CAREER: Au Catalysis: From Versatile Synthetic Methods to Complex Natural Structure

本项目致力于发现和发展金催化的烯类化合物的选择性和高效合成方法。串联工艺通过金催化丙炔酯的3,3-重排，提供了获得功能化烯（即烯丙酯）的途径。烯基氧羰基中间体是由金活化原位生成的烯烯酯形成的，具有高活性，可以沿着各种反应途径进行，从而有效地形成多功能合成中间体，包括高功能化的环丁烷、环戊烯酮、环己烯酮、双环酮、无环烯酮、二烯酯、不饱和酰基硅烷和烯酸酯。使用带有手性配体（膦或n杂环碳）的阳离子Au(I)配合物，可以实现对映选择性转化，尽管S-Au-L配合物具有线性性质。提出的金化学的合成潜力将在(+)-蜘蛛精胺的有效全合成中得到说明，蜘蛛精胺是蜘蛛类生物碱的母体结构。功能有机分子，包括复杂的天然产物和药物实体，往往是各种结构基序的复杂组合。对这些关键结构单元的有效和选择性的访问对于综合努力的成功是必不可少的，并且通常决定了项目的经济结果。尽管合成化学家在他们的曲目中有无数的方法来研究各种关键的合成中间体，但对开发新方法的需求不断增长，这些新方法：(a)具有催化性，选择性和高效率；(b)具有广泛的官能团耐受性；(c)在非常温和的反应条件下运行。通过这个奖项，有机和大分子化学项目支持了内华达大学里诺分校化学系张黎明博士的研究。张教授和他的学生正在开发新的合成方法，为一系列多功能合成中间体提供更有效和更经济的方法。这些由金络合物催化的反应，代表着朝着可持续发展和绿色化学的目标迈出了实质性的一步。

This project addresses the discovery and development of Au-catalyzed reactions of allenes as selective and highly efficient synthetic methods. A tandem process offers access to functionalized allenes (i.e., allenylic esters) via Au-catalyzed 3,3- rearrangement of propargylic esters. Alkenyl oxocarbenium intermediates, formed upon Au activation of the in situ-generated allenylic esters, are highly reactive and can proceed along various reaction pathways, leading to efficient formation of versatile synthetic intermediates, including highly functionalized cyclobutanes, cycopentenones, cyclohexenones, bicyclic ketones, acyclic enones, dienylic esters, unsaturated acylsilanes, and enoates. Using cationic Au(I) complexes with chiral ligands (phosphines or N-heterocyclic carbenes), enantioselective transformation can be implemented in spite of the linear nature of the S-Au-L complex. The synthetic potential of the proposed Au chemistry will be illustrated in an efficient total synthesis of (+)-aspidospermidine, the parent structure of Aspidosperma alkaloids. Functional organic molecules, including complex natural products and pharmaceutical entities, are often intricate combinations of various structural motifs. Efficient and selective access to these key structural units is essential for the success of synthetic endeavors and often dictates economic outcome of a project. Although synthetic chemists have in their repertoire a myriad of approaches toward various key synthetic intermediates, there is an ever-growing demand for developing new methods that (a) are catalytic, selective, and highly efficient; (b) possess broad functional group tolerance; and (c) operate under exceedingly mild reaction conditions. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Liming Zhang, of the Department of Chemistry at the University of Nevada - Reno. Professor Zhang and his students are developing novel synthetic methods providing more efficient and economical approaches to a range of versatile synthetic intermediates. These reactions, catalyzed by complexes of gold, represent substantial steps toward the goals of sustainability and green chemistry.