The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• by the participation of the phosphate group by reverse anomeric effect. However, according to the authors, the phosphate groups acting as a neighbouring participating group forming the corresponding oxocarbenium ion intermediate 73 (path B, Scheme 13) seemed to be more plausible. Non-ester

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• crystallographic data using the 3-fluoropyrrolidinium cation and 3-fluoropyrrolidine. Subsequently, we explored the relative energy of all favored conformations of all different stereoisomers of 2,3-, 2,4-, and 3,4-difluoropyrrolidines at the B3LYP-D3BJ/6-311++G** level. A generalized anomeric effect, arising from

• Lewis interactions from a natural bond orbital perspective. Keywords: anomeric effect; fluoropyrrolidine; gauche effect; stereochemistry; Introduction The pyrrolidine ring structure is prevalent in numerous natural alkaloids and is an important feature of the proline and hydroxyproline residues that

• C–F bonds in this case were vicinal. Compounds lacking α-fluorine atoms (i.e., 9, 10, 12, and 16) possessed a notably higher energy, indicating the impact of the anomeric effect. To further illuminate these findings, a natural bond orbital (NBO) analysis was conducted across the entire array of

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• -mannosides is conventionally achieved with [142][157][269], or even without [270], neighboring group participation (e.g., Ac, Bz). The favorable anomeric effect ensures efficient glycosylation reactions. The synthesis of α-mannosides is widely established, allowing the chemical synthesis of the longest

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• fluoride α-1a to form bis-mannosides α-8 in good yields (Scheme 2). In a series of pivaloyl-protected mannosides 3 a substrate-controlled α-selectivity due to the favoring effect of both neighboring ester-type protecting groups and the anomeric effect was observed [3]. On the other hand, mixing of glycosyl

• mannose α-11. Glucosides 14 were isolated in a moderate yield, but without any α,β-selectivity due to the mismatched interaction between the anomeric effect and neighboring protecting group assistance. The diminished selectivity compared to the series of pivaloyl-protected glucosides 10 leads to the

• glucosides 18 in similar anomeric ratios with excess of the α-anomer. As expected, in the absence of an ester type protecting group at C2 position, for both series of benzyl protected glycosides α-selectivity was observed solely due to the anomeric effect. The Lewis acidic medium of liquid SO2 was also

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• hydrogen atom to orient towards anions (chloride) in the vicinity and the 3'-nitrogen lone pair engages in a lp → σ* anomeric effect with the antibonding orbital from the adjacent P–O5' bond (Figure 2A). This conjugation is surmised to cause considerably increased rigidity of the phosphoramidate sugar

Regioselectivity of glycosylation reactions of galactose acceptors: an experimental and theoretical study

• Enrique A. Del Vigo,
• Carlos A. Stortz and
• Carla Marino

Beilstein J. Org. Chem. 2019, 15, 2982–2989, doi:10.3762/bjoc.15.294

• in α-anomers could be associated with the lower capacity of the O-5 atom to establish hydrogen bond interactions due to the anomeric effect [34]. For donor 4, the regioselectivity observed for 1α, 1β, and 2α was lower than that observed for 3, but for 2β, the only product detected was the 1→4

Influence of per-O-sulfation upon the conformational behaviour of common furanosides

• Alexey G. Gerbst,
• Vadim B. Krylov,
• Dmitry A. Argunov,
• Maksim I. Petruk,
• Arsenii S. Solovev,
• Andrey S. Dmitrenok and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2019, 15, 685–694, doi:10.3762/bjoc.15.63

• : O4–C1–O1–CH2 torsion was set to +60° or −60° depending on α- or β-configuration of the sugar in accordance with the exo-anomeric effect. Other starting torsions in the propyl group had trans-orientation. Geometry optimizations of all the thus obtained structures were carried out at ab initio HF/6-311

Conformational signature of Ishikawa´s reagent using NMR information from diastereotopic fluorines

• Laize A. F. Andrade,
• Lucas A. Zeoly,
• Rodrigo A. Cormanich and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2019, 15, 506–512, doi:10.3762/bjoc.15.44

• : anomeric effect; gauche effect; NMR spectroscopy; organofluorine compounds; Introduction The active species of Ishikawa´s reagent [N,N-diethyl-(1,1,2,3,3,3-hexafluoropropyl)amine, 1] [1] (Figure 1) has diastereotopic substituents (fluorines), which can be useful to provide conformational insights by using

