Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• . Prerequisite for a regio- and diastereoselective carbometalation. Various strategies leading to the formation of cyclopropanols. General approach to the preparation of cyclopropanol and cyclopropylamine derivatives. Preparation of cyclopropenyl methyl ethers 3a–d. Regio- and diastereoselective carbocupration

• of cyclopropenyl methyl ethers 3a,c. Diastereoselective formation of cyclopropanols. Diastereoselective carbometalation/oxidation of nonfunctionalized cyclopropenes 6. Preparation of diastereoisomerically pure and enantioenriched cyclopropanols and cyclopropylamines. Supporting Information

Synthesis of functionalized diazocines for application as building blocks in photo- and mechanoresponsive materials

• Widukind Moormann,
• Daniel Langbehn and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 727–732, doi:10.3762/bjoc.15.68

• step the hydroxy groups in 8a and 8b were protected as tert-butyl ethers (Scheme 2) to prevent oxidation in the following oxidative C–C coupling [31]. The tert-butyl ether was chosen as the protecting group because it is stable towards the oxidizing conditions of the C–C coupling reactions and the

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• chloride/N,N-dimethylformamide in the presence of a catalytic amount of p-toluenesulfonic acid ended up with only the formation of OPA. Regeneration of phenols from methyl ethers have also been tested by Boovanahalli et al. [26] by using an ionic liquid such as 1-butyl-3-methylimidazolium bromide ([Bmim]Br

Synthesis of 2H-furo[2,3-c]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction

• Vaida Milišiūnaitė,
• Rūta Paulavičiūtė,
• Eglė Arbačiauskienė,
• Vytas Martynaitis,
• Wolfgang Holzer and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2019, 15, 679–684, doi:10.3762/bjoc.15.62

• synthetic methods has been developed for the construction of carbon–heteroatom bonds using these types of catalysts. For example, the gold(I) catalyst [(Ph3PAu)3O]BF4 was applied in the regioselective intramolecular cyclization of alkynols to construct bicyclic ethers [37], while the silver(I) catalyst

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• obtained β-ketoenamides are alkenes with a remarkable assembly of functional groups: they are enamides, enol ethers and α,β-unsaturated carbonyl compounds at the same time. In addition, their methyl ketone subunit is required for some of the subsequent transformations, e.g., the synthesis of pyridin-4-ols

• are not directly accessible [44]. In contrast, products that are formally derived from 3-aryl-substituted alkoxyallenes can smoothly be prepared from the corresponding alkyl propargyl ethers E (Scheme 7). Their deprotonation with n-butyllithium proceeds with a proton shift delivering the intermediate

• enantiopure components. Bis-β-ketoenamides KE44–46 derived from aromatic dicarboxylic acids. Conversion of alkyl propargyl ethers E into aryl-substituted β-ketoenamides KEAr and selected products KE78–80 obtained by this route. Condensation of LANCA-derived β-ketoenamides KE with ammonium salts to give 5

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• , hydrogenolysis of the benzyl ethers under continuous flow (0.3–1 mL/min) and H2 pressure (30–60 bar) using an H-cube apparatus was found to be effective at removing the benzyl ethers, but arduously slow (>48 h) from the limited surface-mediated interactions with the Pd/C cartridge. By comparison, batch

Design, synthesis and spectroscopic properties of crown ether-capped dibenzotetraaza[14]annulenes

• Krzysztof M. Zwoliński and
• Julita Eilmes

Beilstein J. Org. Chem. 2019, 15, 617–622, doi:10.3762/bjoc.15.57

• much better understanding of complex biological systems [1]. Since the serendipitous discovery of crown ethers by Charles Pedersen in 1967 [2], there have been significant advances in the design and synthesis of sophisticated multidentate macrocycles with mixed-donor sites [3] and high selectivity

Selective benzylic C–H monooxygenation mediated by iodine oxides

• Kelsey B. LaMartina,
• Haley K. Kuck,
• Linda S. Oglesbee,
• Asma Al-Odaini and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2019, 15, 602–609, doi:10.3762/bjoc.15.55

• , it shows incompatibility with functional groups such as alkenes, phenols, phenyl ethers, and alcohols, which are readily oxidized. The dibenzylic C–H bonds of fluorene and xanthene were also able to be functionalized. Xanthene (4a) was over-oxidized to the ketone (xanthone, 5a) in 57% yield (Figure 3

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• Scheme 1 occur smoothly with formaldimines 3 derived from aliphatic amines, but in the case of primary aromatic amines harsher reaction conditions are required [6]. To date, no synthesis of 1-alkoxyimidazole N-oxides derived from alkoxyamines (‘hydroxyamine ethers’) has been reported. An alternative

LCST phase behavior of benzo-21-crown-7 with different alkyl chains

• Yan Deng,
• Xing Li,
• Qiao Zhang,
• Zheng Luo,
• Chengyou Han and
• Shengyi Dong

Beilstein J. Org. Chem. 2019, 15, 437–444, doi:10.3762/bjoc.15.38

• .15.38 Abstract The introduction of hydrophobic units into crown ethers can dramatically decrease the critical transition temperature of LCST and realize macroscopic phase separation at low to moderate temperature and concentration. Minor modifications in the chemical structure of crown ethers (benzo-21

