New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• reactive complex with the LUMO. These results are further backed up by control experiments demonstrating that catalytic quantities of hydroiodic acid were less effective in promoting this reaction than molecular iodine, and hidden Brønsted acid catalysis is unlikely to be operational in these studies. In

cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

• Dimpee Gogoi,
• Runjun Devi,
• Pallab Pahari,
• Bipul Sarma and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2016, 12, 2816–2822, doi:10.3762/bjoc.12.280

• cyclization make this methodology highly practical for the use in organic synthesis. Recently, we have reported the synthesis of diverse trans-4-arylchroman-3-ols via Brønsted acid catalysed regio- and stereoselective IFCEA cyclization of 2-(aryloxymethyl)-3-aryloxiranes [22][23]. The use of IFCEA cyclization

• Friedel–Crafts cyclization (Scheme 2, upper panel) and the products are relevant in the field of natural product-like molecules, because the synthesized molecules are close analogs of a natural product (brazilin). Moreover, the use of TsOH·H2O as an easily-accesible Brønsted acid catalyst with low loading

• convenient Brønsted acid-catalyzed, metal-free, stereoselective synthesis of 6a,7,8,12b-tetrahydro-6H-naphtho[2,1-c]chromen-6a-ols as B-ring-modified analogues of brazilin using starting materials derived from inexpensive 1-tetralone and phenol derivatives. Our worries concerning the formation cis–trans

Diels–Alder reactions in confined spaces: the influence of catalyst structure and the nature of active sites for the retro-Diels–Alder reaction

• Ángel Cantín,
• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2016, 12, 2181–2188, doi:10.3762/bjoc.12.208

• effect within the pore and diffusion limitations are discussed. Introduction of Lewis or Brønsted acid sites on the walls of the zeolite strongly increases the reaction rate. However, contrary to what occurs with mesoporous molecular sieves (MCM-41), Beta zeolite does not catalyse the retro-Diels–Alder

• terephthalate that is used for the large-scale manufacture of plastic bottles among others. The authors do not find transport limitations within the zeolite framework to the rate of the reaction [27]. Interestingly, when Brønsted acid containing zeolites (Al-β) are used as catalyst, there is a decrease in the

• Lewis and Brønsted acid sites in the conversion (a) and selectivity (b) of the DAR. Effect of pore size in the conversion (a) and selectivity (b) of the DAR. Comparison of conversion (a) and selectivity (b) of the DAR catalysed by Al-Beta zeolite and MCM-41. Comparison of conversion (a) and selectivity

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• synthesis by offering power for improving reaction efficiency and/or realizing impossible processes [46][47][48][49][50][51][52][53][54][55]. Recently, we developed an enantioselective addition of aldehydes to vinylpyridines and vinylarenes catalyzed by synergistic catalysis of iminium catalyst and Brønsted

• acid [56]. Herein we wish to disclose the first synergistic catalytic enantioselective [3 + 2] annulation reaction between 2-vinylcyclopropanes and enals via 1,4-addition (Scheme 1, reaction 2). The process proceeds highly regio- and enantioselectively with C=C bonds in enals. Notably, a synergistic

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• convenient and cheap Brønsted acid, transformed a range of epoxides [20] into the corresponding nitrato alcohols. Shepson substituted ethylene oxide for commercially available isoprene epoxide and generated eight stereo- and structurally isomeric IPNs. Within this mixture 3° nitrate rac-7, 1° nitrate rac-8

A practical way to synthesize chiral fluoro-containing polyhydro-2H-chromenes from monoterpenoids

• Oksana S. Mikhalchenko,
• Dina V. Korchagina,
• Konstantin P. Volcho and
• Nariman F. Salakhutdinov

Beilstein J. Org. Chem. 2016, 12, 648–653, doi:10.3762/bjoc.12.64

• strong Brønsted acid and may be presented as H+(BF3·OH)− [27][28]. Based on these data, it may be supposed that in the case of a 5-fold excess of water relative to BF3·Et2O, the reaction medium may contain both BF3·H2O and products of the partial hydrolysis of BF3·Et2O that may act both as catalysts and

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• chiral thiourea organocatalyst and a Brønsted acid (AH) could provide better results in terms of reactivity and enantioselectivity. Thus, in 2011, they published an article where it was proved that the synergic system between the thiourea ent-4 and mandelic acid led to the final products 5 with a

• external Brønsted acid. Proposed transition state TS7 for the Friedel–Crafts reaction of indole and α,β-unsaturated acyl phosphonates catalyzed by ent-4. Possible transition states TS8 and TS9 in the asymmetric addition of indoles 2 to the β,γ-unsaturated α-ketoesters 26 catalyzed by ent-4. Transition

