of aminochlorination, aziridination and intermolecular S_N2 reaction

• Yiwen Xiong,
• Ping Qian,
• Chenhui Cao,
• Haibo Mei,
• Jianlin Han,
• Guigen Li and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 1802–1807, doi:10.3762/bjoc.10.189

• directly from cinnamate esters using N,N-dichloro-p-toluenesulfonamide and benzylamine as nitrogen sources. The key transformations include a Cu-catalyzed aminohalogenation and aziridination, followed by an intermolecular SN2 nucleophilic ring opening by benzylamine. The reactions feature a wide scope of

• , the reaction could be conducted in a one-pot model, under operationally convenient conditions [36][37][38][39] through Cu-catalyzed aminohalogenation, aziridination and intermolecular SN2 nucleophilic ring opening without isolation of haloamine intermediate (Scheme 1). Results and Discussion According

• results, a proposed reaction mechanism for this one-pot reaction is illustrated in Scheme 4, which contains the sequence of aminochlorination, aziridination and followed by the SN2 nucleophilic ring-opening. The first step is the Cu-catalyzed aminochlorination reaction of methyl cinnamate 1a resulting in

Proton transfers in the Strecker reaction revealed by DFT calculations

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 1765–1774, doi:10.3762/bjoc.10.184

• -aminopropanonitrile 8. Starting from 4, a concerted SN2-type pathway was also examined, which directly leads to the nitrile compound 8; see Scheme 6. In this pathway, the proton is transferred from the NH3+ group to the hydroxy group via a two-water-molecule bridge. At the same time, the H2O elimination and the

Orthogonal dual thiol–chloroacetyl and thiol–ene couplings for the sequential one-pot assembly of heteroglycoclusters

• Michele Fiore,
• Gour Chand Daskhan,
• Baptiste Thomas and
• Olivier Renaudet

Beilstein J. Org. Chem. 2014, 10, 1557–1563, doi:10.3762/bjoc.10.160

• alkyne–azide cycloaddition (CuAAC) [18] or SN2 reaction [19]. In addition, orthogonal chemoselective ligations were proved more attractive strategies to prepare hGCs in high yields, in part because they require less synthetic and purification steps. For example, oxime and CuAAC ligations have been used

Magnesium bis(monoperoxyphthalate) hexahydrate as mild and efficient oxidant for the synthesis of selenones

• Andrea Temperini,
• Massimo Curini,
• Ornelio Rosati and
• Lucio Minuti

Beilstein J. Org. Chem. 2014, 10, 1267–1271, doi:10.3762/bjoc.10.127

• different alkyl phenyl selenides to the corresponding selenones. Since the phenylselenonyl group is an excellent leaving group, selenone 2 readily undergoes SN2 type substitution reactions with common nucleophiles [7][8] as shown in Scheme 2. A wide range of heterocyclic compounds can be obtained by

• intermediates which readily undergo intramolecular SN2 type substitution reactions to afford a range of heterocyclic compounds (Table 2, entries 2–7) and benzeneseleninic acid. Thus, the oxidation of β-hydroxyalkyl phenyl selenide 1e gave, in tetrahydrofuran and in the presence of dipotassium hydrogen phosphate

Regioselective S_N2' Mitsunobu reaction of Morita–Baylis–Hillman alcohols: A facile and stereoselective synthesis of α-alkylidene-β-hydrazino acid derivatives

• Silong Xu,
• Jian Shang,
• Junjie Zhang and
• Yuhai Tang

Beilstein J. Org. Chem. 2014, 10, 990–995, doi:10.3762/bjoc.10.98

• Silong Xu Jian Shang Junjie Zhang Yuhai Tang Department of Chemistry, School of Science, Xi’an Jiaotong University, Xi’an 710049, P. R. China 10.3762/bjoc.10.98 Abstract A highly regioselective SN2' Mitsunobu reaction between Morita–Baylis–Hillman (MBH) alcohols, azodicarboxylates, and

• –Hillman; SN2' reaction; Introduction Hydrazines and their derivatives are an important class of compounds in organic chemistry. They are widely used in the fields of pesticides, polymers, dyestuff, and pharmaceutical agents [1]. They are also versatile building blocks for accessing many important

• pioneering SN2' Mitsunobu reaction of MBH alcohols with carboxylic acids [31][32], we envisioned that direct treatment of simpler MBH alcohols with azodicarboxylates and PPh3 (Mitsunobu conditions) would chemoselectively provide trisubstituted hydrazines of type 3, via a distinct SN2' Mitsunobu reaction

