Highly Enantioselective Conjugate Additions of Aldehydes to Vinyl Sulfones

The development of new asymmetric methodologies that afford different structures in an enantioselective fashion is one of the most exciting goals for chemists nowadays. In this subject, lately, the use of sulfones has become a fast growing field. From the works of Tan and Shibata until the last works of Palomo, sulfones have demonstrated their versatility and power in organocatalytic asymmetric reactions. Moreover, the easy removal of sulfones with Mg or Hg/Na makes this group a perfect choice to afford easily naked alkyls. Remarkably, bissulfones can be used as nucleophiles or electrophiles, being vinyl sulfones excellent electrophiles, while bismethylensulfones derivatives such as fluoro are excellent nucleophiles. This double possibility has been studied by several research groups, leading to new methodologies that allow obtaining formally simple alkylation in an enantioselective fashion, by using organocatalysis. The aim of this tutorial review is to summarize the last trends in the use of sulfones in organocatalytic processes, giving a complete scenario of these new reagents.

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“…22 The reaction afforded 1,4-adducts with good yields and enantioselectivities, albeit with moderate diastereoselectivities (Scheme 4).…”

Section: Ramonmentioning

confidence: 98%

Sulfones: new reagents in organocatalysis

2010

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“…Palomo and co‐workers recently studied the partial substitution of the bis(sulfone) 74 against other activating groups such as nitriles or esters 38. In this context, it was shown that aryl‐substituted α‐ethoxycarbonyl vinyl sulfones 93 could successfully be reacted with the different aldehydes 73 , whereas the corresponding aryl‐substituted α,β‐unsaturated malonates failed under the same reaction conditions (Scheme ).…”

Section: Sulfones As Activators Of Electrophilesmentioning

confidence: 99%

Asymmetric Organocatalysis with Sulfones

et al. 2010

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Asymmetric organocatalysis has become a powerful tool for the synthesis of optically active compounds. Whereas early research mainly focused on combining simple reagents as a proof-of-concept for asymmetric organocatalysis, recent investigations are directed towards extending the concept to more target- and diversity-oriented synthesis. As a result of the many transformation possibilities and their ability to generate both nucleophilic and electrophilic reaction partners, sulfones have become especially important substrates in the field of organocatalysis.

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“…Soon afterwards, Palomo and coworkers described the addition of aldehydes to vinyl disulfones, E-α-ethoxycarbonyl vinyl sulfones (57), and E-α-cyano vinyl sulfones (59), promoted by diphenylprolinol derivative XXVI [57]. The reaction afforded the 1,4-adducts with good yields and enantioselectivities, and with moderate diastereoselectivities (Scheme 5.32).…”

Section: Aldehyde Conjugate Additions To Vinyl Sulfonesmentioning

confidence: 99%

Enamines in Catalytic Enantioselective Conjugate Additions

Rios

Moyano

2010

Catalytic Asymmetric Conjugate Reactions

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The use of chiral secondary amines as asymmetric catalysts (asymmetric aminocatalysis; AA) was pioneered during the early 1970s both by Hajos and Parrish [1] and, independently, by Eder et al. [2] in their reports on the first examples of highly enantioselective, proline-catalyzed intramolecular aldol cyclizations. In spite of some subsequent significant applications of this transformation -most notably, in Woodward's asymmetric total synthesis of erythromycin [3] -the potential of AA was largely overlooked during the following three decades. Following the rediscovery of proline in 2000 as a catalyst in the intermolecular aldol reaction by List et al. [4] and, soon after, the introduction of iminium catalysis by D. W. C. MacMillan [5] (Scheme 5.1), the development of AA -and of the broader field of asymmetric organocatalysis (AO) -has been impressive. Today, AO has become a powerful and well-established synthetic tool for the enantioselective construction of chiral organic compounds [6], that complements -and, in some instances, also improves -the more traditional approaches based on metal-catalyzed reactions [7] and on biocatalysis [8].Carbon nucleophiles that contain relatively acidic methylene groups have been widely applied in direct Michael additions, whereas simple enolizable carbonyl compounds need generally to be converted into more reactive species such as enol ethers or enamines prior to their use. Since chemical transformations that avoid additional reagents, the generation of waste, and extended working times are highly desirable, a more promising, and atom-economic strategy would involve the direct addition of unmodified carbonyl compounds to Michael acceptors. Covalently bonded aminocatalysts operate through two different mechanisms, by transforming the carbonyl substrates either into activated nucleophiles (enamine intermediates), or into electrophiles (iminium intermediates). Very recently, MacMillan and coworkers have disclosed a third way of activation that takes place via cation-radical chemistry singly occupied molecular orbital (SOMO) catalysis (Scheme 5.2) [9].Catalytic Asymmetric Conjugate Reactions. Edited by Armando Córdova

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Highly Enantioselective Conjugate Additions of Aldehydes to Vinyl Sulfones

Abstract: Joined together, organocatalysts aldehydes and sulfones: A diaryl prolinol silyl ether was found to catalyse efficiently and enantioselectively the conjugate addition of aldehydes to vinyl sulfones (see scheme). The ample synthetic utility of the resulting adducts is illustrated.

Cited by 78 publications

References 60 publications

Sulfones: new reagents in organocatalysis

Sulfones: new reagents in organocatalysis

Asymmetric Organocatalysis with Sulfones

Enamines in Catalytic Enantioselective Conjugate Additions

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