A Lewis acid-promoted Pinner reaction

• Dominik Pfaff,
• Gregor Nemecek and
• Joachim Podlech

Beilstein J. Org. Chem. 2013, 9, 1572–1577, doi:10.3762/bjoc.9.179

• used. A possible mechanism of this reaction is given in Scheme 7. Double silylation leads to the formation of a good leaving group and the highly electrophilic benzylic carbon is attacked by the nitrile yielding a nitrilium cation. The reaction is finalized by hydrolysis furnishing the carboxamide

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• the trans double bond in the opening of a cyclopropane with an adjacent hydroxy or mesylate leaving group, regardless of the initial configuration of the cyclopropane (Scheme 3, reaction 2) [27]. Braddock has demonstrated that the internal 3,4-E olefin is obtained exclusively in Prins reactions

• stereoselective fashion from displacement of a leaving group at C10, a means for the selective formation of a syn-1,3-diol at C11 and C13 is required. Rychnovsky has demonstrated that alkylation of 4-cyano-1,3-dioxanes (cyanohydrin acetonides) constitutes a practical and valuable approach to syn-1,3-diol

• contain all of the carbon atoms of epoxide fragment 5 in the correct oxidation state. The remaining steps required to access the epoxide consist of acetonide deprotection, displacement of the tosylate or another appropriate leaving group to obtain the terminal epoxide, and silyl protection. Conclusion

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

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

• isolated by distillation in a yield of 24%. Reduction of the amount of sodium iodide from 5 to 1.1 equivalents did not result in a more favourable product distribution. The course of this reaction becomes clear in the light of the pseudohalide concept: the thiocyanate functionality acts as a leaving group

Utilizing the σ-complex stability for quantifying reactivity in nucleophilic substitution of aromatic fluorides

• Magnus Liljenberg,
• Tore Brinck,
• Tobias Rein and
• Mats Svensson

Beilstein J. Org. Chem. 2013, 9, 791–799, doi:10.3762/bjoc.9.90

• ) followed by elimination of the leaving group [6]. In the case of attack of anionic nucleophiles (such as MeO−) on fluorinated aromatics, the intermediate σ-complex is anionic and the leaving group is F−, whereas in the case of neutral nucleophiles (such as NH3) the intermediate σ-complex is zwitterionic

• and the leaving group is HF. The departure of H and F can proceed along different mechanisms [7][8][9]. Several methods for predicting local reactivity, or regioselectivity, in SNAr reactions have been reported. Among the earlier ones is the Iπ-repulsion theory based on calculating the fractional

• leaving group was Cl−/HCl or Br−/HBr both for anionic and neutral nucleopiles, because of difficulties in finding relevant σ-complex structures. Instead an approach where we assumed a concerted substitution step and used such transition-state structures gave quantitatively useful results [5]. Recent

Kinetics and mechanism of the anilinolysis of aryl phenyl isothiocyanophosphates in acetonitrile

• Hasi Rani Barai and
• Hai Whang Lee

Beilstein J. Org. Chem. 2013, 9, 615–620, doi:10.3762/bjoc.9.68

• greater magnitude of ρXY value with more basic anilines than that with less basic anilines is also acceptable. Accordingly, the authors propose the following reaction mechanism: (i) a stepwise process with rate-limiting leaving-group departure from the intermediate for more basic anilines based on the

• TSb-H and TSf. The anilinolyses of tetracoordinate phosphorus with the Cl– leaving group have been extensively studied in this lab, and the obtained data of primary normal DKIEs involving deuterated anilines are rationalized by TSf-type in which hydrogen bonding of an amine hydrogen atom occurs on the

• negative βX values for less basic anilines are not ascribed to (i) a desolvation step prior to the rate-limiting nucleophilic attack, because the aniline nucleophile is neutral and the MeCN solvent is dipolar aprotic; and to (ii) a TS imbalance phenomenon, because the leaving group of isothiocyanate is too

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

• of β-elimination. This constitutes a tremendous synthetic asset and explains the popularity and importance of radical-based methods for the manipulation and modification of oxygen-rich compounds such as carbohydrates and cyclitols. It is, however, possible to transform an alcohol into a leaving group

