Enantioselective total synthesis of (R)-(−)-complanine

• Krystal A. D. Kamanos and
• Jonathan M. Withey

Beilstein J. Org. Chem. 2012, 8, 1695–1699, doi:10.3762/bjoc.8.192

• complanata, and known to be a causative agent in inflammation. An organocatalytic, asymmetric oxyamination of a homoconjugated all-Z-dienal intermediate provides versatile and efficient access to the natural product. Keywords: complanine; enantioselective synthesis; marine fireworm; nitrosoaldol

• was synthesized in a sequence of nine linear steps, beginning with (R)-malic acid [3]. As part of our research endeavours directed towards the organocatalytic synthesis of 1,2-amino alcohols, we have developed a new asymmetric strategy leading to (R)-(−)-complanine. This approach utilizes an

• asymmetric organocatalytic O-nitrosoaldol reaction as the source of chirality, with accompanying amination of the aldehyde functional group resulting in a concise and efficient synthesis. Results and Discussion Herein we report the concise and efficient synthesis of (R)-(−)-complanine, via a highly effective

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• -dihydroquinolines in optically enriched forms found in a myriad of bioactive natural products and synthetic compounds. Keywords: chromenes; 1,2-dihydroquinolines; enantioselective; Michael addition; organocatalytic; thiochromenes; Introduction Chromenes or benzopyrans and their sulfur and nitrogen analogues are

• , organocatalytic enantioselective methodologies have gained much attention from many research groups worldwide [22][23][24][25][26][27][28][29]. In the meantime, organocatalytic tandem Michael conjugate additions of heteroatom-centered nucleophiles to α,β-unsaturated compounds appear as one of the most reliable

• the literature up to 2011. Keeping an overview of organocatalytic modes of activation, and taking the less reactive Michael acceptor into account, we discuss here only the iminium/enamine activation or dual activation by iminium and hydrogen-bonding interaction strategies followed by cyclization, for

Cyclization of ortho-hydroxycinnamates to coumarins under mild conditions: A nucleophilic organocatalysis approach

• Florian Boeck,
• Max Blazejak,
• Markus R. Anneser and
• Lukas Hintermann

Beilstein J. Org. Chem. 2012, 8, 1630–1636, doi:10.3762/bjoc.8.186

• coumarins could be an ideal test case to show the utility of using organocatalytic rationales for solving a synthetic problem. Results and Discussion The reaction of (E)-ethyl 2’-hydroxycinnamate (1) to coumarin (2) was chosen as the assay to find catalytic activity under mild conditions (Table 1). It was

• ][20][21][22][23][24][25][26][27][28][29]. The reaction should be of particular utility in the generation of coumarin derivatives in the late stages of multistep syntheses of sensitive targets. This work also illustrates the utility of using organocatalytic rationales (mechanistic predictions) for

A quantitative approach to nucleophilic organocatalysis

• Herbert Mayr,
• Sami Lakhdar,
• Biplab Maji and
• Armin R. Ofial

Beilstein J. Org. Chem. 2012, 8, 1458–1478, doi:10.3762/bjoc.8.166

• Herbert Mayr Sami Lakhdar Biplab Maji Armin R. Ofial Department Chemie, Ludwig-Maximilians-Universität München, Butenandstr. 5-13 (Haus F), 81377 München, Germany 10.3762/bjoc.8.166 Abstract The key steps in most organocatalytic cyclizations are the reactions of electrophiles with nucleophiles

• Organocatalytic reactions are complex multicomponent reactions, and a detailed description of the kinetics of the complete catalytic cycles is not yet possible. We have demonstrated, however, that important information can be obtained by specifically synthesizing relevant intermediates and studying the kinetics

• ]. Relative reactivities of deoxy- and O-methylated Breslow intermediates [114]. Reactivity scales for electrophiles and nucleophiles relevant for organocatalytic reactions (references and further reactivity parameters: [4]). Acknowledgements We thank the Deutsche Forschungsgemeinschaft (Schwerpunktprogramm

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• Sergei Zari Tiiu Kailas Marina Kudrjashova Mario Oeren Ivar Jarving Toomas Tamm Margus Lopp Tonis Kanger Department of Chemistry, Tallinn University of Technology, Akadeemia tee 15, 12618 Tallinn, Estonia 10.3762/bjoc.8.165 Abstract The organocatalytic Michael addition of malonates to symmetric

• investigated the organocatalytic approach to the asymmetric desymmetrization of the title compounds with malonates. Three types of organocatalysts providing noncovalent interactions were used for this purpose: Cinchona alkaloids (I–V), thiourea derivatives (VI, VII) and squaramide derivatives (VIII, IX