• generalized anomeric effect, as well as by the fluorine gauche effect. The former corresponds to a stabilizing effect originated from the electron delocalization from the nitrogen lone pair to an antiperiplanar C–F antibonding orbital (nN → σ*C–F), similarly to that observed for some pnictogen compounds and

• ) show that conformers 1Ab and 1Ac exhibit distinct (a small and a large) 3JH,F(pro-S) and 3JH,F(pro-R) values, probably as a result of the generalized anomeric effect nN → σ*C-F that affects the electron density along the C1–F bond; a smaller 3JH,F(1) is expected as a C1–F bond is longer and weaker

Electron-deficient pyridinium salts/thiourea cooperative catalyzed O-glycosylation via activation of O-glycosyl trichloroacetimidate donors

• Mukta Shaw,
• Yogesh Kumar,
• Rima Thakur and
• Amit Kumar

Beilstein J. Org. Chem. 2017, 13, 2385–2395, doi:10.3762/bjoc.13.236

• the glycosyl donor by increasing the acidity of ammonium salt X to form an oxocarbenium intermediate B. Further, the nucleophilic attack of the acceptor to the oxocarbenium ion B would produce the desired glycoside 5. Higher α-selectivity may be attributed to the anomeric effect. Conclusion In

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

• position 2 on the ring or by the anomeric effect when neighboring group participation is not possible [54][55]. Seemingly impossible Lewis acid-mediated processes are then available for the other hydroxy groups on the unprotect donor molecule and some examples are highlighted below. 3.3.1 Access of 1,2-cis

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

• is non-trivial [6][8][10][12][13]; and indeed the debate about the factors influencing the overall rate of reaction and the synchronicity of steps has yet to achieve consensus [11][14][15]. Factors such as solvent [13], catalyst pKa [9], –OR basicity [6][16][17], the kinetic anomeric effect [18], the

• 8 (Figure 1). The kinetic anomeric effect was invoked previously to rationalise the relative reactivity of 15 with respect to endo-cyclic 8 [18]. One would anticipate a significant change in rate to accompany the reduction of charge-stabilising oxygen atoms within 8 to afford 4; yet kH+(8)/kH+(4

• rates of hydrolysis for six-membered 15 and 8 could be explained with the kinetic anomeric effect. Consistent with this, the X-ray crystal structure of an analogous yet conformationally constrained bicyclic orthoester possesses an unusually elongated axial C─O bond (Figure 2a), which undergoes

Investigation of the role of stereoelectronic effects in the conformation of piperidones by NMR spectroscopy and X-ray diffraction

• Cesar Garcias-Morales,
• David Ortegón-Reyna and
• Armando Ariza-Castolo

Beilstein J. Org. Chem. 2015, 11, 1973–1984, doi:10.3762/bjoc.11.213

• hyperconjugation, which is related to the anomeric effect (effect where a heteroatomic substituent adjacent to a heteroatom within a cyclohexane ring prefers the axial orientation instead of the equatorial) [6][7][8][9][10][11][12]. Moreover, stereoelectronic effects have been related to the stabilization of

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• changes between 3 and 4 are a consequence of the configurational change within the tetrahydropyran ring (Figure 6). Compound 4 is approximately 0.9 kcal mol−1 more stable than 3 (calculated in CHCl3 using the MMFF94 force field). Obviously, the anomeric effect has a strong influence on the preferred

De novo macrolide–glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

• Richard T. Desmond,
• Anniefer N. Magpusao,
• Chris Lorenc,
• Jeremy B. Alverson,
• Nigel Priestley and
• Mark W. Peczuh

Beilstein J. Org. Chem. 2014, 10, 2215–2221, doi:10.3762/bjoc.10.229

• of the monosaccharide. The new macrocycles/macrolides were characterized by X-ray crystallography. Their structures showed that, in addition to the ester and alkene units, the dihedral angle about the glycosidic linkage (exo-anomeric effect) influenced the overall shape of the molecules

• . Glycosylation of an available hydroxy group on the macrocycle gave a hybrid macrolide with features common to erythromycin and sophorlipid macrolactone. Weak antibiotic activity (MICs <100 μg/mL) was observed for several of the compounds. Keywords: antibiotic; carbohydrate; exo-anomeric effect; macrolide

• and foremost, the axial (5) versus equatorial (6) positioning of the anomeric oxygen, and subsequently the aglycone, dictates the orientation of the D-glucose- and macrocyclic planes. Relatedly the exo-anomeric effect [28][29] plays a role in determining the orientation of the backbone of the

