Chiral 2,3‐Disubstituted Indolines from Indoles and Aldehydes by Organocatalyzed Tandem Synthesis Involving Reduction by Trichlorosilane

Abstract

Abstract:The organocatalytic trichlorosilane reduction system has been successfully utilized to develop a multi-step tandem approach for the easy preparation of chiral 2-methyl-3-alkylindolines starting from simple 2-methylindoles and aldehydes. A broad range of chiral 2-methyl-3-alkylindoline products was obtained with high yields and enantioselectivities and excellent stereoselectivities by this approach.

The Development of Organocatalytic Asymmetric Reduction of Carbonyls and Imines Using Silicon Hydrides

“…Three years later, it was extended to the tandem synthesis of chiral 2-methyl-3-alkylindolines starting from simple 2-methylindoles and aldehydes. [41] Different from previous work, no external water was needed as it can be generated from the Friedel-Crafts aldol reaction step. Catalyst 19 b was proved to be highly efficient in this multi-steps tandem approach (Scheme 6e).…”

“…It was postulated to react with trichlorosilane to generate HCl in situ , which was necessary to facilitate isomerisation of the indole to electrophilic indolenium ions. Three years later, it was extended to the tandem synthesis of chiral 2‐methyl‐3‐alkylindolines starting from simple 2‐methylindoles and aldehydes [41] . Different from previous work, no external water was needed as it can be generated from the Friedel‐Crafts aldol reaction step.…”

HMPA-Catalyzed One-Pot Multistep Hydrogenation Method for the Synthesis of 1,2,3-Trisubstituted Indolines

“…An organic Lewis base/HSiCl 3 system has proven to be a powerful combination for the reduction of C=N, C=O and C=C bonds by us and others. [17][18][19][20][21][22][23][24][25] In 2011, we developed the first organic Lewis base/HSiCl 3 system for the asymmetric hydrosilylation of 2,3-disubstituted indoles affording high stereoselectivities and good substrate generality (Scheme 1). 17 We also developed the first organic Lewis base catalyzed tandem approach to get chiral 2,3-disubstituted indolines from indoles and aldehydes.…”

“…17 We also developed the first organic Lewis base catalyzed tandem approach to get chiral 2,3-disubstituted indolines from indoles and aldehydes. 18 In 2016, we successfully developed the first direct reductive hydrazination of hydrazines with ketones/aldehydes for the preparation of 1,1-disubstituted hydrazines. 19 Enlightened by these results, we envisioned that a highly efficient method could be obtained for the preparation of 1,2,3-trisubstitued indolines if the Lewis base catalyzed Friedel-Crafts reaction, reduction and direct reductive amination process could be realized in one pot.…”

Rational Design of Simple Organocatalysts for the HSiCl3 Enantioselective Reduction of (E)-N-(1-Phenylethylidene)aniline

“…In this context, the asymmetric transfer hydrogenation of imines represents a simple and attractive approach to target the synthesis of enantiopure amines, and a variety of catalytic methodologies have been developed for this purpose [4][5][6][7][8][9][10][11][12]. The use of trichlorosilane and related reagents for this purpose has attracted much attention in recent years, having shown their capacity for the transfer hydrogenation of a variety of groups, such imines [4][5][6][7][8][9][10][11][12], enones [13,14], nitro groups [15,16], and N-heteroarenes [17,18], in the synthesis of substituted hydrazines [19], and in the reduction of CO 2 in the presence of amines [20][21][22][23]. Thus, the organocatalytic reduction of ketimines with trichlorosilane provides an efficient methodology for the asymmetric preparation of amines [24][25][26].…”