• catalyzed by thiourea ent-4 in the presence of D-mandelic acid as a Brønsted acid additive. Friedel–Crafts alkylation of indoles catalyzed by the chiral thioamide 6. Scalable tandem C2/C3-annulation of indoles, catalyzed by the thioamide ent-6. Plausible tandem process mechanism for the sequential, double

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• -catalyst. With the addition of chiral Brønsted acid co-catalyst 27, high yields and good to excellent levels of enantioselectivity were achieved in the addition of both aryl and aliphatic alkynes (Scheme 8B). The azomethine amine products 24 and 26 can be deprotected using SmI2. To our knowledge, this

Latent ruthenium–indenylidene catalysts bearing a N-heterocyclic carbene and a bidentate picolinate ligand

• Thibault E. Schmid,
• Florian Modicom,
• Adrien Dumas,
• Etienne Borré,
• Loic Toupet,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 1541–1546, doi:10.3762/bjoc.11.169

• -diisopropylphenyl)imidazolidin-2-ylidene) demonstrated excellent latent behaviour in ring closing metathesis (RCM) reaction and could be activated in the presence of a Brønsted acid. The versatility of the catalyst 4a was subsequently demonstrated in RCM, cross-metathesis (CM) and enyne metathesis reactions

• , we proceeded to synthesize complex 4b, featuring the 5-bromo-2-picolinate moiety. Using a similar methodology, the desired complex was obtained with 42% yield. The activation of the new picolinic complex 4a was initially evaluated in the presence of trifluoroacetic acid (TFA), a Brønsted acid easy to

• bulkier ancillary ligand SIPr, appeared as highly stable, well-defined species. These species were shown to activate in the presence of a Brønsted acid and precatalysts 2 and 4a showed an excellent latent behaviour. The best reaction rates were obtained in the RCM of DEDAM with complex 4a after activation

Efficient deprotection of F-BODIPY derivatives: removal of BF₂ using Brønsted acids

• Mingfeng Yu,
• Joseph K.-H. Wong,
• Cyril Tang,
• Peter Turner,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2015, 11, 37–41, doi:10.3762/bjoc.11.6

• organic acid TFA or the inorganic acid HCl. These conditions are complementary to those previously reported for converting F-BODIPYs to the parent dipyrrins using either strong bases or Lewis acids. Compared to existing methods, the Brønsted acid conditions are relatively mild and operationally simple

Galactan synthesis in a single step via oligomerization of monosaccharides

• Marius Dräger and
• Amit Basu

Beilstein J. Org. Chem. 2014, 10, 2658–2663, doi:10.3762/bjoc.10.279

• observations suggest that desilylation is most likely the result of transient Brønsted acid formation during the reaction and not due to fluoride ion generation. In an attempt to tune silyl ether deprotection rates and promote formation of longer oligomers, we examined the glycosylation of a bulkier TBDPS

Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

• András Demjén,
• Márió Gyuris,
• János Wölfling,
• László G. Puskás and
• Iván Kanizsai

Beilstein J. Org. Chem. 2014, 10, 2338–2344, doi:10.3762/bjoc.10.243

• isocyanides in the presence (5–30 mol %) of Lewis or Brønsted acid at ambient temperature or under heating (50–140 °C). The main disadvantages of this protocol involve long reaction times (3–18 hours) and requisite purification protocols (column chromatography and/or recrystallisation) besides limited

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• 2010, using the bifunctional chiral phosphine G1, bearing both Brønsted acid and Lewis base units, as the catalyst, asymmetric domino aza-MBH/aza-Michael reactions of activated alkenes and N-tosylimines with Michael acceptor moieties at their ortho positions were accomplished to give chiral 1,3

• , both aryl and alkyl. The addition of a Brønsted acid to the reaction system slightly improved the yields and diastereocontrol. In addition, the resulting tetrahydropyridines could be transformed to more complex dihydroxylated piperidine derivatives. At almost the same time, an intramolecular variant of

Synthesis of α-amino amidines through molecular iodine-catalyzed three-component coupling of isocyanides, aldehydes and amines

• Praveen Reddy Adiyala,
• D. Chandrasekhar,
• Jeevak Sopanrao Kapure,
• Chada Narsimha Reddy and
• Ram Awatar Maurya

Beilstein J. Org. Chem. 2014, 10, 2065–2070, doi:10.3762/bjoc.10.214

• development of a mild, inexpensive and efficient catalytic protocol for the amidine synthesis is highly needed. Iodine is expected to act as a Lewis acid or Brønsted acid in methanol [20]. Apart from oxidation, catalytic iodine provides mild and efficient ways for the formation of C–C and C–N bonds [20]. As a

