Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols

• Katrina Tait,
• Alysia Horvath,
• Nicolas Blanchard and
• William Tam

Beilstein J. Org. Chem. 2017, 13, 2888–2894, doi:10.3762/bjoc.13.281

• A variety of different acid catalysts was screened and the results are summarized in Table 1. In the presence of a Lewis acid catalyst (Table 1, entries 1–3), the reaction did not proceed as seen with FeCl3 (Table 1, entry 1) or produced ring-opened product 26 in low yields (Table 1, entries 2 and 3

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

• and amides have been developed, controlled by the reagents employed. With the Brønsted base KOt-Bu and CBrCl3 as radical initiator, benzo[d]imidazo[2,1-b]thiazoles are synthesized via attack at the α-carbon and keto carbon of the β-ketoester moiety. In contrast, switching to the Lewis acid catalyst

• ][21][22]. Interestingly, by replacing the radical initiator and Brønsted base system with a Lewis acid catalyst, benzo[4,5]thiazolo[3,2-a]pyrimidin-4-ones were formed instead (Scheme 1b). This highlights the versatility of β-ketoesters where the regioselectivity of the reaction is directed by the

• 10 mol % of the Lewis acid at 100 °C using toluene as solvent (Table 2). In(OTf)3 was a better catalyst for this reaction with 95% yield (Table 2, entry 3). Reactions with ZnII and YbIII triflates proceeded with moderate yields while AgI, CuII and CoII were unreactive (Table 2, entries 4–8). Other

Consecutive hydrazino-Ugi-azide reactions: synthesis of acylhydrazines bearing 1,5-disubstituted tetrazoles

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2017, 13, 2596–2602, doi:10.3762/bjoc.13.256

• %) in trifluoroethanol (TFE) at room temperature for 24 h. The presence of catalytic amounts of zinc chloride as Lewis acid in this reaction had already been reported to improve the yields [33]. Indeed, initial studies without the catalyst afforded the desired products 10a in only 28% yield (120 °C, 30

Synthesis of 1,3-cis-disubstituted sterically encumbered imidazolidinone organocatalysts

• Jan Wallbaum and
• Daniel B. Werz

Beilstein J. Org. Chem. 2017, 13, 2577–2583, doi:10.3762/bjoc.13.254

• (OTf)3 in THF. This Lewis acid proved to be the Lewis acid of choice since the reaction proceeds without loss of optical purity [30]. The naphthyl residue was chosen since it revealed a high selectivity in the desired organocatalytic transformation. Table 1 depicts the scope with respect to 1-naphthyl

• -cis-disubstituted diastereomers of up to 52%. Different methyl amides derived from α-amino acids and bulky aromatic carbaldehydes were employed to access the MacMillan-type catalysts. The key to the success is the activation with ytterbium triflate as Lewis acid and the use of dehydrating molecular

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

• condensed with tert-butyl sulfinamide (S)-1 in the presence of Ti(OEt)4 as Lewis acid and water scavenger [31][32][33]. However, the removal of precipitated TiO2 was tedious and time consuming. Therefore, dry CuSO4 as Lewis acid and water scavenger at ambient temperature [34] represented a versatile method

• propargylamines 7 in high yields and satisfactory diastereomeric ratios by cleaving off the TMS protecting group with TBAF. In previous investigations, the choice of solvent and Lewis acid were controversially discussed [13][14][45][46][47][48][49][50][52][53][54][55]. Nonpolar solvents (DCM < THF < Et2O

• > Ti(OiPr)4 [14] > BF3 > MgBr2 > ZnCl2 > ZnEt2) have been recommended for activation [45]. However, the Lewis acid BF3 was shown to give products with inverted configuration of the newly formed chiral center [47]. While several authors obtained increased yields upon addition of AlMe3 [1][45][46

Is the tungsten(IV) complex (NEt₄)₂[WO(mnt)₂] a functional analogue of acetylene hydratase?

• Matthias Schreyer and
• Lukas Hintermann

Beilstein J. Org. Chem. 2017, 13, 2332–2339, doi:10.3762/bjoc.13.230

• . More specifically, gold complex AuCl(PPh3) is not usually considered an alkyne hydration catalyst itself, but turns into a catalytically active gold(I) cation after activation with silver salt or Lewis acid [31][32][33][34]. Under the forcing microwave reaction conditions in aqueous methanol

Synthesis and photophysical properties of novel benzophospholo[3,2-b]indole derivatives

• Mio Matsumura,
• Mizuki Yamada,
• Atsuya Muranaka,
• Misae Kanai,
• Naoki Kakusawa,
• Daisuke Hashizume,
• Masanobu Uchiyama and
• Shuji Yasuike

Beilstein J. Org. Chem. 2017, 13, 2304–2309, doi:10.3762/bjoc.13.226

• -effect transistors (OFETs) and luminescent materials [1][2][3][4][5][6][7][8][9]. The phosphorous atom of trivalent phosphorus compounds has a high chemical reactivity. Therefore, several reactions on the phosphorus atom such as oxidation, alkylation, and coordination to a Lewis acid can produce the

