An amine protecting group deprotectable under nearly neutral oxidative conditions

• Shahien Shahsavari,
• Chase McNamara,
• Mark Sylvester,
• Emily Bromley,
• Savannah Joslin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2018, 14, 1750–1757, doi:10.3762/bjoc.14.149

• carbamate and 6-nitroveratryl carbamate) [9][10] and fluoride (e.g., trimethylsilylethyloxycarbonyl (Teoc) group) [11][12]. The 1,3-dithian-2-ylmethoxycarbonyl (Dmoc) group first reported by Kunz and co-workers provides a different dimension of orthogonality of amine protection in terms of deprotection

The phenyl vinyl ether–methanol complex: a model system for quantum chemistry benchmarking

• Dominic Bernhard,
• Fabian Dietrich,
• Mariyam Fatima,
• Cristóbal Pérez,
• Hannes C. Gottschalk,
• Axel Wuttke,
• Ricardo A. Mata,
• Martin A. Suhm,
• Melanie Schnell and
• Markus Gerhards

Beilstein J. Org. Chem. 2018, 14, 1642–1654, doi:10.3762/bjoc.14.140

• capacity of 500–2500 m3/h resulted in background pressures of less than 0.1 mbar before expansions. This facilitated measurements of clusters of methanol and PVE in the zone of silence of the expansion at an average distance of 10 mm to the nozzle. A calcium fluoride beam splitter, lenses and windows were

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 applied for other anomeric modifications, such as fluorination, reported by Kunz et al. for the synthesis of the α-D-mannofuranosyl fluoride 126, however, in moderate yield (Scheme 27) [118]. The advantage of this approach lies in the mild fluorine source, triethyloxonium tetrafluoroborate, which

Cobalt-catalyzed C–H cyanations: Insights into the reaction mechanism and the role of London dispersion

• Eric Detmar,
• Valentin Müller,
• Daniel Zell,
• Lutz Ackermann and
• Martin Breugst

Beilstein J. Org. Chem. 2018, 14, 1537–1545, doi:10.3762/bjoc.14.130

• ) to yield complex 5a. In contrast to previous computational studies on manganese(I)-catalyzed fluoro-allylation reactions where β-fluoride and HF eliminations played an important role [41], similar reactions involving amine eliminations seem to be not relevant in this reaction. Furthermore, a

Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst

• Kimihiro Komeyama,
• Shunsuke Sakiyama,
• Kento Iwashita,
• Itaru Osaka and
• Ken Takaki

Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118

• give the chromium alkoxide L [24]. Finally, the Cr–O bond is cleaved by TMSCl, generating the active chromium salt for the transmetalation and the silyl ether M, the desilylation of which with a fluoride anion results in the formation of a homoallylic alcohol 4. Conclusion The cobalt/chromium-catalyzed

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• fluoride source. The reactions were guided by the formation of intermediate 70. Anchimeric assistance via the phenonium ion intermediate 71 and subsequent ring-opening rearrangement delivered the 1,1-difluorinated products 72 in the presence of catalyst 73 [54]. On the other hand the anchimeric assistance

• could be achieved even by using a 50 mol % catalyst loading. A nucleophilic attack of the fluoride ion to the intermediate 104 or a possible ligand coupling pathway via 105 could justify the product formation (Scheme 23). Waser et al. developed an asymmetric alkynylation of β-ketoesters and amides 107

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

• Felix Scheidt,
• Christian Thiehoff,
• Gülay Yilmaz,
• Stephanie Meyer,
• Constantin G. Daniliuc,
• Gerald Kehr and
• Ryan Gilmour

Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88

• fluorooxygenation of readily accessible N-allylcarboxamides via an I(I)/I(III) manifold to generate 2-oxazolines containing a fluoromethyl group. Catalysis is conditional on the oxidation competence of Selectfluor®, whilst HF serves as both a fluoride source and Brønsted acid activator. The C(sp3)–F bond of the

Local energy decomposition analysis of hydrogen-bonded dimers within a domain-based pair natural orbital coupled cluster study

