Asymmetric Synthesis of the cis-1,2-Diaryltetralin Vepdegestrant Core via an Enantioselective Intramolecular Corey-Chaykovsky Epoxidation

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2024-11-08 DOI:10.1021/acs.oprd.4c00379

David J. Bernhardson, Sarai Lara-Boykin, James Christopher McWilliams, Yexenia Nieves-Quinones, Liam S. Sharninghausen, Robert A. Singer, Zheng Wang, Zebediah C. Girvin

引用次数: 0

Abstract

An asymmetric synthesis of cis-1,2-diaryltetralin (2), a key chiral intermediate in the synthesis of Vepdegestrant (1), an orally available PROTAC being evaluated for the treatment of ER+/HER2- breast cancer, is reported. Chirality is initially introduced via a catalytic enantioselective intramolecular Corey-Chaykovsky epoxidation utilizing isothiocineole, a chiral sulfide. Although several asymmetric intermolecular epoxidations using chiral sulfides have been reported, our approach represents a unique intramolecular variant. The subsequent introduction of the cis-1,2-diaryl motif is achieved via diastereoselective hydrogenation.

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通过不对称选择性分子内 Corey-Chaykovsky 环氧化作用不对称合成顺式-1,2-二芳基四氢萘 Vepdegestrant 核心化合物

报告了顺式-1,2-二芳基四氢萘 (2) 的不对称合成，这是合成 Vepdegestrant (1) 的一个关键手性中间体，Vepdegestrant 是一种口服 PROTAC，目前正在评估用于治疗 ER+/HER2- 乳腺癌。手性最初是通过利用手性硫化物异硫代乙烯进行催化对映选择性分子内 Corey-Chaykovsky 环氧化反应而引入的。尽管已经报道了几种利用手性硫化物进行的不对称分子间环氧化反应，但我们的方法是一种独特的分子内变体。随后通过非对映选择性氢化引入顺式-1,2-二芳基基团。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.