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• , oxazoles, thiazoles and triazoles incorporated into peptide structures will be described. Pyrrolidines 2-substituted pyrrolidine-based dipeptide mimics were obtained from an Ugi-4CR followed by a Pd-catalyzed Sn2 cyclization as described by Banfi et al. [51] . Herein, the Ugi reaction provided a small

Substrate dependent reaction channels of the Wolff–Kishner reduction reaction: A theoretical study

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 259–270, doi:10.3762/bjoc.10.21

• at the reaction center was prepared by the use of Z matrices. For instance, in the gas phase SN2 reaction Cl− + H3C–Br → Cl–CH3 + Br−, Cl···C and C···Br intermediate distances were assumed. The geometry was optimized under the constraint of the fixed Cl–C and C–Br distances. After the partial

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• ], who proposed a slow SN2(P) attack by amines on (phenyl)phosphoramidothioic dichloride(s) 8 due to the lower electrophilicity of the latter (Scheme 2). The intermediate [(ArNH)2P(S)Cl 9 undergoes a fast base-catalyzed E1cB-reaction to 10, which then reacts with an additional equivalent of aniline to

• . Notably, the follow-up reaction of 12 with N1,N1-dimethyldiaminocyclohexane gives a 1:1 mixture of cis/trans-cyclodiphosphazane 14a/14b, which does not reflect the distribution of cis/trans-isomers in the starting material. This indicates that the reaction does not strictly proceed via an SN2(P) mechanism

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• concerted SN2’ pathway was judged energetically unfavourable, two possible mechanistic channels were supposed to account for the observed stereoselectivity: anti addition followed by anti-elimination or syn addition followed by syn-elimination. Calculations showed that the former pathway was energetically

Triol-promoted activation of C–F bonds: Amination of benzylic fluorides under highly concentrated conditions mediated by 1,1,1-tris(hydroxymethyl)propane

• Pier Alexandre Champagne,
• Alexandre Saint-Martin,
• Mélina Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2013, 9, 2451–2456, doi:10.3762/bjoc.9.283

• the reaction are currently underway in our laboratory. SN2 reaction of activated alkyl fluorides and calculated transition state for the reaction of morpholine with benzyl fluoride with three molecules of water. Proposed activation of C–F bonds mediated by a triol. Initial screening. Fine-tuning

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• DDS 1 and thioglycosides 2–7 are required. The large scale synthesis of DDS 1 was achieved according to a published procedure [26]. The required β-thioglycosides 2–7 were prepared via their corresponding glycosyl bromides followed by SN2 displacement of the anomeric bromide with thiourea [41] or Na2S

One-pot sequential synthesis of isocyanates and urea derivatives via a microwave-assisted Staudinger–aza-Wittig reaction

• Diego Carnaroglio,
• Katia Martina,
• Giovanni Palmisano,
• Andrea Penoni,
• Claudia Domini and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2013, 9, 2378–2386, doi:10.3762/bjoc.9.274

• undesired side-product formation and, consequently, a lower yield. Therefore, the choice of the right solvent and reaction conditions is the key to the success of this transformation. Our initial attempts focused on the synthesis of azido derivatives in MeCN. Although generally performed in DMF, the SN2

Regioselective 1,4-trifluoromethylation of α,β-unsaturated ketones via a S-(trifluoromethyl)diphenylsulfonium salts/copper system

• Satoshi Okusu,
• Yutaka Sugita,
• Etsuko Tokunaga and
• Norio Shibata

Beilstein J. Org. Chem. 2013, 9, 2189–2193, doi:10.3762/bjoc.9.257

• –Hillman adducts (via SN2’ [16] or successive SN2’/SN2’ mode [17]). Sevenard and co-workers reported the nucleophilic 1,4-trifluoromethylation to chromones, coumarins and cyclohex-2-enone using the Ruppert–Prakash reagent, which was achieved by blocking the carbonyl moiety of the substrates with a bulky

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• allene synthesis by copper-mediated SN2’-substitution [51] (Table 1, see below). In order to establish suitable reaction conditions, we first examined the synthesis of the butyl-substituted model substrate 6a. Treatment of propargyl tosylate 5a with the organocopper reagent formed in situ from n-BuMgCl

