From Understanding to Prediction: Gold- and Platinum-Based π‑Acid Catalysis for Target Oriented Synthesis

• Published in: Accounts of chemical research Vol. 47; no. 3; pp. 925 - 938
• Main Author: Fuerstner, Alois
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18.03.2014
• Subjects: Arenas; Catalysis; Cross coupling; Metalorganic compounds; Metathesis; Olefins; Synthesis; Synthesis (chemistry)
• ISSN: 0001-4842; 1520-4898
• DOI: 10.1021/ar4001789

During the last century, conceptual advances in organometallic chemistry were often rapidly embraced by target oriented synthesis. Feedback provided by such preparative scrutiny has greatly benefitted method development; particularly prominent are examples from the entire cross coupling arena, as well as olefin metathesis. Seen against this backdrop, it is somewhat surprising that the explosive growth of research into π-acid catalysis has not yet yielded a matching number of implementations into the synthesis of structurally complex targets of biological significance. In contrast to the massive output of methodological and mechanistic investigations, few studies illustrate the strategic use of gold, silver, or platinum catalysis in late stages of such multistep endeavors. These elaborate and highly precious compounds demand utmost confidence in the reliability and robustness of the method to be applied. In this Account, we analyze the possible reasons for this imbalance, after a short summary of the conceptual basis of carbophilic activation of π-bonds with the aid of soft transition metal cations or complexes. We pinpoint mechanistic subtleties, which, at least in part, produce a great deal of structural diversity but can jeopardize predictive power. With the advances in the understanding of π-acid catalyzed processes in general, however, this uncertainty is gradually vanishing and the entire field is transitioning from comprehension to prediction. This is expected to foster advanced applications, while recent progress in asymmetric gold catalysis further improves the preparative significance. The presented work in this Account illustrates our own commitment to the field as well as our growing confidence in the maturity of platinum and gold catalysis. The carbophilic activation of π-bonds, particularly of alkynes, provides a method to manipulate functional groups that is orthogonal to traditional carbonyl chemistry. We illustrate this notion by presenting a new approach to hydroxypyrone derivatives that has enabled the total synthesis of the fragile polyunsaturated cyclophane derivative neurymenolide A. The synthesis of the pyrrole alkaloid streptorubin by an enyne cycloisomerization is equally instructive. In addition, different manifestations of transannular hydroxyl addition reactions across alkyne partners mark the late stages of our conquests of amphidinolide F, polycavernoside A, and spirastrellolide F. Together with a few model studies and a personal selection of recent highlights from other groups, these examples augur well for future applications of π-acid catalysts in the realm of target oriented synthesis.