Dehydration of carboxylic acids and tertiary amides promoted by sulfonium salts for ketene and ketene iminium generation and cycloaddition

多年来，OmegaChem发展了两个专业领域，即开发新的、稳定的试剂(主要是硫酸盐)和药物化学研究(基于合同)。该公司目前正在寻求其他应用，这些应用将a)开辟新的途径，b)引起有机化学家的普遍兴趣，c)理想地服务于他们的第二个专业领域，即针对生物相关类别的药物制备功能化多环框架。在这方面，酮烯特别吸引人：它们是通过羧酸或衍生物脱水制备的，在分子内环加成时生成各种双环酮，从而解决了所有目标。在这项提议中，我们希望开发一种温和的、低温的羧酸和酰胺脱水方法，使用硫盐来生成酮和酮亚胺离子，这些离子将被内部的烯烃或炔烃原位捕获。将研究环的大小、官能团的兼容性以及底物上的取代。我们不仅可以开发新的硫酸盐，包括在欧米茄化学公司提出的试剂库中，我们还将开发与这些试剂相联系的新化学。该项目是OmegaChem发展战略的一部分，旨在提高他们的专业知识，并进一步确认他们作为加拿大脱水转化专用硫试剂专家的独特国际领导地位。**

OmegaChem has developed two fields of expertise over the years, namely in the development of new, stable reagents (principally sulfonium salts) and in the research in medicinal chemistry (contract-based). The company is now seeking other applications that will a) open new avenues, b) be of general interest to organic chemists, and c) ideally serve their second field of expertise, namely the preparation of functionalized polycyclic frameworks toward biologically relevant classes of drugs. Ketenes are particularly appealing in this context: they are prepared by dehydration of carboxylic acids or derivatives and, upon intramolecular cycloaddition, generate varied bicyclic ketones, thus addressing all objectives. In this proposal, we want to develop a mild, low temperature dehydration of carboxylic acids and amides using sulfonium salts to generate ketenes and ketene iminiums ions that will be trapped in situ with an internal alkene or alkyne. Ring size, functional group compatibility as well as substitution on the substrate will be studied. Not only may we develop new sulfonium salts to be included in the arsenal of reagents proposed by OmegaChem, we will also develop new chemistry accessible with such reagents. This project is part of OmegaChem development strategy to advance their expertise and further affirm their unique international leadership as Canadian experts in specialized sulfonium reagents for dehydrative transformations.**