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

• organocatalysis has allowed for selective C–C bond formation by using small organic molecules [25][26][27][28][29][30][31]. In contrast to metal complexes, chiral or achiral organocatalysts are easily attached on supports. They do not suffer from metal leaching and they can be reused more readily [32][33][34][35

• support in asymmetric organocatalysis. The use of chiral imidazolidinones in organocatalysis has been extensively reported for a wide range of enantioselective reactions involving α,β-unsaturated aldehydes, such as the Diels–Alder reactions [50], 1,3-dipolar cycloadditions [51] and Friedel–Crafts

• 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

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

• ; organocatalysis; serine; threonine; tyrosine; Introduction Any adept researcher within the field of organic synthetic chemistry will be mindful of the outstanding importance of amino acids as inexpensive chiral starting materials in the synthesis of a nearly infinite variety of synthetic end products. This

• considerable period of time, having its origins in biochemical studies, but has not become widespread until recent developments related to organocatalysis further improved and popularized its application. Hopefully, the present work will convince chemists unfamiliar with the procedure how it in many cases can

• asymmetric organocatalysis In the previous section, the developmental history of acidic acylation methodologies for chemoselective O-acylation of hydroxyamino acids has been chronicled, from its inception in the early 1940s until the 1990s. In particular, the identification and application of suitable

Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars

• Christopher Albler,
• Ralph Hollaus,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2014, 10, 2230–2234, doi:10.3762/bjoc.10.231

• azide reduction followed by final deacetylation using methanolic sodium methoxide furnishes the title compounds. Keywords: allylation; carbohydrates; epoxidation; indium; multivalent glycosystems; organocatalysis; Introduction The indium-mediated allylation of carbonyl compounds has proven to be a

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• carbonates, Michael additions, γ-umpolung additions, and acylations of alcohols. Keywords: asymmetric catalysis; chiral phosphine; nucleophilic; organocatalysis; organophosphorus; synthesis; Introduction During the past two decades, tertiary phosphine catalysts have been applied extensively in a wide range

• , and generally display poor enantioselectivities for phosphine organocatalysis. For example, 2,2´-bis(diphenylphosphino)-1,1´-binaphthyl (BINAP) is an excellent chiral diphosphine ligand for metal-catalyzed asymmetric reactions, but it displays extremely poor reactivity and enantioselectivity in many

• nucleophilic phosphine-catalyzed reactions. For these reasons, effective chiral catalysts for nucleophilic phosphine catalysis are scarce, seriously limiting the development of asymmetric variants. At present, the synthesis of new chiral phosphines designed specifically for nucleophilic organocatalysis remains

Organophosphorus chemistry

• Paul R. Hanson

Beilstein J. Org. Chem. 2014, 10, 2087–2088, doi:10.3762/bjoc.10.217

• inhibitors. More specifically, the Thematic Series spans new methods in C–P bond formation, chiral phosphines in nucleophilic organocatalysis, chiral N-phosphinyl auxiliaries, cyclic phosphonamide reagents in the total synthesis of natural products, phosphinate-containing heterocycles, new routes to

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

• temporal evolution has been followed using a microreactor continuous-flow technique. Keywords: charge tag; electrospray; mass spectrometry; organocatalysis; proline; template; Introduction Electrospray ionization (ESI) mass spectrometry [1] has not only developed into a standard characterization method

• reactions with high efficiency and selectivity are nowadays known so that organocatalysis complements current catalytic fields such as organometallic or enzymatic catalysis as an independent subdomain [24][25][26][27][28][29][30]. Parallel to the enormous growth of organocatalytic applications in synthesis

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• no reaction was observed [37]. With these data in mind, we decided to evaluate a few reactions of cinnamyloxy benzotriazolyl derivative 1g. However, instead of using preformed enamines, we chose to utilize a combination of metal- and organocatalysis, wherein the enamine is formed in situ [38

Visible-light photoredox catalyzed synthesis of pyrroloisoquinolines via organocatalytic oxidation/[3 + 2] cycloaddition/oxidative aromatization reaction cascade with Rose Bengal

• Carlos Vila,
• Jonathan Lau and
• Magnus Rueping

Beilstein J. Org. Chem. 2014, 10, 1233–1238, doi:10.3762/bjoc.10.122

• /oxidative aromatization cascade using Rose Bengal as an organo-photocatalyst. A variety of pyrroloisoquinolines have been obtained in good yields under mild and metal-free reaction conditions. Keywords: alkaloids; [3 + 2] cycloaddition; organocatalysis; oxidation; photochemistry; photoredox catalysis; Rose

