Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• ) – derived from a renewable resource like sugar cane biomass – for the incorporation of chiral pyrrolidine-based motifs capable to catalyze relevant asymmetric reactions. The incorporation of an organocatalyst into a polymer support requires either conjugation to the polymer or functionalization with a

• catalysts for applications in continuous-flow catalysis [8]. In an endeavor to develop a cheaper and renewable polymer-supported organocatalyst, herein we describe the multicomponent synthesis of furfuryl-containing prolyl pseudo-peptide catalysts and their subsequent utilization in the preparation of PFA

Mechanochemical synthesis of poly(trimethylene carbonate)s: an example of rate acceleration

• Sora Park and
• Jeung Gon Kim

Beilstein J. Org. Chem. 2019, 15, 963–970, doi:10.3762/bjoc.15.93

• important for chain-length control. Liquid-assisted grinding was applied for the synthesis of high molecular weight polymers, but it failed to protect the polymer chain from mechanical degradation. Keywords: aliphatic polycarbonate; green polymerization; mechanochemistry; organocatalyst; poly(trimethylene

• mechanism is currently obscure. To have a better understanding of LAG on chain protection, extensive studies are currently in progress. Conclusion A mechanochemical method, ball milling, was applied to the synthesis of poly(trimethylene carbonate). The representative organocatalyst, DBU, exhibited excellent

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• hydrogen bonding organocatalyst for the reaction between 1-dimethylamino-3-tert-butyldimethylsilyloxy-1,3-butadiene (Rawal’s diene) and aldehydes with excellent enantioselectivities (aromatic aldehyde: up to 86–98% ee) in 2003 [27]. Activation via a single-point hydrogen bond between one of the hydroxy

• groups of the TADDOL and the carbonyl oxygen of the aldehyde was proposed to be a crucial factor for the success of this organocatalyst in the reaction. Two years later, they reported another efficient diol-based hydrogen bonding organocatalyst, BAMOL, for catalyzing the same oxo-DA reactions with a

• library of aldehydes (aromatic: 97–99% ee; aliphatic: 84–98% ee) [28]. Thereafter, many different kinds of hydrogen bonding-based organocatalysts have been developed for oxo-DA reactions [29][30][31][32][33][34][35]. One kind of organocatalyst in particular, which is based on an oxazoline template with

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• lower toxicity, air sensitivity and lower costs [34]. A huge repertoire of organocatalyzed reactions have been published in recent years with high efficiencies and selectivities [29][33][35][36][37][38][39]. Proline as a natural amino acid is a perfect example of an organocatalyst. Both enantiomers are

Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles by water-mediated cycloaddition reactions of enaminones and tosyl azide

• Lu Yang,
• Yuwei Wu,
• Yiming Yang,
• Chengping Wen and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2018, 14, 2348–2353, doi:10.3762/bjoc.14.210

• with activated dipolarophiles. As synthetic tools being able to provide 1,2,3-triazoles using an organocatalyst or other non-metal catalysts, this method shows distinctive advantages in enabling the production of 1,2,3-triazoles free of any heavy metal contamination [36][37][38]. Generally, the

Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives

• Zheng-Yi Li,
• Hong-Xiao Tong,
• Yuan Chen,
• Hong-Kui Su,
• Tangxin Xiao,
• Xiao-Qiang Sun and
• Leyong Wang

Beilstein J. Org. Chem. 2018, 14, 1901–1907, doi:10.3762/bjoc.14.164

• different nitroolefins catalyzed by organocatalyst 2. Reagents and conditions: catalyst 2 (5 mol %), nitroolefin (0.5 mmol), acetylacetone (1 mmol), toluene (0.32 mL) and water (0.16 mL), rt. Catalysts synthesized and screened in this study. Synthetic routes for organocatalysts 1–4. Possible proposed

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

• bromines to alkenes, using ortho-substituted iodobenzene 62 as an organocatalyst (Scheme 19) [75]. A control experiment indicated that only trace amounts of products were observed in the absence of iodoarene catalyst (2%). A similar work involving a rearrangement of imides, which delivered α,α

