Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• reactions as those reported above, phosphoramidates, prepared by AT reactions, can also act as an organocatalyst. Indeed, with the strongly polarized P–O bond on one hand, and the P–N or P–NH bond on the other hand phosphoramides are good Lewis bases [96][97][98]. Hexamethylphosphoric triamide (HMPA) (or

• analogues) was the first phosphoramide derivative that was extensively studied as an organocatalyst [98][99]. However, HMPA was classified as a human carcinogen [100]. One of the first examples of the use of chiral phosphoramide ligands (Scheme 32-i) in organocatalysis was described by Denmark et al. who

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• favored by the spartein auxiliary. The enantioselectivity was found to be time and temperature dependent. Simple stirring of the intermediate (−)-sparteine–lithium complex of 13a for 1 h at 25 °C prior to alkylation resulted in an increase in enantiomeric excess of 14a. The organocatalyst 16 has also been

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• and strongly basic conditions [19]. Kang et al. achieved a highly enantioselective synthesis of an isoindolo[2,1-a]quinoline derivative by affecting an intramolecular ring closure on (E)-3-(2-(isoindolin-2-yl)phenyl)acrylaldehyde using camphorsulfonic acid and a chiral pyrrolidine organocatalyst [20

Organocatalytic asymmetric fluorination of α-chloroaldehydes involving kinetic resolution

• Kazutaka Shibatomi,
• Takuya Okimi,
• Yoshiyuki Abe,
• Akira Narayama,
• Nami Nakamura and
• Seiji Iwasa

Beilstein J. Org. Chem. 2014, 10, 323–331, doi:10.3762/bjoc.10.30

• enantioselective α-fluorination of racemic α-chloroaldehydes with a chiral organocatalyst yielded the corresponding α-chloro-α-fluoroaldehydes with high enantioselectivity. It was also revealed that kinetic resolution of the starting aldehydes was involved in this asymmetric fluorination. This paper describes the

• catalysis; chlorination; fluorination; organocatalyst; organo-fluorine; Introduction Fluorinated organic molecules are of considerable interest in pharmaceutical and agricultural chemistry owing to the unique properties of the fluorine atom [1][2]. These compounds, especially with one or more fluorinated

• resolution. Results and Discussion In our previous study [8], enantioselective fluorination of racemic 2-chloro-3-phenylpropanal (2a) was carried out with 3 equiv of NFSI in the presence of organocatalyst (S)-1 to yield the corresponding α-chloro-α-fluoroaldehyde 3a in good conversion. Isolation of the

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• . Fluorination makes β-lactam derivatives more reactive towards lipase-catalysed methanolysis. Hyperconjugation rigidifies the ring pucker of a fluorinated organocatalyst 14, leading to higher enantioselectivity. General strategy for the synthesis of fluorinated N-heterocycles via deoxyfluorination. During the

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

• aldehydes was performed under synergistic activation of the substrate by gold catalyst 20c and organocatalyst 116 (Scheme 30). The 5-membered hetero- and carbocycles 115 were obtained in moderate to good yield and interesting level of diastereo- and enantioselectivity, supporting the perfect compatibility

Gallium-containing polymer brush film as efficient supported Lewis acid catalyst in a glass microreactor

• Rajesh Munirathinam,
• Roberto Ricciardi,
• Richard J. M. Egberink,
• Jurriaan Huskens,
• Michael Holtkamp,
• Herbert Wormeester,
• Uwe Karst and
• Willem Verboom

Beilstein J. Org. Chem. 2013, 9, 1698–1704, doi:10.3762/bjoc.9.194

• channel wall. Polymer brushes have proven to provide a unique platform in supported catalysis [14][15]. Previously, we have described the successful immobilization and evaluation of catalysts (e.g., basic organocatalyst [6], metallic nanoparticles [16], and enzymatic catalyst [17]) to the microchannel

