Asymmetric organocatalysts amines

Chiral secondary amines such as nonracemic imidazolidin-4-ones have been found to be effective asymmetric organocatalysts in the Diels-Alder cyclization of cyclopentadiene and a,p-unsaturated aldehydes [60]. A tyrosine-derived imidazoli-din-4-one was immobilized on PEG to provide a soluble, polymer-supported catalyst 110. In the presence of 110, Diels-Alder cycloaddition of acrolein 112 to 1,3-cyclohexadiene 111 proceeded smoothly to afford the corresponding cycloadduct 113 with high endo selectivity and enantioselectivity up to 92% ee (Scheme 3.31) [61]. 

Scheme 9.43 Asymmetric a-amination of aldehydes using organocatalysts (3e,f).

Barbas et al. described the construction of a quaternary stereocentre via the direct asymmetric a-amination of 3-(4-bromophenyl)-2-methylpropanal with dibenzyl azodicarbo>ylate using tetrazole 5a as the organocatalyst. The amination product was used for the enantioselective total synthesis of the cell adhesion inhibitor BIRT-377 (Scheme 9.44). 

As continuation of this work, a planar chiral [2.2]paracyclophane monophosphine has been applied successfully as an organocatalyst in asymmetric allylic amination of MBH adducts. Up to 71 % ee was achieved using (i )-298 as a catalyst (Scheme 3.127). ... 

Binaphthyl-derived Cyclic Amines and Their Salts as Asymmetric Organocatalysts... 

The majority of the organocatalysts that are commonly employed are chiral Lewis or Brpnsted bases, and the catalytic potential of base functionalities has been referred to in previous chapters to some extent already. As discussed before, the use of chiral primary or secondary amines for enamine or iminium activation belongs to the most important applications of asymmetric organocatalysts nowadays. In addition, also the interplay between an acidic (thio)urea and a basic amine separated by a chiral linker was shown to enable the simultaneous activation of both the electrophile and nucleophile. In addition to such bifunctional thiourea-containing acid-base catalysts, chiral catalysts containing a (Lewis or... 

The product of asymmetric amination, diamine 84, was reported to be able to catalyze asymmetric fluorination of a-branched aldehydes, yielding 1, 2-fluorine alcohols with up to 90% ee (Scheme 5.23) [44], Worthy to note that the chiral center of the catalyst is orientated on the nitrogen atom and it is the first example of asymmetric organocatalyst with enantiomeric nitrogen as the only source of chirality. 

Wang and co-workers reported a novel class of organocatalysts for the asymmetric Michael addition of 2,4-pentandiones to nitro-olefms [131]. A screen of catalyst types showed that the binaphthol-derived amine thiourea promoted the enantiose-lective addition in high yield and selectivity, unlike the cyclohexane-diamine catalysts and Cinchona alkaloids (Scheme 77, Table 5). 

The 1,3-dipolar cycloaddition of azomethine yUdes with olefins gives rise to pyrrolidines which represent structural elements of organocatalysts, natural products, and drug candidates. Asymmetric metal-catalyzed variants attracted considerable attention over the last few years [64], Recently, Vicario et al. reported an organo-catalytic [3 -i- 2] cycloaddition of azomethine ylides and a,p-unsaturated aldehydes mediated by a chiral secondary amine [65]. 

The introduction of a-heteroatom functionalization into an aldehyde or ketone is a very useful class of transformation. Performing it directly and asymmetrically, using organocatalysts, has been reviewed for reactions such as amination, oxygenation, halo- genation, and sulfenylation (44 references).260... 

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. 

Two representative organocatalytic reaction systems can be considered for nucleophilic a-substitution of carbonyl compounds, the issue of this chapter. One involves the in situ formation of a chiral enamine through covalent bond between organo-catalyst (mainly a chiral secondary amine such as proline) and substrate (mainly an aldehyde), followed by asymmetric formation of new bond between the a-carbon of carbonyl compound and electrophile. Detachment of organocatalyst provides optically active a-substituted carbonyl compound, and the free organocatalyst then participates in another catalytic cycle (Figure 6.1a) [2]. 

Together with cinchona-PTC-mediated a-alkylations, the asymmetric nucleophilic a-substitution of carbonyl derivatives by using cinchona alkaloids as organocatalysts in nonbiphasic homogeneous conditions also have been extensively studied (e.g., arylation, hydroxylation, amination, hydroxyamination, and sulfenylation). 

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