Cyclization–endoperoxidation cascade reactions of dienes mediated by a pyrylium photoredox catalyst

• Nathan J. Gesmundo and
• David A. Nicewicz

Beilstein J. Org. Chem. 2014, 10, 1272–1281, doi:10.3762/bjoc.10.128

• hydroperoxides with pendant alkenes or alkynes have been developed. Selected examples include Pd(II)-catalyzed hydroalkoxylation reactions of unsaturated hydroperoxides [9], Au(I)-catalyzed endoperoxidation of alkynes [10] and Brønsted acid-catalyzed enantioselective acetalization/oxa-Michael addition cascade

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• reaction with the chloride ion released during the initial imine acylation. Finally, a combination between Brønsted acid and metal catalysis, promote the isomerization of V to oxazole 21. It is noteworthy, that the gold catalyst seemed to be essential only for the formation of the gold-acetylide

• great chemical diversity of the products of MCRs. Moreover, imines can participate in MCRs as electrophilic or nucleophilic partners, azadienes, dienophiles and 1,3-dipoles. All these reactions may benefit from the presence of a Lewis acid, a Brønsted acid or a transition metal catalyst. Silver

• . However, an alternative reaction pathway, involving a concerted [3 + 2] cycloaddition of 64 to the imine, cannot be ruled out. Additionally, the use of sterically demanding amines results in lower yields. It is noteworthy, that the same reactions performed in the presence of a weak Brønsted acid instead

Secondary amine-initiated three-component synthesis of 3,4-dihydropyrimidinones and thiones involving alkynes, aldehydes and thiourea/urea

• Jie-Ping Wan,
• Yunfang Lin,
• Kaikai Hu and
• Yunyun Liu

Beilstein J. Org. Chem. 2014, 10, 287–292, doi:10.3762/bjoc.10.25

• equiv of p-TSA has been found to significantly improve the yield (Table 1, entry 14). This result may be attributed to the double activation effect involving both Lewis and Brønsted acid (see Scheme 3). With the optimal conditions in hand, we conducted the investigation on examining the application

Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations

• Ouldouz Ghashghaei,
• Consiglia Annamaria Manna,
• Esther Vicente-García,
• Marc Revés and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2014, 10, 12–17, doi:10.3762/bjoc.10.3

• respect, taking imine 1a (R1 = p-MeOC6H4; R2 = p-ClC6H4) and isocyanide 2a (R3 = t-Bu), we tested the standard reaction in THF, MeCN, and CH2Cl2 as solvents using a variety of Lewis and Brønsted acid activating agents (20–100 mol %) including: InCl3, Sc(OTf)3, AuCl3, AgOTf, GaCl3, NbCl5, camphorsulfonic

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• functionalization of alkenes rely on the use of “oxidative strategies” exploiting the [Au(I)/Au(III)] or [Au(I)Au(I)/Au(II)Au(II)] catalytic couples that can be accessed through the use of a suitable exogenous oxidant (Figure 2, path c) [9]. Last but not least, the potential role of Brønsted acid co-catalysis

• process for the formation of new C–O bonds. In this direction numerous examples of metal and Brønsted-acid catalyzed condensations of alcohols, phenols and carboxylic acids to inactivated olefins have been reported [16]. Interestingly, He and co-workers compared the catalytic attitude of TfOH and

• PPh3AuOTf in the addition of various nucleophiles to alkenes, demonstrating how the gold complex and triflic acid can exhibit complementary efficiency [17]. This finding suggests that although Brønsted acid co-catalysis is a possible competing process, under suitable conditions the gold-catalyzed pathway is

A combined continuous microflow photochemistry and asymmetric organocatalysis approach for the enantioselective synthesis of tetrahydroquinolines

• Erli Sugiono and
• Magnus Rueping

Beilstein J. Org. Chem. 2013, 9, 2457–2462, doi:10.3762/bjoc.9.284

• the synthesis of tetrahydroquinolines from readily available 2-aminochalcones using a combination of photochemistry and asymmetric Brønsted acid catalysis. The photocylization and subsequent reduction was performed with catalytic amount of chiral BINOL derived phosphoric acid diester and Hantzsch

• uniform irradiation through the entire reactor and the complete reaction medium, in comparison with reactions performed in conventional batch systems. Here we report the development of continuous-flow photochemical reaction in combination with asymmetric Brønsted acid catalysis for the synthesis of

• source and catalytic amount of chiral Brønsted acid 3. The effect of temperature, flow rate and concentration on the reaction yield and enantioselectivity are summarized in Table 1. As shown in Table 1, performing the reaction in a pyrex test tube (i.d.: 12 mm; λ > 300 nm) with 1 mol % of Brønsted acid 3

