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

• reaction was performed under mild conditions using PTSA·H2O as the additive. Subsequently, the asymmetric aldol reaction of aliphatic aldehydes with isatins was achieved by the same group by using a structurally slightly modified organocatalyst (cat. 5, Scheme 18) [34]. Malonic acid as the additive and

• hydrogen bonds with organocatalyst (cat. 5) and isatin substrate. A novel N-prolinylanthranilamide-based pseudopeptide organocatalyst (cat. 6) was designed by Bunge et al. for the enantioselective aldol reaction of 2,2-dimethyl-1,3-dioxan-5-one with isatins, affording the products in good yield and with

• designed another DACH-derived organocatalyst cat. 12 bearing an additional phenolic hydroxy group for the asymmetric aldol reactions of isatins with ketones. Cat. 12 can efficiently catalyze the reactions, affording the final compounds in excellent yields (up to 98% yield) and with good

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

• increased to 50% ee for diastereoisomer 7a when using chlorobenzene as the solvent at room temperature (Table 2, entry 5). It is worth noting that bifunctional organocatalyst VII appears to be more effective in terms of diastereocontrol than previously employed Brønsted base/Lewis acid system TMG/ZnI2

• the bifunctional organocatalyst structure and reaction conditions will be required for further improvements of the challenging cascade process. Organocatalysts screened in the cascade reaction. Synthesis of catalyst VIII. Asymmetric sulfa-Michael/nitroaldol reaction of nitroalkenes 1–3 with 1,4

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

• José M. Andrés,
• Miriam Ceballos,
• Alicia Maestro,
• Isabel Sanz and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61

• , homologous to V, was used as organocatalyst. Taking the supported thiourea V as the catalyst of choice, the effects of the catalyst loading, the temperature, the ratio of nucleophile, and the use of different solvents were studied for the reaction of 1a and 3a. Fortunately, the reduction of the amount of

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

• have exhibited efficient catalytic activity in the asymmetric Mannich reaction. In fact, the use of simple trans-(1R,2R)-aminoindanol (1c) as an efficient organocatalyst in the enantioselective synthesis of natural products as the TMC-954 core [12][13], has been recently reported. These examples show

• the high catalytic potential that this versatile motif exhibits [14]. The concept of bifunctionality has been extensively explored in organocatalysis in the last decade [15][16]. The bifunctional organocatalyst contains two chemical groups that interact simultaneously with the substrates. This mode of

• -type alkylation reaction of indoles To the best of our knowledge, the first example of an aminoindanol-containing bifunctional organocatalyst was reported by Ricci and co-workers in 2005 [18]. In this pioneering study, the authors used the easily prepared cis-(1R,2S)-aminoindanol-based thiourea

(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

• depicted in the left, in Scheme 2, seems to be operative, when the R group of the organocatalyst possesses a moiety, that is able to form hydrogen bonds, being the hydrogen bond donor. Employing this logic, many organocatalysts have been developed, possessing various groups, that are able to form hydrogen

• of a bifunctional catalyst. The first family of these bifunctional catalysts, that are going to be discussed, are the "primary amine-thioureas". Initially, catalyst 4 was studied as an organocatalyst in the addition of isobutyraldehyde (1) to (E)-methyl 2-oxo-4-phenylbut-3-enoate (2) for the

• malonates 6, to obtain 3,4,4-trisubstituted cyclohexanones 7 [17]. It is noted that the organocatalyst employed is the same with the previous example, catalyst 4. Furthermore, this reaction is taking place in the presence of PPY and high pressure was utilized. The authors proposed that PPY deprotonates the

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

• cinchona class of alkaloids are a dynamic and versatile type of organocatalyst that should be included in the screening libraries of chemists seeking to develop asymmetric methodologies. Review Morita–Baylis–Hillman (MBH) and MBH-carbonate reactions The first reports of an asymmetric reaction catalyzed by

• a cinchona organocatalyst with a 6’-OH functionality came from Hatakeyama and co-workers in 1999 who demonstrated the use of β-ICPD in an asymmetric Morita–Baylis–Hillman (MBH) reaction [15][16][17][18] what is essentially an asymmetric C3-substituted ammonium enolate reaction (Scheme 1) [19][20

• having a substituent at the 4-position of the ketimine. In a related study, Takizawa and co-workers demonstrated that the quinine derived organocatalyst, α-ICPN [23] produced the enantiomeric product in a similar process using acrolein 10 as the conjugate partner (Scheme 3b) [24]. Chen and co-workers

Asymmetric α-amination of β-keto esters using a guanidine–bisurea bifunctional organocatalyst

