Organocatalysis conjugate addition

Keywords Aminocatalysis Conjugate addition Cycloaddition Ttninintn ion Organocatalysis... 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

In this area, Krische and co-workers have developed a family of catalytic transformations based on the use of enones as latent enolates. Nucleophilic activation of the enone is induced via carbometallation, nucleophilic organocatalysis or hydrometallation. The following examples illustrate some aspects of these new catalytic conjugate addition/electrophilic trapping reactions. 

The Conjugate Addition Reaction a Very Convenient Platform for Asymmetric Organocatalysis... 

Alternatively, the iminium-activation strategy has also been apphed to the Mukaiyama-Michael reaction, which involves the use of silyl enol ethers as nucleophiles. In this context, imidazolidinone 50a was identified as an excellent chiral catalyst for the enantioselective conjugate addition of silyloxyfuran to a,p-unsaturated aldehydes, providing a direct and efficient route to the y-butenolide architecture (Scheme 3.15). This is a clear example of the chemical complementarity between organocatalysis and transition-metal catalysis, with the latter usually furnishing the 1,2-addition product (Mukaiyama aldol) while the former proceeds via 1,4-addition when ambident electrophiles such as a,p-unsaturated aldehydes are employed. This reaction needed the incorporation of 2,4-dinitrobenzoic acid (DNBA) as a Bronsted acid co-catalyst assisting the formation of the intermediate iminium ion, and also two equivalents of water had to be included as additive for the reaction to proceed to completion, which... 

Once in the modern organocatalysis era and with the mechanistic rationale for the iminium activation concept in hand, many different and more efficient methodologies have been developed for this particular reaction. For example, and still focused on the use of secondary amines as catalysts, imidazolidine 53a and proline-tetrazole 2a catalysts have been developed for the conjugate addition of malonates to acyclic enones (Scheme 3.17). For the 53a-catalyzed reaction, this proceeded well in terms of yields and enantioselectivities for a wide range of differently substituted arylideneacetones and for cyclohexenone but yields tend to decrease when more bulky substituents were placed around the carbonyl moiety. Importantly, the enantioselectivity of the reaction was very dependent upon the nature of the malonate reagent, observing that dibenzyl malonate and diethylmalonate furnished the best results. The most... 

Carbons and Carbon Supported Catalysts in Hydroprocessing 2 Chiral Sulfur Ligands Asymmetric Catalysis 3 Recent Developments in Asymmetric Organocatalysis 4 Catalysis in the Refining of Fischer-Tropsch Syncrude 5 Organocatalytic Enantioselective Conjugate Addition Reactions A Powerful Tool for the Stereocontrolled Synthesis of Complex Molecules... 

With respect to the catalysts employed in conjugate additions, a big collection of efficient stable and environmentally friendly natural or newly designed chiral organocatalysts has already been developed. These catalysts are usually cheap to prepare and readily accessible in a range of quantities. They fall into four major classes Lewis bases, Lewis acids, Brpnsted bases, and Brpnsted acids [If]. The identification of the generic modes of activation of these catalysts has been crucial to the success of organocatalysis. 

Lately, sulfones have become especially important substrates in organocatalysis [87]. First studies on the asymmetric conjugate addition of aldehydes to vinyl sulfones were carried out by Alexakis and Mossd employing as catalyst bipyrrolidine 30 (25 mol%) for the addition of linear and a-branched aldehydes to l,l-bis(benzenesulfonyl)ethylene [88], Large excess of aldehyde (10 equivalents) was required and moderate levels of enantioselection were obtained for linear aldehydes (53-80% ee), while reactions with a-branched nucleophiles led to racemic or very low selectivities (0-12% ee). With respect to the mechanism, the acyclic synclinal model proposed by Seebach and GoUnski [70] involving a trans enamine intermediate was postulated. 

A decade has now passed since the studies of my laboratory and those of David MacMillan s refocused the considerable attention of the conununity on the profound potential of small organic molecules to catalyze asymmetric reactions. In this time, the scope of organocatalysis has enlarged considerably with respect both to the type of reactions catalyzed (aldol, cycloaddition, redox, asymmetric assembly and domino reactions, conjugate addition reactions, etc.) and the mechanisms used... 

For some years the group of Li Deng has been investigating carefully the use of Cinchona alkaloids in asymmetric organocatalysis resulting in the development of numerous highly useful applications 424). Recently, they developed a catalytic tandem conjugate addition/protonation protocol to access compounds with tertiary... 

Wu EH, Hong R, Khan JH, Liu XF, Deng L (2006) Asymmetric Synthesis of Chiral Aldehydes by Conjugate Additions with Bifunctional Organocatalysis by Cinchona Alkaloids. Angew Chem Int Ed 45 4301... 

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