Asymmetric organocatalysts 1.4- addition reactions

As one type of the most important organocatalysts, phase-transfer catalysts found wide application in asymmetric Michael addition reactions [50]. In 1986, Conn et al. [51] reported the asymmetric Michael addition of indanone derivative to methyl vinyl ketone (MVK) catalyzed by their original catalyst 54 (Scheme 5.25). The... 

Among several organocatalysts derived from L-proline (1) as a chiral source, pyrrolidine-tertiary amine conjugates constitute a powerful and useful family in asymmetric synthesis [115]. In 1994, Kawara and Taguchi reported pioneering work on the use of such catalysts in asymmetric Michael addition reactions [116]. Since then, several related catalysts have been developed. Figure 1.5 lists representative examples. 

Chiral phosphoric acids powerful organocatalysts for asymmetric addition reactions to imines (S. J. Connon, 2006) [5a]. 

The advancements in supramolecular catalysis are not limited to transitions-metal catalyzed reactions. Clarke and coworkers recently reported the preparation of a library of organocatalysts and their application in the asymmetric Michael addition of ketones to nitroalkenes [37]. They proposed use of a supramolecular catalyst formed... 

Pyrrolidin-2-yltetrazole has been found to be a versatile organocatalyst for the asymmetric conjugate addition of nitroalkanes to enones.45 Using this catalyst, this transformation requires short reaction times, tolerates a broad substrate scope, and possibly proceeds via generation of an iminium species. 

Asymmetric addition of ketenes to aldehydes is a highly attractive synthetic access to yfi-lactones with perfect atom economy [134, 135]. This reaction can be catalyzed efficiently by using chiral amines as organocatalysts. As early as 1967 Borr-mann et al. described an organocatalytic asymmetric ketene addition to aldehydes [136] chiral tertiary amines, in particular (—)-N,N-dimethyl-a-phenylethylamine or (—)-brucine, were used as catalysts [136]. The resulting lactones were obtained with modest enantioselectivity of up to 44% ee. 

In addition, immobilized catalysts related to the MacMillan imidazolidinone-type organocatalyst 5 have been used for the asymmetric Diels-Alder reaction (Section... 

The naturally occurring cinchona alkaloids (Figure 8.1), as described in other chapters of this book, have proven to be powerful organocatalysts in most major chemical reactions. They possess diverse chiral skeletons and are easily tunable for diverse catalytic reactions through different mechanisms, which make them privileged organocatalysts. The vast synthetic potential of cinchona alkaloids and their derivatives in the asymmetric nucleophilic addition of prochiral C=0 and C=N bonds has also been well demonstrated over the last decade. 

High enantioselectivites in the aza-Michael reaction have been achieved using alternate organocatalysts, and the addition of benzotriazole to nitroolefins occurs with up to 94% ee using bifimctional catalysts such as (11.64). Guerin and Miller have developed an alternate approach to the enantioselective introduction of triazoles based on the asymmetric conjugate addition of azide followed by a 1,3-dipolar cycloaddition of the product with an alkyne. In this approach, the addition of hydrazoic acid to Michael acceptors such as (11.133) proceeds with good ee in the presence of the dipeptide (11.134). ... 

Importantly, prolinamide catalysts (Figure 6.3) work well in Michael addition reactions using nitro-olefins as acceptors. iV-Tritylprolinamide 33 and aminonaphthyridine-derived ProNap 34 served as organocatalysts in asymmetric Michael additions of aldehydes and cyclohexanone to nitro-alkenes. Proline-functionalised C3-symmetric 1,3,5-triallq lbenzene 35 was screened in the reaction of cyclohexanone to nitrostyrene to afford the Michael adducts in good yields and diastereoselectivity but low enantioselectivity. 

Sugar-hased prolinamide 16m has also been employed as catalyst for the asymmetric Michael addition of cyclohexanones to p-nitroslyrenes. During optimisation of the reaction conditions, the authors found that the polarity of the solvent does not modify the yield or stereoselectivity, but the best ee was obtained under neat conditions at -20 °C. Ammonium ionic liquids 41a,b are also efficient organocatalysts for the asymmetric Michael addition of aldehydes to nitro-olefins giving the adducts with excellent yields and enantioselectivities and modest to high diastereoselectivities. 

In 2007 Sun and coworkers reported the use of the proline derived triamine 17 in the presence of weak acids as a highly stereoselective organocatalyst for the asymmetric Michael addition of cyclohexanone to nitroalkenes (Scheme 11.16). All selected aromatic nitroalkenes gave excellent yields and selectivities, with the exception of electron-deficient substrates (Ar = 4-CN-Ph, 4-N02-Ph), which also require much longer reaction times. 

High yields of 2-substituted chromans are readily attained from the asymmetric intramolecular oxa-Michael addition reaction of phenols bearing an (f -a,P-unsaturated ketone or thioester moiety mediated by a cinchona-alkaloid-urea-based bifunctional organocatalyst (140BC119). Molecular iodine-catalyzed reaction of phenols with a,P-unsaturated alcohols affords a wide range of 2,2-disubstituted chromans (14T5221). Chiral derivatives result from the intramolecular allylic alkylation of phenols bearing an... 

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