Catalytic Asymmetric Mukaiyama–Mannich Reaction of Cyclic C-Acylimines with Difluoroenoxysilanes: Access to Difluoroalkylated Indolin-3-ones

Abstract

A catalytic enantioselective Mukaiyama-Mannich reaction of cyclic C-acylimines with difluoroenoxysilanes is reported. (S)-TRIP enables the enantioselective synthesis of a series of novel difluoroalkylated indolin-3-ones bearing a quaternary stereocenter in up to 97% yield and 98% ee. The synthetic utility of this protocol is highlighted by efficient conversion of the products to the corresponding indolin-3-one derivatives without any erosion of the enantiopurity.

Organocatalytic Asymmetric Transformations Involving the Cyclic Imine Moiety in Indole and Isoindole Related Heterocycles

“…However, 2‐aryl‐3 H ‐indol‐3‐ones are not easily accessible and have to be prepared through a troublesome stepwise transformation . Just recently, the Ma group designed a convenient and efficient route to access these valuable cyclic ketimines (Scheme ) from the corresponding 2‐aryl‐substituted indoles 16a inspired by the work reported by Sperry and co‐workers …”

“…Recently, Ma's group reported a catalytic asymmetric Mukaiyama–Mannich reaction of 2‐aryl‐3 H ‐indol‐3‐ones 1c with aryl‐substituted difluoroenoxysilanes 30 catalyzed by ( S )‐BINOL‐derived phosphoric acid Cat. 10 . A number of novel difluoroalkylated indolin‐3‐ones 31 bearing a tetrasubstituted stereocenter could be prepared in a highly stereoselective fashion (up to 98% ee ) (Scheme ).…”

Oxidative Asymmetric Aza‐Friedel–Crafts Alkylation of Indoles with 3‐Indolinone‐2‐carboxylates Catalyzed by a BINOL Phosphoric Acid and Promoted by DDQ

“…[10] Very recently,a ne nantioselective Mukaiyama-Mannich reaction of cyclic C-acylimines with difluoroenoxysilanes was reported by using a-arylcyclic ketimines. [11] However, to the best of our knowledge,t he construction of hetero-dimerized 2,2'-bis-indoline-3-ones that contain two adjacent chiral quaternaryc enters from 3-indolinone-2-carboxylates through an oxidative Mannich reaction by using ac hiral phosphoric acidh as not been reported.…”

Enantioselective Synthesis of Difluoroalkylated Isoindolinones via Chiral Spirocyclic Phosphoric Acid Catalyzed Mannich-Type Reaction

“…3 Among the methods for the synthesis of difluoroalkylated derivatives, 4 the Mannich-type reaction of difluoroenoxysilanes with C=N group of ketimines or aldimines as starting materials is the most efficient approach. [5][6][7][8] In 2010, Shi group reported the asymmetric Mannich-type reaction of difluoroenoxysilanes with hydrazones by employing a chiral Lewis acid catalyst (Scheme 1a). 5 In 2011, the Akiyama group achieved the first Brønsted acid catalyzed asymmetric construction of -ami-no-,-difluorocarbonyl compounds with up to 94% ee (Scheme 1b).…”

“…7 And recently, the Ma group developed a chiral BINOL-derived phosphoric acid catalyzed construction of difluoroalkylated indolin-3ones (Scheme 1d). 8 Despite these creative and elegant strategies, development of catalytic asymmetric transformation Scheme 1 Asymmetric Mannich-type reactions using difluoroenoxysilanes as nucleophiles…”