Asymmetric synthesis of (1R,5S)-2-methyl-6,7-benzomorphan via Aza-Prins reaction

被引：2

作者：

Galvez, Jose A. ^{[1
]}

Badorrey, Ramon ^{[1
]}

Mahia, Alejandro ^{[2
,3
]}

Diaz-de-Villegas, Maria D. ^{[1
]}

机构：

[1] Univ Zaragoza, Inst Sintesis Quim & Catalisis Homogenea ISQCH, Dept Quim Organ, CSIC, Pedro Cerbuna 12, E-50009 Zaragoza, Spain

[2] Univ Zaragoza, Fac Ciencias, Dept Bioquim & Biol Mol & Celular, Zaragoza, Spain

[3] Biocomputat & Complex Syst Phys Inst BIFI, Joint Unit EEAD CSIC BIFI, Joint Unit IQFR CSIC BIFI, Zaragoza, Spain

来源：

CHIRALITY | 2021年 / 33卷 / 09期

关键词：

asymmetric synthesis; Aza-Prins reaction; benzomorphan; morphine analogues; SCAFFOLD; (-)-PENTAZOCINE; ANALGESICS;

D O I：

10.1002/chir.23338

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

(1R,5S)-2-Methyl-6,7-benzomorphan has been synthesised from (R)-(benzyloxy)(phenyl)acetaldehyde. On a 2-mmol scale Bi (OTf)(3) promoted Aza-Prins reaction with N-tosylhomoallylamine afforded an 88/12 mixture of 6-oxa-2-azabicyclo[3.2.1]octanes. Major diastereoisomer was converted to enantiomerically pure (2S,4S)-2-benzyl-1- methylpiperidin-4-ol via a high-yielding sequence hydrogenolysis/N-detosylation/N-methylation. Acid-catalysed intramolecular Friedel-Crafts cyclisation of the piperidinol afforded (1R,5S)-2-methyl-6,7-benzomorphan in five steps with a yield of 25%.

引用

页码：543 / 548

页数：6

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