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

本项目将致力于催化剂控制的不对称烯丙基化和烷基化反应的发展。尽管存在许多不对称烯丙化和烷基化反应的方法，但需要新的方法来进行复杂的合成中间体的高效和实用的反应。一个中心假设是，亲核的烯丙基金属和烷基金属络合物将通过跨金属作用在原位形成，这些物种将与亲电试剂发生配体控制的反应。初步研究发现了一类新的具有双齿中性N-杂环卡宾配体的亲核烯丙基钯配合物，用于N-酰基吡咯和亚烷基丙二腈的催化烯丙化反应。计划发展反应条件温和、范围广的立体选择性共轭烯丙基化反应。此外，还将提出亲电体烷基化反应的新机理，即由第一排过渡金属与硼酸生成烷基金属络合物。还将进行研究，以阐明转化的机制。通过这一奖项，有机和高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。贾沃教授的研究工作围绕着C-C键形成的选择性方法的发展展开。这种化学方法将有助于环境友好的化学合成方法，因为转化将是实用和高效的，这将使转化的环境成本降至最低。该方法的成功开发将对制药和农业中的合成产生影响。

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.