• -enantiomer. Conclusion We have developed a highly enantioselective method for the desymmetrization of aromatic unsaturated 1,4-diketones through organocatalytic reactions with malonates. The reaction is catalyzed by thiourea and squaramide derivatives with Cinchona alkaloids and affords products in very high

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

• Marcus Frings,
• Isabelle Thomé and
• Carsten Bolm

Beilstein J. Org. Chem. 2012, 8, 1443–1451, doi:10.3762/bjoc.8.164

• was known for chiral bifunctional amine-based sulfonamides that two hydrogen bond donors were not strictly required in the enantioselective organocatalytic ring opening of meso-anhydrides [48][54], this particular transformation was chosen as initial test reaction. Cyclic anhydride 4 served as

• – remains to be elucidated. An organocatalytic activity of thiourea(-like) (S)-3, however, was clearly demonstrated. Next, our attention was focused on sulfoximine-based thioureas with the potential of double hydrogen bond donation. Two structural alternatives were envisaged as represented by compounds (R

• -phenylsulfoximine ((S)-2) used in this study. Structures of chiral mono- and bifunctional (bis-)thioureas that have been used as organocatalysts. Synthesis of compound (S)-3. Organocatalytic desymmetrization of the cyclic anhydride 4 with (S)-3. Attempted synthesis of sulfonimidoyl-substituted thiourea (R)-9

Cation affinity numbers of Lewis bases

• Christoph Lindner,
• Raman Tandon,
• Boris Maryasin,
• Evgeny Larionov and
• Hendrik Zipse

Beilstein J. Org. Chem. 2012, 8, 1406–1442, doi:10.3762/bjoc.8.163

• be based on results obtained with the MP2-5 model, if not noted otherwise. Methyl cation affinity values obtained for N-centered Lewis bases using this approach are collected in Table 1. For organocatalytic processes especially the Lewis bases 12, 14, 18, 24, 44, 45 and 52-65 are of note. Pyridine is

• MCA values for a large number of trialkylphosphanes and alkyldiphenylphosphanes. For organocatalytic processes especially the phosphanes 89, 98, 117, 120–124 are of note. Analysis of the results for unbranched trialkylphosphanes indicates that longer alkyl chains increase the MCA values in a

• . The HOMO–LUMO gap, in contrast, shows no significant correlation with the degree of pyramidalization but depends largely on the substitution pattern. Mosher’s cation affinities (MOSCA) For the multitude of stereoselective organocatalytic transformations the affinity of chiral Lewis bases towards

Highly enantioselective access to cannabinoid-type tricyles by organocatalytic Diels–Alder reactions

• Stefan Bräse,
• Nicole Volz,
• Franziska Gläser and
• Martin Nieger

Beilstein J. Org. Chem. 2012, 8, 1385–1392, doi:10.3762/bjoc.8.160

• organocatalytic Diels–Alder reactions to build up a tricyclic system. Herein, an asymmetric induction up to 96% enantiomeric excess was obtained by the use of imidazolidinone catalysts. This approach can be utilized to construct the tricyclic system in numerous natural products, in particular the scaffold of

• , organocatalytic methods are especially attractive for the preparation of compounds that do not tolerate metal contamination, e.g., active pharmaceutical ingredients. MacMillan’s imidazolidinone-based organocatalysts are general catalysts for a variety of asymmetric transformations. The first highly

• enantioselective organocatalytic Diels–Alder reaction was reported by MacMillan in his pioneering work in 2000 [17]. The activated iminium ion, formed through condensation of imidazolidinone and an α,β-unsaturated aldehyde, underwent reactions with various dienes to yield [4 + 2]-cycloadducts in excellent yields

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

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

• Subhas Chandra Pan Department of Chemistry, Indian Institute of Technology Guwahati, North Guwahati, Assam, 781039, India 10.3762/bjoc.8.159 Abstract Organocatalytic C–H activation reactions have recently been developed besides the traditional metal-catalysed C–H activation reactions. The recent

• non-asymmetric and asymmetric C–H activation reactions mediated by organocatalysts are discussed in this review. Keywords: asymmetric; C–H activation; non-asymmetric; organocatalysis; organocatalytic; Introduction C–H activation reactions have recently been found to be a powerful method for the

• chemoselective) reactions have been reported [1][2][3]. However, one drawback of this approach is the requirement of the removal of the metal impurity from the products. An organocatalytic approach is attractive in this sense as it is metal-free, cost-effective, and favoured by the pharmaceutical industry for

Organocatalytic asymmetric Michael addition of unprotected 3-substituted oxindoles to 1,4-naphthoquinone

• Jin-Sheng Yu,
• Feng Zhou,
• Yun-Lin Liu and
• Jian Zhou

Beilstein J. Org. Chem. 2012, 8, 1360–1365, doi:10.3762/bjoc.8.157

• Jin-Sheng Yu Feng Zhou Yun-Lin Liu Jian Zhou Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of Chemistry, East China Normal University, 3663 N. Zhongshan Road, Shanghai, 200062, P. R. China 10.3762/bjoc.8.157 Abstract We reported the first example of organocatalytic

