Controllable access to trifluoromethyl-containing indoles and indolines: palladium-catalyzed regioselective functionalization of unactivated alkenes with trifluoroacetimidoyl chlorides.

Hefei Yang,Le-Cheng Wang,Dongling Zheng,Zhengkai Chen,Yu Zhang,Xiao-Feng Wu

doi:10.1039/d2sc00546h

Abstract

The synthesis of diverse products from the same starting materials is always attractive in organic chemistry. Here, a palladium-catalyzed substrate-controlled regioselective functionalization of unactivated alkenes with trifluoroacetimidoyl chlorides has been developed, which provides a direct but controllable access to a variety of structurally diverse trifluoromethyl-containing indoles and indolines. In more detail, with respect to γ,δ-alkenes, 1,1-geminal difunctionalization of unactivated alkenes with trifluoroacetimidoyl chloride enables the [4 + 1] annulation to produce indoles; as for β,γ-alkenes, a [3 + 2] heteroannulation with the hydrolysis product of trifluoroacetimidoyl chloride through 1,2-vicinal difunctionalization of alkenes occurs to deliver indoline products. The structure of alkene substrates differentiates the regioselectivity of the reaction.

Highlights

Transition-metal-catalyzed difunctionalization of alkenes has emerged as a powerful synthetic strategy for the assembly of structurally complex molecules.[1]
We commenced our studies by using tri uoroacetimidoyl chloride 1a and 4-pentenoic acid derivative 2a with an 8
The results indicated that only THF could afford the 1,1-geminal difunctionalization product 3a with an alkenyl moiety at 3-position of indole in 37% yield (Table 1, entries 1–5)

Summary

Introduction

Transition-metal-catalyzed difunctionalization of alkenes has emerged as a powerful synthetic strategy for the assembly of structurally complex molecules.[1]. We report our research nding of a palladiumcatalyzed bidentate-directed 1,1-geminal and 1,2-vicinal difunctionalization of unactivated alkenes with tri uoroacetimidoyl chlorides for the regioselective synthesis of biologically important tri uoromethyl-containing indoles and indolines[13] (Scheme 1d). The results indicated that only THF could afford the 1,1-geminal difunctionalization product 3a with an alkenyl moiety at 3-position of indole in 37% yield (Table 1, entries 1–5).

Results

Conclusion