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

Synthesis of trifunctional cyclo-β-tripeptide templates

• Frank Stein,
• Tahir Mehmood,
• Tilman Plass,
• Javid H. Zaidi and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2012, 8, 1576–1583, doi:10.3762/bjoc.8.180

• according to Scheme 1 by using the commercially available 4-Fmoc-hydrazinobenzoyl AM NovaGel resin from Merck Biosciences. After coupling of the three β-amino acids by using the standard Boc-protocol, the hydrazide linker was oxidized to generate nitrogen as a good leaving group. Nucleophilic attack of the

Unprecedented deoxygenation at C-7 of the ansamitocin core during mutasynthetic biotransformations

• Tobias Knobloch,
• Gerald Dräger,
• Wera Collisi,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2012, 8, 861–869, doi:10.3762/bjoc.8.96

• leaving group β-positioned to the keto group, thereby facilitating elimination to enones 17 (Scheme 5). In the case of compound 12, which predominantly exists in a form lacking the typical cyclized carbinolamide moiety, the C-9 keto group can preserve its electronic properties, thus facilitating the

Chemistry of polyhalogenated nitrobutadienes, 10: Synthesis of highly functionalized heterocycles with a rigid 6-amino-3-azabicyclo[3.1.0]hexane moiety

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Armin de Meijere and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2012, 8, 621–628, doi:10.3762/bjoc.8.69

• -bistriazolyltrichloronitrobutadiene 14 (92% yield) was obtained [22] and turned out to be an appropriate substrate for a transamination, as the triazole is an excellent leaving group. Thus, by treatment of 14 with p-phenetidine the 4-triazolyl-4-(4-ethoxyphenylamino)butadiene 15 was obtained in 83% yield. Subsequent reaction of 15

2-Allylphenyl glycosides as complementary building blocks for oligosaccharide and glycoconjugate synthesis

• Hemali D. Premathilake and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2012, 8, 597–605, doi:10.3762/bjoc.8.66

• Hemali D. Premathilake Alexei V. Demchenko Department of Chemistry and Biochemistry, University of Missouri – St. Louis, One University Boulevard, St. Louis, MO 63121, USA 10.3762/bjoc.8.66 Abstract The O-allylphenyl (AP) anomeric moiety was investigated as a new leaving group that can be

• efficient oligosaccharide assembly. Keywords: carbohydrates; glycosylation; leaving group; oligosaccharides; orthogonal strategy; selective activation; Introduction Current knowledge about the key roles of carbohydrates is still limited. However, thanks to the explosive growth of the field of glycobiology

• part of the ongoing research effort to develop versatile building blocks, we present herein the development of a new ortho-allylphenyl (AP) leaving group. In line with other efforts [23][24][25][26], the AP group was specifically designed to address the drawbacks of O-pentenyl glycosides and to create

Synthesis and biological evaluation of nojirimycin- and pyrrolidine-based trehalase inhibitors

• Davide Bini,
• Francesca Cardona,
• Matilde Forcella,
• Camilla Parmeggiani,
• Paolo Parenti,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2012, 8, 514–521, doi:10.3762/bjoc.8.58

• ; protein data bank (PDB) entries 2JF4 and 2JG0 [12]) shows the presence of two subsites: Subsite +1 accommodating the leaving-group, the “recognition” site, and subsite −1 as the “catalytic” site. Due to the biological relevance of trehalose and trehalase, several trehalose mimetics have been proposed as

Fifty years of oxacalix[3]arenes: A review

• Kevin Cottet,
• Paula M. Marcos and
• Peter J. Cragg

Beilstein J. Org. Chem. 2012, 8, 201–226, doi:10.3762/bjoc.8.22

• with their nitrogen atoms pointing away from it [26]. 3.1.2 Functionalized alkyl ethers: Functionalized alkyl halides of the type XCH2Y, where X is a leaving group and Y is a functional group, have also been used to introduce a variety of groups into the lower rim of oxacalix[3]arenes. Thus

