Palladium(0)-Catalyzed Intermolecular Asymmetric Allylic Dearomatization of Polycyclic Indoles

Abstract

An intermolecular Pd-catalyzed allylic dearomatization reaction of polycyclic indoles with substituted allylic carbonates was realized in the presence of a newly synthesized chiral phosphoramidite ligand. Various polycyclic indoline and indolenine derivatives were successfully synthesized in excellent yields (up to 99%) with excellent enantioselectivity (up to 98% ee). The obtained products could undergo versatile transformations, increasing the application potential of the method in organic synthesis.

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

“…The same research group later developed a Pd-allylic dearomatization of indoles with several allylic carbonates bearing an alkyl or aryl substituent at the C2 position ( Scheme 9 b). 79 In this case, the binaphthol-based monophosphoramidite L15 , which differs from ligand L13 with respect to the substituents of the exocyclic amine, played a key role in achieving excellent enantiocontrol (up to 98% ee ). It should be mentioned that indolenines derived from indoles with a fused cyclopentane are not stable upon purification by chromatography.…”

Pd‐Catalyzed Intermolecular Dearomative Heck Reaction of Indole Derivatives

“…At first, some simple indole substrates were investigated, such as 2,3‐dimethylindole and tryptamine derivatives, but no dearomatized product was obtained. Then tetrahydrocyclopenta[ b ]indole derivatives were utilized because of their high activities showed in other dearomatization reactions . Inspired by the reported intramolecular Heck‐type dearomatization reaction of indoles, electron‐withdrawing N‐protecting group was introduced, leading to a higher reactivity and regioselectivity of the Heck reaction.…”

Organocatalyzed Asymmetric Friedel‐Crafts Reactions: An Update

“…Moreover, the enantioselective allylic dearomatization happened with trisubstituted α‐naphthol 121 p with high yield and moderate ee . Finally, the substituent could be tolerated at other positions to provide the dearomatization products 124 q – r (Scheme , Table ) …”

“…A broad range of β‐naphthols was treated with allenamide 122 to give the corresponding chiral β‐naphthalenones, easily ( 127 a – i ) bearing an all‐carbon quaternary center in excellent yields (up to 98 % yield) with modest chemo‐ and enantioselectivity (up to 97 : 3 e.r .) (Scheme ) …”

“…A probable reaction mechanism including a concerted asynchronous S N 2′‐like displacement is suggested in Scheme …”