Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• functionalized nitrovinylacetamides are rare. Chiral thioureas [28][38][39] have evolved as powerful hydrogen bonding catalysts for the asymmetric synthesis of spirocyclopentaneoxindoles, which have been demonstrated as acceptable but still considerably limited. Organocatalytic iminium–enamine cascade reactions

Ultrasound-promoted organocatalytic enamine–azide [3 + 2] cycloaddition reactions for the synthesis of ((arylselanyl)phenyl-1H-1,2,3-triazol-4-yl)ketones

• Gabriel P. Costa,
• Natália Seus,
• Juliano A. Roehrs,
• Raquel G. Jacob,
• Ricardo F. Schumacher,
• Thiago Barcellos,
• Rafael Luque and
• Diego Alves

Beilstein J. Org. Chem. 2017, 13, 694–702, doi:10.3762/bjoc.13.68

• Biotechnology of Natural and Synthetic Products, Universidade de Caxias do Sul, Caxias do Sul, RS, Brazil Departamento de Quimica Organica, Universidad de Cordoba, Campus de Rabanales, Cordoba, Spain 10.3762/bjoc.13.68 Abstract The use of sonochemistry is described in the organocatalytic enamine–azide [3 + 2

• have been used for this cycloaddition reaction [20][21][22][23][24][25][26][27][28][29]. Organocatalytic approaches based on β-enamine–azide or enolate–azide cycloadditions have been employed to synthesize 1,2,3-triazole scaffolds [30][31][32]. Depending on the organocatalyst employed, different

• ]. There are only a few contributions describing the use of sonochemistry for the preparation of functionalized 1,2,3-triazoles [68][69][70][71][72][73][74]. As a recent example, our research group described the use of sonochemistry in the organocatalytic enamine–azide [3 + 2] cycloadditions of β-oxo

Towards the development of continuous, organocatalytic, and stereoselective reactions in deep eutectic solvents

• Davide Brenna,
• Elisabetta Massolo,
• Alessandra Puglisi,
• Sergio Rossi,
• Giuseppe Celentano,
• Maurizio Benaglia and
• Vito Capriati

Beilstein J. Org. Chem. 2016, 12, 2620–2626, doi:10.3762/bjoc.12.258

Continuous-flow synthesis of primary amines: Metal-free reduction of aliphatic and aromatic nitro derivatives with trichlorosilane

• Riccardo Porta,
• Alessandra Puglisi,
• Giacomo Colombo,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2016, 12, 2614–2619, doi:10.3762/bjoc.12.257

• , are accessible via several synthetic routes. In the last years nitro compounds have been the subject of numerous studies since they served as reactants in many, highly efficient, organocatalytic transformations [3][4][5][6][7]. Furthermore, the introduction of an amino group offers a well-known

Highly chemo-, enantio-, and diastereoselective [4 + 2] cycloaddition of 5H-thiazol-4-ones with N-itaconimides

• Shuai Qiu,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2016, 12, 2293–2297, doi:10.3762/bjoc.12.222

• [6], allylation [7], conjugate addition to enones [8], and γ-addition with allenoates [9]. All these examples focused on nucleophilic addition reactions of the C5 atom of 5H-thiazol-4-ones. Recently, we described an organocatalytic asymmetric [4 + 2] cyclization of 5H-thiazol-4-ones with a series of

Economical and scalable synthesis of 6-amino-2-cyanobenzothiazole

• Jacob R. Hauser,
• Hester A. Beard,
• Mary E. Bayana,
• Katherine E. Jolley,
• Stuart L. Warriner and
• Robin S. Bon

Beilstein J. Org. Chem. 2016, 12, 2019–2025, doi:10.3762/bjoc.12.189

• , organocatalytic cyanation. In addition, the use of filtrations and crystallisations for purification, in combination with control of reaction rate and heat output in the cyanation step, makes this procedure readily scalable. Results and Discussion In order to install the cyano group of ACBT 8 under mild

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Enantioselective addition of diphenyl phosphonate to ketimines derived from isatins catalyzed by binaphthyl-modified organocatalysts

