Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• sugar during GT-catalysed reactions, GTs are also classified as inverting or retaining (Figure 1). Inverting GTs operate via a SN2 mechanism in a single displacement step where an acid/base residue enhances the nucleophilicity of the acceptor, via an oxocarbenium-like transition state. Unlike inverting

• GTs, there is much controversy of the molecular mechanism of retaining GTs [13][14][15]. Retention of the anomeric carbon stereochemistry can occur either following a two-step displacement SN2 type mechanism (as in retaining GH), or via a “SNi-like” mechanism, that involves a front-side single

• nucleophilic attack of the acceptor, however, little information is known on the pathways involved in these reactions (SN2 or SNi-like), because of the few examples of such enzymes characterization in literature, when compared to canonical O- and N-GTs. S-Glycosyltransferases Few examples of natural S

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• for further functionalizations by stereospecific nucleophilic SN2-type displacement reactions with different nucleophiles [66][85][86][87]. Accordingly, it comes as no surprise that their asymmetric synthesis has been intensively investigated in the past, either relying on asymmetric (transition

Mechanochemical N-alkylation of imides

• Anamarija Briš,
• Mateja Đud and
• Davor Margetić

Beilstein J. Org. Chem. 2017, 13, 1745–1752, doi:10.3762/bjoc.13.169

• a precedence in the application of weaker base in mechanochemical synthesis of triphenylphosphoranes [32]. Often DMF is used as solvent in imide alkylation reactions, which promotes SN2 reactions [33] and its low volatility is advantageous over more environmentally friendly solvents which might be

• . Computational section To elucidate reasons for the observed regioselectivities, the reactions of uracil and 7,8-dimethylalloxazine with benzylamine and ethyl bromide were studied by DFT calculations using the B3LYP/6-311+G**//B3LYP/6-31G*+ZPVE method. The transition-state calculations of the SN2 reaction of

Synthesis and metal binding properties of N-alkylcarboxyspiropyrans

• Alexis Perry and
• Christina J. Kousseff

Beilstein J. Org. Chem. 2017, 13, 1542–1550, doi:10.3762/bjoc.13.154

• mL) or the absence of polar aprotic solvent-mediated acceleration of this SN2 process (Table 1, compare entries 6, 7 and 8). The relative instability of indolium salts is well-documented [26] and our attempts to purify compounds 3 by silica gel chromatography or recrystallisation were unsuccessful

• -bromocarbonyls such as bromoacetic acid are excellent SN2 electrophiles, and N-alkylation of 2,3,3-trimethylindolenine (1) with bromoacetic acid (2a) was successful, if somewhat sluggish, at room temperature. Reaction of the crude indolium salt 3a with 3-methoxy-5-nitrosalicylaldehyde (5) was also conducted at

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• glycosylated with the opposite stereochemistry at the anomeric position to the donor in an SN2-like mechanism that is reasonably well understood. Retaining GTs provide glycosides with the same stereochemistry at the anomeric position as the donor. However, the mechanism(s) is less well understood and is still

• group contains two heteroatoms, X and Y that can be activated at the remote atom (Y) by an electrophilic species (H of an alcohol) or a metal cation resulting in a reactive intermediate. This complex could then undergo an SN2-like attack of a hydroxy group to furnish the glycoside with inversion of

• SN2-like reaction (Scheme 9). The most unfortunate drawbacks of the procedure include the need for a large excess of the alcohol acceptor and the multistep synthesis of the galactosyl donor. The synthesis of the monoprotected activated galactosyl donor requires the use of protecting groups, however

Substitution of fluorine in M[C₆F₅BF₃] with organolithium compounds: distinctions between O- and N-nucleophiles

• Anton Yu. Shabalin,
• Nicolay Yu. Adonin and
• Vadim V. Bardin

Beilstein J. Org. Chem. 2017, 13, 703–713, doi:10.3762/bjoc.13.69

• elimination of LiF. In contrary, the cation–anion bonds in O-nucleophiles and in N-nucleophiles are ionic (M = K, Na) and the fluoride affinities of K+ and Na+ are smaller than that of Li+. These factors determine the reaction route with K[C6F5BF3] by a simple SN2 mechanism. Preparation of

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• , each CD sample was exposed to the same concentration (0.001 M) of divalent metal cations Cu2+, Cd2+, Sn2+ or Zn2+ in solution and the fluorescence response monitored. The starch-based S-CDs showed an interesting PL response, whereas the fluorescence output increased when in solution with all metal ions

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• substituted carbocycles [119][120]. An example in described in Scheme 22. The 5-membered ring is formed via a K2CO3 mediated SN2 – conjugate addition sequence between malononitrile and 6-bromo-2-hexenoate derivatives 67a,b. Dicyanocyclopentanes 68a,b are treated with tributyltin hydride/AIBN giving the

Nucleophilic displacement reactions of 5′-derivatised nucleosides in a vibration ball mill

