Highly enantioselective organocatalytic synthesis of piperidines. Formal synthesis of (−)-Paroxetine

Valero, Guillem; Schimer, Jiří; Císařová, I.; Veselý, Ján; Moyano, Albert; Rios, Ramón

doi:10.1016/j.tetlet.2009.02.049

Cited by 92 publications

(30 citation statements)

References 45 publications

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“…[12] In our research group, we have lately been focusing on the development of new asymmetric methodologies based on organocatalysis. [13] As fruits of our research, very recently we developed a highly enantio-selective anthrone addition to a,b-unsaturated aldehydes. [14,15] In this context, our attention was caught by the observation that, with the exception of guanidine-catalyzed reactions, good enantioselectivities in anthrone-maleimide cycloadditions were attained only when the chiral amine catalysts had hydroxy groups and the reaction was effected in aprotic solvents.…”

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Bifunctional Thiourea‐Catalyzed Asymmetric Addition of Anthrones to Maleimides

et al. 2010

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For the first time, the addition of anthrones to maleimides catalyzed by bifunctional thiourea catalysts is reported. The thiourea moiety is able to activate the maleimide and the tertiary amine deprotonates the anthrone, furnishing the final DielsAlder or Michael adducts in excellent yields and enantioselectivities.Keywords: anthrones; Diels-Alder cycloaddition; enantioselective; maleimides; Michael addition; organocatalysis Anthrones are important compounds in natural products and in medicinal chemistry.[1] They are isolated, either in the free form or as O-or C-glycosides, from a wide variety of natural sources (plants, shrubs), such as rhubarb, Cassia, and "Cµscara sagrada" bark, among others.[2] From the chemical standpoint, anthrones and their enol tautomers, the 9-anthrols, play a central role in the chemistry of anthracenes, because by oxidation of the central ring they afford 9,10-anthraquinones, extremely valuable compounds as pigments or anticancer agents.[3] On the other hand, the reduction of anthrones provides anthracenes, useful in the preparation of dyestuffs and of optoelectronic materials.[4]The parent anthrone, namely 9A C H T U N G T R E N N U N G (10H)-anthracenone, has been classically used as a reagent for the analytical determination of sugars and many of its derivatives have interesting biological properties: antimicrobial, laxative, antipsoriatic or as telomerase inhibitors.[5] Recently, it has been found that some anthrone derivatives may display potent and selective antitumour activity. [6] Anthrone has been used as the diene component in Diels-Alder cycloadditions with a variety of dienophiles. [7,8] Kinetic studies performed by Koerner and Rickborn [8] on the reaction between anthrone and Nmethylmaleimide showed that a substantial acceleration took place in basic solvents such as DMF, pyridine or triethylamine, or upon the addition of a small quantity of triethylamine to a chloroform or THF solution of the reactants.[8] These results were interpreted by a catalytic oxyanion acceleration of the process, probably via the anthrone enolate (Scheme 1).Building upon these results, Riant and Kagan investigated the effect of chiral bases in the same reaction, [9] finding that quinidine and prolinol were the most enantioselective catalysts (up to 61% ee was achieved with a 10 mol% loading of quinidine in chloroform at À50 8C). Later on, Yamamoto and coworkers [10] described the asymmetric cycloaddition of anthrone and maleimides catalyzed by C 2 -chiral 2,5-bis(hydroxymethyl)pyrrolidines, obtaining good enantioselectivities in some instances (up to 87% ee). The enantioselective Diels-Alder cycloaddition of substituted anthrones with maleimides catalyzed by chiral bicyclic guanidines, which takes place with excellent yields and enantioselectivities (85-99% ee) when run in dichloromethane solution at À20 8C, was reported in 2006 by Tan and co-workers.[11] This reaction showed, however, a very strong temperature dependence, and the enantiomeric purity of the Diels-Alder adduct was much...

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Bifunctional Thiourea‐Catalyzed Asymmetric Addition of Anthrones to Maleimides

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“…[67] In all substrates studied, these piperidines were produced as a mixture of two diastereomers with 3:1 to 5:1 ratios. This diastereoselectivity was demonstrated by the authors to correspond to the equatorial or axial position of the hemiaminal hydroxy group of the trans piperidine.…”

Section: Domino Michael-intramolecular Heterocyclization Reactionsmentioning

confidence: 99%

Recent Developments in Asymmetric Organocatalytic Domino Reactions

2012

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Since about the year 2000, the research area of asymmetric organocatalysis has grown rapidly to become one of the most fascinating and current fields in organic chemistry. In the last years, asymmetric domino reactions have widely benefited from this fast-growing field, as exemplified by the development of an explosive number of novel and powerful asymmetric organocatalytic domino processes, which allowed the easy construction of complex chiral molecular architectures from simple materials with high yields and very often remarkable enantioselectivities in a metal-free environment. Indeed, the possibility to join two or more organocatalytic reactions in one asymmetric domino process has become a challenging goal for chemists, due to several advantages from economical and environmental points of view, avoiding costly protecting groups and time-consuming purification procedures after each step, for example. This review aims to update the latest developments of this hot and fascinating field, covering the literature since the beginning of 2009.

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“…Several examples of conjugate addition/cyclization sequences of small building blocks have also been reported recently. Thus, chiral cyclohexenones (141) [47], secondary cyclohexyl-substituted amines (146) [48], dihydropyrones (150) [49], cyclohexenes (153) [50], and piperidines (156) [51] Scheme 8.31 Domino Michael-aldol reaction of α, β-unsaturated ketones with β-ketoesters.…”

Section: Organocatalytic Domino Michael Reactions/electrophilic Trappingmentioning

confidence: 99%