Pd(0)-Catalyzed Alkenylation and Allylic Dearomatization Reactions between Nucleophile-Bearing Indoles and Propargyl Carbonate

Abstract

Spiroindolenine derivatives were synthesized by intermolecular Pd-catalyzed dearomatization of indoles. The reaction between nucleophile bearing indoles and propargyl carbonate proceeds in a cascade fashion providing spiroindolenines or spiroindolines in good to excellent yields.

Palladium(0)‐Catalyzed Intermolecular Asymmetric Cascade Dearomatization Reaction of Indoles with Propargyl Carbonate

“…In 2014, the Rawal group and we independently reported an intermolecular cascade dearomatization reaction of indole‐based bisnucleophiles with propargyl carbonate, leading to a series of spiroindolenines and spiroindolines. Moderate enantioselectivity (≤77 % ee ) was achieved for limited substrates (Scheme , reaction 1) . Rawal and co‐workers found that the indole N−H moiety could participate in the cyclization process when the nucleophilic side chain was decorated at the C2 position of the C3 methyl substituted indole (Scheme , reaction 2) .…”

Synthesis of Spirocyclic Indolenines

“…A similar strategy, which was developed around the same time by the You and Rawal groups, is the use of propargyl carbonates in intermolecular reactions; these reactions are proposed to proceed first by the interception of a typical η 3 ‐π‐allenylpalladium species by a nucleophile tethered onto the indole, before undergoing a protonation–spirocyclisation sequence to form the spirocyclic indolenine products (Scheme ). The contribution by You and co‐workers concerns the reaction of malonates 182 with methyl propargyl carbonate, [Pd 2 (dba) 3 ] and an appropriate phosphine ligand, to afford spirocyclic indolenines 183 in moderate to excellent yield, with preliminary results suggesting that an asymmetric variant is possible using ( R )‐segphos or related derivatives . Meanwhile, Rawal and co‐workers reported the reaction of a variety of indole‐tethered pro‐nucleophiles, [Pd 2 (dba) 3 ], xantphos, and in some cases a base, to furnish an impressive variety of spirocyclic indolenines 185 / 186 , generally in good yield .…”

“…The contribution by Youa nd co-workersc oncerns the reaction of malonates 182 with methyl propargyl carbonate, [Pd 2 (dba) 3 ]a nd an appropriate phosphine ligand,t oa fford spirocyclic indolenines 183 in moderate to excellent yield, with preliminaryr esults suggesting that an asymmetricv ariant is possible using (R)-segphos or relatedd erivatives. [106] Meanwhile, Rawal and co-workersr eported the reaction of av ariety of indole-tethered pro-nucleophiles, [Pd 2 (dba) 3 ], xantphos, and in some cases ab ase, to furnisha ni mpressive variety of spirocyclic indolenines 185/186,g enerally in good yield. [107] Recently,R awal and co-workersa lso described an asymmetric adaptation of this reaction, where in as imilar fashion to You and co-workers, chiral phosphine ligands( 188)w ere used to furnish the indolenines 189 in good to excellent yield and with high enantioselectivity.…”

“…Scheme25. Intermoleculara ddition to p-allylintermediatesgenerated from propargylic systems (You et al; [106] Rawal et al [107,108] ).…”

Palladium-catalyzed construction of quaternary carbon centers with propargylic electrophiles

“…In an analogous process, You et al found that the nitrogen nucleophile can be replaced by a malonate in 126 (Scheme 28), 40 thus giving rise to the installation of new all-carbon quaternary centers in spiroindolenines 127 with the same regioselectivity. A range of ester side-chains and indole substituents were successfully examined (127a-c).…”