Asymmetric total synthesis of (-)-javaberine A and (-)-epi-javaberine A based on catalytic intramolecular hydroamination of N-methyl-2-(2-styrylaryl)ethylamine
Asymmetric total synthesis of (-)-javaberine A and (-)-epi-javaberine A based on catalytic intramolecular hydroamination of N-methyl-2-(2-styrylaryl)ethylamine
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DOI：
10.1016/j.tet.2021.132165
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发表时间：
2021-06-17
期刊：
影响因子：
2.1
通讯作者：
Yamamoto, Yasutomo
中科院分区：
文献类型：
--
作者：
Uenishi, Saho;Kakigi, Rina;Yamamoto, Yasutomo
采用n -甲基-2-（2-苯基芳基）乙胺不对称氢胺化和Bischler-Napieralski环化两种异喹啉合成方法，实现了(-)-爪哇碱A及其表映体的不对称全合成。用锂酰胺-手性双恶唑啉催化n -甲基氨基烯4分子内不对称加氢胺化反应，得到对映选择性好、收率高的四氢异喹啉-劳达苷。(S)-去甲基化通过polonovski型反应得到(S)-去甲基化。成功地合成了(S)-norlaudanosine与同型三丁酸缩合，然后进行Bischler-Napieralski环化、LiAlH4还原和o -去甲基化，得到了与天然爪哇碱A对映体相对应的(8R,14S)-(-)-爪哇碱A，与天然爪哇碱A的c14 -外聚体相对应。(C) 2021 Elsevier Ltd版权所有。
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 (8R,14S)-(-)-javaberine A, corresponding to antipode of natural javaberine A. (8S,14S)-(-)-Javaberine A, which corresponds to C14-epimer of natural javaberine A, was also successfully synthesized. (C) 2021 Elsevier Ltd. All rights reserved.