• Olga Eguaogie,
• Patrick F. Conlon,
• Francesco Ravalico,
• Jamie S. T. Sweet,
• Thomas B. Elder,
• Louis P. Conway,
• Marc E. Lennon,
• David R. W. Hodgson and
• Joseph S. Vyle

Beilstein J. Org. Chem. 2017, 13, 87–92, doi:10.3762/bjoc.13.11

• conditions) [16]. Following Sikchi and Hultin’s original description of nucleoside derivatisation in a low-energy, planetary ball mill [17], commercial, higher energy vibration mills have been used to facilitate established [18][19][20][21] and unprecedented [22] nucleoside transformations. Remarkably, SN2

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• corresponding SN2-type products 6a–d in 63 to 70% isolated yields. Alternatively, the alcohol 5 produced the corresponding acetate 7 which, mediated by Ce(III), was successfully converted into the corresponding γ-aminoallylphosphonates 8a–d. Keywords: allylic substitution; γ-aminoallylphosphonate; Arbuzov

• phosphites gave the corresponding phosphonates 4b and 4c in 60–62% yields. The reaction of secondary alcohols 3b and 3c with trialkyl phosphites was also surveyed. Under the previous reaction conditions (solvent-free, 80 °C, without any additive) an SN2’-type reaction followed by an Arbuzov rearrangement

Superelectrophilic activation of 5-hydroxymethylfurfural and 2,5-diformylfuran: organic synthesis based on biomass-derived products

• Dmitry S. Ryabukhin,
• Dmitry N. Zakusilo,
• Mikhail O. Kompanets,
• Anton A.Tarakanov,
• Irina A. Boyarskaya,
• Tatiana O. Artamonova,
• Mikhail A. Khohodorkovskiy,
• Iosyp O. Opeida and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2016, 12, 2125–2135, doi:10.3762/bjoc.12.202

• (Table 2), this reaction, most probably, proceeds through an SN2 pathway, where “pure” heteroaromatic cation B is not formed. At least the reaction may go through late transition state, in which the C–O bond in the CH2O+H2 group is rather elongated, resulting in a larger positive charge on this carbon

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• orientation indicating 5’S absolute configuration as anticipated from the SAE mnemonic in compound 8. As the C5’ and C6’ stereocenters in 14 are derived from the regioselective SN2 opening of epoxide 8 by NaN3, the configuration at the C6’ (carrying azido group) was therefore assigned as 6’R. In the 1H NMR

TMSBr-mediated solvent- and work-up-free synthesis of α-2-deoxyglycosides from glycals

• Mei-Yuan Hsu,
• Yi-Pei Liu,
• Sarah Lam,
• Su-Ching Lin and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2016, 12, 1758–1764, doi:10.3762/bjoc.12.164

• pseudoequatorial position [78] and the ensuing SN2-like displacement by the alcohol contributes to the improvement of the α-selectivity (Scheme 2, route A). Alternatively, it is possible that a 2-deoxyglycosyl bromide is first generated mainly in the more stable α-form [61]. The glycosyl bromide intermediate then

• undergoes double SN2-like substitution by TPPO and the alcohol to give the α-glycoside as the major product [77] (Scheme 2, route B). Conclusion A simple, efficient, and environmentally friendly method for preparing S- and O-2-deoxyglycosides was established. S-2-Deoxyglycosides were obtained with moderate

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

• Atul A. Dhavan,
• Rahul D. Kaduskar,
• Loana Musso,
• Leonardo Scaglioni,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159

• assume that the reaction occurred via inversion of the configuration at the hydroxylated carbon, based on an intramolecular SN2 cyclocarbamation by the Boc group [20][21]. The small coupling constant (J = 2.6 Hz) between the two hydrogens on the oxazolidinone ring confirmed that the compound was the anti

One-pot synthesis of 4′-alkyl-4-cyanobiaryls on the basis of the terephthalonitrile dianion and neutral aromatic nitrile cross-coupling

• Roman Yu. Peshkov,
• Elena V. Panteleeva,
• Wang Chunyan,
• Evgeny V. Tretyakov and
• Vitalij D. Shteingarts

Beilstein J. Org. Chem. 2016, 12, 1577–1584, doi:10.3762/bjoc.12.153

• -regioselectivity of the bulylation of monoanion 3i is typical for an alkylation with primary alkyl halides of cyanocyclohexadienyl anions derived by two-electron reduction of aromatic mononitriles in liquid ammonia, which was studied earlier and was found to proceed via an SN2 mechanism [26][35]. Conclusion We

Dinuclear thiazolylidene copper complex as highly active catalyst for azid–alkyne cycloadditions

