Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• step. As suggested in the initial works of McKenna, the mechanism occurs by an oxophilic substitution on the silicon atom whereas bromide acts as a leaving group to produce the intermediate I (Figure 14). This intermediate is then dealkylated following a similar path than that occurring with the

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• with the same aglycon leaving group can be used enabling an iterative glycosylation, simplifying the overall synthetic design. For a preactivation based glycosylation reaction to be successful the intermediate formed upon preactivation must be stable prior to the addition of the acceptor and yet

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• for elaborate protecting and leaving group manipulations, functionalization, tedious purification, and sophisticated characterization. Achieving high stereocontrol in glycosylation reactions is arguably the major hurdle that chemists experience. This review article overviews methods for intramolecular

• concepts have been invented: a “molecular clamp” approach, intramolecular aglycone delivery (IAD), and leaving group-based methods (approaches A–C, Figure 1). This review will discuss recent developments in the field of intramolecular glycosylations with the main emphasis on the developments of the past

• place away from the reactive centers. These attachment strategies clearly distinguish the molecular clamp method from other intramolecular concepts wherein the attachment involves one of the reactive sites, acceptor hydroxy group in IAD or the leaving group of the donor. “Molecular clamping” was

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

1-Imidoalkylphosphonium salts with modulated C_α–P⁺ bond strength: synthesis and application as new active α-imidoalkylating agents

• Jakub Adamek,
• Roman Mazurkiewicz,
• Anna Węgrzyk and
• Karol Erfurt

Beilstein J. Org. Chem. 2017, 13, 1446–1455, doi:10.3762/bjoc.13.142

• products [3][4][5][6][7][8][9][10][11][12]. Most of the α-amidoalkylating reagents possess the structure of α-functionalized N-alkylamides 1, where Z = OH, OR, OCOR, Cl, Br, I, NHCOR, SO2Ar, 1-benzotriazolyl or PPh3+ X− and acts as a nucleofugal leaving group (Scheme 1) [3][8][9][10][13][14][15][16][17][18

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

• by participation of the C2–OH group to release 1,3-dimethylimidazolidin-2-one (DMI), the anomeric leaving group. The epoxide is then opened by the nucleophile when added to the reaction mixture. In pathway C the α-DMC complex is displaced directly by the added nucleophile to liberate DMI, once again

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

• Josef Jansa,
• Ramona Schmidt,
• Ashenafi Damtew Mamuye,
• Laura Castoldi,
• Alexander Roller,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2017, 13, 895–902, doi:10.3762/bjoc.13.90

• [3,4-a]quinolizin-6-ium structure 12 was established, which was confirmed by single crystal X-ray structure analysis (see Supporting Information File 1), proving also iodide as the corresponding anion [39] which acts as a leaving group in the coupling reaction and also could origin from the CuI co

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support

• Johnny N. Naoum,
• Koushik Chandra,
• Dorit Shemesh,
• R. Benny Gerber,
• Chaim Gilon and
• Mattan Hurevich

Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81

• effective reagent compared to the other additives used. DMAP is used as a catalyst in acylation reactions as it acts via a nucleophilic addition mechanism [34][37][40]. In nucleophilic catalysed acylation, the mechanism involves a step in which the DMAP replaces the leaving group on the carbonyl group

Decarboxylative and dehydrative coupling of dienoic acids and pentadienyl alcohols to form 1,3,6,8-tetraenes

• Ghina’a I. Abu Deiab,
• Mohammed H. Al-Huniti,
• I. F. Dempsey Hyatt,
• Emma E. Nagy,
• Kristen E. Gettys,
• Sommayah S. Sayed,
• Christine M. Joliat,
• Paige E. Daniel,
• Rupa M. Vummalaneni,
• Andrew T. Morehead Jr,
• Andrew L. Sargent and
• Mitchell P. Croatt

Beilstein J. Org. Chem. 2017, 13, 384–392, doi:10.3762/bjoc.13.41

• and coupling this to a substrate with a benzylic or allylic leaving group [19][20]. Typical Pd(0)-catalyzed decarboxylative coupling reactions utilize an allylic or benzylic ester with either an anion-stabilizing group adjacent to the carboxyl group (i.e., carbonyl [19][21][22], nitrile [23][24][25

