Organocatalytic asymmetric selenofunctionalization of tryptamine for the synthesis of hexahydropyrrolo[2,3-b]indole derivatives

• Qiang Wei,
• Ya-Yi Wang,
• Yu-Liu Du and
• Liu-Zhu Gong

Beilstein J. Org. Chem. 2013, 9, 1559–1564, doi:10.3762/bjoc.9.177

• ]. These leading findings indicate that either Lewis base or Brønsted acid shows catalytic activity for the selenofunctionalization reaction. Since chiral phosphoric acids have been shown to be Brønsted acid/Lewis base bifunctional organocatalysts [29][30][31][32][33], we ask whether the chiral BINOL-based

Re₂O₇-catalyzed reaction of hemiacetals and aldehydes with O-, S-, and C-nucleophiles

• Wantanee Sittiwong,
• Michael W. Richardson,
• Charles E. Schiaffo,
• Thomas J. Fisher and
• Patrick H. Dussault

Beilstein J. Org. Chem. 2013, 9, 1526–1532, doi:10.3762/bjoc.9.174

• a Brønsted acid. Keywords: allylation; hemiacetal; O,O-acetal; O,S-thioacetal; peroxyacetal; Re2O7; S,S-acetal; Introduction The synthetically important conversions of hemiacetals to acetals, thioacetals, or homoallyl ethers are typically achieved through activation of the substrate with a strong

• ], we needed to prepare a number of 3-alkoxy-1,2-dioxolanes. Brønsted acid-promoted etherification of hemiacetals (1,2-dioxolan-3-ols) required harsh conditions and proceeded in good yields only for unhindered alcohols [18]. We were curious whether Re2O7, a catalyst known to activate alcohols via a

• ions [21][22]. As illustrated in Table 5, tetrahydrofuranol and tetrahydropyranol both undergo condensation with a simple thiol in the presence of Re2O7 to provide the monothioacetal in good yield; only traces of the S,S-dithioacetal were observed. The same reaction, when catalyzed by a Brønsted acid

Thiourea-catalyzed Diels–Alder reaction of a naphthoquinone monoketal dienophile

• Carsten S. Kramer and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 1414–1418, doi:10.3762/bjoc.9.158

• of one equivalent of Brønsted acid 8 had no effect (Table 2, entry 4), the addition of TADDOL (9) improved the reaction speed (Table 2, entry 5). By the use of Schreiner's catalyst 10 [7], the highest conversion speed was observed (Table 2, entry 6). After this finding, Jacobsen's thioureas 11 [13

Mild and efficient cyanuric chloride catalyzed Pictet–Spengler reaction

• Ashish Sharma,
• Mrityunjay Singh,
• Nitya Nand Rai and
• Devesh Sawant

Beilstein J. Org. Chem. 2013, 9, 1235–1242, doi:10.3762/bjoc.9.140

• -dimethylaminobenzaldehyde. These aldehydes failed to produce the cyclized product in desired yield under conventional Brønsted acid catalysis and often produced the oxidized products under harsher reaction conditions. TCT under an inert atmosphere allowed for a clean reaction with a broad substrate scope and application

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118

• with various solid-phase Brønsted acid catalysts in supercritical carbon dioxide (Figure 7), Poliakoff and co-workers studied the effect of varying the concentration of the organic reagent in the liquid CO2 solvent [46]. The high pressures required (100–400 bar) stipulated the use of a sealed reaction

Gold-catalyzed oxycyclization of allenic carbamates: expeditious synthesis of 1,3-oxazin-2-ones

• Benito Alcaide,
• Pedro Almendros,
• M. Teresa Quirós and
• Israel Fernández

Beilstein J. Org. Chem. 2013, 9, 818–826, doi:10.3762/bjoc.9.93

• (Scheme 2). Adding a catalytic amount of Brønsted acid (PTSA) into the reaction system did slightly improve the yield of 3a. Solvent screening demonstrated that dichloromethane was the best choice in the reaction. As revealed in Scheme 2, a variety of allenic carbamates 2 were also suitable for such

