Spirocyclization of Isatin with Chiral α-Aminothiols: Diastereoselective Synthesis of (-)- and (+)-4'-(Methoxycarbonyl)spiro[indoline-3,2'-thiazolidin]-2-one

Reactions of isatin with chiral α-aminothiols have been studied. With L-cysteine, only decomposition products were formed under various reaction conditions, whereas D- and L-penicillamine afforded mixtures of diastereomeric 4'-carboxy-5',5'-dimethylspiro[indoline- 3,2'-thiazolidin]-2-ones ( 4a and 4b or 5a and 5b ) in the ratio 1 : 1. The reaction of isatin with methyl L- and D-cysteinates under mild reaction conditions (methanol-benzene, room temperature) proceeded diastereoselectively with the formation of (-)- and (+)-4'-(methoxycarbonyl)spiro[indoline-3,2'-thiazolidin]-2-one ( 6a and 8 ) in 38 and 30% yields, respectively. Optically inactive 4'-(methoxycarbonyl)spiro[indoline-3,2'-([2',5']dihydrothiazol)]-2-one ( 7 ) was isolated as a side product in 7 and 3% yield, respectively. Structure of the obtained products was determined by spectral methods, including NOE difference measurements and by X-ray crystallography.