Gold(I)-Catalyzed Cascade Cyclization of Anilines with Diynes: Controllable Formation of Eight-Membered Ring-Fused Indoles and Propellane-Type Indolines

Abstract

Heterocycle-fused indoles or indolines are distributed widely in a variety of natural products, bioactive agents, and pharmaceuticals. Herein, we describe the development of gold-catalyzed cascade reactions of anilines with diynes to form eight-membered ring-fused indoles and propellane-type indolines, both of which proceed through an intramolecular 5-endo-dig hydroamination followed by an 8-endo-dig cycloisomerization. Controllable formation of eight-membered ring-fused indoles and propellane-type indolines was achieved through selection of the ligands and/or solvents. Protic solvents such as alcohols or IPr ligand favored the formation of eight-membered ring-fused indoles, whereas the use of Buchwald’s type ligands and/or nonpolar solvents gave propellane-type indoline predominantly. This reaction provides rapid access to two types of fused nitrogen heterocycles from simple aniline derivatives.

Synthesis of Medium-Sized Heterocycles by Transition-Metal-Catalyzed Intramolecular Cyclization

“…Ohno and co-workers reported gold(I)-catalyzed cascade reactions of anilines 93 to form eight-membered ring-fused indoles 94 or propellane-type indoline 95 ( Scheme 34 ) [ 79 ]. Depending on the reaction conditions, with IPr ligands and protic solvents such as ethanol, the formation of eight-membered ring-fused indoles 94 is favored.…”

“…A substrate scope expansion was achieved via the application of the method on some previously unreactive substrates and substrates bearing additional substituents on the indole core. Ohno and co-workers reported gold(I)-catalyzed cascade reactions of anilines 93 to form eightmembered ring-fused indoles 94 or propellane-type indoline 95 (Scheme 34) [79]. Depending on the reaction conditions, with IPr ligands and protic solvents such as ethanol, the formation of eightmembered ring-fused indoles 94 is favored.…”

Catalytic Synthesis of Dibenzazepines and Dibenzazocines by 7‐Exo‐ and 8‐Endo‐Dig‐Selective Cycloisomerization

“…Generally, the cycloisomerization of enynes using a benzene ring as an ene moiety can be categorized by Baldwin's rule and the most well‐established cycloisomerization is 6‐ endo ‐ dig cyclization [2,3] . Despite the extensive development of gold‐catalyzed cycloisomerization, there have been a few reports on the construction of a more than seven‐membered ring [4–8] . Especially, the selective transformation of compounds with various cyclization patterns and/or multiple reaction sites is still a challenging topic.…”

“…Waldmann and co‐workers achieved the 8‐ endo ‐ dig ‐selective cycloisomerization of o ‐propargyloxy styrenes to provide benzoxines (Scheme 1b) [6] . The electron‐donating resonance effect of oxygen atom was essential for the selective 8‐ endo ‐ dig reaction [7] and the substituent (R 2 ) hampered the reaction site for 6‐ endo ‐ dig cyclization. Notably, examples of gold‐catalyzed 8‐ endo‐dig ‐selective cycloisomerization, not via a 7‐ endo ‐ dig intermediate, are still rare [7] .…”

“…The electron‐donating resonance effect of oxygen atom was essential for the selective 8‐ endo ‐ dig reaction [7] and the substituent (R 2 ) hampered the reaction site for 6‐ endo ‐ dig cyclization. Notably, examples of gold‐catalyzed 8‐ endo‐dig ‐selective cycloisomerization, not via a 7‐ endo ‐ dig intermediate, are still rare [7] . Hashmi and co‐workers reported the 7‐ exo‐dig ‐selective cycloisomerization of a biaryl possessing a homopropargyl substituent to give dibenzocycloheptatrienes (Scheme 1c) [8] .…”