A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• also in the work reported by Shankar et al. [10], already mentioned in chapter 1. The authors established a solvent-catalyzed GBB-3CR to synthesize glycosylated imidazo[1,2-a]pyridines 33 starting from 1-formyl glycals 32; using HFIP as the solvent, the addition of any metal catalyst was not needed

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• ., glycals, nucleosides and nucleobases) [80]. In 2018, Hu and co-workers reported a complementary approach for the pentafluoroethylation of aryl iodides using TMSCF3 for the formation of CuCF2CF3 [81]. They suggested that in the presence of CuCl, KF and TMSCF3, the corresponding CuCF3 species will be formed

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• signal of the anomeric OH group at 5.79 ppm. Next, the ensuing elimination step was carried out to explore the access to transition state analogues [22] potentially mimicking the sp2 character of the oxocarbenium intermediate in the enzymatic transfer reaction. In addition, exo-glycals are versatile

• -benzyl-protected gluco and galacto derivatives [20][27][30][31]. In addition to exocyclic glycals mimicking putative planar transition states of substrates involved in enzymatic reactions, such as glycosyl transfer, mutase, and epimerization, endo-glycals are also of interest [21][22][32][33][34][35

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

Robust perfluorophenylboronic acid-catalyzed stereoselective synthesis of 2,3-unsaturated O-, C-, N- and S-linked glycosides

• Madhu Babu Tatina,
• Xia Mengxin,
• Rao Peilin and
• Zaher M. A. Judeh

Beilstein J. Org. Chem. 2019, 15, 1275–1280, doi:10.3762/bjoc.15.125

• investigate them as promoters for the Ferrier rearrangement. We envisioned that organoboronic acids can activate the allylic acetate of glycals making them susceptible to nucleophilic attacks under conditions favoring a strong polarization of the allylic acetate moiety (see Figure 4). Herein, we report a

• phenylboronic acid-catalyzed synthesis of 2,3-unsaturated C-, O-, N- and S-glycosides via Ferrier rearrangement under very mild conditions. We also demonstrate the scope of the reaction using a wide range of glycals and C-, O-, N- and S-nucleophiles. Results and Discussion We began our study by investigating

• of 2,3-unsaturated O-, C-, S- and N-linked glycosides (enosides) in high yields and mostly α-anomeric selectivity through the reactions of D-glucal 1a, 2-acetoxy D-glucal 4a and L-rhamnal 6a with various C-, O-, N- and S-nucleophiles. Application of this protocol using other glycals is underway in

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• vinyl ethers as key step of reaction sequences developed. Keywords: 3-amino glycals; diastereoselective additions to aldehydes; pluramycins; ring-closing metathesis; vinyl ethers; Introduction Several classes of medicinally useful molecules with antibiotic and anticancer activity contain in their

• was developed based on a Stille coupling to install the C-linked sugar residue [3]. Moreover, the addition of lithiated glycals to quinone derivatives followed by a rearrangement was also studied for the synthesis of kidamycin according to a “reverse polarity” strategy [4][5]. Considering that the

• diastereoisomer, the carbamate-protected 3-aminoglycal of L-saccharosamine 2, employing the (S)-(−)-methyl lactate as common starting material. The efficiency and generality of this methodology was also demonstrated by a new synthesis of C-3 unbranched amino glycals, L-daunosamine 3 and L-ristosamine 4

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

• also employed with glycals like 86 and 87 reacting with p-methoxyphenol as an alternative to the Ferrier rearrangement in the synthesis of 2-C-methylene glycosides and other rearrangement products 88–92, some of which cannot be obtained in a classical Ferrier reaction (Scheme 16) [69][70][71][72]. The

• ]. Stereoselective β-D-mannoside synthesis [60]. TIPS-assisted synthesis of 1,2-cis arabinofuranosides [63]. TIPS: triisopropylsilyl. The Mitsunobu reaction with glycals leads to interesting rearrangement products [69]. Synthesis of disaccharides using mercury(II) bromide as co-activator in the Mitsunobu reaction

