Pyrrolidine derivatives from /-tartaric acid

Enantiopure (R)- and (S)-nipecotic acid (Nip) derivatives 64 were obtained following classical resolution of ethyl nipecotate with either enantiomer of tartaric acid and successive recrystallization of the corresponding salts [153, 154, 156] or by resolution of racemic nipecotic acid with enantiomerically pure camphorsul-fonic acid [154]. N-Boc protected pyrrolidine-3-carboxylic acid (PCA) 65 for the synthesis of homo-ohgomers [155] was prepared by GeUman from trans-4-hydroxy-L-prohne according to a known procedure [157]. 

In 1998, Ruiz et al. reported the synthesis of new chiral dithioether ligands based on a pyrrolidine backbone from (+ )-L-tartaric acid. Their corresponding cationic iridium complexes were further evaluated as catalysts for the asymmetric hydrogenation of prochiral dehydroamino acid derivatives and itaconic acid, providing enantioselectivities of up to 68% ee, as shown in Scheme 8.18. 

Many chiral auxiliaries are derived from 1,2-amino alcohols [7], including oxazolidinones (1) [7-9], oxazolines (2) [10,11], bis-oxazolines (3) [12,13], oxa-zinones (4) [14], and oxazaborolidines (5) [15-17]. Even the 1,2-amino alcohol itself can be used as a chiral auxiliary [18-22]. Other chiral auxiliary examples include camphorsultams (6) [23], piperazinediones (7) [24], (S)-l-amino-2-(methoxymethyl)-pyrrolidine (SAMP) (8) and (R)-l-amino-2-(methoxymethyl)-pyrrolidine (RAMP) [25], chiral boranes such as isopinocampheylborane (9) [26], and tartaric acid esters (10). Some of these auxiliaries have been used as ligands... 

Improved syntheses of (-l-)-lentiginosine (125) and (7R)-7-hydroxylen-tiginosine (126), inhibitors of amyloglucosidases, have been reported. In multi-step syntheses based upon a 1,3-dipolar cycloaddition of a pyrrolidine N-oxide derived from L-tartaric acid to 3-buten-l-ol, 125 and 126 were prepared in 25% and 37% overall yields from a common indolizidine intermediate. The enantiomers of these compounds could be similarly prepared using D-tartaric acid as a starting material. ... 

Asymmetric Hydrogenation.—The asymmetric hydrogenation of a-acylamino-acrylates and cinnamates using chiral rhodium(i) diphosphine complexes as catalysts is now established as one of the best methods for obtaining optically pure a-amino-acids (see previous reviews in this series). In the past year, some new chiral diphosphines have been added to the already considerable number of such ligands. A bis(diphenylphosphino)-derivative of pyrrolidine in conjunction with Rh can be used to hydrogenate a-acetamidocinnamates and itaconic acid with chiral inductions of 90%, whereas an Rh -diphos complex derived from natural tartaric acid effects the reduction of some a-acylaminoacrylic acids to natural (5)-a-acylamino-acids with optical yields of between 80 and 100%. ... 

Liskamp has reported the synthesis and the screening in asymmetric catalysis of a library of polymer-supported peptidosulfonamide [147]. Rt) or (5 -pyrrolydines 222 prepared in six steps from D or Z-tartaric acid were anchored onto Argonaut resin (0.41 mmol/g) to afford the corresponding supported pyrrolidines 223 (Scheme 91). The polymeric peptidosulfonamides 224 and 225 were then synthesized in four steps from the immobilized pyrrolidines 223. The different chiral polymers were tested in the titanium-mediated diethylzinc addition to benzaldehyde,/ -chlorobenzaldehyde, cyclohexanecarboxaldehyde and phenylacetaldehyde. Both yield and ee were very low with all these supported-ligands for the enantioselective reaction with the two aliphatic aldehydes. With aromatic aldehydes, the best results were observed with both leucine-derived supported peptidosulfonamides 224d and 225d. 

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