CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• , CF3SO2Cl reacts with oxygen nucleophiles to generate triflate derivatives as highly electron-withdrawing substituent in order to act in nucleophilic substitutions and metal-catalysed coupling reactions as an excellent leaving group [2]. The reaction of CF3SO2Cl with nitrogen nucleophiles provides

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• with a catalytic amount of potassium persulfate to activate CF3SO2Na (Scheme 7) [26]. The heteroatom must be a good leaving group or part of it (X = Br, Cl, NHCOMe, N3, OP(O)(OEt)2). A mechanistic investigation demonstrated the role of oxygen: 93% isotopic purity of the ketone product was obtained when

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• utilized as a leaving group during the nucleophilic attack by the corresponding alcohol. A series of control experiments were conducted to gain insights into the mechanism of the two contrasting reactions. Firstly, two separate coupling reactions between 2-aminobenzothiazole (1a) and methyl acetoacetate

Fluorination of some highly functionalized cycloalkanes: chemoselectivity and substrate dependence

• Attila Márió Remete,
• Melinda Nonn,
• Santos Fustero,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2017, 13, 2364–2371, doi:10.3762/bjoc.13.233

• 2D NMR and X-ray data fluorohydrine derivative (±)-5 through chemodifferentiation in a moderate yield (Scheme 2, Figure 1). This result indicated that in the case of compound (±)-4, the C-4 hydroxy group is transformed into a leaving group on interaction with Deoxofluor, followed by a fluoride attack

• of the alcoholic group at C-4 in (±)-8 into a leaving group, an intramolecular cyclization takes place to afford oxazine (±)-9. Subsequently, this oxazine, in the presence of an excess Deoxofluor gives fluorinated derivative (±)-10. Finally, in the presence of fluoride as base, deprotonation (T9

• located in the γ-position through a β to γ flip (Scheme 7). The formation of isoxazolines (±)-15 and (±)-16 in the presence of 1 equiv of Deoxofluor involves rather simple reaction steps as only one of the hydroxy groups is transformed into a leaving group in each case (T13 and T14, respectively). In

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

• not possible to isolate any of the desired product 13. It is possible that varying the reaction solvent might alter the reactivity profile, but this was not investigated in this study. We did explore a triflate leaving group in this reaction (not shown), but this gave a complex mixture of products

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