• -crown-7, B21C7s) can effectively control the thermo-responsive properties. Keywords: crown ethers; hydrophobic units; lower critical solution temperature; LCST; thermo-responsiveness; supramolecular chemistry; Introduction The introduction of stimuli-responsiveness into artificial materials is vital

• (>50 °C) are necessary to realize LCST phase separation, which significantly restricts an application in functional materials. In order to achieve LCST behavior of crown ethers at moderate concentrations and temperatures, two methods would be applied: combining multiple B21C7 units into a single

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

• (Scheme 1, reaction 3) [23][26][27][28][29][30][31][32][33]. Thus, methylenecyclopropanes have been prepared by diastereoselective addition of Grignard reagents to cyclopropenylmethyl ethers, possessing a hydroxymethyl directing substituent at C3, in the absence or in the presence of a catalyst (copper or

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• ''-hexamethylphosphorotriamide) as the additive in DMSO. With a similar oxidative radical ring-opening and cyclization strategy, our group developed a novel method for ring-opening and cyclization of MCPs 1 with ethers 40 afforded 2-substituted 3,4-dihydronaphthalenes 41 in moderate to excellent yields (Scheme 11) [68]. This

• of MCPs with AgSCF3. oxidative radical ring-opening and cyclization of MCPs with α-C(sp3)-–H of ethers. Oxidative radical ring-opening and cyclization of MCPs with aldehydes. Cu(I) or Fe(II)-catalyzed oxidative radical trifluoromethylation/ring-opening/cyclization of MCPs derivatives (acrylamide

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

• separation the hydroxy groups in (2R,3R)-50 were protected as silyl ethers to allow oxidation at C5 to produce pyrrolidine-2-one (4R,5R)-47 (Scheme 12) which was later transformed into (2S,3R)-34 as already shown (Scheme 11) [61]. From L-malic acid (S)-Acetoxypyrrolidin-2,5-dione (51), readily available from

• -hydroxyglutamate [(2S,4R)-81] (Scheme 20) [82]. To synthesize (2S,4S)-81 the inversion of configuration at C4 executed by Mitsunobu reaction preceded oxidation at C5 and the ring opening [82]. O-Benzyl ethers of (2S,4R)-3 and (2S,4S)-3 were prepared by the same methodology [50]. Another approach to the

First synthesis of cryptands with sucrose scaffold

• Patrycja Sokołowska,
• Michał Kowalski and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2019, 15, 210–217, doi:10.3762/bjoc.15.20

• two carbon atoms at the C-1’ position as well as at other terminal positions. Thus, all three hydroxy groups were protected as allyl ethers which were subsequently converted into -CH2CH2OH units (Scheme 3). Activation of the free OH groups in 18 as mesylates 19 and subsequent reaction with tripodal

A simple and effective preparation of quercetin pentamethyl ether from quercetin

• Jin Tatsuzaki,
• Tomohiko Ohwada,
• Yuko Otani,
• Reiko Inagi and
• Tsutomu Ishikawa

Beilstein J. Org. Chem. 2018, 14, 3112–3121, doi:10.3762/bjoc.14.291

• limited amount of MeI. On the other hand, Shi et al. [34] obtained a mixture of 7,4'-dimethyl and 3,7,4'-trimethyl ethers 3 when 2 was treated with 3.5 equiv of MeI and a mixture of 3,7,4'-trimethyl 3, 3,7,3',4'-tetramethyl 4 and pentamethyl ethers 1 with 5 equiv of MeI. The latter three-component mixture

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• enlargement via selective cyclopropane ring opening [46][47][48][49]. Consequently, the synthesis started from the previously described bicyclic silyl enol ethers 1α/β (Scheme 1) [50][51]. The two anomers of 1 were individually transformed into the trimethylsilyl (TMS)-protected sugars 2α/β by adapting and

• that the type of silyl enol ether drastically influenced the yield of the corresponding siloxydifluorocyclopropane. Whereas the TMS enol ethers were not suitable for the reaction due to instability of the silyl group, the tert-butyldimethylsilyl (TBDMS) enol ethers were poorly reactive most likely due

• duplexes and torsion angles of c) 6’F-bc4,3-DNA/DNA, and d) 6’F-bc4,3-DNA/RNA duplexes extracted from a 100 ns molecular dynamics trajectory. Synthesis of the gem-difluorinated glycal 4 from the silyl enol ethers 1α/β. Reagents and conditions: a) BSA, DCM, rt, 17 h, 86%; b) BSA, DCM, rt, 18 h, 88%; c

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• the past few years. Starting materials are allyl ethers of salicylic aldehydes or ketones 5 and the stable ylide ethyl (triphosphoranylidene)acetate (6), which upon microwave irradiation undergo a tandem Claisen rearrangement/Wittig olefination/cyclization sequence. This sequence was pioneered by the

