1369894-05-2Relevant academic research and scientific papers
Organocatalytic asymmetric synthesis of trisubstituted pyrrolidines via a cascade reaction
Noole, Artur,Pehk, Tonis,Jaerving, Ivar,Lopp, Margus,Kanger, Tonis
experimental part, p. 188 - 198 (2012/05/20)
A new bifunctional thiourea II catalyzed methodology was developed for the synthesis of chiral trisubstituted pyrrolidines using 4-aminocrotonate 1a/1b and nitroolefins 2a-g as starting materials. Two different N-protected 4-aminocrotonates 1a and 1b were tested for the reaction with 1a giving the desired product 3a with a high diastereomeric ratio (>20:1) but with low enantioselectivity (ee up to 7%). N-Tosyl-4-aminocrotonate 1b, however, yielded the product with moderate dr (up to 68:32) but with high ee in the case of the major trans-trans-isomers 4a-g (ee from 92% to 98%) and modest enantiomeric excess for the minor trans-cis-isomers 4a′-g′ (ee up to 57%). This methodology was also successfully applied when (E)-β-methyl-trans-β- nitrostyrene 2h was used as the starting nitroalkene to provide the product with dr 70/30 and with ee of 63% and 67%, respectively. The absolute configuration of both isomers was established using chiral derivatization with Mosher's and mandelic acids, with the relative stereochemistry being determined via NMR analysis.