• Ahmet Altun,
• Frank Neese and
• Giovanni Bistoni

Beilstein J. Org. Chem. 2018, 14, 919–929, doi:10.3762/bjoc.14.79

• , and London dispersion terms. Herein, this technique is employed in the study of hydrogen-bonding interactions in a series of conformers of water and hydrogen fluoride dimers. Initially, DLPNO-CCSD(T) dissociation energies for the most stable conformers are computed and compared with available

• . This information is used to rationalize the trend of stability of various conformers of the water and hydrogen fluoride dimers. Keywords: DLPNO-CCSD(T); hydrogen-bond interaction; interaction energy; local energy decomposition; London dispersion; Introduction Hydrogen bonds are of fundamental

• applied to the study of H-bond interactions in a series of conformers of water (H2O) and hydrogen fluoride (HF) dimers, which are shown in Figure 1. These systems are representative examples of H-bond interactions and are often used as model systems for newly developed methods, including EDA schemes [18

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• use of photolabile protecting groups [38] of allyloxycarbonyl groups deprotected by Pd(0) [39] and of fluoride-labile groups [40] in place of the standard acyl protection of nucleobases has made possible the acquisition of short sequences of heteropolymer pro-oligonucleotides. However, none of these

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

• was used by Wang for the more extended synthesis of a dodecasaccharide oxazoline (Scheme 6) [78]. In this case selective removal of the PMB protecting group at OH-3 was followed by glycosylation with a pentasaccharide glycosyl fluoride donor, comprising one galactose, one glucose, and three mannose

The selective electrochemical fluorination of S-alkyl benzothioate and its derivatives

• Shunsuke Kuribayashi,
• Tomoyuki Kurioka,
• Shinsuke Inagi,
• Ho-Jung Lu,
• Biing-Jiun Uang and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2018, 14, 389–396, doi:10.3762/bjoc.14.27

• fluorination of sulfides having various EWGs at their α-position using Et3N·3HF [9][10]. Since then, we have systematically studied the electrochemical fluorination of numerous organic compounds, heterocycles, and macromolecules by using various fluoride salts such as Et3N·nHF (n = 3–5) and Et4NF·nHF (n = 3–5

• triarylamine mediator gave much better yields of benzoyl fluorides compared to the direct electrolysis [23]. Therefore, we became interested in the anodic behavior of S-alkyl benzothioates in the presence of fluoride ions. With this in mind and in order to provide an additional application of our

• electrolytic conditions. Electrolysis was performed at a constant current (40 mA) with platinum electrodes (2 cm × 2 cm) in several solvents containing various fluoride salts in an undivided cell at room temperature and current was passed basically until 1a was consumed. The results are summarized in Table 1

Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

• Masanori Inaba,
• Tatsuya Sakai,
• Shun Shinada,
• Tsuyuka Sugiishi,
• Yuta Nishina,
• Norio Shibata and
• Hideki Amii

Beilstein J. Org. Chem. 2018, 14, 182–186, doi:10.3762/bjoc.14.12

• transformation. After many experiments, we found that the use of ethyl 2-formylbenzoate (10) [36] instead of nitrile 2 resulted in the formation of 1a with 27% ee upon exposure to organocatalyst 9b (0.1 equiv) and tetramethylammonium fluoride (0.5 equiv, Scheme 5). Conclusion In summary, we have demonstrated a

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• were reported recently. In 2015, the group of Lin, Zheng and Xiao [21] disclosed a trifluoromethylation reagent, the difluorocarbene precursor difluoromethyltriphenylphosphonium bromide (DFPB), which could be applied in the trifluoromethylation of aromatic iodides without addition of external fluoride

• (Scheme 9). It was found that DBU can promote the decomposition of difluorocarbene to give fluoride which then reacts with difluorocarbene to a trifluoromethyl anion. Both electron-rich and electron-deficient substrates were converted to the corresponding analogues in moderate to good yields, without

• rearrangement to give unstable difluoromethyl amine II. Decomposition of II produces intermediate III by releasing a fluoride ion which was trapped by difluorocarbene affording the trifluoromethyl anion. The latter reacts with copper to CuCF3. The desired Ar–CF3 was formed by the reaction of CuCF3 with the

Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• an enantiopure isotopomer of benzyl fluoride to identify whether the reaction conditions favour a dissociative (SN1) or associative (SN2) pathway. [2H]-Isotopomer ratios in the reactions were assayed using the Courtieu 2H NMR method in a chiral liquid crystal (poly-γ-benzyl-L-glutamate) matrix and

• years, there has been an increasing interest in C–F bond activation [2], with a view to using organic bound fluoride as a leaving group in substitution reactions that typically require more activated leaving groups. Such an approach could circumvent the requirement for protecting groups in multistep

• synthesis by capitalizing on the low reactivity of the C–F bond. Paquin et al. have published extensively on non-metal based methods for benzylic C–F bond activation [3][4][5][6][7]. The reactivity relies on protic activation driven by the capacity of organic fluoride to form hydrogen bonds [8][9

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• deprotected by treatment with tetrabutylammonium fluoride buffered with acetic acid, and the resulting lactol was converted to the imidate donor 11 which was coupled to the orthogonally protected acceptor, an azide 12, using triflic acid as promotor (Scheme 2). Subsequent hydrolytic cleavage of the

• isopropylidene group furnished diol 13. Regioselective boron trifluoride diethyl etherate-promoted glycosylation of the 6-OH group in 13 with Kdo-fluoride donor 14 afforded an inseparable mixture of α- and β-anomeric products (α/β = 9:1) [78]. Phosphitylation of the remaining OH group in position 4’ and facile

• fluoride required an excess of Lewis acid as promotor which was incompatible with the acid-labile protecting groups present in the key diglucosamine precursor. Therefore, a new N-phenyltrifluoroacetimidate Kdo donor 35 was developed (Scheme 4) [21]. The disaccharide acceptor 34 was prepared by

Microfluidic radiosynthesis of [¹⁸F]FEMPT, a high affinity PET radiotracer for imaging serotonin receptors

• Thomas Lee Collier,
• Steven H. Liang,
• J. John Mann,
• Neil Vasdev and
• J. S. Dileep Kumar

Beilstein J. Org. Chem. 2017, 13, 2922–2927, doi:10.3762/bjoc.13.285

• nM. Microfluidic chemistry Reaction optimization of radiofluorination methods vary depending on the microfluidic systems being used but we can typically optimize 18F-labeling reaction conditions in one or two days from a single batch of [18F]fluoride. This is significantly more efficient than

• classical vial-based radiofluorination methods which, generally involves several experimental days and analysis as each reaction, including azeotropic drying of [18F]fluoride, must be carried out individually. The microfluidic radiosynthesis of [18F]FEMPT was optimized by treating the reactions as 2

• individual steps, using the Discovery mode of the Advion NanoTek® microfluidic synthesizer [16]. The first step is the preparation of the labeling reagent [18F]fluoroethyltosylate (10) via tetraethylammonium fluoride ([18F]TEAF). The second step is the reaction of the [18F]fluoroethyltosylate (10), with the

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

• -difluorobutane-1,4-diol (anti-5) starting from commercially available cis-but-2-ene-1,4-diol (Scheme 1) [17]. The vicinal-difluoride group was introduced by a two-step sequence, with initial nucleophilic epoxide [18] opening by a fluoride source [19], followed by nucleophilic deoxyfluorination [9][10][11]. In

•  1 was high-yielding [17], two disadvantages were apparent. First, the epoxide opening takes 2.5 days at 115 °C and uses an expensive fluoride source (Landini’s reagent [18]: Bu4NH2F3). It was found that Bu4NH2F3 made in-house gave significantly reduced yields. Second, the use of the benzyl ether

• to afford fluorohydrin (±)-9, containing the thermodynamically favoured five-membered ring [24]. This is clearly indicated by the appearance of a doublet of doublets for the primary alcohol OH proton. DAST-mediated deoxofluorination then led to (±)-10, in which an alkyl fluoride signal at −232 ppm

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• -carboxybenzyl moiety to afford 4. Finally, removal of the tert-butyldiphenylsilyl group using tert-n-butylammonium fluoride, followed by oxidation with the Jones reagent, provided the C-terminal carboxylic acid 5. In 2011, Lequeux and co-workers used rather the Julia–Kocienski olefination to access Phth-Gly-ψ

