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

• glycochemists. The protecting building blocks on the glycosides contribute significantly in attaining the required stereochemistry of the resulting glycosides. Strategic installation of suitable protecting groups in the C-2 position, vicinal to the anomeric carbon, renders neighbouring group participation

• , whereas protecting groups in the distal C-3, C-4, and C-6 positions are often claimed to exhibit remote group participation with the anomeric carbon. Neighbouring group participation and remote group participation are being widely studied to help the glycochemists design the synthetic protocols for

• multistep synthesis of complex oligosaccharides and in turn, standardise the process of the glycosylation towards a particular stereochemical output. While neighbouring group participation has been quite effective in achieving the required stereochemistry of the produced glycosides, remote participation

Low-budget 3D-printed equipment for continuous flow reactions

• Jochen M. Neumaier,
• Amiera Madani,
• Thomas Klein and
• Thomas Ziegler

Beilstein J. Org. Chem. 2019, 15, 558–566, doi:10.3762/bjoc.15.50

•  1 shows the detailed reaction conditions for methanol, propargyl alcohol and 4-pentynol. The two-step reaction starting from pyranose 4 gave overall yields in the range from 43% to 69%. Due to the neighbouring group participation of the acetyl group at C-2, only β-anomers of the respective

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• [75]. Synthesis of various fructofuranosides according to Mitsunobu and proposed neighbouring group participation [23]. The Mitsunobu reaction allows stereoslective acetalization of dihydroartemisinin [77]. Synthesis of alkyl thioglycosides by Mitsunobu reaction [81]. Preparation of

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• ] (ENGases, EC 3.2.1.96), a class of enzyme which specifically cleave between the innermost two GlcNAc residues of N-glycans attached to N-linked glycoproteins, all operate via a two-step mechanism involving neighbouring group participation of the 2-acetamide group and an oxazoline as a high energy

• protected (typically peracetylated) GlcNAc or other 2-acetamido sugar [37][38][39][40]. Oxazoline formation is achieved by activation of the leaving group at the anomeric centre and neighbouring group participation by the 2-acetamide. Unfortunately application of these reaction conditions to oligosaccharide

The synthesis of the 2,3-difluorobutan-1,4-diol diastereomers

• Robert Szpera,
• Nadia Kovalenko,
• Kalaiselvi Natarajan,
• Nina Paillard and
• Bruno Linclau

Beilstein J. Org. Chem. 2017, 13, 2883–2887, doi:10.3762/bjoc.13.280

• resulted in 56% yield after column chromatography. 19F NMR analysis of the crude product showed a dr of 98:2 in favour of (±)-syn-4. However, given a diastereomerically pure starting material was used, this indicates that SN1 or neighbouring group participation pathways may have occurred, although only to

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• clear evidence that a gem-difluorinated compound had also formed: presumably this was compound 34 arising through neighbouring group participation and migration of the phenyl group [38]. A similar problem was encountered in the synthesis of α,β-difluorinated-γ-amino acids (e.g., 5, Figure 1), which was

• next deoxyfluorination reaction (Scheme 4). Gratifyingly, the p-nitro group of 39a was found to completely shut down the neighbouring group participation pathway; the desired trifluoroalkane 40a was obtained in good yield with no evidence of rearrangement or epimerization. It was also possible to

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

• found in maize (UGT708A6), rice (OsCGT), buckwheat (FeCGT), Mangifera indica (MiCGT), Arabidopsis thaliana (AtCGT), fungi (UrdGT2 and SsfS6) or bacteria (iroB). General mechanisms of the O-GHs-catalysed hydrolysis. Neighbouring group participation mechanism of retaining the O-GHs-catalysed hydrolysis

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

• reaction, the preferred attack of the thymine nucleobase from the β-face is being assisted by the acetoxy group at C2 due to neighbouring group participation [24]. The orthogonally protected thymine analogue 2 is an important intermediate and could be utilized further for the synthesis of amipurimycin 1

