Access to Spiroindolines and Spirodihydrobenzofurans via Pd-Catalyzed Domino Heck Spiroyclization through C–H Activation and Carbene Insertion

Abstract

A new palladium-catalyzed domino approach for the synthesis of attractive spirocyclic indolines and dihydrobenzofurans was developed. The reaction proceeds through a sequential intramolecular Heck spirocyclization, remote C-H activation, and diazocarbonyl carbene insertion. Various spiroindolines and spirodihydrobenzofurans containing two quartenary carbon stereocenters were readily obtained in good to excellent yields. A preliminary study of asymmetric spirocyclization using chiral monophosphoramidite as a ligand was also conducted, enabling access to highly valuable chiral spiroindolines with up to 80% ee.

Stereoselective Domino Reactions in the Synthesis of Spiro Compounds

“…After careful investigation, the reaction proceed smoothly in the presence of PPh3 as ligand, Cs2CO3 as the base and THF as the solvent, enabling access to the expected spirocyclic dihydrobenzofurans 617 in good yields (Scheme 131). 135 Scheme 131 Synthesis of spiroindolines 616 and spirodihydrobenzofurans 617.…”

Pd-Catalyzed Domino Reactions Involving Alkenes To Access Substituted Indole Derivatives

“…Better results in the yields were reported by switching from 2-aryl-N-(2-bromoaryl)acrylamides to 2-aryl-N-(2iodoaryl)acrylamides. 35 Beside the positive effect of the halide, also the choice of the ligand showed a strong impact on the reaction, in particular the monophosphoramidite ligand L5 furnished excellent yields of the spiroindoline products 89, performing the reaction in toluene at 80 °C, in the presence of CsF as base (Scheme 32).…”

Synthesis of Spiroindenyl-2-Oxindoles through Palladium-Catalyzed Spirocyclization of 2-Bromoarylamides and Vinyl Bromides

“…The alkylpalladium II species can cleave C-H bonds of an aryl group tethered to the alkene moiety to generate C,C-palladacycles. The palladacycles may undergo intramolecular cyclization [24][25][26][27][28][29][30][31][32][33][34][35] or be captured with external reagents [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55]. These types of reactions not only represent a novel strategy to activate C-H bonds that are not in proximity to directing groups, but also provide easy access to complex polycyclic compounds.…”

“…During recent years, quite a few reactions of this type have been developed. Spiropalladacycles have undergone cyclization [30][31][32][33][34][35] and have been trapped by a variety of external reagents including diaziridinone [44], benzynes [45][46][47], car-benoids [48,49], alkynes [50,51], CH 2 Br 2 [52], alkyl chlorides [53], and aryl iodides [54,55], affording various spirocyclic products.…”