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

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