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• used for the glycosylation of glycals and thioglycosides to produce disaccharides. In this paper, we review the use of hypervalent iodine-mediated glycosylation reactions for the synthesis of nucleosides and oligosaccharide derivatives. Keywords: glycosylation; hypervalent iodine; Lewis acid

• synthesis employing glycals and thioglycosides as sugar donors. In this review, we survey the synthesis of nucleoside and disaccharide derivatives under oxidative conditions mostly based on the hypervalent iodine-mediated glycosylation reactions. Review Synthesis of 4’-thionucleosides Over the last decade

• react with oxidative agents, it was expected to form a cationic intermediate as in the case of allylsilanes described above. A direct coupling of glycals with nucleobases is challenging, since it is formally a C–N bond-forming reaction with cleaving of the inactive C–H bond at the γ-position. Actually

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• stereoselective trans iodo-benzoylation of glycals using a combination of IBX and molecular iodine, that is considered as a source of I+ formed from the in situ generated hypoiodite species [30]. The controlled oxidation of various N-(alkyl)- and N-(aryl)pyrroles with Dess–Martin periodinane also leads to

AuBr₃-catalyzed azidation of per-O-acetylated and per-O-benzoylated sugars

• Jayashree Rajput,
• Srinivas Hotha and
• Madhuri Vangala

Beilstein J. Org. Chem. 2018, 14, 682–687, doi:10.3762/bjoc.14.56

• ]. Thus, various research groups employed either a remote alkyne group possessing versatile glycosyl donors [7][8][9][10][11][12][13][14][15][16] or used glycals [17] for effective O-, C-, and S-glycosylation reactions using gold(I) and gold(III) catalysts. Among the gold-catalyzed activation of non

• -glycosides are also accessible by AuCl3/phenylacetylene-promoted Ferrier rearrangement of glycals [17], thus, demonstrating the efficient catalysis by alkynophilic and carbophilic Au complexes. Although the alkynophilicity and carbophilicity of Au complexes are well explored, very little is known about the

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

• with phosphorus acids) for stereoselective O-glycoside bond formation [30]. Similarly, Galan et al. reported a method for the preparation of 2-deoxyglycosides from glycals under the influence of cooperative catalysis (chiral phosphoric acids/thiourea derivatives) [31]. Encouraged by these reports and

• for the activation of glycals to provide stereoselective 2-deoxyglycosides with high yields [38]. Based on this fact, we anticipated that for electron-deficient pyridinium salts the pKa value would be further diminished in the presence of hydrogen-bonding cocatalysts such as thiourea derivatives. The

Synthesis of D-manno-heptulose via a cascade aldol/hemiketalization reaction

• Yan Chen,
• Xiaoman Wang,
• Junchang Wang and
• You Yang

Beilstein J. Org. Chem. 2017, 13, 795–799, doi:10.3762/bjoc.13.79

• chain elongations of aldoses employing the Henry reaction, the aldol reaction, and the Wittig reaction for the preparation of ketoheptoses [20][21][22], sugar lactones were also often utilized for the synthesis of D-manno-heptulose via reactions with C-nucleophiles or conversion into exocyclic glycals

Orthogonal protection of saccharide polyols through solvent-free one-pot sequences based on regioselective silylations

• Serena Traboni,
• Emiliano Bedini and
• Alfonso Iadonisi

Beilstein J. Org. Chem. 2016, 12, 2748–2756, doi:10.3762/bjoc.12.271

• . Among the screened polyols in Table 2, glycals 7 and 8 were the only substrates to exhibit a lower regioselectivity, the silylation rate being comparable at the primary (O-6) and the allylic (O-3) position, to provide a mixture of products (Table 2, entries 6 and 7). A similar competitive reactivity was

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

• University, Taipei 106, Taiwan Department of Chemistry, National Central University, Jhongli 320, Taiwan 10.3762/bjoc.12.164 Abstract The thio-additions of glycals were efficiently promoted by a stoichiometric amount of trimethylsilyl bromide (TMSBr) to produce S-2-deoxyglycosides under solvent-free