• , together with our efforts in the synthesis of unsymmetric 3,3-diaryloxindoles [29], we try to develop a catalytic asymmetric method to enantioenriched 3,3-diaryloxindoles. In 2007, Jørgensen and coworkers pioneered the organocatalytic asymmetric addition reactions to quinones [30][31] which turned out to

• following steps. Even if there is much potential for further improvement in the ee, this sequential reaction represented the first example of catalytic asymmetric synthesis of 3,3-diaryl oxindoles. Conclusion In summary, we have developed the first example of organocatalytic Michael addition of unprotected

Asymmetric one-pot sequential Friedel–Crafts-type alkylation and α-oxyamination catalyzed by a peptide and an enzyme

• Kengo Akagawa,
• Ryota Umezawa and
• Kazuaki Kudo

Beilstein J. Org. Chem. 2012, 8, 1333–1337, doi:10.3762/bjoc.8.152

• ][6][7][8][9][10][11]. Especially because organocatalysts have been demonstrated to possess a high feasibility for sequential reactions [12][13][14][15][16], it is expected that a sequential reaction including an organocatalytic FCAA step could provide highly functionalized indole compounds [17][18

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

• , entries 18–19). The absolute configurations of the products were assigned by comparing the optical rotation of 3a with the value reported in the literature [48] (see the Supporting Information File 1 for details). In conclusion, we have developed the first organocatalytic decarboxylative Mannich reaction

Organocatalytic asymmetric allylic amination of Morita–Baylis–Hillman carbonates of isatins

• Hang Zhang,
• Shan-Jun Zhang,
• Qing-Qing Zhou,
• Lin Dong and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2012, 8, 1241–1245, doi:10.3762/bjoc.8.139

Combined bead polymerization and Cinchona organocatalyst immobilization by thiol–ene addition

• Kim A. Fredriksen,
• Tor E. Kristensen and
• Tore Hansen

Beilstein J. Org. Chem. 2012, 8, 1126–1133, doi:10.3762/bjoc.8.125

• their organocatalyst loadings were determined on the basis of CHN analysis, as only the organocatalytic moiety contains nitrogen. Generally, the yield of polymer beads, calculated on the basis of recovered material versus the combined mass of starting materials, varied between ca. 60–80%. Only an azo

• function in asymmetric transformations when compared to the unsupported catalysts. Asymmetric organocatalytic transformations using immobilized Cinchona organocatalysts With supported Cinchona organocatalysts 10–12 available, numerous organocatalytic transformations were potentially available for

Asymmetric total synthesis of smyrindiol employing an organocatalytic aldol key step

• Dieter Enders,
• Jeanne Fronert,
• Tom Bisschops and
• Florian Boeck

Beilstein J. Org. Chem. 2012, 8, 1112–1117, doi:10.3762/bjoc.8.123

• Dieter Enders Jeanne Fronert Tom Bisschops Florian Boeck Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany 10.3762/bjoc.8.123 Abstract The first organocatalytic asymmetric synthesis of smyrindiol, by using an (S)-proline catalyzed enantioselective

• diastereoselectivity, with a slight preference (18% versus 15%) towards the anti-isomer xanthoarnol (Scheme 2).We now wish to present the first diastereo- and enantioselective, organocatalytic, asymmetric synthesis of smyrindiol. Results and Discussion Retrosynthetic analysis Previously the proline-catalyzed

• acetonitril in the presence of water was found to cleave the acetonide selectively, yielding smyrindiol (1), whose spectroscopic data were identical to those published in the literature [9]. Conclusion In summary, we have developed the first asymmetric organocatalytic total synthesis of smyrindiol, using an

Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Pavol Jakubec,
• Dane M. Cockfield,
• Madeleine Helliwell,
• James Raftery and
• Darren J. Dixon

Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64

• reaction combining an enantioselective organocatalytic Michael addition with the diastereoselective nitro-Mannich/lactamisation cascade. Protodenitration and chemoselective reductive manipulation of the heterocycles was used to install contiguous and fully substituted stereocentres in the synthesis of

• an enantioenriched form by using an organocatalytic Michael addition methodology, which was developed by our group and others [54][55][56][57][58][59]. In pursuit of this we have successfully harnessed the power of the nitro-Mannich/lactamisation cascade in a formal synthesis of (3S,4R)-paroxetine

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

• Magnus Rueping Teerawut Bootwicha Erli Sugiono Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany 10.3762/bjoc.8.32 Abstract The asymmetric organocatalytic hydrogenation of benzoxazines, quinolines, quinoxalines and 3H-indoles in continuous-flow