Silica sulfuric acid: a reusable solid catalyst for one pot synthesis of densely substituted pyrrole-fused isocoumarins under solvent-free conditions

• Sudipta Pathak,
• Kamalesh Debnath and
• Animesh Pramanik

Beilstein J. Org. Chem. 2013, 9, 2344–2353, doi:10.3762/bjoc.9.269

•  2). When the reaction was carried out in aqueous solution under reflux the reaction did not proceed at all (Table 1, entry 1). Previous results showed that an activation by a Brønsted acid was necessary to carry out the reaction successfully [38]. Therefore, we screened various Brønsted acid

• , both for aromatic and aliphatic amines. We restrained the reaction to using PEG–OSO3H as a Brønsted acid–surfactant combined catalyst in aqeous solution under refluxing conditions as well as under solvent-free conditions (Table 1, entries 7 and 8). Although under solvent-free conditions the required

• chemical processes. Hence, we have carried out the synthesis by dissolving the substrate 7 and aniline in a minimum volume of chloroform, soaked them on the solid surface of solid Brønsted acid catalysts, such as silica gel and melamine sulfonic acid (MSA), dried the mixture under vacuum, and heated the

Gold-catalyzed glycosidation for the synthesis of trisaccharides by applying the armed–disarmed strategy

• Abhijeet K. Kayastha and
• Srinivas Hotha

Beilstein J. Org. Chem. 2013, 9, 2147–2155, doi:10.3762/bjoc.9.252

• trisaccharide. Instead, disaccharide 3 (53%) and 1,6-anhydro sugar 5 (20%) were isolated as major products [37]. Interestingly, propargyl mannoside 1 (12%) along with benzyl glycoside 6 and lactol 7 were noticed in 5% and 4% yield, respectively (Scheme 1). The Brønsted acid (HBr) released from AuBr3 in the

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• independently discovered that the efficiency of the same Michael reaction was greatly improved in the presence of a Brønsted acid (Scheme 23) [90]. Some of the improvements included shorter reaction time, higher yields, and use of a weaker light source (CFL). The most effective acid catalysts, of which TFA was

• Michael acceptors. Conjugated addition of α-amino radicals to Michael acceptors assisted by a Brønsted acid. Conjugated addition of α-amino radicals derived from anilines to Michael acceptors. Oxygen switch between two pathways involving α-amino radicals. Interception of α-amino radicals by

One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor

• Mark C. Bagley,
• Vincenzo Fusillo,
• Robert L. Jenkins,
• M. Caterina Lubinu and
• Christopher Mason

Beilstein J. Org. Chem. 2013, 9, 1957–1968, doi:10.3762/bjoc.9.232

• material. In the Bohlmann–Rahtz reaction, the use of a Brønsted acid catalyst allows Michael addition and cyclodehydration to be carried out in a single step without isolation of intermediates to give the corresponding trisubstituted pyridine as a single regioisomer in good yield. Furthermore, 3

• continuous flow reactor examined the cyclodehydration of Bohlmann–Rahtz aminodienone intermediates in the presence of a Brønsted acid catalyst [44][45]. This relatively simple cyclization reaction was utilized previously as we had already established its facility under microwave irradiation and so it

• = Ph) [51], in the presence of acetic acid as a Brønsted acid catalyst for transfer to flow processing. A range of conditions were investigated (Table 1) and, in each case, 1H NMR spectroscopic analysis of the crude reaction mixture revealed if unreacted starting materials were present. Microwave

Gold(I)-catalysed one-pot synthesis of chromans using allylic alcohols and phenols

• Eloi Coutant,
• Paul C. Young,
• Graeme Barker and
• Ai-Lan Lee

Beilstein J. Org. Chem. 2013, 9, 1797–1806, doi:10.3762/bjoc.9.209

• , entries 8–10). Firstly, no reaction is observed in the absence of a catalyst (Table 1, entry 8). The Brønsted acid catalyst HNTf2 does form chroman 8, but in a poorer isolated yield (21%, Table 1, entry 9) and the silver salt [76] AgNTf2 as a catalyst does not provide any 8, yielding only 9 and 10 (Table

•  1, entry 10). The former is consistent with literature reports that Brønsted acid-catalysed reactions give poor yields when the phenol is not para-substituted [19]. Therefore, it seems that the gold(I) catalyst is most efficient in catalysing the one-pot formation of chroman 8. With these results in

• temperature (Table 2, entries 4, 7, 8 and 10). In contrast to the Brønsted acid procedure [19], the substitution position has limited effect on the efficiency of the gold-catalysed reaction, with p-cresol (5b), m-cresol (5c) and o-cresol (5d) all forming the desired chromans 8b–d in decent to good yields