Organocatalytic Asymmetric Michael–Michael Cascade for the Construction of Highly Functionalized N-Fused Piperidinoindoline Derivatives

Abstract

Application of indolin-3-one derivatives in a cascade reaction for efficient assembly of complex molecules is a much less explored research area. It is demonstrated that structurally interesting polysubstituted piperidino[1,2-a]indoline compounds containing four contiguous stereocenters including one tetrasubstituted carbon center can be readily obtained with good yields (up to 94% yield) and excellent enantioselectivities (up to >99% ee) by employing indolin-3-one derivatives as substrates via bifunctional catalysis.

Oxidative Dearomative Cross-Dehydrogenative Coupling of Indoles with Diverse C-H Nucleophiles: Efficient Approach to 2,2-Disubstituted Indolin-3-ones

“…Therefore, great efforts have been devoted to the construction of these structures. Current syntheses are mainly based on four strategies, i.e., the oxidative rearrangement of 2,3-disubstituted indoles [49][50][51][52][53], cyclization reactions from acyclic starting materials [54][55][56][57][58][59][60][61][62], direct transformation from corresponding 3H-indol-3-ones or indolin-3-ones [63][64][65][66][67][68][69][70][71], and oxidative dearomatization of indoles [72][73][74][75][76]. Direct C-H functionalization of indoles with different C-H nucleophiles presents an atom-economic protocol without prior installation of activating groups and is thus very attractive.…”

Recent Developments in the Synthesis of Chiral Compounds with Quaternary Centers by Organocatalytic Cascade Reactions

“…Later, we developed another efficient Michael–Michael cascade reaction for the construction of piperidino[1,2‐ a ]‐indolines 133 , the core skeleton of which can be frequently found in a wide range of bioactive natural products, between indolin‐3‐one derivatives 132 and nitroolefins (Scheme ) . Contrary to the significant advances in the development of 2‐oxindole chemistry, indolin‐3‐one derivatives have received very little attention from synthetic chemists, and the application of this type of substrate in cascade reactions is still an underdeveloped research field.…”

Organocatalytic Asymmetric Cascade Aerobic Oxidation and Semipinacol Rearrangement Reaction: A Visible Light‐Induced Approach to Access Chiral 2,2‐Disubstituted Indolin‐3‐ones

“…[1] Moreover,t hey are frequently harnessed as commons ynthetic intermediates for the total synthesis of many indole alkaloids and other molecules with importantb ioactivities. [2] As such, the development of catalytic enantioselective methods to access chiral2 ,2-disubstituted indolin-3-ones has attracted a special attentiono fc hemists in the past few years.T od ate, two asymmetric addition strategies involvingw ith 2-monosubstitutedi ndoline-3-ones and their derivatives as nucleophiles [3] and using 3H-indol-3-onesa se lectrophiles [4] have been estab- [a] Scheme3.Experimental studies to elucidate the mechanism. The conversion and the ratio of 2a:3a were determined by crude 1 HNMR analysis.…”

“…[6a] Almost at the same time, Xiao and Lu and co-workersr eported cascade photooxidation and semipinacol rearrangement (i.e. 1,2-shift) directly from 2-aryl-3alkyl-substituted indoles by using Ru(byp) 3 Cl 2 as the photoredox catalyst( Scheme 1B). [6b] Meanwhile, they attempted an enantioselective manifold, and presented ar epresentative chiral productw ith 60 % ee by using an extra BINOL-derived chiral phosphoric acid (CPA) catalyst.…”

“…[9c-f] Probably due to the decreased interference of DPZ to chiral catalysts in the stereocontrolp rocess for its high catalytic efficacy-enabled low catalystl oading, the cooperative catalysis with DPZ usually provided higher enantioselectivity than utilizing other commonly used photocatalysts. Given the comparability of DPZ and Ru(bpy) 3 Cl 2 in the electrochemical properties, accordingly,w ew ere intrigued to challenge such a pendentbut important task by using DPZ as the photocatalyst. The methodw ill offer as ustainable transition-metal free catalytic manifold [5e] to synthesize chiral 2-aryl-2-alkyl-substituted indolin-3-ones.…”