Dependency of the regio- and stereoselectivity of intramolecular, ring-closing glycosylations upon the ring size

• Patrick Claude,
• Christian Lehmann and
• Thomas Ziegler

Beilstein J. Org. Chem. 2011, 7, 1609–1619, doi:10.3762/bjoc.7.189

• intramolecularization of glycosylation reactions have been studied so far. For recent reviews on this subject see [1][2][3][4]. In the “leaving-group-based concept”, the glycosyl acceptor is attached to the leaving group of the glycosyl donor and O-glycosidic bond formation occurs synchronously to the cleavage of the

• leaving group [5][6][7][8][9]. In the “aglycon-delivery concept”, the glycosyl acceptor is attached to a labile acetal [10][11][12][13][14] or silylene group [15][16][17], which is cleaved and the glycosyl acceptor is “delivered” to the anomeric center upon its activation. In the “prearranged-glycoside

• concept”, the sole true intramolecular glycosylation approach which was developed in our [18][19][20] and Valverde’s group [21], glycosyl donor and acceptor are linked by a stable tether attached to positions not directly involved in the glycosylation step. Upon activation of the leaving group, an

A simple and convenient one-pot synthesis of substituted isoindolin-1-ones via lithiation, substitution and cyclization of N'-benzyl-N,N-dimethylureas

• Keith Smith,
• Gamal A. El-Hiti,
• Amany S. Hegazy and
• Benson Kariuki

Beilstein J. Org. Chem. 2011, 7, 1219–1227, doi:10.3762/bjoc.7.142

• -methoxybenzamides as the starting materials; in this case the methoxy group acts as a leaving group, which avoids the need for an oxidation step [45]. However, this approach still requires an additional step to remove the tert-butyl group and incorporation of the 3-substituent into the starting material. As a

Lithium phosphonate umpolung catalysts: Do fluoro substituents increase the catalytic activity?

• Anca Gliga,
• Bernd Goldfuss and
• Jörg M. Neudörfl

Beilstein J. Org. Chem. 2011, 7, 1189–1197, doi:10.3762/bjoc.7.138

• metallophosphonate catalyst must act as a nucleophile, an anion (d1-synthon) stabilization group, and as well as a leaving group (nucleofuge). Comparative computational assessments of carbanionic d1-species, which have been proposed as crucial intermediates according to the Lapworth and Breslow mechanisms, show

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

• carbohydrate into an unsaturated derivative with an allylic alcohol as leaving group [16]. After the coupling reaction, dihydroxylation of the C=C double bond would restore the carbohydrate structure (Scheme 1) [17]. As well as Mitsunobu chemistry [18], the allylic nature of the electrophile opens up the way

• trichloroacetimidate 23 by treatment with trichloroacetonitrile and base. The trichloroacetimidate is a leaving group that has the advantage of being easily and stereospecifically synthesised from the alcohol under basic conditions. We recently used the trichloroacetimidate as leaving group in palladium catalysed

The role of silver additives in gold-mediated C–H functionalisation

• Scott R. Patrick,
• Ine I. F. Boogaerts,
• Sylvain Gaillard,
• Alexandra M. Z. Slawin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2011, 7, 892–896, doi:10.3762/bjoc.7.102

• of 5. This observation clearly shows that silver can have a positive role in the carboxylation of C–H bonds. Conclusion The C–H functionalisation of arenes using (NHC)gold(I) complexes has been shown to be significantly affected by the leaving group on the gold. The gold(I) chloride may only react by

Gold-catalyzed propargylic substitutions: Scope and synthetic developments

• Olivier Debleds,
• Eric Gayon,
• Emmanuel Vrancken and
• Jean-Marc Campagne

Beilstein J. Org. Chem. 2011, 7, 866–877, doi:10.3762/bjoc.7.99

• of a cobalt complex. In 1994, Murahashi [8] described in a seminal paper the propargylic substitution of monosubstituted alkynes bearing a good leaving group on the propargylic alcohol moiety, where a mechanism through a copper-allenylidene intermediate was postulated. Subsequently, asymmetric

