CAREER: Chemical Methods for Organic Synthesis Using Nucleophilic Allyl- and Alkylmetal Catalysts

摘要本项目主要研究催化控制的不对称烯丙基化和烷基化反应的发展。虽然对映选择性烯丙基化和烷基化反应的方法很多，但复杂合成中间体的高效、实用反应还需要新的方法。一个中心假设是，亲核烯丙基金属和烷基金属配合物将通过金属转化机制在原位形成，这些物质将与亲电试剂发生配体控制的反应。初步研究发现了一类具有双齿中性n -杂环羰基配体的亲核烯丙基钯配合物，用于催化n -酰基吡咯和烷基基丙二腈的烯丙基化反应。计划发展范围广、反应条件温和的立体选择性共轭烯丙基化反应。此外，还将提出硼酸与第一排过渡金属生成烷基金属配合物的亲电试剂烷基化反应的新机制。还将进行研究以阐明这种转变的机制。通过这个奖项，有机和大分子化学项目支持了加州大学欧文分校化学系伊丽莎白·贾沃教授的研究。Jarvo教授的研究工作围绕着形成C-C键的选择性方法的发展。这种化学将有助于环境友好的化学合成方法，因为转化将是实用和有效的，这将最大限度地减少转化的环境成本。该方法的成功发展将对制药和农业工业的合成产生影响。

Proposal Abstract This project will address the development of catalyst-controlled asymmetric allylation and alkylation reactions. While many methods for enantioselective allylation and alkylation reactions exist, new methods are required for efficient and practical reactions of complex synthetic intermediates. A central hypothesis is that nucleophilic allylmetal and alkylmetal complexes will be formed in situ by transmetallation mechanisms and these species will undergo ligand-controlled reactions with electrophiles. Preliminary studies have uncovered a new class of nucleophilic allylpalladium complexes with bidentate neutral N-heterocyclic carbene ligands, which have been used to develop catalytic allylation reactions of N-acylpyrroles and alkylidene malononitriles. The development of stereoselective conjugate allylation reactions of broad scope with mild reaction conditions is planned. In addition, new mechanisms for alkylation reactions of electrophiles by generating alkylmetal complexes from boronic acids with first row transition metals will be proposed. Studies to elucidate the mechanisms of the transformation will also be performed. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Elizabeth Jarvo of the Department of Chemistry at the University of California, Irvine. Professor Jarvo's research efforts revolve around the development of selective methods for the formation of C-C bonds. Such chemistry will contribute to environmentally benign methods for chemical synthesis as the transformations will be practical and efficient, which will minimize the environmental cost of the transformation. Successful development of the methodology will have an impact on synthesis in the pharmaceutical and agricultural industries.