• accessible alcohol for a leaving group. This reaction was advanced to be possible in a two-component fashion, allowing for the conversion of dienoic acids and pentadienyl alcohols into 1,3,6,8-tetraenes with the only stoichiometric byproducts being water and carbon dioxide. These reactions currently require

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• based on the crystal structure of the DEBS DH [92], in which the conserved His acts as a general base to deprotonate at C-2, while an Asp residue serves as a general acid to stabilize the C-3 hydroxy leaving group. However, only the His has been shown by site-directed mutagenesis to be essential [111

Continuous N-alkylation reactions of amino alcohols using γ-Al₂O₃ and supercritical CO₂: unexpected formation of cyclic ureas and urethanes by reaction with CO₂

• Emilia S. Streng,
• Darren S. Lee,
• Michael W. George and
• Martyn Poliakoff

Beilstein J. Org. Chem. 2017, 13, 329–337, doi:10.3762/bjoc.13.36

• does not contain a “CO2 unit” that can serve as a leaving group. This was indeed the case as, at 250 °C, 85% selectivity, 70% yield for 16 was observed when the reaction was run in scCO2 (Scheme 3a). In the absence of CO2 as a solvent the formation of imidazolidinone 16 was not observed. When the

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

• Patrick T. Campos,
• Leticia V. Rodrigues,
• Andrei L. Belladona,
• Caroline R. Bender,
• Juliana S. Bitencurt,
• Fernanda A. Rosa,
• Davi F. Back,
• Helio G. Bonacorso,
• Nilo Zanatta,
• Clarissa P. Frizzo and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 257–266, doi:10.3762/bjoc.13.29

• , followed by aromatization finally generates product 5 (Scheme 1). The trichloromethyl (CCl3) substituent as a leaving group in β-alkoxyvinyl trichloromethyl ketones has been previously used by us for the synthesis of similar heterocycles [27][28]. Products 5–7 are considered to be very attractive building

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• considerable reactivity difference between α- and β-thioglucosides was observed with the α-anomer consistently being more reactive. This suggested that the exact alignment of the leaving group is important for the reactivity, but a similar difference was not observed for other superarmed glycosyl donors

• and with N-phenyltrifluoroacetimidate as the leaving group [57][58]. A somewhat similar influence has been observed with the much less steric demanding 4,6-O-benzylidene protective group [59]. A related stereoselectivity is induced by the DTBS group in arabinofuranosylations. Boons and collaborators

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

• and nucleoside substrate (e.g., the leaving group [11] or nucleobase protection [12]) are therefore often required. We anticipated that some of these issues could be ameliorated through mechanochemical mixing of reactants and substrates, with diverse solubility profiles, using minimal or no added

• -dependency also observed with KSeCN under Finkelstein conditions [38]. Finally, our approach also offers the convenience of employing tosylate and halide precursors rather than relying on the esoteric tresylate leaving group system. Model reactions of 5′-chloro-5′-deoxyadenosine (1a) with 4

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• derivatives are nowadays used as powerful tools in organic chemistry [6]. Synthetic selenoglycosides are versatile synthons in glycosylation reactions as glycosyl donors for the synthesis of glycosides and oligosaccharides, where their aglycon acts as a leaving group [7][8][9]. They can be selectively

Selective synthesis of thioethers in the presence of a transition-metal-free solid Lewis acid

• Federica Santoro,
• Matteo Mariani,
• Federica Zaccheria,
• Rinaldo Psaro and
• Nicoletta Ravasio

Beilstein J. Org. Chem. 2016, 12, 2627–2635, doi:10.3762/bjoc.12.259

• the green chemistry point of view would be the direct substitution of alcohols (that are also available at low cost) with thiols. In this case the only byproduct will be water. However, due to the lack of a good leaving group the use of an acid catalyst is mandatory. Both Brønsted and Lewis acids can

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• plays a dominant role in catalysis [3][4][5]. Also for the pistol ribozyme, evidence exists that an adenine-N3 in the active site is significant for the cleavage activity, most likely by 5’-O-leaving group stabilization through proton shuttling [6][7]. Another example for a specific role of an adenine

Et₃B-mediated and palladium-catalyzed direct allylation of β-dicarbonyl compounds with Morita–Baylis–Hillman alcohols

• Ahlem Abidi,
• Yosra Oueslati and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2402–2409, doi:10.3762/bjoc.12.234

