Asymmetric Dearomatization of Indoles through a Michael/Friedel–Crafts‐Type Cascade To Construct Polycyclic Spiroindolines

Abstract

A highly efficient asymmetric dearomatization of indoles was realized through a cascade reaction between 2-isocyanoethylindole and alkylidene malonates catalyzed by a chiral N,N'-dioxide/Mg(II) catalyst. Fused polycyclic indolines containing three stereocenters were afforded in good yields with excellent diastereo- and enantioselectivities through a Michael/Friedel-Crafts/Mannich cascade. When 2-substituted 2-isocyanoethylindoles were used, spiroindoline derivatives were obtained through a Michael/Friedel-Crafts reaction.

Synthesis of Spirocyclic Indolenines

“…Sakai and co‐workers further proved the efficacy of this strategy when they reported a single example of an AgBF 4 mediated nucleophilic addition to a pendant nitrile 291 , affording amidine 292 in 74 % yield (Scheme ) . More recently, Feng and co‐workers utilised an intriguing intermolecular Michael/Fridel–Crafts/Mannich cascade sequence between isonitrile 293 and alkylidene malonate 294 . This process was catalysed by a combination of Mg(OTf) 2 with ligand 295 to afford a variety of spirocyclic indolenines 296 in excellent yield and with high diastereoselectivity and enantioselectivity…”

“…[161] More recently,F eng and co-workersu tilised an intriguing intermolecular Michael/Fridel-Crafts/Mannich cascade sequence between isonitrile 293 and alkylidene malonate 294. [162] This process was catalysed by ac ombination of Mg(OTf) 2 with ligand 295 to afford av ariety of spirocyclic indolenines 296 in excellent yield and with high diastereoselectivity ande nantioselectivity.…”

“…Spirocyclisation by addition to an itrile/isonitrile (Kobayashi et al; [160] Sakai et al; [161] Fengetal. [162] ).…”

The Future of Catalysis by Chiral Lewis Acids

“…Because of their nucleophilic reactivity, indoles have been the featured substrates in the vast majority of applications, and a wide variety of chiral catalysts have been used to activate an α,β-unsaturated nitro compound [181][182][183], α,β-unsaturated ester [184][185][186], trifluoropyruvate [187,188], or imine [189] for electrophilic substitution. Applications to phenols [190] have been more limited (Scheme 40).…”

Highly Diastereo‐ and Enantioselective Synthesis of Tetrahydro‐5H‐Indolo[2,3‐b]quinolines through Copper‐Catalyzed Propargylic Dearomatization of Indoles

“…In this regard, Yang and co-workers reported an elegant asymmetric total synthesis of (À)-communesin Fb y utilizing Ir-catalyzed allylic dearomatization/annulation cascade very recently. [4] On the other hand, the intermolecular catalytic asymmetric dearomatization (CADA) reactions of indoled erivatives with amphiphilic reagents,w hich could act as both electrophile and nucleophile, have been extensively explored, [5] constructing the polycyclic indolines efficiently.O ver the past decades, great progress has been made on the Ru-and Cu-catalyzed propargylic substitution reactions via the metal-allenylidene complexes. [6,7] As our ongoinge fforts towards the development of catalytic asymmetric dearomatization reactions, [8][9][10] we envisioned that ac opper-catalyzed asymmetric propargylic dearomative [ 4 + +2] cycloaddition of simple substituted indoles with ac opper-allenylidene amphiphilic intermediate would afford the tetracyclic core structure of indole alkaloids commu-nesinsA -H and perophoramidine (Scheme 1).…”