Gold‐Catalyzed Polycyclization Toward Natural Products Synthesis

Abstract

Over the last years, gold catalysis has gained considerable significance in organic synthesis, since it allows atom economy and synthetic efficiency for the transformation of relatively simple substrates into valuable, highly complex molecular architectures. The gold‐catalyzed polycyclization reactions of alkynes and enynes have been particularly successful toward the synthesis of natural products. This review highlights the recent developments in polycyclization area according to the key gold‐catalyzed step.

Second-Generation Total Synthesis of Prorocentin

“…On the way to the natural product, however, the TBS–ether formation is unnecessary, and an additional step can, therefore, be saved (Scheme ). Thus, alkyne 17 was engaged into a high-yielding Sonogashira reaction, with alkenyl iodide 19 representing the “eastern” sector of prorocentin, which set the stage for the critical gold-catalyzed spirocyclization reaction. − In line with our expectations, ,,, this key transformation worked exquisitely well when cocatalyzed by [(JohnPhos)­Au­(MeCN)]­SbF 6 ( 21 , 10 mol %) and pyridinium p -toluenesulfonate (PPTS, 10 mol %) in CH 2 Cl 2 ; within the limits of detection ( 1 H NMR), compound 24 was the only isomer present in the crude mixture. The gold complex is thought to trigger the decisive first 6- endo -dig cyclization, which ultimately translates into the 6/6-spirocyclic array ( 20 → 22 ), whereas the Brønsted acid cocatalyst accounts for the fully regioselective isomerization of the exo -methylene group to the endocyclic position, likely at the stage of the transient oxocarbenium intermediate 23 ; at the same time, the reversibility of the acid-catalyzed step ensures thermodynamic control over the configuration of the doubly anomeric spiroacetal center. − …”

Total Syntheses of Nominal and Actual Prorocentin

“…Based on the lessons learned in our previous approach to limaol, a gold-catalyzed spirocyclization reaction of an appropriate alkyne precursor was deemed the ideal gateway to the isomeric tricyclic BCD ring systems in 1 and 2 (Scheme ). − An alkyne is a ketone surrogate that allows potential sensitivity issues associated with the use of highly functionalized carbonyl compounds to be avoided altogether; on treatment with a carbophilic Lewis acid, however, the triple bond is amenable to highly chemoselective activation in the presence of other π-bonds and heteroatoms alike …”

Facile synthesis of the spiro-pyridoindolone scaffoldviaa gold-catalysed intramolecular alkynol cyclisation/hydroindolylation

“…1 In particular, the gold-catalysed π-activation of unsaturated systems and the trapping of the electrophilic species obtained in inter- or intramolecular fashion with multiple nucleophilic centers led to the development of elegant domino processes to synthesize (hetero)cyclic scaffolds in a simple fashion. 2 In this context, domino processes that combine the gold-catalysed π-activation of alkynes and subsequent indole functionalization, have been established as a promising approach for the synthesis of complex polycyclic indole derivatives, and also for the synthesis of indole-based natural products. 3 The synthesis of the tetracyclic indole skeleton via the intramolecular cyclisation of indole-tethered alkynols/ynamides and the trapping of the resultant electrophilic intermediate with the oxygen-centred nucleophile in the presence of a gold complex has been pioneered by the groups of Bandini and Gong–Yang respectively.…”