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

职业：Au 催化：从多功能合成方法到复杂的天然结构

• 批准号: 0748484
• 负责人: Liming Zhang
• 金额: $ 50万
• 依托单位: Board of Regents, NSHE, obo University of Nevada, Reno
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0748484&HistoricalAwards=false
• 关键词: CAREER; Au; Catalysis; Versatile; Synthetic

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.

本计画致力于发现及发展金催化的联烯反应，作为选择性及高效率的合成方法。串联方法提供了获得官能化联烯（即，丙二烯基酯）通过Au催化的炔丙基酯的3，3-重排。在原位生成的丙二烯基酯的Au活化后形成的烯基氧代碳鎓中间体是高度反应性的，并且可以沿着各种反应途径进行，导致有效形成通用合成中间体，包括高度官能化的环丁烷、氰烯酮、环己烯酮、双环酮、无环烯酮、二烯基酯、不饱和酰基硅烷和烯酸酯。使用具有手性配体（膦或N-杂环卡宾）的阳离子Au（I）络合物，尽管S-Au-L络合物的线性性质，但可以实现对映选择性转化。建议的Au化学的合成潜力将被说明在一个有效的全合成（+）-aspidosperma生物碱的母体结构的spidosperma亚精胺。功能性有机分子，包括复杂的天然产物和药物实体，通常是各种结构基序的复杂组合。有效和选择性地获得这些关键结构单元对于合成努力的成功至关重要，并且通常决定了项目的经济成果。尽管合成化学家拥有多种方法来制备各种关键合成中间体，但对开发新方法的需求不断增长，这些方法应具有（a）催化性、选择性和高效性;（B）具有广泛的官能团耐受性;（c）在极其温和的反应条件下操作。有了这个奖项，有机和高分子化学计划正在支持内华达州-里诺大学化学系的张黎明博士的研究。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经济的方法。这些由金络合物催化的反应，代表了迈向可持续性和绿色化学目标的实质性步骤。