Organocatalytic Highly Enantioselective Conjugate Addition of Aldehydes to Alkylidine Malonates

Zhao, Gui‐Ling; Veselý, Ján; Sun, Junliang; Christensen, Kirsten E.; Bonneau, Charlotte; Córdova, Armando

doi:10.1002/adsc.200700570

Cited by 53 publications

(16 citation statements)

References 58 publications

(9 reference statements)

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“…This reaction was highly trans selective in the formation of 2-substituted cyclopentanecarbaldehydes (65), and also tolerated aryl and alkyl substituents on the enone, as well as the presence of heteroatoms (Scheme 5.34).…”

Section: Other Reactionsmentioning

confidence: 99%

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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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Section: Other Reactionsmentioning

confidence: 99%

“…In 2008, Córdova and coworkers developed an elegant aldehyde addition to alkylidene malonates, catalyzed by the diphenylprolinol derivative XXVI [65]. The reaction furnished the corresponding 1,4 addition products in outstanding yields and enantioselectivities, and with good diastereoselectivities (Scheme 5.37).…”

Section: Other Reactionsmentioning

confidence: 99%

Enamines in Catalytic Enantioselective Conjugate Additions

Rios

Moyano

2010

Catalytic Asymmetric Conjugate Reactions

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“…In 2001, Barbas and coworkers reported the first asymmetric conjugate additions of ketones to alkylidene malonates in moderate to good enantioselectivities using pyrrolidine‐based organocatalyst . Some groups demonstrated the asymmetric Michael addition of ketones to alkylidene malonates using pyrrolidine‐derived urea or thiourea catalyst and sulfonamide organocatalysts . On the contrary, Wang et al reported a thiourea‐sulfonamide organocatalyst that rapidly promoted the conjugate addition of 1,3‐diketones to nitroalkenes.…”

Section: Introductionmentioning

confidence: 99%

“…33,34 Some groups demonstrated the asymmetric Michael addition of ketones to alkylidene malonates using pyrrolidine-derived urea or thiourea catalyst and sulfonamide organocatalysts. [35][36][37][38][39][40] On the contrary, Wang et al 41 reported a thiourea-sulfonamide organocatalyst that rapidly promoted the conjugate addition of 1,3-diketones to nitroalkenes. Thiourea-sulfonamide organocatalysts bearing multiple hydrogen bonding donors were able to efficiently accelerate asymmetric reactions, improving yields and enantioselectivities.…”

Section: Introductionmentioning

confidence: 99%

Stereoselective conjugate addition of ketones to alkylidene malonates using thiourea‐sulfonamide organocatalyst

et al. 2018

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In this study, stereoselective conjugate addition of ketones to alkylidene malonates using organocatalyst has been developed. The reaction in the presence of 20 mol% of a novel thiourea-sulfonamide organocatalyst afforded conjugate adducts in moderate to high yields (up to 81%) under mild reaction conditions. Excellent diastereoselectivity (up to 98:2 dr) and enantioselectivity (up to 88% ee) were achieved.

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“…Recently, an organocatalytic4 route was developed with satisfactory results for the direct addition of ketones or aldehydes to activated olefins, especially to nitroolefins5 as well as to α,β‐unsaturated aldehydes,6 ketones,7 and sulfones8. The addition of the same donors9 to alkylidene malonates is beginning to be realized but is still underdeveloped in terms of generality, efficacy, and selectivity 10,11. Recently, a number of efforts have been made by others10 and us11 to address some of the issues with the addition of a ketone or aldehyde to alkylidene malonates with the use of organocatalysts.…”

Section: Introductionmentioning

confidence: 99%

An Organocatalyzed Asymmetric Michael Addition of Cyclic Ketones to 1,3‐Diene‐1,1‐dicarboxylates

Chowdhury

Ghosh

2013

Eur J Org Chem

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The purely organocatalyzed direct Michael addition of cycloalkanones to 1,3‐diene‐1,1‐dicarboxylates was effected by a combination of (S)‐2‐(4‐toluenesulfonamidomethyl)pyrrolidine and acetic acid. Addition products were formed in high yield and with good regio‐, diastereo‐, and enantioselectivity. The catalysis took place through a dual activation mode, that is, a nucleophilic enamine activation of the donor ketone and an eletrophilic hydrogen‐bonding activation of the acceptor diene dicarboxylate. The addition products could easily undergo a stereoselective ketone reduction and subsequent lactonization to give compounds with high synthetic potential.

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Organocatalytic Highly Enantioselective Conjugate Addition of Aldehydes to Alkylidine Malonates

Abstract: The first highly enantioselective, direct organocatalytic conjugate addition of unmodified aldehydes to alkylidinemalonates is presented. The reaction gives access to b-formyl-substituted malonates and highly functionalized lactones with up to 14:1 dr and generally 94 to > 99% ee.

Cited by 53 publications

References 58 publications

Enamines in Catalytic Enantioselective Conjugate Additions

Enamines in Catalytic Enantioselective Conjugate Additions

Stereoselective conjugate addition of ketones to alkylidene malonates using thiourea‐sulfonamide organocatalyst

An Organocatalyzed Asymmetric Michael Addition of Cyclic Ketones to 1,3‐Diene‐1,1‐dicarboxylates

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