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

• is illustrated by the recent works reporting the reaction of bis(diethylamino)chlorophosphine (95) with the acetal 96 in the presence of a Lewis acid to yield the phosphonodiamide 97. Then the nucleophilic addition of adenine and the hydrolysis of the phosphonodiamide function in phosphonic acid

New bio-nanocomposites based on iron oxides and polysaccharides applied to oxidation and alkylation reactions

• Daily Rodríguez-Padrón,
• Alina M. Balu,
• Antonio A. Romero and
• Rafael Luque

Beilstein J. Org. Chem. 2017, 13, 1982–1993, doi:10.3762/bjoc.13.194

• benzene or other aromatic substrates is well-known to be an important step in the preparation of relevant building blocks in organic synthesis, such as diphenylmethane and substituted diphenylmethanes [50]. Therefore, many studies have been focus on the preparation of novel Lewis acid catalysts, such as

• can be deduced from the intense and well-defined bands observed at 1449 and 1600 cm−1, which can be attributed to Lewis acid centers (Figure 4A). Additionally, in the spectrum of Fe2O3-PS4-MNP, having bands at 1440 and 1618 cm−1, indicates the peculiar Lewis acidity of this material (Figure 4B

• Brønsted acid sites with a more marked Lewis acidity. The Fe2O3-PS4-MNP material presents instead only Lewis acid sites, while the Fe2O3-PS4 does not show appreciable acidity to be quantized (Table 2). Acidity measurements from both methodologies (PY DRIFT, PY and DMPY pulse chromatography titration data

NHC-catalyzed cleavage of vicinal diketones and triketones followed by insertion of enones and ynones

• Ken Takaki,
• Makoto Hino,
• Akira Ohno,
• Kimihiro Komeyama,
• Hiroto Yoshida and
• Hiroshi Fukuoka

Beilstein J. Org. Chem. 2017, 13, 1816–1822, doi:10.3762/bjoc.13.176

• irrespective of the Lewis acid. When a mixture of benzils 1b and 1c (0.5 equiv each) was treated with 2a (1.0 equiv) under similar conditions, the products 4ba and 4ca were formed in 52% and 20% yields, respectively. However, cross products having three different aroyl groups were not detected at all. Thus

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• turned out that scandium clearly outperforms other rare earth cations hereby, which makes it thus difficult to say if this is really a classical phase-transfer-catalysed reaction or rather a Lewis acid catalysed transformation controlled by a chiral counter anion (it is well known that chiral counter

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

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• -aminobenzophenone, 2-nitrobenzyl bromide, among others, which require an additional reduction step [17][18][29][49][50][51]. Ethyl polyphosphate (PPE) and trimethylsilyl polyphosphate (PPSE) are mild irreversible dehydrating agents of the Lewis acid type. They have found application for synthetically useful

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

• the pyranose was observed in any instance. In a 2007 follow-up study, Plusquellec and colleagues optimized a Lewis-acid-directed glycosylation approach in the presence of divalent cations to synthesize galactosyl furanosides using the same thioimidoyl-activating group. The optimized conditions (Table

• diastereoselectivity of the reaction is good, the mechanism unique, and the synthesis of the donor is reasonably easy and inexpensive. However, to date no follow-up study has been published. 3.3 Lewis acid-mediated activation Lewis acid-mediated methods for anomeric activation of protected donors in glycosylation are

• position 2 on the ring or by the anomeric effect when neighboring group participation is not possible [54][55]. Seemingly impossible Lewis acid-mediated processes are then available for the other hydroxy groups on the unprotect donor molecule and some examples are highlighted below. 3.3.1 Access of 1,2-cis

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• significantly upon addition of PtCl2(PhCN)2. Concomitantly, a small amount of uncoordinated PhCN is observed in the 1H NMR spectrum. The coordinated Pt centre, as a Lewis acid, promotes the release of the OH proton from A and its transfer onto one of the alkyne carbon atoms to form intermediate B. The resulting

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• reactor (3 mL) containing MAGSILICA (inducting material) and silica-supported Ti(OiPr)4 (Lewis acid). The final substitution is reported at 85 °C (25 kHz) that gives olanzapine in 83% yield. These individual synthesis steps can be depicted in the form of a block diagram (Figure 3A). Since each synthesis

• and one separation step. In the first step, a Friedel–Crafts acylation of isobutylbenzene (1 equiv) and propionyl chloride (1.17 equiv) in the presence of AlCl3 as Lewis acid was carried out in a tubular reactor. The residence time is one minute, and the temperature is maintained at 87 °C. The outlet

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• investigate other cyclization approaches towards these chroman derivatives. In 2005, Borhan and co-workers described the construction of tetrahydrofuran and tetrahydropyran structures from 1,2,n-triols via an elegant cyclization involving Lewis acid-mediated cyclization of in situ generated cyclic orthoesters

• conditions were maintained for this transformation in order to prevent the nucleophilic attack of H2O leading to the formation of 23. However, the formation of 23 instead of 22 clearly indicates that the in situ generated cyclic orthoester, after getting activated by Lewis acid, did not experience a

