Appel-reagent-mediated transformation of glycosyl hemiacetal derivatives into thioglycosides and glycosyl thiols

• Tamashree Ghosh,
• Abhishek Santra and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 974–982, doi:10.3762/bjoc.9.112

• biphasic reaction conditions. The thioglycoside formation became very slow without the addition of TBAB and the same product was obtained in a poor yield over a much longer period of time. In contrast, rapid SN2-substitution of the bromide ion at the anomeric center in α-glycosyl bromide with a

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

• complete regioselectivity, in favour of an SN2′ pathway, to give 1,3-disubstituted N-Dpp allylamines, generally with good yield (Table 2). In all cases, (E)-isomers were obtained. At the time, these data represented the first examples of a 100% regioselective ring opening of simple vinyl aziridines by

• with sodiomalonate and sodium bisphenylsulfonylmethide, again with complete regiocontrol via an SN2′-like reaction to give ring-opened products in acceptable yield (Table 2, entries 7, 8, 11, 12). When aziridines 1 and 2 were reacted with methyl magnesium iodide in Et2O solution, the previously good

• regiocontrol we had observed in the ring opening was not maintained: unlike the reaction of allyl magnesium chloride (Table 2, entry 5) a mixture of products arising from nucleophilic attack at both C-2 and C-4 was isolated, with a preference for a SN2′-like reaction again observed (Scheme 4). The reactions of

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

• congestion in the bond-making process in a stepwise process with a rate-limiting bond formation (or a normal SN2 reaction) [13][14][15]. The magnitudes of the kH/kD values invariably decrease as the aniline becomes less basic. The magnitudes of the kH/kD values invariably increase for X = (4-MeO, 4-Me, H, 4

• , resulting in the positive ρX. The very small value of kH/kD = 0.66 with X = 3-Cl and Y = 4-Cl could be supporting evidence. The relatively small magnitude of ρXY = −0.18 with less basic anilines could be another piece of supporting evidence, because the normal SN2 mechanism (or stepwise mechanism with rate

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

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

• magnesium bromide (20), takes place first. The subsequent addition of CuCl very likely generates a copper organic intermediate, which is then coupled with a second equivalent of 19 to yield 2 and its isomer 21 (1,2-hexadien-5-yne, propargylallene). Formally, the dimerization of 19 to 2 involves two SN2

• coming close to a general route to introduce functionality into bisallenes at the present time seems to be the double SN2'-reaction of 2,4-hexadiyne-1,6-diol (63, e.g. R1 to R4 = aryl) and its derivatives with various nucleophiles (Scheme 13) [49][50]. Thus, heating the diols 63 with an aromatic or

• %. Structurally comparable bisallene diols could be prepared, as shown by Krause and Poonoth [80][81], from bisoxiranes 100 by opening these with Grignard reagents in the presence of copper salts; this is again a double SN2'-process (Scheme 25). The resulting derivatives 101 are useful precursors for a double

Synthesis of 4” manipulated Lewis X trisaccharide analogues

• Christopher J. Moore and
• France-Isabelle Auzanneau

Beilstein J. Org. Chem. 2012, 8, 1134–1143, doi:10.3762/bjoc.8.126

• Lattrell-Dax nitrite mediated inversion [58][59][60] of the 4-OH in galactoside 15 provided the glucoside 17, which was used as the common precursor to analogues 18 and 19. Treatment with sulfuryl chloride [61] gave the 4-chloro galactoside 18 in good yield, whereas triflation at O-4 followed by SN2

Sonogashira–Hagihara reactions of halogenated glycals

• Dennis C. Koester and
• Daniel B. Werz

Beilstein J. Org. Chem. 2012, 8, 675–682, doi:10.3762/bjoc.8.75

• SN2-type reaction takes place leading to the α-gluco-configured C-glycoside 15a in a moderate yield of 30% (Table 4). The aluminium centre coordinates the epoxide oxygen allowing the hydride to attack from the same side, leading to β-configured alkyl-C-glycosides. The epoxidation/ring-opening sequence

An easy α-glycosylation methodology for the synthesis and stereochemistry of mycoplasma α-glycolipid antigens

