Synthetic approaches to N- and 4-substitued 1,4-dihydro-3(2H)-isoquinolinone derivatives

Michael J. O’Sullivan, Richard J. D. Hatley, Christopher R. Wellaway, Sean P. Bew, Christopher J. Richards

Research output: Contribution to journalArticlepeer-review

Abstract

Reaction of methyl-2-(2-formylphenyl)acetate with primary amines in a reductive amination/cyclisation process resulted in N-substituted 1,4-dihydro-3(2H)-isoquinolinones. With H 2NCH 2R sodium borohyride is a suitable reductant (11 examples), but H 2NCHR 1R 2 required a transfer hydrogenation using ammonium formate catalysed by palladium on carbon (9 examples). 4-Substituted-1,4-dihydro-3(2H)-isoquinolinones were synthesised by deprotonation (n-butyllithium) and addition of R 3CH 2Br (12 examples with R 3 = alkyl, Ar, CH[dbnd]CH 2, C[tbnd]CH). Modest diastereoselectivity was achieved with 1,4-dihydro-3(2H)-isoquinolinones derived from H 2NCHMeR 2 [R 2 = (η 5-C 5H 4)Co(η 4-C 4Ph 4) - max. dr = 1.9: 1], but use of H 2NCHMeFc (Fc = ferrocenyl) provided a new method of 1,4-dihydro-3(2H)-isoquinolinone N-deprotection with formic acid.

Original languageEnglish
Article number132455
JournalTetrahedron
Early online date22 Sep 2021
DOIs
Publication statusE-pub ahead of print - 22 Sep 2021

Keywords

  • Deprotection
  • Ferrocenyl
  • Isoquinolinone
  • Reductive amination
  • α-Alkylation

Cite this