Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• and pinacol/semipinacol rearrangements, the 1,2-shift does not require a leaving group or carbocation intermediate, as the neighboring π system is capable of accepting the migrating group. While the reaction is generally reversible, the product can be favored through four common strategies: (1) the

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• ). Access to allylic alcohol 8 was also achievable (55%, E/Z = 56:44) in a tin-free process using a sulfonyl leaving group, via α-lithiation of sulfone 15 [18] and in the presence of LTMP (Scheme 7). γ-Hydroxysulfone 16 was formed competitively (44%, dr = 50:50), by direct addition of the lithiated sulfone

• hexane (69%, E/Z = 62:38) and the amount of dimer 24 curtailed (8%) by reducing the amount of LTMP from 2 to 1.2 equiv. The viability of a benzyl ether (Scheme 10) in the carbenoid eliminative cross-coupling offered a straightforward way to probe any effect of the size of the leaving group on

• -lithio terminal epoxides or N-Bus-aziridines with α-lithio ethers. Where 1,2-disubstituted alkenes are generated the E/Z stereoselectivity is modest, and preliminary results suggest the size of the leaving group does not play a significant role. However, the geometry of alkene formation might be

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• group is a leaving group resulting in the formation of phenanthridines is unprecedented. As is outlined in this paper we set out to investigate the scope and limitations of this reaction resulting in the formation of the phenanthridine skeleton. We also report on the application of this methodology to

• . To be effective, the desired cyclization needs a second methoxy substituent ortho- or para- to the leaving group, which in this case is an aromatic methoxy substituent. Based on these results we suggest two possible mechanisms for these transformations. Both would proceed through an intermediary

• methoxy group as a leaving group have been documented [16]. Our previous research, as shown in Scheme 1, indicated that exposure of the oxime ether 7 to UV radiation resulted in the formation of the phenanthridine 8. Attempts to synthesize the related oxime ethers from biaryl compounds 13a, 13c and 13e

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• has a remarkable structural feature: the phosphate moiety is located at the benzylic position as well as at the position α to an amide group, which makes it a good leaving group for the design and development of new reactions. Accordingly, diethyl (2-oxoindolin-3-yl) phosphates 2 have been used

• -3-yl) phosphate 2 is activated by protonation with a haloid acid. Subsequently the phosphate leaving group is eliminated to generate the carbocation intermediate III, which is then followed by rapid combination with a nucleophilic halide ion to form a 3-monohalooxindoles 3 or 4. Conclusion In

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• -atom (80, Scheme 9b) [66]. A similar protocol was adopted by van de Watering in their recent syntheses [67][68]. Sulfides The C2 tethering of indoles with sulfur can be achieved in neutral medium by treatment with various SL2 (L is a leaving group) moieties [69][70]. This is a common method for the

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

• polymerization [18], C) chemical synthesis. The use of enzymes has undeniable advantages because it offers the possibility to use unprotected sugars as substrates and guarantees remarkable control of the regio- and stereoselectivity during glycosylation. Mono- or oligosaccharides bearing a reactive leaving group

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• additions [92]. Using MBH acetates 63 as substrates, olefin hydroallylation products 64 were obtained via E1cB elimination of the acetate leaving group driven by the enolate intermediate (Scheme 25B). Six-membered lactones (Scheme 25A, 65a–c) were obtained in a cascade reaction when alkenyl alcohols were

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• leaving group with isopropylmagnesium chloride gave the desulfinylated product 9e in 79% yield, and the starting sulfoxide 8 was recovered in 10% yield (Table 1, entry 7). Considering the reaction efficiency, accessibility of precursors, and functional group tolerance, the use of isopropylmagnesium

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• ][9][10][11] and other compounds that show different types of biological activities [12][13]. The way to achieve these transformations is by intramolecular cyclizations, involving the free primary amine, and appropriate reactive positions (those positions bearing a leaving group) in the electrophile

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• ][43][44][45]. Analogous ring-contraction reactions have been described for substrates possessing a good C2 leaving group [42][46][47][48][49][50]. We initially considered converting thioglycosides 14–19 to benzyl glycosides because thioglycosides give glycosyl fluorides on reaction with diethylamino

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• respect to the apparent versatility of this reagent and more variations could be envisaged. Addition of amines to carbamide derivatives (pathway c) The third main pathway to access biguanides from amines involves the use of carbamide derivatives linked to a leaving group on one carbon atom. These reagents

• can act as a “bisamidine transfer agent” by the addition of an amine, and subsequent elimination of the leaving group. Two types of “biguanide transfer agents” have been developed so far. Depending on the nature of the leaving group they can be separated into either pyrazole or thiomethyl agents

• within 15 minutes in DMF at 110 °C and 62% yield. Addition on S-methylamidinothiourea: Another possibility to create an “amidine transfer reagent” is to install a thiomethyl leaving group on the bisamidine structure. This can be easily achieved using S-methylguanylisothiourea as already described by

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

• –base (HSAB) theory the fluoride leaving group is considered to be a hard Lewis base [12][13]. Consequently, a series of fluoride-activating systems containing hard Lewis acidic centers have been published following the first report [7][14][15][16][17]. Among these promoters Sn(II) species (SnCl2–AgX, X

• 1-O-methyl glucoside α-S9 as a glycosyl donor, we have demonstrated that methoxide can act as a mediocre leaving group in liquid SO2 (Scheme S1, Supporting Information File 1). Other limitations for the glycosylation with mannosyl fluoride α-1a include steric hindrance and the presence of a Lewis

