SusChEM: Direct functionalization of aldehydes enabled by aminocatalysis

美国国家科学基金会化学部化学合成项目支持新墨西哥大学化学与化学生物系王伟教授的研究。王教授和他的学生基于氨基催化的概念开发了具有成本效益和环境友好的有机合成技术。本研究的目的是为有机转化开发和利用新的有机催化活化模式。新的化学物质被转化为强大的合成方法，从简单和容易获得的化学物质开始，简单和原子经济地合成多种构建模块。在温和的反应条件下也进行了合成。这些“一锅”级联方法用于制造复杂的分子结构，解决了现代有机合成中的关键挑战。这些方法包括提高合成效率、使用可持续和廉价的化学品、避免使用有毒物质以及减少废物和危险副产品。由于操作简单，反应条件温和，环境友好，本研究非常适合各级科学家的教育。王教授的小组在为来自科学领域代表性不足的群体的学生提供教育和培训方面处于有利地位。该项目继续努力，旨在扩大氨基催化的范围，超越已建立的烯胺和胺催化的激活模式。王教授和他的团队挑战了机理教条，证明了由亲核添加到最小离子的加合物中的胺部分可以在随后的亲核取代反应中作为离开基团。中间胺加成产物的原位释放为氨基催化醛直接功能化创造了新的前景。本研究表明，通过对催化剂和反应物的电子和位阻性质的精心控制，合理设计和选择胺类催化剂，优化反应条件，可以开发出新的强大的催化级联反应。鉴于醛类化合物的易接近性、反应性和广泛的结构多样性，在高效的一锅反应中构建了一系列新的合成构件和具有重要生物学意义的复杂分子结构。该教育计划延续了以往的传统，在夏季招收本科生，尤其是来自少数族裔的学生，到王博士的实验室进行研究。王博士还将他的学术实验室的研究成果和实验融入到他的本科生的经历中。

The Chemical Synthesis Program of the NSF Chemistry Division supports the research of Professor Wei Wang in the Department of Chemistry & Chemical Biology at the University of New Mexico. Professor Wang and his students develop cost-effective and environmentally friendly technologies for organic synthesis based on the concept of aminocatalysis. The goal of this research is to develop and exploit new organocatalytic activation modes for organic transformations. New chemistries are transformed into powerful synthetic methods for the facile and atom-economic synthesis of versatile building blocks starting from simple and readily available chemicals. The syntheses are also conducted under mild reaction conditions. These "one-pot" cascade methods, used to make complex molecular architectures, address critical challenges in modern organic synthesis. The methods include the improvement of synthetic efficiency, the use of sustainable and inexpensive chemicals, the avoidance of toxic agents, and the reduction of waste and hazardous byproducts. As a consequence of operational simplicity, mild reaction conditions and environmental friendliness, this research is well suited for the education of scientists at all levels. Professor Wang's group is well positioned to provide education and training for students from groups that are underrepresented in science.This project continues efforts aimed at expanding the scope of aminocatalysis beyond the well-established activation modes of enamine and iminium catalysis. Professor Wang and his team challenge mechanistic dogma by showing that amine moieties in adducts which result from nucleophilic additions to iminum ions can serve as leaving groups in ensuing nucleophilic substitution reactions. In situ release of the intermediate amine addition products creates a new scenario for aminocatalytic direct functionalization of aldehydes. This research demonstrates that through careful manipulation of the electronic and steric properties of catalysts and reactants, judicious design and selection of amine catalysts, and optimization of reaction conditions, new and powerful catalytic cascade reactions are developed. Given the ready accessibility, reactivity and broad structural diversity of aldehydes, a wide array of new synthetic building blocks and biologically-important complex molecular architectures are constructed in efficient one-pot reactions. The educational plan continues a tradition to recruit undergraduate students especially from underrepresented minority groups over the summer to conduct research in Dr. Wang's laboratory. Dr. Wang also integrates the research results and experiments from in his academic laboratory into his undergraduate students' experiences.