• resulted in virtually identical overall yields of coumarins 8 and did therefore not offer any advantage (Table 1). For the synthesis of furanocoumarins 3 and their ring-expanded oxepino analogues 11 the 8-allylcoumarins 8 were first O-allylated. The resulting allyl ethers 9 underwent ring-closing

• catalyst A in dichloromethane at ambient temperature, higher dilution and after prolonged reaction time. For the synthesis of furanocoumarins 3 the allyl ethers 9 were first subjected to a Ru hydride-catalyzed double bond isomerization [55][56] to furnish enol ethers 10 as inseparable mixtures of

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

• vinyl ethers as key step of reaction sequences developed. Keywords: 3-amino glycals; diastereoselective additions to aldehydes; pluramycins; ring-closing metathesis; vinyl ethers; Introduction Several classes of medicinally useful molecules with antibiotic and anticancer activity contain in their

• corresponding alkynyl alcohols requires the handling of toxic tin reagents [8][9]. During these last years, ring-closing metathesis (RCM) of vinyl ethers have proved to be an efficient method for the preparation of chiral glycal scaffolds [11][12][13][14][15][16][17][18] as demonstrated in some total syntheses

• of marine polycyclic ethers [19][20][21]. However, to the best of our knowledge, this methodology was never evaluated for the synthesis of this kind of nitrogen-containing substrates. Taking into account our interest about the development of new synthetic approaches to pluramycins [22][23], we

Generation of 1,2-oxathiolium ions from (arysulfonyl)- and (arylsulfinyl)allenes in Brønsted acids. NMR and DFT study of these cations and their reactions

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov,
• Olesya V. Khoroshilova and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2018, 14, 2897–2906, doi:10.3762/bjoc.14.268

• ethers E from the corresponding species B. The ethers E are hydrolyzed to compounds 4. Reactions of allenes 2 with other nucleophiles (methanol, benzene, acetonitrile) led to the formation of complex mixtures of reaction products. It must be noted that no reaction proceeded in HFIP without TfOH. The

Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

• Rebeka Jójárt,
• Szabolcs Pécsy,
• György Keglevich,
• Mihály Szécsi,
• Réka Rigó,
• Csilla Özvegy-Laczka,
• Gábor Kecskeméti and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

• applied for their 2-substituted counterparts [22]. Concerning the nature of the C-3 substituent, methyl ethers 1 and 4 were overally the most reactive. Compounds bearing a 3-OH group 2 and 5 reacted slower due to the more activated nature of the phenolic ring A. It can be stated that the reaction time and

• temperature greatly depends on the nature of the C-3 substituent and on the position of the bromine, not on the size and polarity of the P-coupling agent. In the case of 3-benzyl ethers 3 and 6, solvent change from acetonitrile to toluene was required. This might be attributed to the decreased polarity of the

• 3-benzyloxy compounds 3 and 6. We have recently disclosed our finding that toluene is an appropriate solvent for C(sp2)–N coupling reactions of 2- or 4-bromo-13α-estrone 3-benzyl ethers [30]. The structures of the newly-synthesized derivatives 8–13 were established through 1H, 13C, 31P, COSY, HSQC

Enhanced single-isomer separation and pseudoenantiomer resolution of new primary rim heterobifunctionalized α-cyclodextrin derivatives

• Iveta Tichá,
• Gábor Benkovics,
• Milo Malanga and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2018, 14, 2829–2837, doi:10.3762/bjoc.14.261

• . investigated the regioselective synthesis of tris(4-tert-butylphenyl)methyl ethers on the primary rim of α-CD which resulted in predominant AD species [20]. Trityl groups for regioselective bi- and trifunctionalization of α-CD were also investigated [21]. Thus, the use of either a direct single-step or

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• ][20][21][22], oligomers [23][24], polycyclic ethers [25], heterocycles [26], nonbenzenoid aromatics [27], and spirocycles [28][29]) by decreasing the number of steps. Different metathesis catalysts used in this study are shown in Figure 1. Review Annulation Grela and co-workers [30] demonstrated a

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• cyclization, since there is precedence of accessing medium-sized ring ethyl vinyl ethers when employing TiCl3/LiAlH4/NEt3 in DME instead of TiCl4/Zn/pyridine [23]. Direct reduction of ester 14 to the aldehyde proved to be surprisingly difficult with either DIBAL-H or LiAlH4, when the alkynyl side chain was in

One-pot synthesis of epoxides from benzyl alcohols and aldehydes

• Edwin Alfonzo,
• Jesse W. L. Mendoza and
• Aaron B. Beeler

Beilstein J. Org. Chem. 2018, 14, 2308–2312, doi:10.3762/bjoc.14.205

• into carbonyls [8][9][10][11][12][13][14][15][16][17], and application to cascade or domino reactions [18][19]. More recently, our group has used benzyl epoxides for the photoredox generation of carbonyl ylides which are leveraged in the synthesis of cyclic ethers [20]. This work has led us to search

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• the [3]rotaxane 23 which bears two cofacially oriented TTF crown ethers on a divalent ammonium axle. The distance between the wheels is convenient for TTF-dimer interactions. In the non-switched neutral state of both TTFs, the wheels adopt a syn co-conformation caused by weak non-covalent interactions