Reductions of aldehydes and ketones with a readily available N-heterocyclic carbene borane and acetic acid

• Vladimir Lamm,
• Xiangcheng Pan,
• Tsuyoshi Taniguchi and
• Dennis P. Curran

Beilstein J. Org. Chem. 2013, 9, 675–680, doi:10.3762/bjoc.9.76

• acid functions as a Brønsted acid to activate the carbonyl group towards attachment by 1. This is different from NaBH4, which reacts quickly with acetic acid to liberate H2 and form a modified reducing agent, NaBH(OAc)3 [21][22]. Even with heating, the direct acid/base reaction of 2 and acetic acid was

Asymmetric Brønsted acid-catalyzed aza-Diels–Alder reaction of cyclic C-acylimines with cyclopentadiene

• Magnus Rueping and
• Sadiya Raja

Beilstein J. Org. Chem. 2012, 8, 1819–1824, doi:10.3762/bjoc.8.208

• Magnus Rueping Sadiya Raja Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany 10.3762/bjoc.8.208 Abstract A new chiral Brønsted acid-catalyzed aza-Diels–Alder reaction of cyclic C-acylimines with cyclopentadiene has been developed. The reaction provides

• ][29][30][31][32]. To the best of our knowledge the enantioselective Brønsted acid catalyzed aza-Diels–Alder reaction of imines with less-electron-rich dienes has not been reported. Thus, we decided to examine the unprecedented Brønsted acid catalyzed aza-Diels–Alder reaction of cyclic C-acylimines

• when the reaction was performed in toluene at −60 °C in the presence of catalyst 4a (Table 1, entry 1). A slight increase in enantioselectivity was observed when the reaction was conducted at −78 °C (Table 1, entry 2). Subsequently, different catalysts were applied in the Brønsted acid catalyzed hetero

Synthesis and ring openings of cinnamate-derived N-unfunctionalised aziridines

• Alan Armstrong and
• Alexandra Ferguson

Beilstein J. Org. Chem. 2012, 8, 1747–1752, doi:10.3762/bjoc.8.199

• , aziridine 1a was found to undergo ring opening under Lewis and Brønsted acid catalysed conditions with a range of nucleophiles to provide amino-acid derivatives in good to excellent yield (Figure 2). The ring openings proved to be completely regioselective for the C3-benzylic position of aziridine 1a. This

Organocatalytic cascade aza-Michael/hemiacetal reaction between disubstituted hydrazines and α,β-unsaturated aldehydes: Highly diastereo- and enantioselective synthesis of pyrazolidine derivatives

• Zhi-Cong Geng,
• Jian Chen,
• Ning Li,
• Xiao-Fei Huang,
• Yong Zhang,
• Ya-Wen Zhang and
• Xing-Wang Wang

Beilstein J. Org. Chem. 2012, 8, 1710–1720, doi:10.3762/bjoc.8.195

• -pyrazolines starting from α,β-unsaturated ketones and phenylhydrazine or N-tert-butyloxycarbonylhydrazine in the presence of a chiral Brønsted acid or a phase-transfer catalyst [70][71]. Compared with monosubstituted hydrazines in organocatalytic asymmetric synthesis, disubstituted hydrazines were also

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• . Akiyama and co-workers screened different Brønsted acid catalysts for their reaction, with PTSA emerging as the most effective catalyst [11]. Employing an optimized set of conditions, the reaction was conducted with different amines, and good to excellent yields (40–92%) were obtained (Scheme 2). A

• plausible mechanism for these reactions is depicted in Scheme 3. After initial imine formation, a Brønsted acid promoted 1,5-hydride shift occurs yielding an imino-amine intermediate. Cyclization of the newly formed amine affords the desired aminal product. In 2011, Seidel and co-workers reported an indole