• Hee Seung Jang,
• Yubin Kim and
• Dae Young Kim

Beilstein J. Org. Chem. 2016, 12, 1551–1556, doi:10.3762/bjoc.12.149

• reaction time, and low temperature required for good enantioselectivity. Thus, new approaches for the organocatalytic enantioselective addition of diphenyl phosphonate to isatin imines are highly desired. In connection with our ongoing research program on the design and application in asymmetric catalysis

• phosphonate to ketimines derived from isatins catalyzed by binaphthyl-modified bifunctional organocatalysts (Figure 1). Results and Discussion To determine suitable reaction conditions for the organocatalytic enantioselective addition reaction of diphenyl phosphonate to ketimines derived from isatins, we

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• developed organocatalytic conjugate addition–enantioselective protonations of α,β-unsaturated imides using thiols. Thiols are attractive nucleophiles due to their acidity, which facilitates deprotonation by amine bases and also reduces undesired competitive deprotonation and epimerization of the enolizable

• conjugate addition products. Additionally, the thiolate conjugate bases are highly nucleophilic, allowing ready access to sulfur functionalized products. A common theme among the organocatalytic literature examples is the use of hydrogen-bonding catalysts, which can activate the imides by hydrogen bonding

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• 1 as a suitable synthetic target. Our plan was to design and implement a new synthetic route that integrated some of our newly developed bifunctional organocatalytic reactions, as well as cascade technologies, to rapidly and stereoselectively build up the core of this fascinating molecule. Herein we

• amine, following our well-established protocol [6][7][8][9][10][11][12]. The key quaternary stereocentre of keramaphidin B, we envisaged, would be installed through an enantio- and diastereoselective organocatalytic Michael addition [13][14][15] between pronucleophile 8 and the known substituted furanyl

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• same group reported the organocatalytic asymmetric addition reactions of isatins with electron-rich aromatics sesamols using the cinchona alkaloid-derived thiourea catalyst (cat. 17) under mild conditions. In the presence of 10% catalyst, sesamols reacted with isatins smoothly in tert-butyl ether at

• for the reactions, although the starting materials were poorly solubilized. However, ten equivalents of aldehyde were used in the reactions. Similarly, Gong and co-workers reported an organocatalytic α-alkylation of enolizable aldehydes with 3-indolyl-3-hydroxyoxindoles co-catalyzed by the cinchona

Asymmetric α-amination of 3-substituted oxindoles using chiral bifunctional phosphine catalysts

• Qiao-Wen Jin,
• Zhuo Chai,
• You-Ming Huang,
• Gang Zou and
• Gang Zhao

Beilstein J. Org. Chem. 2016, 12, 725–731, doi:10.3762/bjoc.12.72

• organocatalysis and metal catalysis for the construction of this type of structures. For example, Chen et al. reported the first organocatalytic enantioselective amination reaction of 2-oxindoles catalyzed by biscinchona alkaloid catalysts [8]. Zhou [9][10] and Barbas [11][12], have independently reported similar

• organocatalytic processes. In the field of metal catalysis, Shibasaki et al. reported the reaction between C3-substituted oxindole and azodicarboxylates, using homodinuclear or monometallic Ni-Schiff base complexes as catalysts [13]; Feng et al. also developed a similar procedure with chiral N,N’-dioxide-Sc(III

• ) complexes as catalysts [14]. Despite these impressive advances, current catalytic systems still more or less suffer from limitations such as long reaction times, relatively large catalyst loading in most organocatalytic systems and in some cases unsatisfactory yields and/or enantioselectivities. Therefore

Stereoselective amine-thiourea-catalysed sulfa-Michael/nitroaldol cascade approach to 3,4,5-substituted tetrahydrothiophenes bearing a quaternary stereocenter

• Sara Meninno,
• Chiara Volpe,
• Giorgio Della Sala,
• Amedeo Capobianco and
• Alessandra Lattanzi

Beilstein J. Org. Chem. 2016, 12, 643–647, doi:10.3762/bjoc.12.63

• obtain this class of compounds and only recently organocatalytic stereoselective cascade reactions have emerged as the most successful, and straightforward approach to access them [7][8]. Aminocatalytic [9][10][11][12] and non-covalent organocatalytic cascade sulfa-Michael/Michael [13][14][15] and sulfa

