An efficient route to N-alkylated 3,4-dihydroisoquinolinones with substituents at the 3-position.

Aoi Tazawa,Isao Azumaya,Junki Ando,Minoru Tanaka,Kohei Ishizawa,Hidemasa Hikawa

doi:10.1039/c7ra13627g

Aoi Tazawa, Isao Azumaya + Show 4 more

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https://doi.org/10.1039/c7ra13627g

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Abstract

A facile synthetic procedure for the production of N-alkylated 3,4-dihydroisoquinolinone derivatives is described. The desired products were obtained by N-alkylation of 3,3′-dimethyl-3,4-dihydroisoquinoline derivatives followed by oxidation of the resulting iminium salts. Reaction conditions for both steps were very mild and the desired cyclization products could be obtained in good yield. This strategy allows the generation of N-substituted 3,4-dihydroisoquinolinone derivatives with substituents at the 3-position.

Highlights

A facile synthetic procedure for the production of N-alkylated 3,4-dihydroisoquinolinone derivatives is described
As previous reports are limited to 3unsubstituted analogues,[10] we examined whether this strategy was compatible with 3-substituted dihydroisoquinolinone derivatives
Tandem cyclization of 7 using oxalyl chloride followed by iron(III) chloride afforded a tricyclic intermediate, which was pyrolyzed by MeOH–H2SO4 to give 3,3-dimethyl-3,4dihydroisoquinoline in 89% yield

Summary

Introduction

A facile synthetic procedure for the production of N-alkylated 3,4-dihydroisoquinolinone derivatives is described. For the preparation of the 3,3-dimethyl-dihydroisoquinolinium salt 9 (Scheme 3), dihydroisoquinoline 8 was reacted with methyl bromoacetate (2 equiv.) in acetonitrile at 60 C. We examined the oxidation reaction of isoquinolinium salts, including those with other alkyl substituents on the nitrogen atom.[14] As expected, under optimal conditions, the desired dihydroisoquinolinones were obtained in high yields (Scheme 4).

Results

Conclusion