• ) and a lower amount of gold catalyst should slow down the Meyer–Schuster process. It also suggests that, not only the OH group but also the OEt group can act as a good leaving group in these reactions. Indeed, when isolated compound 10 was subjected to Au(III) catalyst in the presence of water, 11 was

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

• carbanion during the nucleophilic displacement of the iodo leaving group (Table 2, entries 1 and 5). It was also observed that in the presence of electron withdrawing groups on aryl rings, the rate of iodide ion mediated aziridine ring expansion to pyrrolines was slow compared to N-vinylaziridines bearing

A comparative study of the Au-catalyzed cyclization of hydroxy-substituted allylic alcohols and ethers

• Berenger Biannic,
• Thomas Ghebreghiorgis and
• Aaron Aponick

Beilstein J. Org. Chem. 2011, 7, 802–807, doi:10.3762/bjoc.7.91

• solved if the allylic alcohol leaving group did not need to be revealed directly before the cyclization event. This led us to consider the use of alternative substrates where the allylic alcohol could be deprotected under the reaction conditions, or the use of other “protecting groups” that would also

• to vary the nature of the allylic leaving group and olefin geometry. These conditions are slightly different to those employed in the study of diols [23][24][25], differing in catalyst identity and loading (1 mol % (Ph3P)AuCl/AgOTf versus 5 mol % Au[P(t-Bu)2(o-biphenyl)]SbF6). As mentioned above, the

• it can then act as a leaving group under Au-catalyzed cyclization conditions. Several additional, commonly used, protecting groups were also screened under the reaction conditions (Figure 5). From the graph, it is apparent that benzyl (13), TBDPS (14), and THP [33] (15) could all be used, but esters

Gold-catalyzed alkylation of silyl enol ethers with ortho-alkynylbenzoic acid esters

• Haruo Aikawa,
• Tetsuro Kaneko,
• Naoki Asao and
• Yoshinori Yamamoto

Beilstein J. Org. Chem. 2011, 7, 648–652, doi:10.3762/bjoc.7.76

• -induced in situ construction of leaving groups and subsequent nucleophilic attack on the silyl enol ethers. The generated leaving compound abstracts a proton to regenerate the silyl enol ether structure. Keywords: alkylation; gold catalysis; leaving group; silyl enol ether; substitution reaction

• the indirect pathway. In conclusion, we have developed an unprecedented alkylation method for silyl enol ethers, using a gold catalyst and ortho-alkynylbenzoic acid esters as alkylating agents. The reaction probably proceeds through the gold-induced in situ construction of a leaving group and

Complete transfer of chirality in an intramolecular, thermal [2 + 2] cycloaddition of allene-ynes to form non-racemic spirooxindoles

• Kay M. Brummond and
• Joshua M. Osbourn

Beilstein J. Org. Chem. 2011, 7, 601–605, doi:10.3762/bjoc.7.70

• allenyloxindole 8 (Table 1). In order to generate the allene, we examined various leaving groups (OMs, OMe, OAc), solvents (THF, Et2O), and cuprates (lower and higher order cyanocuprates). The reaction incorporating a mesylate as a leaving group was problematic due to substrate instability issues, even at low

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• (C–S bond formation). Alternatively, stereoselective alkylation, arylation or acylation of a secondary sulfur-based substrate could generate the quaternary centre (C–C bond formation). Review 1 Carbon–sulfur bond formation 1.1 SN2 displacement of a leaving group Stereospecific nucleophilic attack on

• the preparation of certain families of tertiary thiols and thioethers. For example, SN2 displacement of a mesylate leaving group by thiophenol can be accomplished using α-hydroxy esters 2 (Scheme 1) [12]. The presence of the α-ester group of 3 promotes SN2 reaction in two ways: The electron

• product 6 (Scheme 2). The low yields can be attributed to the formation of β-phenylthioesters 7 by elimination followed by conjugate addition. Even in the presence of the adjacent carbonyl group, competing SN1 dissociation of the benzylic leaving group leads to a loss of enantiomeric purity in some cases