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

• trifluoroethylamine moiety [3][4][5]. However, it is in the field of asymmetric organocatalysis [6][7][8] where the aminoindanol core has gained more importance, being a recurrent structural motif in several organocatalytic species. Some examples are (a) the enantioselective reduction of ketones through the in situ

• acting through hydrogen bonding, such as thiourea, urea, squaramide, and thioamide frameworks. These have been efficiently employed in a few organocatalytic processes such as Friedel–Crafts alkylations, Michael additions, Diels–Alder reactions and aza-Henry reactions, as discussed below. Friedel–Crafts

• derivative 4 to develop the first organocatalytic enantioselective Friedel–Crafts (F–C) alkylation of indoles, employing nitroalkenes as versatile electrophiles. In the presence of catalyst 4, the differently functionalized indole derivatives 2 reacted with aryl and alkyl nitroalkenes 3 in dichloromethane at

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• in the production of 93 and 94 in moderate to excellent enantioselectivities, considering the high molecular complexity achieved in only one step. Recently, Bugaut, Constantieux and co-workers described the enantioselective organocatalytic multicomponent synthesis of 2,6-diazabicyclo[2.2.2]octanones

• stereochemistry of the carbon bearing the R2 group. Very recently, Wang and co-workers used a cinchona alkaloid-based bifunctional thiourea 103 as the catalyst of choice to an organocatalytic domino process. This domino reaction involded a Michael cyclization–tautomerization reaction sequence between isatylidene

• napthoquinone derivatives 140 in excellent yields and selectivities (Scheme 44) [64][65]. In both cases, a bifunctional activation of substrates was proposed by the authors. In 2011, Yan and co-workers reported the organocatalytic cascade Michael hemiketalization, using the same versatile reagent, β-unsaturated

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• co-workers who developed an organocatalytic transamination process using the cupreine catalyst CPN-81, which is substituted with n-butyl at the 9-OH position [59]. In this report, the α-ketoester 79 was reacted with the primary amine o-ClC6H4CH2NH2 80 in the presence of the catalyst. Once again, the

• processes Asymmetric oxidative coupling All carbon quaternary centers are prevalent in both natural and pharmaceutical compounds, but rank amongst the hardest to synthesize in a stereoselective manner. Dixon and co-workers have addressed this through the development of an asymmetric organocatalytic

• with cupreine, cupreidine, β-isoquinidine and β-isocupreidine derivatives. The original 6’-OH cinchona alkaloid organocatalytic MBH process, showing how the free 6’-OH is essential for coordination to the substrate. Use of β-ICPD in an aza-MBH reaction. (a) The isatin motif is a common feature for MBH

Organocatalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones with bifunctional amine-thiourea catalysts bearing multiple hydrogen-bond donors

• Ming-Liang Zhang,
• Deng-Feng Yue,
• Zhen-Hua Wang,
• Yuan Luo,
• Xiao-Ying Xu,
• Xiao-Mei Zhang and
• Wei-Cheng Yuan

Beilstein J. Org. Chem. 2016, 12, 295–300, doi:10.3762/bjoc.12.31

• these observations, the most appropriate conditions for the Henry reaction could be established: 1 equiv of 1a and 10 equiv of 2a with 20 mol % catalyst 3e in 1.0 mL THF at 30 °C (Table 2, entry 4). Under the optimal reaction conditions, the substrate scope and the limitation of this organocatalytic

A quadruple cascade protocol for the one-pot synthesis of fully-substituted hexahydroisoindolinones from simple substrates

• Hong-Bo Zhang,
• Yong-Chun Luo,
• Xiu-Qin Hu,
• Yong-Min Liang and
• Peng-Fei Xu

Beilstein J. Org. Chem. 2016, 12, 253–259, doi:10.3762/bjoc.12.27

• carboxylic acid anhydrides, respectively [17]. To the best of our knowledge, no efficient method toward the synthesis of fully-substituted hexahydroisoindolinones has been developed so far. The synthesis of complicated molecular structures can now be achieved by organocatalytic cascade reactions [18][19][20