A selective and mild glycosylation method of natural phenolic alcohols

• Mária Mastihubová and
• Monika Poláková

Beilstein J. Org. Chem. 2016, 12, 524–530, doi:10.3762/bjoc.12.51

• Acetyl-protecting groups are the simplest choice also for the protection of the glycone part since the deprotection of both, sugar and aromatic moieties, can be accomplished in one step. Naturally occurring O-glycosides possess mostly 1,2-trans-glycosidic linkages. Therefore, neighbouring group

• participation is usually exploited in the trans-O-glycosylation of appropriate aglycones. In the course of our synthetic studies, 1,2-trans-glycosylation reactions utilizing per-O-acetyl-D-glucopyranose as a donor were initially investigated. However, the reaction of 6b with per-O-acetylated-D-glucopyranose

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• excluded. A good example of a mixed reaction mechanism is the glycosylation reported by Tyagi et al. [88], where SN2 glycosylation seems to be dominant, with no neighbouring group participation, which is typical of glycosylation reactions of activated acetylated carbohydrates. A more pure SN2 reaction is

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• deoxyfluorination reagent are highlighted in Figure 12. A unique complication sometimes arises when deoxyfluorination is attempted in N-heterocyclic systems: side reactions can occur, bought about by neighbouring group participation (Scheme 4) [58]. Such processes can lead to rearrangement, and this outcome has

• been rationally exploited to synthesise fluorinated five- [59], six- [60] and seven-membered [61] N-heterocycles that may have been otherwise difficult to access (e.g. 48→49, Scheme 4). Alternatively, neighbouring group participation sometimes results in an unexpected pattern of substitution with

• deoxyfluorination of N-heterocycles, neighbouring group participation can sometimes lead to rearrangement (48→49) or substitution with retention (50→51). A building block approach for the synthesis of fluorinated aziridines 2 and 3. Building block approach for the synthesis of a difluorinated analogue of

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

• achieved with trichloroacetimidate donors 12 [17] or 13 [18], which bear C-2 protecting groups N-trichloroethylcarbamate (N-Troc) and acetate (OAc), respectively, and which are able to undergo neighbouring group participation, to ensure β-anomeric selectivity in the glycosylation reaction [19][20]. Core 1

The application of a monolithic triphenylphosphine reagent for conducting Appel reactions in flow microreactors

• Kimberley A. Roper,
• Heiko Lange,
• Anastasios Polyzos,
• Malcolm B. Berry,
• Ian R. Baxendale and
• Steven V. Ley

Beilstein J. Org. Chem. 2011, 7, 1648–1655, doi:10.3762/bjoc.7.194

• the rate of the reaction on a solid-supported reagent, attributed to neighbouring group participation as a consequence of using a polymeric source of triphenylphosphine [39]. Mechanistically, the Appel reaction has been proposed to proceed via two complex and competing pathways (Scheme 1). In pathway

• neighbouring-group participation assisting in the formation of the active species 9 and 10 in pathway B [39][41][42]. Analysis by gas chromatography of chloride Appel reactions indicated that the relative proportion of chloroform was a lot lower than would be expected if both pathways were followed equally in

The oxanorbornene approach to 3-hydroxy, 3,4-dihydroxy and 3,4,5-trihydroxy derivatives of 2-aminocyclohexanecarboxylic acid

• Ishmael B. Masesane,
• Andrei S. Batsanov,
• Judith A. K. Howard,
• Raju Mondal and
• Patrick G. Steel

Beilstein J. Org. Chem. 2006, 2, No. 9, doi:10.1186/1860-5397-2-9

• overcome the directing influence of the carbamate and deliver the epoxide to the opposite face of diene 5. Similarly, whilst the alternative regiochemistry in the epoxide ring opening product could be achieved exploiting neighbouring group participation by the NBoc group to afford the cyclic carbamate 29