• Anne L. Schöffler,
• Ata Makarem,
• Frank Rominger and
• Bernd F. Straub

Beilstein J. Org. Chem. 2016, 12, 1566–1572, doi:10.3762/bjoc.12.151

• less time-consuming and more cost-efficient synthesis. Commercially available, inexpensive 4,5-dimethylthiazole is used as azole starting material instead of 4-aryl-1,2,4-triazoles. The precursor 1a for the NHC ancillary ligand is synthesized via a double SN2-reaction of two equivalents of thiazole

The hydrolysis of geminal ethers: a kinetic appraisal of orthoesters and ketals

• Sonia L. Repetto,
• James F. Costello,
• Craig P. Butts,
• Joseph K. W. Lam and
• Norman M. Ratcliffe

Beilstein J. Org. Chem. 2016, 12, 1467–1475, doi:10.3762/bjoc.12.143

• . Exclusion of O(1/3)─C(5/4) cleavage It has been noted that annular strain in trans-2,5-dimethyltetrahydrofurans invokes sufficient charge separation to switch the mechanism of ring cleavage from SN2 → SN1 [34]. We therefore sought to exclude the possibility of mechanistic partitioning via some strain

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

• Jaroslav Padevět,
• Marcus G. Schrems,
• Robin Scheil and
• Andreas Pfaltz

Beilstein J. Org. Chem. 2016, 12, 1185–1195, doi:10.3762/bjoc.12.114

• reaction indeed took place. While for iodides evidence for a radical single electron transfer process as the major pathway was found, the corresponding bromides and chlorides seemed to prefer an SN2 mechanism. Rossi et al. [21] showed that substitution products can be obtained in good yields from neopentyl

Unusual traits of cis and trans-2,3-dibromo-1,1-dimethylindane on the way from 1,1-dimethylindene to 2-bromo-, 3-bromo-, and 2,3-dibromo-1,1-dimethylindene

• Rudolf Knorr,
• David S. Stephenson,
• Ernst Lattke,
• Petra Böhrer and
• Jakob Ruhdorfer

Beilstein J. Org. Chem. 2016, 12, 1178–1184, doi:10.3762/bjoc.12.113

• of solid KOt-Bu, which consumed 6 within less than 2 hours at rt. Aqueous work-up with Et2O afforded the dibromide 7 (29 mg, 87%) as the only product (hence, no SN2 reaction by KOt-Bu). NEt3 as the base in place of KOt-Bu required 12 days at rt. c) From 1,1-dimethylindane (9): A mixture of N

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• bicycloisomerization reaction can be readily accessed in two steps. Alkylation of a secondary propargylamide can be achieved by sodium hydride deprotonation of its acidic proton and SN2 substitution of a substituted propargyl bromide (Scheme 5a). Alternatively, the same propargylamide can be alkylated under Mitsunobu

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• ] demonstrated tetra-n-butylammonium nitrate [17] to be a source of nitrate that was capable of efficiently mediating an SN2 ‘1° mesylate for nitrate’ substitution, i.e., 72 to 73 (Scheme 12). Generating the 1° mesylate of rac-70 using methanesulfonyl chloride and pyridine afforded rac-71 in a 77% yield after 16

Scope and mechanism of the highly stereoselective metal-mediated domino aldol reactions of enolates with aldehydes

• M. Emin Cinar,
• Bernward Engelen,
• Martin Panthöfer,
• Hans-Jörg Deiseroth,
• Jens Schlirf and
• Michael Schmittel

Beilstein J. Org. Chem. 2016, 12, 813–824, doi:10.3762/bjoc.12.80

• radius of the B3+ ion is very small (25 pm). In the case of tin(II), a high yield of 6a (up to 90%) was observed but formation of 5a was not detected which indicates a hindrance for the second aldol addition. Presumably due to the low charge density of the Sn2+ ions the second carbonyl function is not

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• groups at C-2 or C-4, or by an internal fluorine attack as in SNi substitution. A simple SN2 displacement leading to configurational inversion is probably suppressed by the steric effects of the axially positioned groups at C-2 and C-4, and repulsive effects of their aligned dipoles [51]. Compounds 11

A practical way to synthesize chiral fluoro-containing polyhydro-2H-chromenes from monoterpenoids

• Oksana S. Mikhalchenko,
• Dina V. Korchagina,
• Konstantin P. Volcho and
• Nariman F. Salakhutdinov

Beilstein J. Org. Chem. 2016, 12, 648–653, doi:10.3762/bjoc.12.64

• may undergo stereoselective trap by H2O to form alcohol epimers 2; these may then undergo a stereospecific SN2 reaction to form fluoride epimers 8; c) the fluorination and/or hydroxylation of cation 10, forming fluoride epimers 8 and alcohol epimers 2, respectively, may be reversible. This has several

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• activated. This triggers an SN2-type attack/Ciamician–Plancher rearrangement [35]/rearomatization cascade process, affording the final products 14 (Scheme 7). More recently, the same authors also provided an elegant and efficient solution to give direct access to cis-vicinal-substituted indane scaffolds