• -annulation cascade reaction with N,N-(dialkylamino)benzaldehydes, a process in which a 1,5-hydride shift occurs followed by larger ring formation [16]. After the evaluation of different Brønsted acid catalysts, diphenylphosphate (20 mol %) was identified as a suitable catalyst for the reaction. Toluene again

Organocatalysis

• Benjamin List

Beilstein J. Org. Chem. 2012, 8, 1358–1359, doi:10.3762/bjoc.8.156

• -molecular-weight organic compounds, in which a metal is not part of the active principle. Organocatalysts donate or remove electrons or protons as their activation mode, hence defining four distinct subareas: Lewis base and Lewis acid catalysis on the one hand, and Brønsted base and Brønsted acid catalysis

Asymmetric organocatalytic decarboxylative Mannich reaction using β-keto acids: A new protocol for the synthesis of chiral β-amino ketones

• Chunhui Jiang,
• Fangrui Zhong and
• Yixin Lu

Beilstein J. Org. Chem. 2012, 8, 1279–1283, doi:10.3762/bjoc.8.144

• great practical value. Indeed, direct approaches such as asymmetric enamine catalysis [14][15][16][17] and Brønsted acid catalysis [18] have been reported, through the activation of ketones or aryl imines [19]. However, substrates for the enamine activation are limited to only acetone and cyclic alkyl

• ketones. Application of aryl methyl ketones in the asymmetric Mannich reaction by enamine catalysis remains elusive. On the other hand, the only chiral Brønsted acid catalytic system based on BINOL-phosphates was reported by Rueping et al. Unfortunately, the yields of the reported reactions were

N-Heterocyclic carbene/Brønsted acid cooperative catalysis as a powerful tool in organic synthesis

• Rob De Vreese and
• Matthias D’hooghe

Beilstein J. Org. Chem. 2012, 8, 398–402, doi:10.3762/bjoc.8.43

• functionalized pyrrolidin-2-ones as valuable scaffolds in heterocyclic chemistry. This Commentary will briefly highlight the concept of N-heterocyclic carbene/Brønsted acid cooperative catalysis as a new and powerful methodology in organic chemistry. Keywords: Brønsted acids; cooperative catalysis; γ-lactams; N

• that the combination of a pentafluorophenyl triazolium carbene 5 and a Brønsted acid with low pKa value may provide new opportunities for the design of reaction pathways in which the carbene and the acid play different roles. The idea to use a very weak base in NHC catalysis has also been described by

• reaction was performed by using a rather strong base (KHMDS, Et3N) to deprotonate the carbene precursor, which led to the formation of a weak Brønsted acid with low yields and poor selectivities as a consequence. The use of weaker bases (carboxylates) resulted in stronger conjugate acids capable of

Continuous-flow catalytic asymmetric hydrogenations: Reaction optimization using FTIR inline analysis

• Magnus Rueping,
• Teerawut Bootwicha and
• Erli Sugiono

Beilstein J. Org. Chem. 2012, 8, 300–307, doi:10.3762/bjoc.8.32

• : asymmetric reduction; binolphosphoric acid; Brønsted acid; Hantzsch dihydropyridine; IR spectroscopy; real-time analysis; Introduction In recent years, a growing interest in microreactor technology has been seen in the scientific community and the development of microfabricated reaction systems is actively

• Hantzsch dihydropyridine 2a as hydrogen source and a catalytic amount of chiral Brønsted acid 1a (Scheme 2) [102]. Initial experiments were carried out at 0.1 mL min−1 flow rate in a commercial glass microreactor, which was attached to the ReactIR flow cell for in situ reaction monitoring. In order to

• , the product was isolated in 87% and 98% yields, respectively (Table 1). Having found the optimum reaction conditions, we next investigated the scope of the Brønsted acid catalyzed reduction of 3-aryl-substituted benzoxazines 3 (Table 2). In general, 3-aryl benzoxazines 3 bearing either electron

