Ru-catalyzed asymmetric transfer hydrogenation of α-acyl butyrolactone via dynamic kinetic resolution: Asymmetric synthesis of bis-THF alcohol intermediate of darunavir

被引：5

作者：

More, Ganesh, V ^{[1
]}

Malekar, Pushpa, V ^{[1
,2
]}

Kalshetti, Rupali G. ^{[1
,2
]}

Shinde, Mahesh H. ^{[1
,2
]}

Ramana, Chepuri, V ^{[1
,2
]}

机构：

[1] CSIR Natl Chem Lab, Div Organ Chem, Dr Homi Bhabha Rd, Pune 411008, Maharashtra, India

[2] Acad Sci & Innovat Res AcSIR, Ghaziabad 201002, India

来源：

TETRAHEDRON LETTERS | 2021年 / 66卷

关键词：

Bis-THF-OH intermediate; Darunavir; Ru-catalysis; Dynamic kinetic resolution; Transfer hydrogenation;

D O I：

10.1016/j.tetlet.2021.152831

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The Ru-catalyzed enantio- and diastereoselective dynamic kinetic resolution of alpha-(benzyloxy/benzoyloxy)acyl-gamma-butyrolactones has been examined via transfer hydrogenation. Employing the in situ prepared (R,R)-Ru-FsDPEN catalyst, the transfer hydrogenation of using formic acid/triethylamine at rt gave the corresponding (S)-3-((S)-2-(benzyloxy/benzoyloxy)-1-hydroxyethyl)dihydrofuran-2(3H)-one with good to excellent diastereo- and enantioselectivity. One of the resulting hydrogenation product prepared on gram scales was utilized for the synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol (1), a key synthetic intermediate of various HIV protease inhibitors such as darunavir with excellent enantio-(95% ee) and diastereoselectivities (dr 95:5). (C) 2021 Elsevier Ltd. All rights reserved.

引用

页数：4