• synthesis [56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80]; however, examples regarding asymmetric reactions as well as organocatalytic reactions are scarce [81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96]. Herein, we present the first

• example of a continuous-flow organocatalytic asymmetric transfer hydrogenation performed in a microreactor. In this work a ReactIR flow cell was coupled with the microreactor and applied as an inline monitoring device for optimizing the reactions. Results and Discussion The continuous-flow microreactor

Continuous-flow enantioselective α-aminoxylation of aldehydes catalyzed by a polystyrene-immobilized hydroxyproline

• Xacobe C. Cambeiro,
• Rafael Martín-Rapún,
• Pedro O. Miranda,
• Sonia Sayalero,
• Esther Alza,
• Patricia Llanes and
• Miquel A. Pericàs

Beilstein J. Org. Chem. 2011, 7, 1486–1493, doi:10.3762/bjoc.7.172

• organocatalytic approaches to the direct enantioselective α-aminoxylation of carbonyl compounds and, shortly after, to the implementation of the α-aminoxylation of aldehydes with proline as catalyst [14][15] (Scheme 1). In 2004, the scope of the reaction was extended to ketones [16][17] and the reaction was

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

• -catalyzed asymmetric fluorinations were discovered by others and ourselves, based on complexes of Pd(II) [46], Cu(II) [47][48][49], Ni(II) [48][50] and Ru(II) [51] as catalysts [4][51]. In parallel, organocatalytic asymmetric electrophilic fluorination of carbonyl compounds by means of phase-transfer

Multicomponent synthesis of artificial nucleases and their RNase and DNase activity

• Anton V. Gulevich,
• Lyudmila S. Koroleva,
• Olga V. Morozova,
• Valentina N. Bakhvalova,
• Vladimir N. Silnikov and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2011, 7, 1135–1140, doi:10.3762/bjoc.7.131

• organocatalytic three-component modification of the Ugi reaction, recently developed by List et al. [25]. The reaction results in diamines 4, thus avoiding the acid residue removal stage. The starting diisocyanides 3 were obtained in good overall yields from commercially available diamines containing 6, 7, 8, 10

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

• malononitriles 375 and N-Boc-protected imines 374 (Scheme 60) [176]. In the alkyne hydroamination (which is based on a bifunctional organocatalytic Mannich-type reaction, subsequent gold-catalyzed alkyne hydroamination and isomerization) thiourea-based hydrogen bonding organocatalyst 373 and PPh3AuNTf2 proved to

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• of the enantiomers of hindered enone 46 by addition, oxidation and elimination of a sulfenic acid under basic conditions (Scheme 18) [45]. Xiao and co-workers developed an organocatalytic process for the addition of thiols to nitroalkenes [46]. Using thiourea organocatalyst 48, conjugate addition of

• of enone 46. Organocatalytic conjugate addition to nitroalkenes 49. Preparation of β-amino acid 54. Sulfur migration within oxazolidine-2-thiones 56. Preparation of thiols 62 by self-regeneration of stereocentres. Synthesis of (5R)-thiolactomycin. Preparation of tertiary thiols and thioethers via α

Shelf-stable electrophilic trifluoromethylating reagents: A brief historical perspective

• Norio Shibata,
• Andrej Matsnev and
• Dominique Cahard

Beilstein J. Org. Chem. 2010, 6, No. 65, doi:10.3762/bjoc.6.65

• of alcohols with 35 in the presence of 1 equiv of Zn(NTf2)2. Formation of trifluoromethyl sulfonates from sulfonic acids and 35. Organocatalytic α-trifluoromethylation of aldehydes with 37. Synthesis of reagent 42 and mechanism of trifluoromethylation. Trifluoromethylation of β-ketoesters and

Enantioselective synthesis of tricyclic amino acid derivatives based on a rigid 4-azatricyclo[5.2.1.0^2,6]decane skeleton

• Matthias Breuning,
• Tobias Häuser,
• Christian Mehler,
• Christian Däschlein,
• Carsten Strohmann,
• Andreas Oechsner and
• Holger Braunschweig

Beilstein J. Org. Chem. 2009, 5, No. 81, doi:10.3762/bjoc.5.81

• (five steps). The required endo-orientation of the acetic acid moiety in 8a•HCl was confirmed by the X-ray structure of the corresponding free base 8a•MeOH (Figure 4). A first evaluation of the bowl-shaped amino acid derivatives 7 and 8 in standard organocatalytic aldol and Mannich reactions showed that

Asymmetric reactions in continuous flow

• Xiao Yin Mak,
• Paola Laurino and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19

• significantly higher when compared to a carousel-type reactor typically used for parallel synthesis. Organocatalytic asymmetric aldol reactions in microflow devices were recently reported by our laboratory [15]. The aldol condensation of various aromatic aldehydes with acetone was carried out at higher