A concise synthesis of 3-(1-alkenyl)isoindolin-1-ones and 5-(1-alkenyl)pyrrol-2-ones by the intermolecular coupling reactions of N-acyliminium ions with unactivated olefins

• Nianhong Lu,
• Lihong Wang,
• Zhanshan Li and
• Wei Zhang

Beilstein J. Org. Chem. 2012, 8, 192–200, doi:10.3762/bjoc.8.21

• terminal alkynes to give the doubly alkyl-substituted acetylenes [1][2][3]; the Brønsted acid and Lewis acid catalyzed coupling of alcohols with indoles to give the 3-alkyl-substituted indoles [4][5][6]; and the Brønsted acid and Lewis acid-catalyzed coupling of alcohols with 1,3-dicarbonyls to give the 2

• ]. We have long been interested in the reactions of N-acyliminium ions produced easily by the Brønsted acid and Lewis acid catalyzed dehydroxylation of α-hydroxyamides [12][13][14]. The high electrophilicity of these species is very suitable for electrophilic addition to carbon–carbon multiple bonds

Efficient, highly diastereoselective MS 4 Å-promoted one-pot, three-component synthesis of 2,6-disubstituted-4-tosyloxytetrahydropyrans via Prins cyclization

• Naseem Ahmed and
• Naveen Kumar Konduru

Beilstein J. Org. Chem. 2012, 8, 177–185, doi:10.3762/bjoc.8.19

• , economical and stereoselective synthesis. To introduce the desired substituents and stereochemistry at the 2, 4 and 6-positions of the tetrahydropyran ring, Prins cyclization has been considered to be the best approach. The reaction can be conducted either with Brønsted acid catalysts – namely TFA [12], AcOH

• and unsymmetrical tetrahydropyrans can be synthesized. p-Toluenesulfonic acid (PTSA) is reported as a versatile Brønsted acid catalyst in various organic transformations [32][33][34]. Previously, PTSA has been used as a catalyst in Prins cyclizations but the product yields were low even under extended

Efficient oxidation of oleanolic acid derivatives using magnesium bis(monoperoxyphthalate) hexahydrate (MMPP): A convenient 2-step procedure towards 12-oxo-28-carboxylic acid derivatives

• Jorge A. R. Salvador,
• Vânia M. Moreira,
• Rui M. A. Pinto,
• Ana S. Leal and
• José A. Paixão

Beilstein J. Org. Chem. 2012, 8, 164–169, doi:10.3762/bjoc.8.17

• -carboxylic acid 11 was obtained, in 85% yield, after the typical work-up procedure [18]. The formation of compound 11 from the 12α-hydroxy-28,13β-olide 2 is likely to occur due to the in situ generation of a Brønsted acid species from bismuth(III) triflate, which promotes ring opening of the 28,13β-olide

Development of the titanium–TADDOLate-catalyzed asymmetric fluorination of β-ketoesters

• Lukas Hintermann,
• Mauro Perseghini and
• Antonio Togni

Beilstein J. Org. Chem. 2011, 7, 1421–1435, doi:10.3762/bjoc.7.166

• , entry 2), whereas the corresponding zirconium complex was inactive (Table 1, entry 3). Both the Brønsted acid HBF4 and the Lewis acid BF3 accelerated the reaction. Substrate 2 with a higher tendency towards enolization (Figure 2) gave higher conversions, but a similar trend. Interestingly, the

Gold(I)-catalyzed synthesis of γ-vinylbutyrolactones by intramolecular oxaallylic alkylation with alcohols

• Michel Chiarucci,
• Mirko Locritani,
• Gianpiero Cera and
• Marco Bandini

Beilstein J. Org. Chem. 2011, 7, 1198–1204, doi:10.3762/bjoc.7.139

• ]. Subsequently, the direct nucleophilic attack by the carboxylate unit would lead to an oxonium intermediate III [50][51] that, after dealkylation, resulted in the final lactone 2. Control experiments have been performed to indentify the presence of a Brønsted acid cocatalysis in the ring-closing procedure (see