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• fluoride leads to deprotonation in the Cα-position of 6i, 6k and 6j, inducing an alkyne rearrangement to form an allene, which rearranges further to provide an α,β-unsaturated imine (Figure 8) [97]. One target application of propargylamines 7 is the Sonogashira cross-coupling with halogenated benzoates

Structure–property relationships and third-order nonlinearities in diketopyrrolopyrrole based D–π–A–π–D molecules

• Jan Podlesný,
• Lenka Dokládalová,
• Oldřich Pytela,
• Adam Urbanec,
• Milan Klikar,
• Numan Almonasy,
• Tomáš Mikysek,
• Jaroslav Jedryka,
• Iwan V. Kityk and
• Filip Bureš

Beilstein J. Org. Chem. 2017, 13, 2374–2384, doi:10.3762/bjoc.13.235

• ]. Moreover, some DPP derivatives also showed aggregation induced emission (AIE) [13][14] and the ability to selectively sense fluoride ions [26][27][28]. The modern era of DPP chromophores has been opened by Gryko et al. [3][11][12][18][20][21][29] who have demonstrated their large and tunable two-photon

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

• contrast, when using the fluorinating reagent in excess, both hydroxy groups are converted to leaving groups to afford intermediate T15. The latter affords aziridinium ion T16 through intramolecular reaction with the amide nitrogen. The subsequent aziridine-ring opening by reaction with fluoride results 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

• ]. Therefore we turned our attention to converting the fluorinated aldehyde 8b (Scheme 1) into the allylic fluoride 16. The crude fluorinated aldehyde 8b was treated with a variety of olefination reagents (e.g., Tebbe; Wittig; reagent 15 [27]). Unfortunately, however, the desired allylic fluoride 16 was either

• have previously reported a concise method for synthesising compounds that contain three vicinal C–F bonds [34]; their method commences with an epoxy alcohol, which undergoes three successive nucleophilic substitutions with fluoride (i.e., deoxyfluorination of the alcohol, epoxide ring opening with

• fluoride, then deoxyfluorination). We therefore sought to apply O’Hagan’s method to the target 6b (Scheme 3, boxed). Accordingly, the enantiopure allylic alcohol 27 [35] was extended through a cross-metathesis reaction to deliver the disubstituted alkene 30 (Scheme 3). Compound 30 became the substrate for

Curcuminoid–BF₂ complexes: Synthesis, fluorescence and optimization of BF₂ group cleavage

• Henning Weiss,
• Jeannine Reichel,
• Helmar Görls,
• Kilian Rolf Anton Schneider,
• Mathias Micheel,
• Michael Pröhl,
• Michael Gottschaldt,
• Benjamin Dietzek and
• Wolfgang Weigand

Beilstein J. Org. Chem. 2017, 13, 2264–2272, doi:10.3762/bjoc.13.223

• –h in yields ranging from 56 to 96% (Table 1). The amount of base required have to be increased from 0.1 to ca. 0.6 equiv due to the formation of HF, which forms n-butylammonium fluoride as a main impurity. Therefore, all complexes were purified by recrystallization from a mixture of acetone and

• hydrolysis to boric acid, hydrogen fluoride and the corresponding curcuminoid in the anionic form (V). The latter finally becomes protonated by one equivalent of HF (VI). If no additional base is present, the hydroxide concentration decreases with ongoing hydrolysis so far, that the reaction effectively

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• the action of fluoride anion at −78 °C. It is worth paying attention that the malonate anion is generated prior the addition of TBAF, because of a high instability of the intermediate nitroso compound NSA2. Using this procedure, bicyclic oxime 13 was prepared in quantitative yield from precursor 12

An efficient synthesis of a C₁₂-higher sugar aminoalditol

• Łukasz Szyszka,
• Anna Osuch-Kwiatkowska,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2017, 13, 2146–2152, doi:10.3762/bjoc.13.213

• ) and traces of secondary amine 13. To a solution of the above crude mixture (43.6 mg) in THF (4 mL) tetrabutylammonium fluoride trihydrate (35 mg) was added and the mixture was stirred overnight at 20 °C. Then it was concentrated and the residue was purified by preparative thin-layer chromatography