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• comparison to conformer 3a' with a pseudo-equatorial methoxycarbonyl group, is assumed to be the anomeric effect [24]. The lengthening of the C–CO2Me bond in conformer 3a compared to conformer 3a' (1.563/1.554 Å), corroborates this hypothesis. The pseudo-axia position of the methoxycarbonyl group is

Modulating NHC catalysis with fluorine

• Yannick P. Rey and
• Ryan Gilmour

Beilstein J. Org. Chem. 2013, 9, 2812–2820, doi:10.3762/bjoc.9.316

• pairs, such as in the case of the fluorine anomeric effect [5], to electron rich sigma bonds (σ→σ*). The stereoelectronic gauche effect in 1,2-difluoroethane is the most prominent example (1; Figure 1) [6][7][8][9]. The counterintuitive preference of vicinal fluorine substituents to adopt a gauche

Stereoselective synthesis of the C79–C97 fragment of symbiodinolide

• Hiroyoshi Takamura,
• Takayuki Fujiwara,
• Isao Kadota and
• Daisuke Uemura

Beilstein J. Org. Chem. 2013, 9, 1931–1935, doi:10.3762/bjoc.9.228

• rationale for the stereoselective formation of 19 is the thermodynamic stability due to the double anomeric effect. Oxidation of the alcohol 19 with SO3∙pyr/Et3N/DMSO [21] afforded aldehyde 20. Next, we carried out the synthesis of PT-sulfones 23 and 24 which were the coupling partners of the aldehyde 20

Diastereoselective synthesis of nitroso acetals from (S,E)-γ-aminated nitroalkenes via multicomponent [4 + 2]/[3 + 2] cycloadditions promoted by LiCl or LiClO₄

• Leandro Lara de Carvalho,
• Robert Alan Burrow and
• Vera Lúcia Patrocinio Pereira

Beilstein J. Org. Chem. 2013, 9, 838–845, doi:10.3762/bjoc.9.96

• tendency to the pseudoaxial orientation of the alkoxy group in nitroso acetals is associated with a stabilization generated by an anomeric effect [1][36]. The protons (H6) and (H4) were both irradiated in 2D NOESY experiments and a cis relationship between them was achieved for all cycloadducts. When the

• [3 + 2] cycloadditions, we believe that in the TS the respective nitronates present a half-chair conformation with the HC(4) substituent and the alkoxy group in an axial position to maximize the stabilization generated by the anomeric effect [9][33][41][42]. Thus, the competitive endo/exo approach of

Carbohydrate-auxiliary assisted preparation of enantiopure 1,2-oxazine derivatives and aminopolyols

• Marcin Jasiński,
• Dieter Lentz and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2012, 8, 662–674, doi:10.3762/bjoc.8.74

• hence yields the (3R)-configured product as the major compound. In contrast, the less hindered lithiated methoxyallene enables a syn-attack supported by a “kinetic anomeric effect”, stabilizing the respective transition state [20] and furnishing the (3S)-configured 1,2-oxazine. In all tested examples

Regio- and stereoselective oxidation of unactivated C–H bonds with Rhodococcus rhodochrous

• Elaine O’Reilly,
• Suzanne J. Aitken,
• Gideon Grogan,
• Paul P. Kelly,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2012, 8, 496–500, doi:10.3762/bjoc.8.56

• the increased length of the ether linkage or due to its spatial orientation. NMR evidence confirmed that the ether in 3a–d sits in the axial position due to the anomeric effect. In the case of substrate 6, the ether sits in the sterically favoured equatorial position. In order to investigate this

Trifluoromethyl ethers – synthesis and properties of an unusual substituent

• Frédéric R. Leroux,
• Baptiste Manteau,
• Jean-Pierre Vors and
• Sergiy Pazenok

Beilstein J. Org. Chem. 2008, 4, No. 13, doi:10.3762/bjoc.4.13

• electron distribution. The geminal combination of an alkoxy or aryloxy group with a fluorine atom offers the possibility of bonding/non-bonding resonance which can be formally expressed by the superposition of a covalent and an ionic limiting structure (Figure 2). Structure The anomeric effect reveals

• length is dependent upon the electronegativity of the atom to which the substituent is attached [49] and reflects the "anomeric effect" shown above [50]. The lengthening of the acceptor bond and the shortening of the donor bond are small, as far as the carbon fluorine bond are concerned. However the