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联烯反应，作为选择性和高效的合成方法。串联过程通过Au催化的丙烯酸酯的3，3-重排来获得官能化的烯(即，烯基酯)。由Au活化原位生成的烯丙酸酯形成的烯基氧卡宾中间体具有很高的活性，可以沿着不同的反应途径进行，导致高效地形成多种合成中间体，包括高度官能化的环丁烷、环戊酮、环己酮、双环酮、无环烯酮、二烯基酯、不饱和酰基硅烷和烯酸酯。使用手性配体(膦或N-杂环卡宾)的阳离子Au(I)配合物，尽管S-Au-L络合物具有线性性质，但仍可实现对映体选择性转化。所提出的Au化学的合成潜力将在高效的全合成()-asidospermidine中得到展示，()-aspidospermidine是Aspidosperma生物碱的母体结构。功能性有机分子，包括复杂的天然产物和药物实体，往往是各种结构基元的复杂组合。有效和有选择地获得这些关键结构单元对于综合努力的成功至关重要，而且往往决定着一个项目的经济结果。尽管合成化学家对各种关键的合成中间体有各种各样的方法，但人们对开发新方法的需求越来越大，这些方法(A)是催化的、选择性的和高效的；(B)具有广泛的官能团耐受性；(C)在非常温和的反应条件下操作。通过这一奖项，有机和高分子化学项目支持内华达大学雷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高效、更经济的方法。这些反应在金络合物的催化下，代表着朝着可持续发展和绿色化学目标迈出的实质性一步。

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.