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• moderate enantioselectivities (up to 61% ee, Scheme 7). The dual activation mode of α,α-diphenyl-L-prolinol (OC-23) for the desymmetrization of meso-N-acylaziridines is proposed in this context (Figure 7). The arylthiol was deprotonated by the pyrrolidinyl-N of the organocatalyst to produce a highly active

• nucleophile, while the meso-N-acylaziridine was activated by the tertiary-hydroxy group of the organocatalyst by hydrogen-bonding interaction with the carbonyl-O of the acyl group in meso-N-acylaziridine. The latter was attacked by the highly active thio anion to furnish chiral β-amino thioethers in good

• phosphine oxide-catalyzed asymmetric ring-opening of meso-epoxides has been realized by Nakajima [83] and co-workers and proved to be very effective. They have prepared a chiral phosphine oxide BINAPO (OC-63) based on a binaphthyl-skeleton, which was utilized as an organocatalyst for the enantioselective

Bioinspired total synthesis of katsumadain A by organocatalytic enantioselective 1,4-conjugate addition

• Yongguang Wang,
• Ruiyang Bao,
• Shengdian Huang and
• Yefeng Tang

Beilstein J. Org. Chem. 2013, 9, 1601–1606, doi:10.3762/bjoc.9.182

• studies. To validate this hypothesis, we performed a systematic investigation of the organocatalytic 1,4-conjugate addition by examining various reaction parameters, including organocatalyst, acid additive, solvent temperature, and reaction temperature (Table 1). The first reaction was performed by

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

• organocatalyst, dienophile 3 and diene 4 were stirred together at room temperature with an equimolar amount of the prospective organocatalyst in the absence of any solvent. The catalytic performance was classified by the acceleration of the reaction time compared to the uncatalyzed reaction (Table 2, entry 1

• ). At first, the use of MacMillan's imidazolidinone organocatalyst 6 [12] was examined, but no catalytic effect was observed (Table 2, entry 2). The usage of L-proline as a bifunctional catalyst only gave a slight improvement compared to the uncatalyzed reaction (Table 2, entry 3). Whereas the addition

Metal-free aerobic oxidations mediated by N-hydroxyphthalimide. A concise review

• Lucio Melone and
• Carlo Punta

Beilstein J. Org. Chem. 2013, 9, 1296–1310, doi:10.3762/bjoc.9.146

• organocatalyst. Once reached, this final goal, combined with the use of molecular oxygen as stoichiometric oxidant under mild operative conditions, would definitely open the way towards much more cost-effective and environmentally friendly oxidative processes. Mediators of laccase. Catalytic role of NHPI in the

Synthesis of the tetracyclic core of Illicium sesquiterpenes using an organocatalyzed asymmetric Robinson annulation

• Lynnie Trzoss,
• Jing Xu,
• Michelle H. Lacoske and
• Emmanuel A. Theodorakis

Beilstein J. Org. Chem. 2013, 9, 1135–1140, doi:10.3762/bjoc.9.126

• ] using D-prolinamide as the organocatalyst (Scheme 1). Performing this reaction at 80 °C gave rise to bicyclic motif 8 in about 70% ee (70 % yield after 12 h), while decreasing the temperature to 25 °C increased the enantioselectivity to over 99% (70% yield after 60 days). To compromise between high

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

• ]. The route required a significant quantity of an orthogonally protected piperazic acid (Figure 10). This was achieved using a new enantioselective organocatalytic protocol with a tetrazole organocatalyst, which afforded dihydro pyridazines from achiral aldehydes [61][62]. Unfortunately, while this

Enantioselective reduction of ketoimines promoted by easily available (S)-proline derivatives

• Martina Bonsignore,
• Maurizio Benaglia,
• Laura Raimondi,
• Manuel Orlandi and
• Giuseppe Celentano

Beilstein J. Org. Chem. 2013, 9, 633–640, doi:10.3762/bjoc.9.71

• shown to promote the enantioselective reduction of different substrates in good chemical yields. In the HSiCl3 addition to the model substrate N-phenylacetophenone imine, the organocatalyst of choice led to the formation of the corresponding amine with good stereoselectivity, up to 75% ee. Theoretical

