Enantio- and Diastereoselective Total Synthesis of Belzutifan Enabled by Rh-Catalyzed Hydrogenation

被引：0

作者：

Le, Diane N. ^{[1
]}

Johnson, Heather C. ^{[1
]}

Lam, Yu-hong ^{[2
]}

Sun, Chunrui ^{[1
]}

Cheng, Lili ^{[3
]}

Belyk, Kevin M. ^{[1
]}

机构：

[1] Merck & Co Inc, Proc Res & Dev, Rahway, NJ 07065 USA

[2] Merck & Co Inc, Modeling & Informat, Rahway, NJ 07065 USA

[3] WuXi AppTec Tianjin, Chem Serv Unit, Tianjin 300457, Peoples R China

来源：

ORGANIC LETTERS | 2024年 / 26卷 / 19期

关键词：

ASYMMETRIC HYDROGENATION; INTERFERON-ALPHA; CELL;

D O I：

10.1021/acs.orglett.4c00982

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Herein, we report a nine-step synthesis of belzutifan enabled by a novel Rh-catalyzed asymmetric hydrogenation to install the contiguous fluorinated stereocenters with high enantioselectivity. Moreover, the final ketone reduction in the synthesis proceeds with high diastereoselectivity, leading to the expedient assembly of the stereotriad. In contrast to the original 16-step synthesis, this route avoids a lengthy bromination-oxidation sequence and introduces the sulfone functionality via nucleophilic aromatic substitution, obviating the need for transition metal catalysis.

引用

页码：4059 / 4064

页数：6

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