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• calixarene; organocatalyst; supramolecular catalyst; Introduction The catalysis of organic reactions by macrocyclic host compounds is a longstanding proposed application of supramolecular chemistry and utilizes the use of noncovalent interactions in catalytic systems to achieve higher reaction rates, more

• asymmetric Michael addition reaction of thiophenol could be catalyzed by inherently chiral calixarenes bearing amino alcohol/phenol structure [47][48]. In order to see the effect of the diarylmethanol moiety, Shirakawa and Shimizu used 43 (Figure 6) as organocatalyst in the Michael addition reaction between

• both catalysts gave the Michael adduct in excellent yields, high ees were obtained only when 54b was used as organocatalyst (up to 94% ee, Scheme 16). During the last decade, squaramide catalysts have become a powerful alternative to the urea/thiourea and guanidine catalysts as multiple hydrogen bond

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• an enantioselective organocatalytic Mannich reaction between isatin-derived benzhydrylketimines 12 and trimethylsiloxyfuran 13 [38]. Using 10 mol % of another type of organocatalyst, such as chiral phosphoric acid 14, the process led at −40 °C in THF to the corresponding butenolides 11 in moderate to

• enantioselectivities (90–94% ee), as shown in Scheme 5. The synthetic utility of this novel methodology was demonstrated through the total synthesis of the natural product (−)-psychotriasine (Scheme 5) and the biologically active compound AG-041R (Scheme 1). By using another type of organocatalyst, such as L

• a carbon–carbon bond-forming reaction occurring between the α-position of an activated alkene and a carbon electrophile such as an aldehyde. Employing a nucleophilic organocatalyst [26], such as a tertiary amine or a phosphine, this simple reaction provides densely functionalized products, such as α

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

• . Conclusion An operationally simple route to 5-fluoromethyl-2-oxazolines from readily accessible N-allylcarboxamides is disclosed based on an I(I)/I(III) catalysis manifold. This metal-free fluorocyclisation employs p-iodotoluene (10 mol %) as an inexpensive organocatalyst and Selectfluor® as oxidant. The

Electrochemically modified Corey–Fuchs reaction for the synthesis of arylalkynes. The case of 2-(2,2-dibromovinyl)naphthalene

• Fabiana Pandolfi,
• Isabella Chiarotto and
• Marta Feroci

Beilstein J. Org. Chem. 2018, 14, 891–899, doi:10.3762/bjoc.14.76

• the latter reaction DBU acts both as base and as organocatalyst [14]. In all cases, an excess of a strong base or high temperature are necessary for the reaction to proceed. An overview on the importance of the Corey–Fuchs reaction for the synthesis of natural products has been pointed out by Heravi

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• depicted in Figure 2, PQS (4a) has an OH moiety that allows for its linkage to the organocatalyst proline 4b. Also, PQS has a lipophilic component that acts as a reaction solvent for hydrophobic dienes. The latter feature allows aldol reactions to take place efficiently in water. The aldol reaction between

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• faster than the NMR time scale. The EDC adduct is then expected to react with the organocatalyst, yielding the alkylimidazolium nucleotide that acts as the kinetically most relevant monomer in the extension reaction. The ethylimidazolium species can be observed as a small peak in 31P NMR spectra. The

• approaches that reduce inhibition or slow conversion. Among them is the removal of hydrolyzed monomer, improved activation chemistries, or in situ (re)activation with the support of an organocatalyst. Despite progress in the field, the ultimate goal of demonstrating enzyme-free replication of RNA strands

• organocatalyst. Acknowledgements We would like to thank H.-P. Mattelaer and E. Kervio for critical comments on the manuscript. The work of the authors on enzyme-free copying is supported by DFG grant No. RI 1063/16-1 to C.R.

