Enantiodivergent preparation of optically active oxindoles having a stereogenic quaternary carbon center at the C3 position via the lipase-catalyzed desymmetrization protocol: effective use of 2-furoates for either enzymatic esterification or hydrolysis.
Both enantiomers of oxindoles 2a-h, having a stereogenic quaternary carbon center at the C3 position and a different N-protective group, were readily prepared by the lipase-catalyzed desymmetrization protocol. Thus, the transesterification of the prochiral diols 3a-h with 1-ethoxyvinyl 2-furoate 5 was catalyzed by Candida rugosa lipase to give (R)-(+)-2a-h (68-99% ee), in which the use of a mixed solvent, (i)Pr(2)O (diisopropyl ether)-THF, was crucial. The same lipase also effected the enantioselective hydrolysis of the difuroates 4a-h in a mixture of (i)Pr(2)O, THF, and H(2)O to provide the enantiomers (S)-(-)-2a-h (82-99% ee). The products 2 obtained by both methods were stable against racemization. These enzymatic desymmetrization reactions were also applicable for other typical symmetrical difuroates 12b and 15b to provide the racemization-resistant products 13b and 16b.
Akai
Shuji
S
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamadaoka, Suita, Osaka 565-0871, Japan.
Tsujino
Toshiaki
T
Akiyama
Emi
E
Tanimoto
Kouichi
K
Naka
Tadaatsu
T
Kita
Yasuyuki
Y
D002175:Candida / Q000201:enzymology*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D004951:Esterification; D005663:Furans / Q000737:chemistry*; D006868:Hydrolysis; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis*; D008049:Lipase / Q000378:metabolism*; D015394:Molecular Structure; D013237:Stereoisomerism
D005663:Furans; D007202:Indicators and Reagents; D007211:Indoles; D008049:Lipase