• ] (Table 1, entries 4 and 5). In the latter case, no formal reduction product (6, R2 = H) was observed which might have been formed by hydrolysis of a stable copper(III) intermediate [51][56]. As expected, all SN2’-substitutions proceeded with excellent anti-stereoselectivity [51]. With propargyl acetate

• % yield, respectively (Table 1, entries 10 and 11). Also these SN2’-substitution took place with complete anti-stereoselectivity. In contrast, decomposition occurred when propargyl acetate 5b was treated with the silyl cuprate (Table 1, entry 12). The next steps towards the substrates of the gold

Synthesis of mucin-type O-glycan probes as aminopropyl glycosides

• David Benito-Alifonso,
• Rachel A. Jones,
• Anh-Tuan Tran,
• Hannah Woodward,
• Nichola Smith and
• M. Carmen Galan

Beilstein J. Org. Chem. 2013, 9, 1867–1872, doi:10.3762/bjoc.9.218

• % overall yield. The sequence involved temporary protection of the free hydroxy at C-3 by reaction with acetic anhydride and pyridine, SN2 displacement of the chloride in monosaccharide 9 with n-tetrabutylammonium iodide (n–TBAI) in refluxing acetonitrile followed by the addition of NaN3. Ester removal was

Gold(I)-catalysed one-pot synthesis of chromans using allylic alcohols and phenols

• Eloi Coutant,
• Paul C. Young,
• Graeme Barker and
• Ai-Lan Lee

Beilstein J. Org. Chem. 2013, 9, 1797–1806, doi:10.3762/bjoc.9.209

• all, instead yielding only Friedel–Crafts products 9 and 10 (Table 1, entries 2 and 3). The ortho- and para-Friedel–Crafts products 9 and 10 are formed via formal SN2' regioselectivity and 9 is presumably the intermediate towards chroman 8 (vide infra). Thus, the higher temperature is clearly

• 19 undergoes the Friedel–Crafts allylation via opposite regioselectivity (a formal SN2 instead of SN2' observed in all other examples so far in Table 2 and Table 3) to form 9, followed by cyclisation to form the observed 8o. Using a γ,γ-disubstituted secondary allylic alcohol 20 also forms chroman 8u

• via an initial SN2 Friedel–Crafts regioselectivity, thus γ,γ-disubstitution on the alkene appears to be responsible for the switch in regioselectivity (Table 3, entry 11). This implies that the initial Friedel–Crafts allylation goes via Markovnikov selectivity. The unsubstituted secondary allylic

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• chiral complexation of the phosphorus/silicon cation, and then followed by an attack with the chloride ion in an SN2 fashion to furnish chlorohydrin enantioselectively (Figure 14). From this description, the activation of SiCl4 was depending on the formation of the chiral complexation of the phosphorus

Synthesis of the calcilytic ligand NPS 2143

• Henrik Johansson,
• Thomas Cailly,
• Alex Rojas Bie Thomsen,
• Hans Bräuner-Osborne and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 1383–1387, doi:10.3762/bjoc.9.154

• pure (R)-3 in parallel using the method by Marquis et al. [13]. Commercially available glycidol 15 activated as the m-nitrobenzene sulfonyl (m-nosyl) ester 5 has previously been shown to be an ideal leaving group in reactions with aryloxy nucleophiles (e.g., 4) as it promotes direct SN2 over SN2

Incorporation of perfluorohexyl-functionalised thiophenes into oligofluorene-truxenes: synthesis and physical properties

• Neil Thomson,
• Alexander L. Kanibolotsky,
• Joseph Cameron,
• Tell Tuttle,
• Neil J. Findlay and
• Peter J. Skabara

Beilstein J. Org. Chem. 2013, 9, 1243–1251, doi:10.3762/bjoc.9.141

• percentage of fluorine present gives rise to a large electron-withdrawing effect [11]. However, perfluoroalkyl halides are not suitable alkylating reagents for SN2 type reactions, which makes the attachment of these types of chains to aromatic cyclic compounds difficult without the use of a spacer group

An aniline dication-like transition state in the Bamberger rearrangement

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2013, 9, 1073–1082, doi:10.3762/bjoc.9.119

• -known reaction, the mechanism of the Bamberger rearrangement is still unclear. Heller et al. suggested that an SN1 mechanism is more likely, but the SN2 one cannot be ruled out [3]. The reaction was proven to occur via the intermolecular rearrangement by the 18O exchange in Scheme 2 [4]. The