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.
For the past five years with the support of this CAREER award, my research lab has kept pushing the frontier of homogeneous gold catalysis, which is a hotly contested contemporary research area of tremendous interest in the organic synthesis community and with potentially high impact in fine chemical synthesis and drug research and development. With a total of 25 papers published in mostly premier peer-reviewed academic journals, we have made pioneering contributions in two important areas in gold chemistry, namely, gold(I)/gold(III) catalysis (Figure 1) and oxidative gold catalysis via highly reactive alpha-oxo gold carbenes (Figure 2). For the latter area, our intermolecular approach by using readily available and mostly benign alkynes offers significant advantages in terms of synthetic efficiency, step economy and mostly importantly operational safety over the well-practiced methods using hazardous and potentially explosive diazo ketones. A range of versatile and efficient synthetic methods have been developed, some of which have been utilized successfully by other researchers in their research works. Training students and developing outstanding, next generation synthetic chemists is an integral part of our research endeavor. Over the five-year period, eight graduate students have been trained with the NSF support, with one graduated with a Ph. D. degree, another with a M. S. degree, and the rest in excellent progress toward their degrees. To offer research experience to undergraduate students and attract them to science and chemistry in particular, I have opened my lab to 10 of them including the three REU students. Most of them, upon graduation, have gone on to either medical schools or graduate schools. As an indication of the vigor of their training, two published papers are based solely or partially on the work done by undergraduates. I have also had more than 10 postdocs and three visiting scholars worked with me. Those left have all assumed either professorships or research scientist positions in the States or aboard.