• conditions in good to excellent yields. In addition, with triphenylphosphine oxide as an additive, the TMSBr-mediated direct glycosylations of glycals with a large range of alcohols were highly α-selective. Keywords: 2-deoxyglycosides; glycals; trimethylsilyl bromide (TMSBr); triphenylphosphine oxide (TPPO

• anomeric mixtures [10]. Glycals have been considered as alternative precursors for producing 2-deoxythioglycosides as well as oligosaccharides. Several methods based on the use of glycals in the presence of Lewis acids for S- or O-2-deoxyglycoside preparations have been developed [51][52][53][54][55][56

Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals

• Henok H. Kinfe,
• Fanuel M. Mebrahtu,
• Mandlenkosi M. Manana,
• Kagiso Madumo and
• Mokela S. Sokamisa

Beilstein J. Org. Chem. 2015, 11, 583–588, doi:10.3762/bjoc.11.64

• their profound biological importance, there are different routes reported for their synthesis but the common ones are: nucleophilic substitution of an activated glycosyl donor with organometallic aryl derivatives, cross-coupling of aryls with glycals, Friedel–Crafts arylation at the anomeric centre of

• the regioselective ring opening of 1,2-cyclopropanated carbohydrates and the radical addition reaction of glycals [11][12][13][14][15]. Although the synthetic methodologies developed for the synthesis of C-glycosides and 2-C-branched sugars are extensively studied, the synthesis of 1,2-cis-2-C

A general metal-free approach for the stereoselective synthesis of C-glycals from unactivated alkynes

• Shekaraiah Devari,
• Manjeet Kumar,
• Ramesh Deshidi,
• Masood Rizvi and
• Bhahwal Ali Shah

Beilstein J. Org. Chem. 2014, 10, 2649–2653, doi:10.3762/bjoc.10.277

• , India 10.3762/bjoc.10.277 Abstract A novel metal-free strategy for a rapid and α-selctive C-alkynylation of glycals was developed. The reaction utilizes TMSOTf as a promoter to generate in situ trimethylsilylacetylene for C-alkynylation. Thanks to this methodology, we can access C-glycosides in a

• particular interest as it is amenable to further modifications into chiral molecules, carbohydrate analogues, and natural products, such as tautomycin [17][18] and ciguatoxin [19][20][21]. In recent past, significant efforts have been directed toward the C-alkynylation of glycals [9][22][23]. However, all

• alkynes is the involvement of multiple steps and thus loss of yields. Recently, Mukherjee and co-workers [35] have reported a one-step C-alkynylation of glycals by using metal in combination with a co-oxidant, i.e., Cu(OTf)2 with ascorbic acid. However, a drawback of the method is its limited

Design and synthesis of multivalent neoglycoconjugates by click conjugations

• Feiqing Ding,
• Li Ji,
• Ronny William,
• Hua Chai and
• Xue-Wei Liu

Beilstein J. Org. Chem. 2014, 10, 1325–1332, doi:10.3762/bjoc.10.134

• currently underway and the results will be reported in due course. Our reported strategy for quick access to 3-amino-2,3-dideoxysugars via regio- and stereoselective tandem hydroamination/glycosylation of glycals. Synthetic modification of α-GalNAc linked glycopeptides to 3-tosylamino-2,3

• -dideoxyneoglycoconjugates via click conjugation. Our proposal for access to 3-tosylamino-2,3-dideoxyneoglycoconjugates via tandem hydroamination/glycosylation of glycals followed by click conjugations. Synthesis of propargyl 3-tosylamino-2,3-dideoxy-α-D-allohexopyranoside (2a). Synthesis of divalent 3-tosylamino-2,3

Efficient carbon-Ferrier rearrangement on glycals mediated by ceric ammonium nitrate: Application to the synthesis of 2-deoxy-2-amino-C-glycoside

