An intramolecular nitro-Mannich route to functionalised tetrahydroquinolines

James C Anderson,Adam Noble,Pascual Ribelles Torres

doi:10.1016/j.tetlet.2012.08.062

Abstract

A simple protocol for the diastereoselective synthesis of 3-nitrotetrahydroquinolines has been developed using an intramolecular nitro-Mannich reaction. In situ formation of an imine generated from treatment of 2-(2-nitroethyl)phenylamine with an aldehyde, in EtOH at room temperature, and subsequent addition of NH4OH, led to the formation of trans-products in high yield and diastereoselectivity for 15 representative examples.

Highlights

A simple protocol for the diastereoselective synthesis of 3-nitrotetrahydroquinolines has been developed using an intramolecular nitro-Mannich reaction
In situ formation of an imine generated from treatment of 2-(2-nitroethyl)phenylamine with an aldehyde, in EtOH at room temperature, and subsequent addition of NH4OH, led to the formation of trans-products in high yield and diastereoselectivity for 15 representative examples
Many methods exist for the synthesis of this ring system, the development of new reactions and protocols to deliver stereochemically pure products is continually needed to enable the synthesis of more refined structures.[2,3]

Summary

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A simple protocol for the diastereoselective synthesis of 3-nitrotetrahydroquinolines has been developed using an intramolecular nitro-Mannich reaction. The tetrahydroquinoline ring system is a common motif in many natural and unnatural biologically active compounds.[1] many methods exist for the synthesis of this ring system, the development of new reactions and protocols to deliver stereochemically pure products is continually needed to enable the synthesis of more refined structures.[2,3] We report here a concise and diastereoselective synthesis of 2-substituted-3-nitro-tetrahydroquinolines that uses an intramolecular nitro-Mannich reaction as the key stereodetermining step. We postulated that treatment of nitroalkane 1 with an aldehyde would give imine 2 which could undergo an intramolecular nitro-Mannich reaction forming 3-nitrotetrahydroquinoline 3 (Scheme 1).

Ar N Ar'

EtOH additive

Findings

HO N