Organocatalytic Synthesis of Drugs and Bioactive Natural Products

Figueiredo, Renata Marcia de; Christmann, Mathias

doi:10.1002/ejoc.200700032

Cited by 371 publications

(72 citation statements)

References 189 publications

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“…More recently it was confirmed that relatively simple organic molecules could be highly effective and remarkably enantioselective catalysts of a variety of fundamentally important transformations (de Figueiredo and Christmann, 2007;Enders et al, 2007;Pellissier, 2007). Several examples on application of organocatalysis in combination with homogeneous catalysis for enantioselective reactions are summarized in Enders et al (2007).…”

Section: Organo-chemical Transformationsmentioning

confidence: 97%

Sustainable chemical technology through catalytic multistep reactions

Murzin

Leino

2008

Chemical Engineering Research and Design

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Section: Organo-chemical Transformationsmentioning

confidence: 97%

Sustainable chemical technology through catalytic multistep reactions

Murzin

Leino

2008

Chemical Engineering Research and Design

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“…[1][2][3][4][5][6][7][8][9][10][11][12] Since the pioneering work in this area by the groups of MacMillan, [13] and Barbas, [14] numerous publications have appeared in which the design, synthesis and uses of a variety of organocatalysts is described. Today, one of the biggest challenges in the synthesis of organic compounds is the implementation of procedures that are more friendly to the environment.…”

Section: Introductionmentioning

confidence: 99%

“…[22,23] The Michael addition is considered as one of the most powerful tools for the formation of C-C bonds. [1][2][3][4][5][6][7][8][9][10][11][12] In recent years, the number of publications on the study of this organocatalytic reaction has increased considerably. [1] In 1980, Seebach and coworkers reported the reaction of achiral enamines with β-nitrostyrene with good yields and excellent diastereoselectivities.…”

Section: Introductionmentioning

confidence: 99%

Use of (R)-Mandelic Acid as Chiral Co-Catalyst in the Michael Addition Reaction Organocatalyzed by (1S,4S)-2-Tosyl-2,5-diazabicyclo[2.2.1]heptane under Solvent-Free Conditions

Avila‐Ortiz

López-Ortíz

Vega‐Peñaloza

et al. 2015

Asymmetric Catalysis

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This article describes a study on the Michael addition reaction of cyclohexanone to nitroolefins catalyzed by the chiral secondary amine (1S,4S)-2-tosyl-2,5-diazabicyclo[2.2.1]heptane. Reactions were carried out under solvent-free conditions to make them more environmentally friendly. Initially, the observed diastereoand enantioselectivities were moderate to good, but were significantly improved by lowering the reaction temperature. Furthermore, a variety of chiral acids were also tested as co-catalysts in both of their enantiomeric forms, which revealed that (R)-mandelic acid affords excellent results in terms of yield and stereoselectivity. Monitoring the reaction by MS-TOF allowed for the detection of key reaction intermediates, and a reasonable reaction mechanism in which both catalysts are involved is proposed.

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“…The employment of a metal-free approach [10] stems from our recent findings on the intramolecular base-catalyzed synthesis of 1, from readily available precursors 3 (Scheme 2).…”

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confidence: 99%

Enantioselective Phase‐Transfer‐Catalyzed Intramolecular Aza‐Michael Reaction: Effective Route to Pyrazino‐Indole Compounds

et al. 2008

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The preparation of enantiomerically pure compounds has become a stringent requirement for pharmaceutical synthesis. [1] In this context, asymmetric catalysis is probably the most attractive procedure for the synthesis of active pharmaceutical ingredients (APIs) due to environmental, operational, and economic benefits.3,4-Dihydropyrazino[1,2-a]indol-1(2H)-ones 1 (see Scheme 1) have attracted much attention due to the broad scope of their biological activities (that is, their antifungal properties, noncompetitive antihistamine activity, and specific inhibition of serotonergic receptors).[2] Moreover, recent patents reported the effectiveness of the corresponding 1,2,3,4-tetrahydropyrazino[1,2-a]indoles 2 (Scheme 1) as antiobesity agents and in the treatment and prevention of noninsulin-dependent diabetes. [3] From these studies, the importance of the absolute configuration of the stereocenters on the pharmacological activity emerged clearly. Moreover, since the piperazine compounds 2 are readily obtainable from 1,[3] the development of an effective stereoselective synthetic route to pyrazino-indol-1-ones 1 would be extremely valuable. The use of chiral pools and the resolution of racemates are the only synthetic routes to 1 and 2 to date. [3][4][5] During our ongoing research addressing the functionalization of polycyclic indoles, [6] we recently communicated an efficient Pd-catalyzed approach to tetrahydro-b-carbolines through regio-and enantioselective C3-allylic nucleophilic alkylation (up to 97 % ee).[7] Unfortunately, all our attempts to exploit such an approach to perform enantioselective indolyl-N1 ring-closing reactions were unsuccessful. Herein, we describe the first highly enantioselective synthesis of molecular motifs of type 1 through a phase-transfer-catalyzed [8] aza-Michael addition.[9]The employment of a metal-free approach [10] stems from our recent findings on the intramolecular base-catalyzed synthesis of 1, from readily available precursors 3 (Scheme 2).[11] However, the use of Lewis acid catalysis in the present ring-closing reaction failed, probably due to the poor electrophilic character of the a,b-unsaturated ester and to low catalyst turnover as a result of starting material/ product inhibition (that is, a metallo-poisoning effect exerted by the strongly coordinating amide group). Searching for an enantioselective variant, we firstly turned our attention to chiral organic bases such as the Cinchona alkaloids and sparteine, which gave disappointing results in the cyclizations of 3 a (X = H; toluene, reflux, 48 h, 0 % ee). We reasoned that the unsatisfactory stereoinduction could be ascribable to the formation of flexible and not sufficiently tight ion pairs between the ammonium salt of the quinuclidine ring and the nucleophilic indolate intermediate (Figure 1 a).

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Organocatalytic Synthesis of Drugs and Bioactive Natural Products

Cited by 371 publications

References 189 publications

Sustainable chemical technology through catalytic multistep reactions

Sustainable chemical technology through catalytic multistep reactions

Use of (R)-Mandelic Acid as Chiral Co-Catalyst in the Michael Addition Reaction Organocatalyzed by (1S,4S)-2-Tosyl-2,5-diazabicyclo[2.2.1]heptane under Solvent-Free Conditions

Enantioselective Phase‐Transfer‐Catalyzed Intramolecular Aza‐Michael Reaction: Effective Route to Pyrazino‐Indole Compounds

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