Mechanochemistry assisted asymmetric organocatalysis: A sustainable approach

• Pankaj Chauhan and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2012, 8, 2132–2141, doi:10.3762/bjoc.8.240

• )-tryptophan (IV) was shown to be an efficient organocatalyst for asymmetric aldol reactions of ketones with aromatic aldehydes in the presence of water by using HSBM (Scheme 4) [37]. The corresponding aldol products 3 were obtained in good yield (64–90%), low to high diastereoselectivity (40:60 to 98:2 dr

• proceeded rapidly in the presence of 20 mol % of VIII under solvent-free ball-milling conditions to provide the desired Michael adducts 8 in 44–97 % yield, 51:49 to 95:5 dr and 62–94% ee. It was also observed that the combination of an organocatalyst with solvent-free ball-milling was more efficient than

• ) [48]. Grinding an equimolar quantity of six/five-membered cyclic β-ketoesters 13 and various nitroalkenes 7, including nitrodienes, in the presence of 5 mol % of cupreine-derived organocatalyst X provided Michael adducts 14 in good to high yield (72–99%) and good to excellent stereoselectivity (85–99

Automated three-component synthesis of a library of γ-lactams

• Erik Fenster,
• David Hill,
• Oliver Reiser and
• Jeffrey Aubé

Beilstein J. Org. Chem. 2012, 8, 1804–1813, doi:10.3762/bjoc.8.206

• asymmetric organocatalyzed reaction in the Michael addition step, (b) combining the individual three steps, and (c) automating the process to produce a demonstrative 256 member γ-lactam library. Asymmetric organocatalyzed Michael addition The success of pyrrolidine as the organocatalyst for the Michael

• calcium hydride. The maleimides 1, the aldehydes 2, the amines 3 and the chiral amine organocatalyst (A–I) were purchased from the Aldrich Chemical Co. and used without further purification. Melting points were performed by using an Optimelt (MPA100) automated melting-point system (Sanford Research

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

• /hemiacetal sequence with chiral or achiral secondary amines as organocatalysts. Thus, a series of achiral pyrazolidine derivatives were obtained with good yields (up to 90%) and high diastereoselectivities (>20:1) with pyrrolidine as an organocatalyst, and enantioenriched pyrazolidines are also achieved with

• screening results are summarized in Table 3. (S)-Proline derivatives 1g–h, 1k, 1l were found to be ineffective for the reaction, because they afford only trace products after one day (Table 3, entries 1, 2, 5 and 6). Although a moderate yield was obtained with organocatalyst 1i bearing a sulfone functional

• pyrazolidine derivatives through the cascade aza-Michael/hemiacetal reaction between disubstituted hydrazines and α,β-unsaturated aldehydes. The asymmetric version of this one-pot cascade reaction has also been realized with (S)-diphenylprolinol trimethylsilyl ether 1m as a secondary amine organocatalyst, and

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

• 2006, using diarylprolinolether as an effective organocatalyst. This method involved an oxa-Michael attack of salicylaldehydes 1 on the α,β-unsaturated aldehydes 2 activated through an iminium ion formation with the catalyst Ib, followed by an intramolecular aldol reaction and the subsequent water

• sieves (4 Å) in the reaction (Scheme 2). Wang et al. [44] investigated the same tandem reaction of salicylaldehydes 1 and α,β-unsaturated aldehydes 2 employing TES-protected diphenylprolinol Ie as organocatalyst with high catalyst loading (30 mol %). With benzoic acid as cocatalyst and dichloroethane as

• solvent, the test reaction provided the chiral chromenes 3 in good yields (up to 98%) and enantioselectivities (99%) at room temperature (Scheme 3). In 2009, Xu et al. [45] developed an efficient protocol for the asymmetric tandem oxa-Michael–aldol reaction using chiral amine/chiral acid organocatalyst

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

• use of tri-n-butylphosphane (20 mol %) as a nucleophilic organocatalyst in MeOH solution allows cyclization to take place under much milder conditions (60–70 °C). Several coumarins were prepared, starting from ortho-hydroxyarylaldehydes, by Wittig reaction with Ph3P=CHCO2Me to (E)-methyl ortho