• Yoshihiro Nishida,
• Yuko Shingu,
• Yuan Mengfei,
• Kazuo Fukuda,
• Hirofumi Dohi,
• Sachie Matsuda and
• Kazuhiro Matsuda

Beilstein J. Org. Chem. 2012, 8, 629–639, doi:10.3762/bjoc.8.70

• , yields >80%) and not accompanied by isomerization at the glycerol moiety. A mixture of 4a and 5a was used in the following chemical transformation (Scheme 2). First, a lyso-glycolipid 6a was derived after deprotection at the sugar hydroxymethyl position and SN2 substitution with cesium palmitate at the

Synthesis of 2-amino-3-arylpropan-1-ols and 1-(2,3-diaminopropyl)-1,2,3-triazoles and evaluation of their antimalarial activity

• Matthias D’hooghe,
• Stéphanie Vandekerckhove,
• Karen Mollet,
• Karel Vervisch,
• Stijn Dekeukeleire,
• Liesbeth Lehoucq,
• Carmen Lategan,
• Peter J. Smith,
• Kelly Chibale and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2011, 7, 1745–1752, doi:10.3762/bjoc.7.205

• opening of the aziridine moiety at C2 due to benzylic stabilization of the developing carbenium ion in an SN2 fashion [30]. As the use of imines bearing a N-tert-butyl group in combination with a substituent in the ortho-position of the aromatic ring is known to afford the corresponding cis-4-aryl-3

• SN2 fashion [30]. The formation of the other regio- and stereoisomers was excluded based on detailed spectroscopic analysis. It should be noted that both diastereomeric antipodes of the class of 1-aryl-2-aminopropan-1,3-diols, i.e., anti- and syn-aminopropanols 9 and 12, can now be prepared

Gold(I)-catalyzed synthesis of γ-vinylbutyrolactones by intramolecular oxaallylic alkylation with alcohols

• Michel Chiarucci,
• Mirko Locritani,
• Gianpiero Cera and
• Marco Bandini

Beilstein J. Org. Chem. 2011, 7, 1198–1204, doi:10.3762/bjoc.7.139

• comparable yield (72%, entry 1) and similar diastereomeric ratio. Here, although the impact of the C─C double bond configuration on the stereochemical outcome of SN2′-type gold-catalyzed intramolecular O- [45] and N-alkylations [37][46] with allylic alcohols was demonstrated, we consider it likely that an

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

• methods (COSY, HSQC) gave an unambiguous indication that, in all cases, the nitrogen nucleophile had attacked C-4, as judged by an upfield shifted 13C signal, and that the unsaturated bond was between C-2 and C-3. Hence these reactions proceeded with essentially complete regioselectivity, with no SN2

• single diastereomer. This is consistent with an SN2 pathway with inversion of configuration, which is as expected for Mitsunobu reactions. The same was true of the other sulfonamide nucleophiles, 7 and 9. Moreover, the erythro configuration of coupling product 15 was proved by the large value of the J4,5

• pseudodisaccharides. Triflamides and nosylamides were similarly effective as nucleophiles in Mitsunobu coupling reactions with allylic alcohols. The Mitsunobu coupling reactions proceeded with inversion of configuration, and SN2’ type reactions with C=C double bond migration were not observed. A palladium catalysed

Toward an integrated route to the vernonia allenes and related sesquiterpenoids

• Da Xu,
• Michael A. Drahl and
• Lawrence J. Williams

Beilstein J. Org. Chem. 2011, 7, 937–943, doi:10.3762/bjoc.7.104

• no computational mechanistic study on these reactions has appeared as a guide in this regard. Admittedly, there are distinct differences between fragmentation and substitution; nevertheless, by analogy to SN2 reactions, C–C fragmentation substrates with angles significantly less than 180° may fail

When gold can do what iodine cannot do: A critical comparison

• Sara Hummel and
• Stefan F. Kirsch

Beilstein J. Org. Chem. 2011, 7, 847–859, doi:10.3762/bjoc.7.97

• reaction does not occur via electrophilic activation. Instead, due to the iodide ion still present in the reaction mixture, the ammonium ion intermediate undergoes SN1 or SN2 substitution, or even E2 elimination of an alkyl group. This system yields products in up to quantitative yields, and successfully

