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

University Of California-Santa Barbara, Santa Barbara CA

Investigators

Abstract

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.