Synthesis and evaluation of new guanidine-thiourea organocatalyst for the nitro-Michael reaction: Theoretical studies on mechanism and enantioselectivity

• Tatyana E. Shubina,
• Matthias Freund,
• Sebastian Schenker,
• Timothy Clark and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2012, 8, 1485–1498, doi:10.3762/bjoc.8.168

• Organic Chemistry I, University of Erlangen-Nuremberg, Henkestraße 42, 91054, Erlangen, Germany 10.3762/bjoc.8.168 Abstract A new guanidine-thiourea organocatalyst has been developed and applied as bifunctional organocatalyst in the Michael addition reaction of diethyl malonate to trans-β-nitrostyrene

• . Extensive DFT calculations, including solvent effects and dispersion corrections, as well as ab initio calculations provide a plausible description of the reaction mechanism. Keywords: bifunctional organocatalyst; DFT calculations; guanidine-thiourea; Michael addition; organocatalysis; transition states

• -thiourea organocatalyst has been published up until now [50][51][52][53]. This encouraged us to synthesize and investigate the potential of new guanidine-thiourea 7 as organocatalyst for the nitro-Michael addition reactions. Here we report the first results of our investigations, accompanied by quantum

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

• bicyclic guanidines [7][9][12]. Xiao et al. reported the addition of nitroalkanes to 4-oxo-enoates, using chiral urea derivatives [7]. Miura et al. achieved an asymmetric addition of α,α-disubstituted aldehydes to maleimides catalyzed by primary amine thiourea organocatalyst [13]. Wang et al. reported the

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

• representative of each class was briefly tested in the desymmetrization of anhydride 4. Under the conditions described above for organocatalyst (S)-3 two catalyses were performed with (S)-12 (10 mol %) and (RS,SC)-19 (5 mol %). Whereas benzene-bridged sulfonimidoyl-containing thiourea (S)-12 provided the product

• reaction. As catalysts, substoichiometric quantities of the sulfonimidoyl-containing thioureas in combination with 10 mol % of trifluoroacetic acid (TFA) were applied. The results are summarized in Table 1. The experiment with 10 mol % of chiral organocatalyst (S)-3 served as starting point (Table 1, entry

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

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

• the first step, a phenyl radical generated from iodobenzene reacts with benzene to afford phenylcyclohexadienyl radical (24) (Scheme 17). Radical 24 is then deprotonated by potassium tert-butoxide to generate the biphenyl radical anion (25), potentially promoted by an organocatalyst. In the last step

• , radical anion 25, a strong reducing agent, transfers one electron to starting iodobenzene and results in the formation of biphenyl, potassium iodide and phenyl radical (Scheme 17). However, the role of the organocatalyst is still not fully understood at this point and detailed mechanistic studies are

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

• immobilization of Cinchona organocatalysts using thiol–ene chemistry, in which catalyst immobilization and bead polymerization is combined in a single step. A solution of azo initiator, polyfunctional thiol, polyfunctional alkene and an unmodified Cinchona-derived organocatalyst in a solvent is suspended in

• organocatalyst precursors. Results and Discussion Building blocks for the preparation of cross-linked thiol–ene resins Research oriented towards thiol–ene chemistry has experienced near explosive growth in the past few years, perhaps due to its efficiency and functional tolerance, but possibly even more due to

• 4–9, thereby adjusting the degree of cross-linking. As for the Cinchona organocatalysts, we wanted to incorporate either unmodified quinine (1), the primary amine organocatalyst 2, or thiourea organocatalyst 3 into the thiol–ene network (Figure 1). While quinine is available directly, primary amine

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

• novel total synthesis should allow the synthesis of larger quantities of the natural compound without having to rely on natural sources. Needless to mention, the unnatural enantiomer could be synthesized if (R)-proline were to be used as the organocatalyst. In addition, the Sonogashira/Lindlar reduction