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

• corresponding ethers. Additionally, it is reported that Reaxa QuadraPureTM MPA is an efficient scavenging reagent that halts the reaction progress. Keywords: allylic alcohol; allylic ether; Au-catalyzed; SN2'; tetrahydropyran; Introduction Saturated oxygen heterocycles are found in a wide variety of

• from our laboratory and others have demonstrated that unsaturated alcohols, such as allylic and propargylic alcohols, are reactive substrates that readily participate in dehydrative formal SN2' reactions [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. The formation of tetrahydropyrans is

• more synthetically useful substrates. Conclusion In conclusion, it has been demonstrated that a variety of allylic ethers undergo Au-catalyzed formal SN2' reactions to form tetrahydropyrans. The reaction of allylic alcohols appears to be faster, although the leaving group is traditionally not

Alkene selenenylation: A comprehensive analysis of relative reactivities, stereochemistry and asymmetric induction, and their comparisons with sulfenylation

• Vadim A. Soloshonok and
• Donna J. Nelson

Beilstein J. Org. Chem. 2011, 7, 744–758, doi:10.3762/bjoc.7.85

• ]. It is well established that the rate determining step in benzenesulfenyl chloride addition is the formation of thiiranium intermediate; specifically the alkene π electrons displace Cl− in an SN2 reaction to give the thiiranium ion [89]. On the other hand, recent studies ruled out the formation of the

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

• propargyl acetate 7 to an enantiomerically enriched allene 8. It has been previously shown that delivery of an alkyl group from an organocuprate in an SN2’ fashion occurs with retention of chiral information in the resulting allene [9]; thus we began by screening cuprate conditions to form the desired

Gold-catalyzed regioselective oxidation of terminal allenes: formation of α-methanesulfonyloxy methyl ketones

• Yingdong Luo,
• Guozhu Zhang,
• Erik S. Hwang,
• Thomas A. Wilcoxon and
• Liming Zhang

Beilstein J. Org. Chem. 2011, 7, 596–600, doi:10.3762/bjoc.7.69

• be formed. While C may revert back to the allene substrate, we suspect that a SN2'-type reaction by an external nucleophile could facilitate the fragmentation of the O–Y bond, ultimately leading to useful products via intermediate D. Herein we report our preliminary studies, which led to a facile

• undergo protonation to form intermediate F with MsO− as the counter anion. An SN2'-type substitution by the anion would afford the observed product. This substitution is facilitated by the fragmentation of the weak N–O bond and the annihilation of the charges. Conclusion We have successfully realized the

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

• substituted carbon atoms is a simple and versatile way to construct stereocentres next to heteroatoms with overall inversion of stereochemistry. Sulfur nucleophiles are commonly used very effectively to accomplish reactions of this type [9]. However, SN2 displacements are very sensitive to steric crowding at

• the reaction centre: SN1 substitution and elimination reactions are almost always favoured over the SN2 pathway in quaternary electrophiles, limiting the use of SN2 reactions for the synthesis of tertiary thiols. 1.1.1 Sulfonate leaving groups The efficiency of sulfonates as leaving groups has allowed

Kinetic evaluation of the solvolysis of isobutyl chloro- and chlorothioformate esters

• Malcolm J. D’Souza,
• Matthew J. McAneny,
• Dennis N. Kevill,
• Jin Burm Kyong and
• Song Hee Choi

Beilstein J. Org. Chem. 2011, 7, 543–552, doi:10.3762/bjoc.7.62

• studies by other groups favored competing SN1 and SN2 pathways for the alkyl chloro-, chlorothio-, chlorothiono-, and dithiochloroformates [50][51][52][53][54][55][56][57][58][59]. Upon evaluating the rates of hydrolysis in aqueous solvents, Queen [54][55] suggested that with increasing electron donation

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

Palladium-catalyzed formation of oxazolidinones from biscarbamates: a mechanistic study

• Benan Kilbas and
• Metin Balci

Beilstein J. Org. Chem. 2011, 7, 246–253, doi:10.3762/bjoc.7.33

• SN2' substitution reaction mechanism [27][28][29][30], nucleophiles attack the double bond from the same side from which the leaving group departs, as shown below (Figure 3). Therefore, we assume that metal is bonded to the allylic system from the same side as the nucleophile attacking the double bond

