Chiral pyrrolidine derivatives

Pyrrolo[l,2- ][l,2]oxazines are a class of compounds with very few references regarding synthesis and reactivity. An interesting preparation has been described by intramolecular cyclization of IV-hydroxy pyrrolidines carrying a methoxyallene substituent at C-2 (242, Scheme 32). These compounds were obtained by addition of a lithiated allene to chiral cyclic nitrones 241. Cyclization occurred spontaneously after some days at relatively high dilution (0.05 M). Compounds 243 (obtained with excellent diastereoselectivity) can be submitted to further elaboration of the double bond or to hydrogenolysis of the N-O bond to form chiral pyrrolidine derivatives (Section 11.11.6.1) <2003EJ01153>. 

Chiral pyrrolidine derivatives, proline, and amino acid-derived imidazolidinones mediate the asymmetric epoxidation of ,/i-unsalurated aldehydes. Protected a,a-diphenyl-2-prolinol catalyses the asymmetric formation of 2-epoxyaldehydes, with hydrogen peroxide or sodium percarbonate as the oxygen sources, with 81-95% conversion with up to 96 4 dr and 98% ee.204... 

Scheme 2.38 Chiral pyrrolidine-derived catalysts for Michael-type addition of ketones to activated olefins.

Armstrong a al. found that stoichiometric use of chiral pyrrolidine-derived iminium salt 63 (Figure 13 could only be isolated in impure form) in the asymmetric epoxidation of phenylcyclohexene gave the oxirane with 22% ee < 1999T2341 >. 

Chiral pyrrolidine derivatives as chiral auxiliaries 90YGK982. 

Zhang et al. investigated the asymmetric 1,3-dipolar cycloaddition of tert-butyl 2-(diphenylmethyleneamino)acetate and nitroalkenes promoted by bifunctional thiourea compounds derived from cinchona alkaloids, affording chiral pyrrolidine derivatives 13 with multisubstitutions. Catalyst lm delivered the best results in terms of catalytic activity, diastereoselectivity and enantioselectivity. Nevertheless, only moderate ee values could be obtained while the diastereoselectivities were generally good (Scheme 10.18) [22]. 

D-Glucosamine serves as a source of the chiral pyrrolidine derivative (80)(sugar numbering).A new multistep synthesis of... 

Iminium-based organocatalysis is somewhat less explored than enamine-based organocatalysis and has been mostly used in the activation of a,/S-conjugated aldehydes and ketones. Therefore, this type of catalysis has unsurprisingly been the subject of a limited number of studies under the umbrella of the metal-organic cooperative catalysis concept. In 2011, the Cdrdova group [55] reported the first enantioselective and chemoselective /3-silyl addition to a./S-unsaturated aldehydes using copper salts and chiral pyrrolidine derivatives as catalysts. As proposed, the chiral secondary amine forms an iminium salt with... 

A computational study of the two possible mechanisms for the asymmetric epoxidation of conjugated aldehydes with H2O2, catalysed by chiral pyrrolidine derivatives lacking proton donor groups, indicates that the more probable route is via formation of an iminium intermediate rather than the general base-catalysed mechanism. The oxidant H2O2 acts as a co-catalyst in the initial formation of the iminium species. The epoxide... 

The marked temperature dependence of the enantioselective addition of diethylz-inc to aryl aldehydes catalysed by (S)-2-(3-methyl-2-pyridyl)-3,5-di-r-butylphenol displays an inversion temperature which is affected by the para-substituent of the aldehyde. Enantioselectivities of up to 78% ee for addition of diethylzinc to ben-zaldehyde have been achieved using (15, 45)-2,5-diazabicyclo[2.2.1]heptane derivatives as catalysts however, a study of chiral compounds related to the Betti base (51a) has identified r-aminonaphthol (51b) as a much more effective catalyst (99% ee) for this reaction. The catalytic efficiency of chiral pyrrolidine derivatives and (25)-3-eJt -(dimethylamino)isobomeol have also been explored. 

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