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• ). Alternative electrophilic components for the Eschenmoser coupling reaction The Eschenmoser coupling reaction [36][37] usually starts from α-substituted ketones, esters, malonates, or nitriles. The group in the α-position must be a good leaving group enabling a facile nucleophilic substitution giving the α

• -thioiminium salt and the cleaved leaving group should be a poor nucleophile in order to suppress the reverse reaction. In most cases halogens (mainly Br and I) fulfill these criteria but for highly congested thioamides only triflates gave desirable yields [36]. Moreover, several new alternatives to the

• order to avoid the relatively long synthesis of the precursors we tried to change Br for another leaving group Y (Scheme 4). First, we prepared 3-chlorooxindole (1f) which is available from β-nitrostyrene and acetyl chloride under FeCl3 catalysis [41]. Unfortunately, the Eschenmoser coupling reaction

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• ring at the C6 position of purine to act as leaving group. Keywords: 2,6-bistriazolyl purines; nucleophilic aromatic substitution; purine nucleosides; triazoles; Introduction Modified purine derivatives are an important class of compounds which possess a wide spectrum of biological activities [1][2

• of an SNAr process on partially deactivated purines as the introduced nucleophiles are mostly seen as electron-donating substituents (e.g., R2N-, RS-, RO-). Herein, we report a synthetic extension of this methodology. We have found that the pronounced leaving group character of 1,2,3-triazoles makes

• ). In most cases the full conversion of the starting material was reached in 15–30 min at room temperature, which clearly showed the excellent leaving group ability of the triazolyl ring. These SNAr reactions can also be performed in DMSO or DMF in the presence of K2CO3, but the completion of these

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• nitrogen with a suitable electrophile, the use of a strong base (e.g., NaH) in combination with the chemical waste being generated (from the leaving group), and potentially unfavorable polar aprotic solvents (DMF, NMP) prompted consideration of a more atom-economical approach. The follow-on work focused on

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• . These data support the hypothesis that the transient formation of a carbenium ion is the rate-limiting step and the absence of significant solvent participation in the latter. Richard also conducted extensive studies on the impact of the nature of the leaving group (I, Br, OSO2R, etc.) and on the aryl

• , and triflate 45f, which was isolated after basic workup of the reaction (59% yield) [63]. Hence, protonation of 44 led to dialkoxysulfonium triflate 47 along with the release of alcohol 9g. The subsequent formation of the excellent sultine leaving group 46 (assumed to be as good of a leaving group as

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• stability over a wide pH value range (up to pH 9.0), irrespective of the temperature. This is because in compound 12, the ferulate moiety is not directly linked to the good leaving group 4NTC (pKa = 6.61 [40]). Instead, it is bonded to the linker with a pKa value that can be compared either to that of

• glycerol (pKa = 13.61) or ʟ-arabinose (pKa = 11.31) [41], meaning that it is a poor leaving group. Moreover, our observations regarding the linker stability are consistent with the known stability of the ester linkages under basic conditions. The usefulness of 4NTC–linker–Fe (12) for the characterization

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• ]. Photolytic generation of difluorocarbene: Difluorodiazirine (44) is a convenient photochemical source of difluorocarbene (Scheme 17). The compound readily produces difluorocarbene upon photolysis. N2 is the leaving group and it is good for LFP studies [54]. Furthermore, pyrolysis is also suitable for

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• leaving group in SNAr reactions with S- and N-nucleophiles [19][20][21]. It is worth to note that 2/6-amino-6/2-triazolylpurines possess high levels of fluorescence [19][22][23][24]. Herein, we describe an extension for SNAr reactions that makes use of the 1,2,3-triazole leaving group of 2,6

• leaving group. This has permitted to obtain a novel series of C6-phosphonated 2-triazolylpurine derivatives. It was also demonstrated that there is no alternative SNAr protocol towards the designed products. The synthetic intermediates, (2-chloro-9H-purin-6-yl)phosphonates, of the alternative pathway are

• : DMSO-d6, 90 °C. Single-crystal X-ray analysis of diethyl (9-heptyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)-9H-purin-6-yl)phosphonate (4d). CCDC-2044976. Structural diversity and synthetic methods of purinylphosphonates. MWI = microwave irradiation; LG = leaving group. Synthetic routes for the formation of

Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD^®/Olah’s reagent under solvent-free conditions

• Yumeng Liang,
• Akihito Taya,
• Zhengyu Zhao,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2020, 16, 3052–3058, doi:10.3762/bjoc.16.254

• and not as fluorination of acyl fluorides. Thus, the acyl fluoride moiety is commonly sacrificed as a “leaving group” in reactions. On the other hand, the transformation to CF3 derivatives from carboxylic acids are traditionally examined. In 1960, Engelhardt [27] performed the deoxyfluorination of

Metal-free nucleophilic trifluoromethylselenolation via an iodide-mediated umpolung reactivity of trifluoromethylselenotoluenesulfonate

• Kevin Grollier,
• Alexis Taponard,
• Arnaud De Zordo-Banliat,
• Emmanuel Magnier and
• Thierry Billard

Beilstein J. Org. Chem. 2020, 16, 3032–3037, doi:10.3762/bjoc.16.252

• substitute the leaving group onto the electrophilic substrate 2. However, because of the release of I2, as side reaction the oxidation of the CF3Se− anion can be also envisaged. This was confirmed by the formation of 25–30% of CF3SeSeCF3 when 1 equivalent of 2a was used (Table 1, entries 3 and 4

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• sources (e.g., Et3N⋅3HF and HF–pyridine) and halonium ion sources (e.g., N-halosuccinimides) are relatively cheap and easily available, halofluorination might be an economic way to obtain vicinal halofluorides that can be transformed further in various ways thanks to the different leaving group abilities

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197