• reaction, is a non-toxic byproduct. However, the poor ability of the hydroxy moiety, as a leaving group, has limited the use of the allyl alcohols as substrates. Correlatively, some efforts have been made in this direction by the use of transition metals such as copper [6], nickel [7], ruthenium (I, II) [8

• to catalyze these reactions by coordination with the hydroxy moiety, thereby increasing its leaving group ability [23][24][25][26][27][28]. Recently, Tamaru and co-workers have intensively investigated the use of triethylborane as an additive with either Pd(PPh3)4 or Pd(OAc)2 as catalysts for the

Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins

• Laszlo Jicsinszky,
• Marina Caporaso,
• Katia Martina,
• Emanuela Calcio Gaudino and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2016, 12, 2364–2371, doi:10.3762/bjoc.12.230

• , which is an important component of DNA sequencing equipment [4]. p-Toluenesulfonyl (Ts) esters are still an irreplaceable leaving group for carbohydrates as well. The Ts → azide exchange in Ts-β-CD is effective in both solution and under high-energy ball milling (HEBM) conditions, whereas it is

• /halogen molar ratios did not change such extent (Table 1). This can be explained satisfactorily by the complexation of the leaving group which might have high affinity to the CD cavity [3][25][26] preventing its departure from the reaction centres resulting in steric blocking. While the halogen → azide

• optimized the prepared compounds were enough pure to record correct NMR spectra to identify the substitution location and completeness. Although in the monosubstituted case usually less reagent/leaving group molar ratios were found [22], in the majority of per-substitutions higher reagent/CD molar ratio was

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• a good leaving group. The Criegee rearrangement was discovered in 1944 in the reaction of decaline ethylperoxoate 127 that rearranged into isomeric ester ketal 128 (Scheme 39) [291]. The mechanism of the Criegee rearrangement was studied using 2-alkoxy-2-propyl per-4-nitrobenzoates [292]. It was

Flow carbonylation of sterically hindered ortho-substituted iodoarenes

• Carl J. Mallia,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1503–1511, doi:10.3762/bjoc.12.147

• yields of the array were obtained for compounds 29 and 30, demonstrating the importance of sterics and electronics adjacent to the leaving group. In both cases, the carbon monoxide insertion is assumed to be slow as both axial positions of the aryl complex would be hindered, meaning the competing proton

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

• former affords a leaving group covalently tethered to a cation which renders the overall rate apparently slow, perhaps through a favoured re-cyclisation. It is noteworthy that the hydroxonium catalytic coefficient for the hydrolysis – albeit measured in water – of a similar yet acyclic ketal (i.e., 2,2

Mutagenic activity of quaternary ammonium salt derivatives of carbohydrates

• Barbara Dmochowska,
• Karol Sikora,
• Anna Woziwodzka,
• Jacek Piosik and
• Beata Podgórska

Beilstein J. Org. Chem. 2016, 12, 1434–1439, doi:10.3762/bjoc.12.138

• methanol, an alternative route involving the reaction of 6-bromohexyl D-glucopyranoside (2′ [32] or 3′) with tertiary amines (trimethylamine in ethanol and with pyridine) was applied; the yields were of 90–94%. Shifting the pyranose leaving group (halogen) by six carbon atoms from C1 makes it easier to

Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

• Guozheng Huang,
• Simon Schramm,
• Jörg Heilmann,
• David Biedermann,
• Vladimír Křen and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 662–669, doi:10.3762/bjoc.12.66

• Mitsunobu reaction represents a powerful method to convert primary and secondary alcohols into ester but also into various derivatives. The mechanism is well described and includes the formation of the triphenylphosphine–DIAD adduct, which then activates the alcohol making it a good leaving group

Studies on the synthesis of peptides containing dehydrovaline and dehydroisoleucine based on copper-mediated enamide formation

• Franziska Gille and
• Andreas Kirschning

Beilstein J. Org. Chem. 2016, 12, 564–570, doi:10.3762/bjoc.12.55

• typically this is achieved by elimination when a leaving group occupies the β-position [2]. Especially peptides containing dehydroalanine as found in argyrin (2) can be prepared from a precursor that contains a selenide substituent in the β-position [3]. Peptides that bear the doubly branched dehydroamino