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• ]. As pointed out by the researchers, the reactions proceeded with the initial formation of trans/cis mixtures of 2-alkyl-1-isopropyl-2-phenyl-1,2-dihydronaphthalene cations, which were converted into the desired cis-fused cycloadducts through the combined action of a gold catalyst and a Brønsted acid

• the Brønsted acid is both a chiral catalyst for the asymmetric cycloaddition and assists to facilitate the gold complex catalyzed hydroamination. Muratore et al. have reported an interesting example of C–N bond formation for the construction of chiral nitrogen-containing fused heterocycles 400 [191

Gold-catalyzed propargylic substitutions: Scope and synthetic developments

• Olivier Debleds,
• Eric Gayon,
• Emmanuel Vrancken and
• Jean-Marc Campagne

Beilstein J. Org. Chem. 2011, 7, 866–877, doi:10.3762/bjoc.7.99

• Friedel–Crafts type reactions with benzylic and propargylic alcohols. Shortly after, Sanz and Zhan discovered, that these reactions could also be carried out under Brønsted acid and FeCl3 catalysis, respectively [26][27][28][29]. Later, the use of copper, indium, bismuth, scandium, ytterbium

When cyclopropenes meet gold catalysts

• Frédéric Miege,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2011, 7, 717–734, doi:10.3762/bjoc.7.82

• activators [31]. Since AgOTf and BF3·OEt2 led to the same naphthalene product 21, the authors suspected that traces of the Brønsted acid (HOTf) present in the silver salt may be the actual catalyst and may also modify the regioselectivity observed in the gold-catalyzed reaction. Thus, several basic additives

• in the presence of electrophilic transition metal complexes. Shi et al. initially suggested that the formation of 22 preferentially occurs with a rather bulky electrophile such as Cu(OTf)2 to avoid repulsion with the aryl group at C2. Conversely, a Brønsted acid (generated by reaction of BF3·OEt2

Gold-catalyzed heterocyclizations in alkynyl- and allenyl-β-lactams

• Benito Alcaide and
• Pedro Almendros

Beilstein J. Org. Chem. 2011, 7, 622–630, doi:10.3762/bjoc.7.73

• . Deauration and proton transfer leads to adduct 27 with concomitant regeneration of the Au(III) species (Scheme 15). Regiocontrolled gold/Brønsted acid co-catalyzed direct bis-heterocyclization of alkynyl-β-lactams allows the efficient synthesis of optically pure tricyclic bridged acetals bearing a 2

• . Possible catalytic cycle for the gold-catalyzed cyclization of MOM protected alkynol derivatives. Gold/Brønsted acid co-catalyzed formation of bridged β-lactam acetals from 2-azetidinone-tethered alkynyl dioxolanes. Acknowledgements Support for this work by the MICINN (Project CTQ2009-09318), Comunidad

Construction of cyclic enones via gold-catalyzed oxygen transfer reactions

• Leping Liu,
• Bo Xu and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2011, 7, 606–614, doi:10.3762/bjoc.7.71

• Leping Liu Bo Xu Gerald B. Hammond Department of Chemistry, University of Louisville, 2320 South Brook Street, Louisville, KY 40292, USA 10.3762/bjoc.7.71 Abstract During the last decade, gold-catalyzed reactions have become a tour de force in organic synthesis. Recently, the gold-, Brønsted acid

• carbon–carbon double bond and the simultaneous installation of a carbonyl group. In this regard, several Lewis or Brønsted acid-catalyzed intermolecular or intramolecular alkyne–carbonyl metatheses have been extensively studied (Scheme 1) [19][20][21][22][23][24][25][26][27]. During the early years of

• intermediate, which then generates an oxetenium intermediate. After several electron transfer steps, the cyclic enone product is formed. A similar [2 + 2] pathway has also been invoked for the Brønsted acid- or Lewis acid-mediated intramolecular and intermolecular alkyne–aldehyde metatheses. If terminal