Changing the Paradigm: Chelation Control with Silyloxy and Halo Carbonyl Compounds

在这个由化学部化学合成项目资助的项目中，宾夕法尼亚大学化学系的Patrick J. Walsh教授将研究有机金属试剂在-或-硅氧基和-或-环醛、酮和醛胺上螯合控制的一般方法。这些底物通常不会螯合。本项目的中心假设是，通过使用温和的亲核试剂与锌路易斯酸结合，可以与强烈抵抗螯合的底物实现cramm螯合。有三个具体目标：1。开发手性-和-硅氧基醛和酮的螯合控制添加物；2. 评估锌试剂螯合α或β环醛和酮的能力；3. 评估锌试剂螯合α或β环亚胺和促进克拉姆螯合添加的能力。该项目可能导致对α或β取代的醛、酮和醛胺进行高度非对映选择性添加的一般方法。这些方法对于制备大量在生物学重要分子中常见的亚结构非常有用，包括syn1,2 -和抗1,3-二醇，syn1,2 -halo醇，顺式环氧化合物和烯丙基环氧化合物，以及抗1,2-氨基醇。这项工作的成功结果将对制药、农化和特种化工行业产生积极影响。此外，该项目将为学生提供优秀的培训，包括那些来自历史上在科学领域代表性不足的群体的学生。

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Patrick J. Walsh of the Department of Chemistry at the University of Pennsylvania will examine general methods for the chelation-controlled addition of organometallic reagents to alpha or beta silyloxy and alpha or beta halo aldehydes, ketones, and aldimimes. These substrates typically do not chelate. The central hypothesis of this project is that Cram-chelation can be achieved with substrates that strongly resist chelation by employing mild nucleophiles in combination with zinc Lewis acids. There are three specific objectives: 1. Developing chelation-controlled additions to chiral alpha and beta silyloxy aldehydes and ketones; 2. Assessing the ability of zinc reagents to chelate alpha or beta halo aldehydes and ketones; 3. Assessing the ability of zinc reagents to chelate alpha or beta halo imines and to promote Cram chelation additions.The project could lead to general methods for highly diastereoselective additions to alpha or beta substituted aldehydes, ketones, and aldimines. These methods are highly useful for the preparation of a large number of substructures commonly seen in biologically important molecules, including syn-1,2- and anti-1,3-diols, syn-1,2-halo hydrins, cis-epoxides and allylic epoxides, and anti-1,2-amino alcohols. The successful results of this work could positively impact the pharmaceutical, agrochemical, and specialty chemical industries. In addition, this project will provide excellent training of students, including those from groups historically underrepresented in the sciences.