Gold-Catalyzed Domino Cycloisomerization/Alkoxylation: An Entry to 3,4-Dihydro-1H-[1,4]oxazino[4,3-a]indole

Abstract

A novel and mild synthetic route for the preparation of functionalized polycyclic indole skeletons via a gold-mediated cycloisomerization/alkoxylation of 1,6-aldehyde-yne has been developed. This atom-economical catalytic process that associates IPrAu(MeCN)BF 4 and an alcohol demonstrated remarkable selectivity in accessing functionalized 3,4-dihydro-1H-[1,4]oxazino[4,3a]indole derivatives of high synthetic utility (21 examples, yields of ≤96%) and could be optimized under asymmetric conditions with an enantiomeric excess of ≤86%.

Coinage Metal-Catalyzed Asymmetric Reactions of ortho-Alkynylaryl and Heteroaryl Aldehydes and Ketones

“…More recently, our group became interested in the development of a domino cycloisomerization and alkoxylation of propargylated indole carbaldehydes with the addition of nucleophilic alcohols [ 47 ]. Indeed, such transformation allowed an access to valuable oxazinoindole derivatives from readily accessible precursors.…”

Straightforward Access to Isoindoles and 1,2-Dihydrophthalazines Enabled by a Gold-Catalyzed Three-Component Reaction

“…Isobenzopyryliums display appealing reactivity patterns, as they can be trapped by appropriate alkynes and alkenes affording [4 + 2] or [3 + 2] cycloaddition products or experience direct nucleophilic attack leading to 2 H -chromenes (Scheme ). − Among metals, gold catalysis flourished over the last decades, Au­(I) catalysts appeared as efficient Lewis’s acids, showing an outstanding ability to activate C–C multiple bonds toward nucleophilic attack . Recently, the potential of gold catalysis has been expanded through the establishment of protocols in which Au­(I) switches its oxidation state to Au­(III) .…”

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

“…9 A Fe(NO 3 ) 3mediated ring-opening arylation of cyclopropanol with an electron-rich pyrrole was recently applied to the synthesis of functionalized alcohols (Scheme 1, eq 2). 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 further turned our attention to oxygen nucleophiles as partners 11 and started our investigation by engaging 2a with MeOH as nucleophile (Table 1). The use of HFIP did not allow the formation of compound 4a (Table 1, entry 1).…”