Asymmetric total synthesis of (−)-javaberine A and (−)-epi-javaberine A based on catalytic intramolecular hydroamination of N-methyl-2-(2-styrylaryl)ethylamine

Abstract

Asymmetric total synthesis of (−)-javaberine A and its epimer was achieved by utilizing two methods for isoquinoline synthesis, asymmetric hydroamination of N -methyl-2-(2-styrylaryl)ethylamine and Bischler-Napieralski cyclization. Intramolecular asymmetric hydroamination of N -methyl aminoalkene 4 was catalyzed by lithium amide–chiral bisoxazoline to give tetrahydroisoquinoline ( S )-laudanosine with good enantioselectivity in excellent yield. N -Demethylation of ( S )-laudanosine was accomplished by Polonovski-type reaction to give ( S )-norlaudanosine. Condensation of ( S )-norlaudanosine with homoveratric acid, and subsequent Bischler-Napieralski cyclization, LiAlH 4 reduction, and O -demethylation furnished (8 R ,14 S )-(−)-javaberine A, corresponding to antipode of natural javaberine A. (8 S ,14 S )-(−)-Javaberine A, which corresponds to C14-epimer of natural javaberine A, was also successfully synthesized. To create your abstract, type over the instructions in the template box below. Fonts or abstract dimensions should not be changed or altered. Leave this area blank for abstract info.