Carbasugar analogues of galactofuranosides: α-O-linked derivatives

• Jens Frigell and
• Ian Cumpstey

Beilstein J. Org. Chem. 2010, 6, 1127–1131, doi:10.3762/bjoc.6.129

• the transition state is approached also under neutral or base-catalysed conditions [14]. Carbon C2 bears a β electron-withdrawing group (the C3 benzyl ether), whereas C1 does not. Hence, from an electronic point of view, SN2 reactions should be more favourable at C1 than at C2. The same concept is a

• major factor in explaining the generally low reactivity of carbohydrates (at non-anomeric positions) in SN2 reactions. Carbapyranose 1,2-epoxides with α-gluco 3 and α-galacto configurations did not give such good results. With amine nucleophiles, attack was often unregioselective [15]: attack at C1

• , our best results were obtained using an oxidation–reduction approach. Attempted SN2 reactions (Mitsunobu reaction or sulfonate displacement) gave inferior results. Hence the C2 alcohols 8 and 11 were oxidised under Swern conditions to give the ketones 15 and 16. Reduction of ketone group in ethyl

β-Hydroxy carbocation intermediates in solvolyses of di- and tetra-hydronaphthalene substrates

• Jaya S. Kudavalli and
• Rory A. More O'Ferrall

Beilstein J. Org. Chem. 2010, 6, 1035–1042, doi:10.3762/bjoc.6.118

• . The normal salt effect exerted by the sodium azide also confirms that the solvolysis proceeds via the formation of a carbocation intermediate rather than by an SN2 mechanism. 1-Chloro- and 1-chloro-2-hydroxy-1,2-tetrahydronaphthalenes Rate constants for solvolysis of cis- and trans-1-chloro-2-hydroxy

Catalysis: transition-state molecular recognition?

• Ian H. Williams

Beilstein J. Org. Chem. 2010, 6, 1026–1034, doi:10.3762/bjoc.6.117

• concept. It is shown that reactant binding is intrinsically inhibitory, and that attempts to design catalysts that focus simply upon attractive interactions in a binding site may fail. Free-energy changes along the reaction coordinate for SN2 methyl transfer catalysed by the enzyme catechol-O-methyl

• reduction in barrier height by means of differential stabilisation. The cases discussed below all exemplify TS molecular recognition and stabilisation relative to the reactant state. Catalyst design: preferential TS binding Methyl group transfer from an electrophile to a nucleophile by an SN2 mechanism is

• -methyldibenzothiophenium ion at 25 °C in methanol [12]. According to the orthodox view, Schowen and co-workers interpreted these observations in terms of a tighter SN2 transition state for the COMT-catalysed reaction than for the non-enzymic reaction, and consequently proposed the “compression hypothesis” for enzymic

Redox-active tetrathiafulvalene and dithiolene compounds derived from allylic 1,4-diol rearrangement products of disubstituted 1,3-dithiole derivatives

• Filipe Vilela,
• Peter J. Skabara,
• Christopher R. Mason,
• Thomas D. J. Westgate,
• Asun Luquin,
• Simon J. Coles and
• Michael B. Hursthouse

Beilstein J. Org. Chem. 2010, 6, 1002–1014, doi:10.3762/bjoc.6.113

• by two SN2 reactions with 1,2-dibromoethane in THF to yield 27(56% yield) after purification by column chromatography (eluting with 1:1 (v/v) CH2Cl2:petroleum ether). Dithiolate 24 was also generated from the analogous reaction with 3. On this occasion, treatment of 24 with excess nickel(II)chloride

Kinetic studies and predictions on the hydrolysis and aminolysis of esters of 2-S-phosphorylacetates

• Milena Trmčić and
• David R. W. Hodgson

Beilstein J. Org. Chem. 2010, 6, 732–741, doi:10.3762/bjoc.6.87

• also give rise to p- and m-nitrophenolate ions during their hydrolyses. High concentrations of both thiophosphate 4 and 2-bromoacetic acid esters 1 (R = pNP) and 1 (R = mNP) were used in order to ensure that the SN2 reactions between these reagents occurred rapidly with minimal scope for hydrolysis of