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• reached only for specific substitution patterns on the amide nitrogen atom and to a lesser extent on the Michael acceptor. In order to overcome these limitations, we decided to incorporate a chiral auxiliary in our substrates combined with a proper chiral phase-transfer organocatalyst to operate an

• diastereoselectivity could not be obtained and we looked for improvements through the use of an appropriate chiral organocatalyst [63][64][65]. Indeed, within the same reaction conditions, the use of cinchoninium catalyst 18a afforded isoindolinone (S)-3a with higher de (54%), (Table 1, entry 5). We assumed such de

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• successful Michael additions to nitroalkenes in aqueous media [20][21], we have also tested the Michael addition of dimethyl malonate to nitroalkene 6 in brine. For this experiment, we have employed the more lipophilic organocatalyst C4, but the desired adduct 7 was formed only in small amount (14

• nitroalkene is bound to the catalyst via a squaramide moiety including an ancillary C–H···O hydrogen bond [45][46]. The dimethyl malonate anion binds via the protonated tertiary amide group. The calculations suggest that using organocatalyst C7 the preferred enantiomers of the product, within like and unlike

• synthesized from ethyl 3-methylbutanoate. The key step is an organocatalytic Michael addition of dimethyl malonate to racemic nitroalkene 6. Using chiral squaramide organocatalyst, the desired Michael adduct 7 was obtained in 75% yield as a mixture of diastereomers (dr 68:32) with very high enantiomeric

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• 96% ee and 73% yield. Conclusion In conclusion, we developed a unique bifunctional chiral organocatalyst via introducing a simple amide functionality at C-1 of the easily available chloramphenicol scaffold, which shows good catalytic reactivity and enantioselectivity in the alcoholytic

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

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• good yields (Scheme 49). The oxidation–reduction potentials were determined by cyclic voltammetry and a catalytic cycle was proposed in which the CF3 radical was generated from CF3SO2Na via the organocatalyst AQN-2-CO2H and visible light (Scheme 49) [72]. Rueping’s group described three examples of

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• , entries 5 and 6). Unfortunately, quinine and the chiral quinine-derived thiourea organocatalyst QT in toluene led to a mixture of racemic products along with 19% and 38% of unreacted starting material, respectively (Table 1, entries 7 and 8). As seen from the screening results, the reaction

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

• enamine complex. Scheme 1b shows our regio-, diastereo- and enantioselective 1,3-chlorosulfenation of meso-cyclopropyl carbaldehydes employing a newly designed organocatalyst 7a·DCA for chiral induction [25]. In the course of these studies we prepared a variety of imidazolidinone organocatalysts with

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• the repeating (CHF)n motif within the target molecule via an iterative synthetic approach (Scheme 1, boxed). We reasoned that an aldehyde such as 7 could undergo electrophilic fluorination, mediated by a chiral organocatalyst [18][19][20], to generate the fluorinated aldehyde 8 as a single

• the method developed by Jørgensen and co-workers (Scheme 1) [20]. Thus, the aldehyde 7a (or 7b) was treated with N-fluorobenzenesulfonimide in the presence of the chiral organocatalyst 10, and after a certain period the fluorinated aldehyde product 8 was reduced in situ. Initial studies with substrate

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

• dots [107] and used as anchoring group for dye-sensitized solar cells [108][109][110] or for the immobilization of organocatalyst [111][112]. Phosphonic acid was also used for coating superparamagnetic iron oxide (e.g., magnetite) assessed as contrast agent in magnetic resonance imaging [113] or to

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• -free conditions were performed using a combination of (S)-binam-L-Pro (A, 5 mol %) and benzoic acid (10 mol %) as organocatalyst [49]. Juaristi and co-workers investigated the mechanistic aspects of α,α-dipeptide derivatives of a (S)-proline- (A′)-catalyzed asymmetric aldol reaction (Scheme 2b) under

• -poor aromatic aldehydes and aromatic ring of the organocatalyst plays a crucial role for excellent yield and selectivity. Apparently the solvent-free system enhances the rigidity of the transition state for more selective reactions under mechanochemical activation. Michael addition Generally strong

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• organocatalyst design was first introduced by reacting 3,5-di(trifluoromethyl)phenyl isothiocyanate with 3,5-di(trifluoromethyl)aniline and 4-chloroaniline in a 1:1 ratio under LAG conditions using methanol as the grinding liquid. This led to quantitative formation of the Schreiner's catalyst 5 and thiourea 17

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• . Moderate to good enantioselectivities were afforded with a range of benzamide substrates. Mechanistic investigations were also carried out. Keywords: axial chirality; benzamide; bifunctional organocatalyst; molecular conformation; multipoint recognition; Introduction Bifunctional organocatalysts have