Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• transformations include the carboxylation of a (trimethylsilylmethyl)cyclopropene in the presence of a fluoride promoter [22], and also the addition of electrophiles to (lithiomethyl)cyclopropenes generated by lithiation of the corresponding methylcyclopropenylsulfone [23] or -sulfoxide [24]. More recently, the

• conditions prior to the Ireland–Claisen rearrangement which eventually produced alkylidenecyclopropane 62 (56%) with high diastereoselectivity. The trimethylsilyl substituent at C2 could then be easily removed by treatment of 62 with tetrabutylammonium fluoride under buffered conditions (AcOH, THF, 0 °C) to

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• methods they are available from 3- or 4-hydroxyglutamic acids by direct hydroxy to fluoride displacement [91][123][124]. Deuterium- [72] and tritium-labelled [125] glutamic acids have also been prepared from 4-hydroxyglutamic acids via 4-mesyloxy derivatives. And finally reduction of the ethoxycarbonyl

Thermophilic phosphoribosyltransferases Thermus thermophilus HB27 in nucleotide synthesis

• Ilja V. Fateev,
• Ekaterina V. Sinitsina,
• Aiguzel U. Bikanasova,
• Maria A. Kostromina,
• Elena S. Tuzova,
• Larisa V. Esipova,
• Tatiana I. Muravyova,
• Alexei L. Kayushin,
• Irina D. Konstantinova and
• Roman S. Esipov

Beilstein J. Org. Chem. 2018, 14, 3098–3105, doi:10.3762/bjoc.14.289

• : 4 h grow at 37 °С after supplementing with 0.4 mM IPTG). Isolation and purification of TthHPRT: A cell pellet was resuspended in 50 mM Tris-HCl, 200 mМ NaCl, and 1 mМ phenylmethylsulfonyl fluoride (PMSF) рН 8.0 (1:10 w/v). The cells were disrupted by sonication for 30 min at 20 kHz at +4 °С. The

Nucleofugal behavior of a β-shielded α-cyanovinyl carbanion

• Rudolf Knorr and
• Barbara Schmidt

Beilstein J. Org. Chem. 2018, 14, 3018–3024, doi:10.3762/bjoc.14.281

• fission may also be used to generate different metal derivatives of the nucleofugal anions as equilibrium components. Fluoride-catalyzed, metal-free desilylation admitted carbonyl addition but blocked the retro-addition. Keywords: alkoxide fission; desilylation; fragmentation; retro-addition; reversible

• compounds: Generated through desilylation of 24 (Scheme 6) by tetrabutylammonium fluoride (Bu4N+F−; ≤0.05 equiv), the ion pair 25 was trapped by pivalaldehyde (4) with formation of 7 along with a comparable amount of the alkene 1. However, the primary alkoxide product, as formed by 25 and 4, was supposedly

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

• yield for two steps. The silyl group of compound 22 was cleaved using tetrabutylammonium fluoride (TBAF) in THF to form alcohol 23 which was used directly in the next step [48]. At this stage, we envisioned that 23 could be also a key intermediate to access the ristosamine derivative by reversing the

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• compounds 6a and 6b by condensation with monoethyl malonate and monobenzyl malonate, in the presence of DCC and DMAP, in 80% and 83% yield, respectively. Starting from intermediates 6a and 6b, treatment with a tetrabutylammonium fluoride solution in diethyl ether at room temperature induced the cyclisation

Stereoselective total synthesis and structural revision of the diacetylenic diol natural products strongylodiols H and I

• Pamarthi Gangadhar,
• Sayini Ramakrishna,
• Ponneri Venkateswarlu and
• Pabbaraja Srihari

Beilstein J. Org. Chem. 2018, 14, 2313–2320, doi:10.3762/bjoc.14.206

• to Wittig olefination reaction with triphenylphosphonium salt of n-nonyl bromide 15 in presence of n-BuLi to produce the corresponding Z-olefin 28 exclusively in 83% yield. Di-desilylation of compound 28 was easily achieved with n-tetrabutylammonium fluoride to furnish the target molecule

• , prepared earlier in our group [24], to furnish the corresponding Z-olefin 29 exclusively in 81% yield. Exposure of 29 to n-tetrabutylammonium fluoride provided the natural product (S)-strongylodiol I (10a) in 82% yield (Scheme 6). The analytical data and specific rotation of the synthetic product were

Cobalt bis(acetylacetonate)–tert-butyl hydroperoxide–triethylsilane: a general reagent combination for the Markovnikov-selective hydrofunctionalization of alkenes by hydrogen atom transfer

• Xiaoshen Ma and
• Seth B. Herzon

Beilstein J. Org. Chem. 2018, 14, 2259–2265, doi:10.3762/bjoc.14.201

• ®, diethylaminosulfur trifluoride (DAST), or tosyl fluoride (see Supporting Information File 1, Table S1, entries 2–4), N-fluorobenzenesulfonimide (NFSI) provided the desired hydrofluorination product 4b in 36% yield (Table 1, entry 2). Carreira and co-workers reported the first hydrochlorination reaction via a cobalt

Dynamic light scattering studies of the effects of salts on the diffusivity of cationic and anionic cavitands

• Anthony Wishard and
• Bruce C. Gibb

Beilstein J. Org. Chem. 2018, 14, 2212–2219, doi:10.3762/bjoc.14.195

• fluoride and chloride did not induce aggregation of positively charged host 2, this cavitand exhibited marked aggregation as a function of bromide and iodide concentration. Specifically, bromide induced small but significant amounts of dimerization, whilst iodide induced extreme aggregation. Moreover, in

• titration with various halide salts. The fifteen salts studied were a matrix of the alkali metal cations Li+, Na+, K+, and Cs+ in combination with the halides F− through I−, the one omission being poorly soluble lithium fluoride (maximum solubility = 0.134 g mL−1). Unsurprisingly, given the pKa values of

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• with mCPBA, reacted with HF to provide the corresponding in situ-generated difluoroiodoarenes. An aziridinium intermediate II, which underwent nucleophilic attack by fluoride on the multisubstituted carbon to afford the endo-cyclized products 29, was proposed in Nevado’s reaction [29]. Employing the

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