• Alafia A. Ansari,
• Y. Suman Reddy and
• Yashwant D. Vankar

Beilstein J. Org. Chem. 2014, 10, 300–306, doi:10.3762/bjoc.10.27

• Alafia A. Ansari Y. Suman Reddy Yashwant D. Vankar Department of Chemistry, Indian Institute of Technology Kanpur 208 016, India 10.3762/bjoc.10.27 Abstract A carbon-Ferrier rearrangement on glycals has been performed by using ceric ammonium nitrate to obtain products in moderate to good yields

• with high selectivity. The versatility of this method has been demonstrated by applying it to differently protected glycals and by employing several nucleophiles. The obtained C-allyl glycoside has been utilized for the synthesis of a orthogonally protected 2-amino-2-deoxy-C-glycoside. Keywords: C

• synthesis of C-glycosides [12][13][14]. Among these, the Ferrier rearrangement [15] of glycals with protic acids [5][16][17] or Lewis acids [18][19][20][21][22] and carbon nucleophiles such as allylsilanes [23], silylacetylenes [24], silyl enol ethers [25], olefins [26], and organozinc reagents [27] has

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• ). Finally, we found that the silyl bromide formation proceeded better in tetrachloromethane. However, to assure solubility of the glycals, small amounts of diethyl ether were added for the coupling step (Table 1, entries 8–10). In all cases, a very slow addition of bromine and bromosilane proved to be

• necessary to ensure optimal yields. With optimized conditions in hand we explored the scope of the silyl ether coupling. Therefore, two different glycals and five different dialkynes were employed. In summary, seven different coupling products 14 were prepared baring alkynes with terminal H, TMS, SiMe2Ph

• 25); Si: SiMe2Ph, SiMe2Bn (2.0 equiv of 25). Silyl ether synthesis and domino carbopalladation reaction. R,R (Glc): isopropylidene. R,R (Gal): benzylidene. aThe respective equivalents of alkynes 16, glycals 15 and bromine as well as reaction times are given in the Experimental. bThe reaction was

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

• glycals using several aromatic and aliphatic alkynes. This Pd-catalyzed cross-coupling reaction presents a facile access to alkynyl C-glycosides and sets the stage for a reductive/oxidative refunctionalization of the enyne moiety to regenerate either C-glycosidic structures or pyran derivatives with a

• substituent in position 2. Keywords: C-glycosides; enyne; glycals; reductive/oxidative refunctionalization; Sonogashira–Hagihara reaction; Introduction Carbohydrates are key players in a plethora of biological processes, such as cell-development, metastasis, cell–cell aggregation and viral infection [1][2

• or hydrolysis. During the past decades C-glycosides have emerged as valuable synthetic targets, not only for medicinal chemists, but also for methodologists [8]. In particular, glycals have transpired as versatile building blocks in the synthesis of various C-glycosides. Most of the reported

Acceptor-influenced and donor-tuned base-promoted glycosylation

• Stephan Boettcher,
• Martin Matwiejuk and
• Joachim Thiem

Beilstein J. Org. Chem. 2012, 8, 413–420, doi:10.3762/bjoc.8.46

• , elimination became the dominant reaction and led to the corresponding glycals. Hence, and based on the workup, the recovery of glycosyl halides was neither practicable nor achieved. Experimental General: All reagents were purchased from commercial sources and used as received. Sodium hydride (NaH) was used as

Synthesis of 2,6-trans- disubstituted 5,6-dihydropyrans from (Z)-1,5-syn-endiols

• Eric M. Flamme and
• William R. Roush

Beilstein J. Org. Chem. 2005, 1, No. 7, doi:10.1186/1860-5397-1-7

• dihydropyrans are common structural elements of many biologically active natural products.[2][3] A number of methods have been developed to synthesize substituted dihydropyrans including: (i) hetero-Diels-Alder cycloadditions,[4][5][6][7] (ii) electrophile-initiated alkylation of glycals,[8][9][10][11] (iii