• . Previously, we established organocatalytic domino reactions to construct very useful molecular architectures [47][48][49][50][51][52][53][54][55][56][57][58][59][60]. Based on this past experience, we decided to develop a one-pot quadruple protocol to construct this difficult molecular architecture using

Diastereoselective Ugi reaction of chiral 1,3-aminoalcohols derived from an organocatalytic Mannich reaction

• Samantha Caputo,
• Andrea Basso,
• Lisa Moni,
• Renata Riva,
• Valeria Rocca and
• Luca Banfi

Beilstein J. Org. Chem. 2016, 12, 139–143, doi:10.3762/bjoc.12.15

• Samantha Caputo Andrea Basso Lisa Moni Renata Riva Valeria Rocca Luca Banfi Department of Chemistry and Industrial Chemistry, University of Genova, I-16146 Genova, Italy 10.3762/bjoc.12.15 Abstract Enantiomerically pure β-aminoalcohols, produced through an organocatalytic Mannich reaction, were

• -aminoalcohols have been proved by Nenajdenko and co-workers to be able to induce good levels of diastereoselectivity in the Ugi reaction [17]. Our attention was drawn by 1,3-aminoalcohols of general formula 5 (Scheme 1), which can be obtained by List's organocatalytic Mannich-type reaction of aldehydes with N

• 2 that were immediately submitted to List's organocatalytic Mannich reaction [29][30]. The resulting aldehydes 3 were not isolated (also in view of their known stereochemical lability) but directly reduced to alcohols 4 [32][33]. Purification was carried out through chromatography and, in some cases

Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality

• Jose I. Martínez,
• Uxue Uria,
• Maria Muñiz,
• Efraím Reyes,
• Luisa Carrillo and
• Jose L. Vicario

Beilstein J. Org. Chem. 2015, 11, 2577–2583, doi:10.3762/bjoc.11.277

Efficient synthetic protocols for the preparation of common N-heterocyclic carbene precursors

• Morgan Hans,
• Jan Lorkowski,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2015, 11, 2318–2325, doi:10.3762/bjoc.11.252

• interested in the preparation of IMes·HBF4 because imidazolium tetrafluoroborates are usually less hygroscopic and easier to crystallize than chlorides [45]. Moreover, when imidazolium salts are used to generate NHCs in situ, for instance to accomplish organocatalytic transformations, the exact nature of the

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• this mechanism, synthetic polycarbonates arising from organocatalytic ring-opening polymerization of cholesterol monomers were reported to create self-assemblies possessing high interior charge density and wide spectrum antimicrobial activity [6]. Interestingly, the causative vector of human gastritis

Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

• Tommaso Pecchioli,
• Manoj Kumar Muthyala,
• Rainer Haag and
• Mathias Christmann

Beilstein J. Org. Chem. 2015, 11, 730–738, doi:10.3762/bjoc.11.83

• ][36]. Moreover, their stability allows to perform reactions under mild and aerobic conditions and in the presence of water, both as co-solvent or the only solvent [37]. In the last years, several reports on water effects in organocatalytic reactions were published [38][39][40][41][42]. The use of

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• [69], magnetic core-shell nanoparticles (with magnetite cores and polyacrylate shells) [70], and thermoresponsive block copolymers [71]. Such catalytic systems can exhibit excellent organocatalytic activity under aqueous conditions, and many of them can be recycled and reused. A rather unique property

• starting point [47][70]. A potential obstacle to the application of organocatalytic systems based on naturally occurring trans-4-hydroxy-L-proline as the catalytic moiety is how to access both series of enantiomeric products, since the enantiomer of the naturally occurring hydroxyproline is not easily

Morita–Baylis–Hillman reaction of acrylamide with isatin derivatives

• Radhey M. Singh,
• Kishor Chandra Bharadwaj and
• Dharmendra Kumar Tiwari

Beilstein J. Org. Chem. 2014, 10, 2975–2980, doi:10.3762/bjoc.10.315

• coupling of an activated alkene with an electrophile (usually aldehydes or imines) in the presence of a catalyst (Figure 1). The reaction is organocatalytic, atomically economical and operationally simple in nature. Most importantly, it results in the synthesis of densely functionalized molecules, also