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• ]. Next, the latter was converted to 4,6-dibromo-5-hydroxy-1-indanone in the presence of a Lewis acid and then transformed to 5-hydroxy-1-indanone as a result of debromination. Adrenergic receptors are metabotropic receptors located on cell membranes and stimulated by catecholamines, especially adrenaline

• phenylselenyl-substituted cyclopentenone 269 was less effective and gave 1-indanone 265 in 28% yield only (Scheme 75) [102]. Another example of this reaction catalyzed by a Lewis acid has also been reported [104]. The flash vacuum pyrolysis has been applied for aromatization of 271 to afford 1-indanone 272 in

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• of the mono- and bisalkynyl-substituted 6H-1,2-oxazines was additionally demonstrated by Lewis-acid-mediated conversion into highly substituted pyridine derivatives [25] by cycloaddition of in situ generated azapyrylium intermediates [26] and alkynes. Inspired by these previously reported results, we

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

• introduction of the methylseleno moiety was performed by nucleophilic substitution of the α-bromide in 5 with methylselenol obtained by in situ reduction of dimethyl diselenide with NaBH4 [23]. The obtained crude methyl β-selenofucoside was anomerized under Lewis acid catalysis to give the anomeric mixture in

• cleavage and in situ acetylation resulted in the pyranose mixture 9αβ with excellent yield (90%, 9α/9β = 4:1) and prevention of unwanted furanoside side products. The seleno moiety was then introduced as described before and 13αβ (13α/13β = 1:3) was obtained in 78% yield. Further Lewis acid catalyzed

The digital code driven autonomous synthesis of ibuprofen automated in a 3D-printer-based robot

• Philip J. Kitson,
• Stefan Glatzel and
• Leroy Cronin

Beilstein J. Org. Chem. 2016, 12, 2776–2783, doi:10.3762/bjoc.12.276

• (triflic) acid (CF3SO3H) as the Lewis acid catalyst to yield 4-isobutylpropiophenone (2). Once this is complete a solution of di(acetoxy)phenyl iodide (PhI(OAc)2) and trimethyl orthoformate (TMOF) in methanol (MeOH) is added to the reaction mixture in order to induce a 1,2-aryl migration to produce the

Benzothiadiazole oligoene fatty acids: fluorescent dyes with large Stokes shifts

• Lukas J. Patalag and
• Daniel B. Werz

Beilstein J. Org. Chem. 2016, 12, 2739–2747, doi:10.3762/bjoc.12.270

• presence of a Lewis acid and DIBAL at low temperatures. MnO2-mediated oxidation afforded the respective aldehyde that was immediately transformed by Wittig reaction. Iodine-catalyzed cis–trans isomerization yielded the desired fatty acid 7 in 35% over three steps (Scheme 2). The analogue with three

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

• thiols and benzylic alcohols under solvent-free conditions in excellent yields [21]. We already reported on the use of amorphous solid acid catalysts in organic synthesis. These solids are formed by dispersing a small amount of an inorganic oxide with Lewis acid nature onto the surface of silica [22]. In

• loading of alumina on silica and a very low number of surface hydroxy groups gave quantitatively the desired product in 2 hours (Table 1, entry 5). The activity of this solid has to be ascribed to the presence of well dispersed Lewis acid sites on the surface, as put in evidence from the FTIR spectrum of

• adsorbed pyridine where the band due to Lewis acid sites is detectable (1456 cm−1). This excellent performance prompted us to investigate the substrate scope of this reaction in the presence of SiAl 0.6. Figure 1 and Figure 2 report alcohols and thiols used as reagents while Figure 3 lists the products

Selective and eco-friendly procedures for the synthesis of benzimidazole derivatives. The role of the Er(OTf)₃ catalyst in the reaction selectivity

• Natividad Herrera Cano,
• Jorge G. Uranga,
• Mónica Nardi,
• Antonio Procopio,
• Daniel A. Wunderlin and
• Ana N. Santiago

Beilstein J. Org. Chem. 2016, 12, 2410–2419, doi:10.3762/bjoc.12.235

• the aldehyde becomes highly reactive toward the nucleophilic attack of o-phenylenediamine, generating dibenzylidenediamine I. Consequently, the 1,2-disubstituted benzimidazole (b) will be formed through bisimine II, under catalytic action of the Lewis acid Er(OTf)3. Thus, the catalyst acts as an

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

• -dicarbonyl compounds with both cyclic and acyclic Morita–Baylis–Hillman (MBH) alcohols, using Et3B as a Lewis acid promoter, is described herein. A wide range of the corresponding functionalized allylated derivatives have been obtained in good yields and with high selectivity. Keywords: allylic substitution

• -enone (1a) and acyclic ethyl 2-(hydroxymethyl)acrylate (1b), under the action of 1,3-dicarbonyl compounds 2, in the presence of an appropriate palladium catalyst and Et3B as a Lewis acid promoter, into the allylation compounds 3–8 with the formation of only water as a byproduct. These derivatives can be

• ). The addition of a Lewis acid (1 equiv of Et3B) started the reaction by activating the hydroxy group, affording the allylation product 7e in 30% isolated yield (Table 4, entry 3). To further improve the performance of this allylation reaction, we employed 2 equiv of Et3B (Table 4, entry 4). The