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

• 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

• reagent for organocatalysis [1]. The methods most widely used for the synthesis of phosphines include the reaction of organometallic compounds with halophosphines, the reaction of metal phosphides with alkyl halides, the reduction of other phosphorus compounds and the hydrophosphination [2]. Research in

On the mechanism of photocatalytic reactions with eosin Y

• Michal Majek,
• Fabiana Filace and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2014, 10, 981–989, doi:10.3762/bjoc.10.97

• discussed on the basis of pH, solvent polarity, lamp type, absorption properties, and quantum yields. Determination of the latter proved to be an especially valuable tool for the distinction between radical chain and photocatalytic reactions. Keywords: mechanism; organocatalysis; photocatalysis; photoredox

Primary-tertiary diamine-catalyzed Michael addition of ketones to isatylidenemalononitrile derivatives

• Akshay Kumar and
• Swapandeep Singh Chimni

Beilstein J. Org. Chem. 2014, 10, 929–935, doi:10.3762/bjoc.10.91

• -component version of the reaction by a domino Knoevenagel–Michael sequence. The Michael adduct 4a was transformed into spirooxindole 6 by a reduction with sodium borohydride in a highly enantioselective manner. Keywords: 3,3'-disubstituted oxindoles; Michael reaction; organocatalysis; primary-tertiary

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• almost quantitative yields of up to 98% and enantiomeric excesses of up to 51%. The cyclodiphosphazane catalysts show the same high activity and give improved enantiomeric excesses of up to 75%, thus representing the first successful application of a cyclodiphosphazane in enantioselective organocatalysis

• the catalyst. Keywords: DFT computations; hydrogen bonding; Michael addition; organocatalysis; phosphazanes; Introduction Organocatalysis has gained great impact in promoting highly enantioselective [1][2][3][4] and eco-friendly [5] reactions. Within the field of organocatalysis hydrogen-bonding (HB

• donors such as (thio)ureas in the tested Michael addition. A fine tuning of the structural motifs might improve enantioselectivity even further. Especially the rigid and sterically crowded PV-cyclodiphosphazane structures will have a high potential for future catalyst designs not only in organocatalysis

Modulating NHC catalysis with fluorine

• Yannick P. Rey and
• Ryan Gilmour

Beilstein J. Org. Chem. 2013, 9, 2812–2820, doi:10.3762/bjoc.9.316

• of functional small molecules [13][14][15][16][17][18][19][20][21][22], often for application in organocatalysis [1]. Common to these studies has been the strategic incorporation of a fluoro substituent vicinal to a catalytically active amino group. Subsequent generation of a (partial) positive

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

• changes can be rationally exploited for the benefit of diverse fields such as medicinal chemistry and organocatalysis. This brief review will examine some of the effects that fluorine substitution can have in N-heterocycles, including changes to the molecules’ stability, their conformational behaviour

• clear that medicinal chemistry is not the only field that stands to benefit from a deeper understanding of these fascinating molecules: for example, attractive prospects are also clear in the field of organocatalysis [13]. 2. Fluorination can influence N-heterocycles’ stability and reactivity If a

• the context of organocatalysis. Fluorination of proline itself, as well as related N-heterocycles, has been shown to increase enantioselectivity in certain organocatalytic processes [13]. For example, Alexakis and co-workers found that the non-fluorinated catalyst 13 (Scheme 2) catalysed an alkylation

A combined continuous microflow photochemistry and asymmetric organocatalysis approach for the enantioselective synthesis of tetrahydroquinolines

• Erli Sugiono and
• Magnus Rueping

Beilstein J. Org. Chem. 2013, 9, 2457–2462, doi:10.3762/bjoc.9.284

• dihydropyridine as hydrogen source providing the desired products in good yields and with excellent enantioselectivities. Keywords: asymmetric transfer hydrogenation; binolphosphate; continuous-flow reactors; flow chemistry; microreactors; organocatalysis; photochemistry; Introduction Tetrahydroquinolines [1][2

An investigation of the observed, but counter-intuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines

• Thomas C. Nugent,
• Richard Vaughan Williams,
• Andrei Dragan,
• Alejandro Alvarado Méndez and
• Andrei V. Iosub

