Catalysts 2,2 -bipyrrolidine

Independently, Alexakis and coworkers reported that 2,2 -bipyrrolidine catalyst 28 showed excellent catalytic activity in several types of asymmetric Michael addition reactions [143], It has been postulated that the isopropyl group on one of the Cj-symmetric pyrrolidine rings should block not only the back face against the approach of Michael acceptors but also shift the equiUbrium towards one of the two rotamers. Since then, closely related catalysts have also been reported [144]. Furthermore, different types of catalysts such as 29 have been shown to be useful in asymmetric Michael addition reactions [145-148],... 

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. 

L-proline as catalyst [ 109]. Further studies on the reaction were carried out by Alexakis et al. using the hydrochloride salt of lV-isopropyl-2,2 -bipyrrolidine (30, Hg. 2.4) as catalyst in CHCI3 as solvent. In this study the highest enantioselectivity (81%) was obtained for the addition of cyclohexanone to nitrostyrene also with a very high diaste-reoselectivity (syn/anli 94/6) [50]. As in the case of the conjugate addition of aldehydes, the observed syn selectivity was in accordance with the Seebach-GoUnski model [70]. 

A new class of C -symmetric 3,3 -dialkoxy-2,2 -bipyrrolidines (e.g., 50) have been designed and developed by Zhang and his co-workers. The catalysts were used in asymmetric organocatalytic Diels-Alder reactions of a,P-unsaturated aldehydes 28 and dienes. Scheme 3.17 [30]. 

After the success of Macmillan s catalysts, other types of chiral amine were disclosed and applied in the FCA reaction as activators of a,(3-unsaturated aldehydes. Reports from a few groups have revealed that diaryIprolinol silyl ethers [11], camphor sulfonyl hydrazine [12], chiral aziridin-2-yl methanols [13], and A-isopropylated bipyrrolidine [14] were efficient catalysts in the enantioselective alkylations of 4,7-dihydroindoles, 1-naphthols, and indoles. NEt3, benzoic acid, or... 

Very recently White and coworkers [62] designed a new catalyst [Fe(CF3-pdp) (CH3CN)2](SbFg)2 (CF3-pdp = V,V -bis(5-(2,6-di-(trifluoro)-methyl-phenyl)-2-pyridylmethyl)-2,2 -bipyrrolidine) that used a trajectory restriction strategy to achieve predictable, catalyst-controlled site-selectivity (Scheme 32). 

Regarding the importance of iminium ion formation and geometry in organo-catalytic Diels-Alder reactions, Zhang and coworkers designed and developed a new class of bipyrrolidines 24 as efficient organocatalysts that can form di-iminium intermediates F with a, J-unsaturated aldehydes (14). The predominant exoproducts were obtained with excellent enantioselectivities (Scheme 38.8). Recently, the Suzuki group reported a class of diamine catalysts (25) derived from hydrazines for this reaction to afford products 4 with a preference for the endo isomer (Scheme 38.8) [15],... 

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