Gold‐Catalyzed One‐Pot Cycloisomerization/Nucleophilic Addition/Rearrangement of Acenaphthylene Carbaldehyde Derivatives

Abstract

Merging the latest advances in the field of gold catalysis and the efficiency of hexafluoro-2propanol (HFIP), a gold-catalyzed orthogonal tandem reaction has been developed to access carbocyclic ketone on naphthalene substrates. The methodology involved a cycloisomerization/nucleophilic addition and a C!O rearrangement. The HFIP solvent most probably acted as a Lewis-acid on isochromene derivatives, through hydrogen donor bond activity. A large range of acenaphthylene carbaldehyde has been engaged in this process coupling gold catalysis and Lewis-acid behavior of HFIP leading to cyclic ketones with a yield ranging from 15 to 91% (27 compounds). The mechanism was investigated, and the reaction most presumably occurred via a classical cyclization process followed by a [Au]-HFIP interaction for the final rearrangement. The interest of such transformation was demonstrated by performing it on a gram-scale. Moreover, a post-functionalization bromination was performed, as well as the isomerization of some functionalized ketones leading to full trans derivatives with a yield ranging from 78 to 90% yields.

Hexafluoroisopropanol (HFIP) as a Multifunctional Agent in Gold-Catalyzed Cycloisomerizations and Sequential Transformations

“…This is reminiscent of the acyl group transfer methodology developed by Kita and co-workers, which has found numerous applications in organic synthesis, only in this case, the vinyl ester is part of a ring and the nucleophile is the solvent itself . Gold-catalyzed cycloisomerization followed by Brønsted acid-mediated rearrangements can be a powerful sequence of reactions with recent application in total synthesis . In this manner, the library of hexafluoroisopropyl ω-ketoesters derived from the lactones of Scheme and HFIP or TFE was rapidly generated without the need for tedious purification procedures (Scheme ).…”

Gold(I)-Catalyzed Functionalization of Pyrrole Derivatives: Stereoselective Synthesis of 7,8-Disubstituted 7,8-Dihydroindolizin-6(5H)-ones

“…10 We recently described a gold-catalyzed domino cycloisomerization/alkoxylation of indole skeletons leading to 3,4-dihydro-1H-[1,4]oxazino[4,3-a]indole 11 and observed a domino process of naphthalene derivatives that combined a C−O rearrangement in the presence of Lewis acid. 12 The importance of access to diverse pyrrole derivatives led us to examine the preparation of 7,8-dihydroindolizin-6(5H)-ones, as a key platform for the synthesis of bioactive compounds (Scheme 1, eq 3). We report herein our preliminary results leading to the functionalization of pyrrole derivatives according to two complementary protocols, employing carbon and oxygen nucleophiles, The syntheses of the starting aldehyde-yne derivatives 2a−s were accomplished through a one-to four-step reaction sequence (Figure 1).…”

Synthesis of an Indazole/Indazolium Phosphine Ligand Scaffold and Its Application in Gold(I) Catalysis

“…HFIP as a solvent has been increasingly employed to facilitate a range of catalyses and has even found its way into the field of gold catalysis . Many of these gold catalysts use HFIP simply as a polar protic solvent with the catalyst still being activated by a silver salt.…”

“…HFIP as a solvent has been increasingly employed to facilitate a range of catalyses 12 and has even found its way into the field of gold catalysis. 13 Many of these gold catalysts use HFIP simply as a polar protic solvent with the catalyst still being activated by a silver salt. Some of the more recent examples, however, use HFIP not only to solubilize the catalyst but also to activate the Au–Cl bond by hydrogen bonding with chloride.…”