• Minami Odagi,
• Yoshiharu Yamamoto and
• Kazuo Nagasawa

Beilstein J. Org. Chem. 2016, 12, 198–203, doi:10.3762/bjoc.12.22

• presence of a guanidine–bisurea bifunctional organocatalyst was investigated. The α-amination products were obtained in up to 99% yield with up to 94% ee. Keywords: α-amination; bifunctional catalyst; guanidine; hydrogen-bonding catalyst; urea; Introduction Asymmetric α-amination of β-keto esters is an

• asymmetric reactions [19][20]. Recently, we disclosed an α-hydroxylation of tetralone-derived β-keto esters 2 using guanidine–bisurea bifunctional organocatalyst 1a in the presence of cumene hydroperoxide (CHP) as an oxidant (Figure 1a) [21]. This reaction provides the corresponding α-hydroxylation products

• expected that guanidine–bisurea bifunctional organocatalyst 1 would be effective in promoting α-amination of β-keto esters as a result of interactions between guanidine and enolate of the β-keto ester, and between urea and azodicarboxylate (Figure 1b). Herein, we describe the catalytic asymmetric α

Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen

• Hans Sterckx,
• Johan De Houwer,
• Carl Mensch,
• Wouter Herrebout,
• Kourosch Abbaspour Tehrani and
• Bert U. W. Maes

Beilstein J. Org. Chem. 2016, 12, 144–153, doi:10.3762/bjoc.12.16

• reactive alkyl-substituted pyridines. Gao showed that NH4I can also be used as an organocatalyst in combination with AcOH to facilitate the oxidation of benzylpyridines to benzoylpyridines [29]. Satoh and Miura showed that when replacing O2 for Na2S2O8 chemoselective methylenation occurred over oxygenation

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• the tricyclic core were controlled via Rh-catalyzed stereoselective C–H insertion and the subsequent reduction from the convex face. Keywords: bifunctional catalysis; hydrogen bonding; organocatalyst; oxa-Michael; prostacyclin; Introduction Prostacyclin (PGI2, Figure 1) is a physiologically active

• nucleophile and relatively unreactive Michael acceptors [27][28][29][30][31][32][33]. We envisioned that our recently developed powerful hydrogen bond (HB)-donor bifunctional organocatalyst [33] could promote the desired reaction of 7 or 8, which can be synthesized from commercial sources 9 or 10. Overall

• decreased the reactivity and enantioselectivity. However, we found that the newly developed organocatalyst E, bearing increased HB-donating abilities, could improve both the reactivity and selectivity. In addition, the Weinreb amide moieties of the AIOM adduct were shown to be efficiently converted to β

Convenient preparation of high molecular weight poly(dimethylsiloxane) using thermally latent NHC-catalysis: a structure-activity correlation

• Stefan Naumann,
• Johannes Klein,
• Dongren Wang and
• Michael R. Buchmeiser

Beilstein J. Org. Chem. 2015, 11, 2261–2266, doi:10.3762/bjoc.11.246

• situ from thermally susceptible CO2 adducts. It is demonstrated that the polymerization can be triggered from a latent state by mild heating, using the highly nucleophilic 1,3,4,5-tetramethylimidazol-2-ylidene as organocatalyst. This way, high molecular weight PDMS is prepared (up to >400 000 g/mol

• effective preparation of PDMS, including high molecular weight polymers. The results of a screening of a range of different NHCs indicate that a nucleophilic action of the organocatalyst is preferred over action as a Brønsted base. Comparison of conversion over time for D4 polymerization (80 °C, bulk) using

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

• Tommaso Pecchioli Manoj Kumar Muthyala Rainer Haag Mathias Christmann Institut für Chemie und Biochemie, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany 10.3762/bjoc.11.83 Abstract The first immobilization of a MacMillan’s first generation organocatalyst onto dendritic support is

• immobilization of imidazolidin-4-one onto hyperbranched polyglycerol (hPG) and its application as multivalent organocatalyst. Results and Discussion To explore the synthetic utility of hPG in organocatalysis, we here report the synthesis and application of a series of three multivalent dendronized imidazolidin-4

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

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

• amphiphilic, chiral organocatalysts (Scheme 10). If necessary, the free amino acids were liberated by subsequent treatment of the hydrochloride salt with aqueous Et3N. Up to >100 g of a given amphiphilic organocatalyst could be prepared in a single acylation, making the convenience of the reaction evident [61

A new charge-tagged proline-based organocatalyst for mechanistic studies using electrospray mass spectrometry

• J. Alexander Willms,
• Rita Beel,
• Martin L. Schmidt,
• Christian Mundt and
• Marianne Engeser

Beilstein J. Org. Chem. 2014, 10, 2027–2037, doi:10.3762/bjoc.10.211

• in the catalytic cycle or just serves as an rate limiting parasitic off-cycle equilibrium [31][33][35][52]. Thus, we aimed to synthesize a charge-tagged L-proline-based organocatalyst for mechanistic studies by ESIMS. Few proline derivatives carrying a covalently fixed charge have been reported by

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