One-pot functionalisation of N-substituted tetrahydroisoquinolines by photooxidation and tunable organometallic trapping of iminium intermediates.

Joshua P Barham,Matthew P John,John A Murphy

doi:10.3762/bjoc.10.316

Joshua P Barham, Matthew P John + Show 1 more

Open Access

https://doi.org/10.3762/bjoc.10.316

Copy DOI

Abstract

Nucleophilic trapping of iminium salts generated via oxidative functionalisation of tertiary amines is well established with stabilised carbon nucleophiles. The few reports of organometallic additions have limited scope of substrate and organometallic nucleophile. We report a novel, one-pot methodology that functionalises N-substituted tetrahydroisoquinolines by visible light-assisted photooxidation, followed by trapping of the resultant iminium ions with organometallic nucleophiles. This affords 1,2-disubstituted tetrahydroisoquinolines in moderate to excellent yields.

Highlights

Tetrahydroisoquinolines (THIQs) are structural motifs prominent within biologically active natural products and pharmaceutical compounds [1,2]
Reports of organometallic additions to THIQs in this context are limited to aryl [25,26,27] and alkynyl [22,28,29,30] nucleophiles and the substrate scope is generally limited to N-aryl THIQs [31]
We sought a general procedure for organometallic trapping of iminium salts generated by oxidative functionalisation; a methodology amenable to a range of tertiary amine substrates and unstabilised carbon nucleophiles

Summary

Introduction

Tetrahydroisoquinolines (THIQs) are structural motifs prominent within biologically active natural products and pharmaceutical compounds [1,2]. Reports of organometallic additions to THIQs in this context are limited to aryl [25,26,27] and alkynyl [22,28,29,30] nucleophiles and the substrate scope is generally limited to N-aryl THIQs [31]. We sought a general procedure for organometallic trapping of iminium salts generated by oxidative functionalisation; a methodology amenable to a range of tertiary amine substrates and unstabilised carbon nucleophiles.

Results

Conclusion