Geometric Isomerisation of Bifunctional Alkenyl Fluoride Linchpins: Stereodivergence in Amide and Polyene Bioisostere Synthesis

Author:

Wienhold Max1,Kweon Byeongseok1,McLaughlin Calum1,Schmitz Matthias2ORCID,Zähringer Till J. B.2,Daniliuc Constantin G.1ORCID,Kerzig Christoph2ORCID,Gilmour Ryan1ORCID

Affiliation:

1. Organisch Chemisches Institut Westfälische Wilhelms-Universität Münster Corrensstraße 36 48149 Münster Germany

2. Department of Chemistry Johannes Gutenberg University Mainz Duesbergweg 10–14 55128 Mainz Germany

Abstract

AbstractAmide groups are pervasive across the chemical space continuum, where their structural and pharmacological importance, juxtaposed with the hydrolytic vulnerabilities, continues to fuel bioisostere development. Alkenyl fluorides have a venerable history as effective mimics (Ψ[CF=CH]) owing to the planarity of the motif and intrinsic polarity of the C(sp2)−F bond. However, emulating the s‐cis to the s‐trans isomerisation of a peptide bond with fluoro‐alkene surrogates remains challenging, and current synthetic solutions only enable access to a single configuration. Through the design of an ambiphilic linchpin based on a fluorinated β‐borylacrylate, it has been possible to leverage energy transfer catalysis to affect this unprecedented isomerisation process: this provides geometrically‐programmable building blocks that can be functionalised at either terminus. Irradiation at λmax=402 nm with inexpensive thioxanthone as a photocatalyst enables rapid, effective isomerisation of tri‐ and tetra‐substituted species (up to E/Z 98 : 2 in 1 h), providing a stereodivergent platform for small molecule amide and polyene isostere discovery. Application of the methodology in target synthesis and initial laser spectroscopic studies are disclosed together with crystallographic analyses of representative products.

Funder

Westfälische Wilhelms-Universität Münster

Alexander von Humboldt-Stiftung

Horizon 2020 Framework Programme

Johannes Gutenberg-Universität Mainz

Deutsche Bundesstiftung Umwelt

Publisher

Wiley

Subject

General Chemistry,Catalysis

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3