Beilstein J. Org. Chem. 2013, 9, 2103–2112, doi:10.3762/bjoc.9.247

• amines). Amines are known to be potent pharmacophores, and medicinal chemists have further leveraged their beneficial properties by using chiral versions to enhance protein binding affinities. Furthermore, chiral amines continue to find expanded roles: in organocatalysis [1][2][3][4], as ligands for

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

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

• Ping-An Wang Department of Medicinal Chemistry, School of Pharmacy, Fourth Military Medical University, Changle Xilu 17, Xi-An, 710032, P. R. China 10.3762/bjoc.9.192 Abstract Enantioselective desymmetrization of meso-aziridines and meso-epoxides with various nucleophiles by organocatalysis has

• emerged as a cutting-edge approach in recent years. This review summarizes the origin and recent developments of enantioselective desymmetrization of meso-aziridines and meso-epoxides in the presence of organocatalysts. Keywords: aziridine; desymmetrization; enantioselectivity; epoxide; organocatalysis

An organocatalytic route to 2-heteroarylmethylene decorated N-arylpyrroles

• Alexandre Jean,
• Jérôme Blanchet,
• Jacques Rouden,
• Jacques Maddaluno and
• Michaël De Paolis

Beilstein J. Org. Chem. 2013, 9, 1480–1486, doi:10.3762/bjoc.9.168

• regioselective oxidation of these substrates is demonstrated, extending the molecular diversity and versatility of these scaffolds. Keywords: C–H oxidation; isomerization; N-arylpyrrole; organocatalysis; Introduction Due to their presence in some natural products [1] and pharmaceuticals [2][3][4], the

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

• tricycle of beticolin 0 (1) and is also a valuable model substrate for the total synthesis of related natural products. Keywords: beticolin 0; Diels–Alder reaction; natural product; organocatalysis; thiourea catalysis; total synthesis; Introduction In the past few years, many different types of

• pioneering research in organocatalysis. C.S.K. acknowledges the Fonds der Chemischen Industrie for a Kekulé scholarship.

Transition-metal and organocatalysis in natural product synthesis

• David Yu-Kai Chen and
• Dawei Ma

Beilstein J. Org. Chem. 2013, 9, 1192–1193, doi:10.3762/bjoc.9.134

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

• . Keywords: natural products; neurodegenerative diseases; neurotrophic small molecule; organocatalysis; total synthesis; Introduction Neurotrophins are a family of endogenous proteins that are vital for neuron function, survival, and regeneration [1][2][3]. As such, they have prompted intense studies toward

• (Figure 2). Results and Discussion During the past 20 years, organocatalysis has emerged as an important field in asymmetric stereoselective synthesis due to its advantages, which include high enantioselectivity, environmental friendliness and ease of handling [27][28][29][30][31][32][33][34][35][36][37

1-n-Butyl-3-methylimidazolium-2-carboxylate: a versatile precatalyst for the ring-opening polymerization of ε-caprolactone and rac-lactide under solvent-free conditions

• Astrid Hoppe,
• Faten Sadaka,
• Claire-Hélène Brachais,
• Gilles Boni,
• Jean-Pierre Couvercelle and
• Laurent Plasseraud

Beilstein J. Org. Chem. 2013, 9, 647–654, doi:10.3762/bjoc.9.73

• under vacuo (method A) or by addition of NaBPh4 (method B). Possible catalytic and deactivation mechanisms are proposed. Keywords: aliphatic polyesters; green polymerization reaction; imidazolium-2-carboxylates; N-heterocarbene precursor; organocatalysis; Introduction Poly(ε-caprolactone) (PCL) and

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

• studies were also performed in order to elucidate the origin of the stereoselection. Keywords: chiral prolines; imine reduction; Lewis bases; organocatalysis; trichlorosilane; Introduction The reaction with stoichiometric amounts of trichlorosilane in the presence of a chiral catalyst is a well

• stereoselettiva di molecole funzionali" is gratefully acknowledged. M. B. thanks COST action CM9505 “ORCA” Organocatalysis. We thank Prof. Franco Cozzi for helpful discussions.

NHC-catalysed highly selective aerobic oxidation of nonactivated aldehydes

• Lennart Möhlmann,
• Stefan Ludwig and
• Siegfried Blechert

Beilstein J. Org. Chem. 2013, 9, 602–607, doi:10.3762/bjoc.9.65

• -free oxidation; N-heterocyclic carbene; organocatalysis; Introduction The development of efficient and selective aerobic oxidation methods for organic substrates is of increasing interest and an attractive goal in green chemistry [1][2][3]. In a recent communication we reported on selective oxidation