Asymmetric total synthesis of (−)-javaberine A and (−)-epi-javaberine A based on catalytic intramolecular hydroamination of N-methyl-2-(2-styrylaryl)ethylamine. (18th June 2021)

• Record Type: Journal Article
• Authors: Uenishi, Saho; Kakigi, Rina; Hideshima, Kumiko; Miyawaki, Akari; Matsuoka, Junpei; Ogata, Tokutaro; Tomioka, Kiyoshi; Yamamoto, Yasutomo
• Is Part Of: Tetrahedron. Volume 90(2021)
• Publication Date: 2021-06-18
• Subjects: Hydroamination -- Lithium amide -- Cyclization -- Heterocycles -- Berberine alkaloid; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2021.132165
• Languages: English
• ISSNs: 0040-4020

Abstract

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, LiAlH4 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. Graphical abstract: 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. Image 1