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

O’Sullivan, Michael J., Hatley, Richard J. D., Wellaway, Christopher R., Bew, Sean P. and Richards, Christopher J. (2021) Synthetic approaches to N- and 4-substituted 1,4-dihydro-3(2H)-isoquinolinone derivatives. Tetrahedron, 100. ISSN 0040-4020

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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.

Item Type: Article
Uncontrolled Keywords: deprotection,ferrocenyl,isoquinolinone,reductive amination,α-alkylation,biochemistry,drug discovery,organic chemistry ,/dk/atira/pure/subjectarea/asjc/1300/1303
Faculty \ School: Faculty of Science
Faculty of Science > School of Chemistry
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Depositing User: LivePure Connector
Date Deposited: 30 Sep 2021 16:53
Last Modified: 27 Nov 2021 01:46
URI: https://ueaeprints.uea.ac.uk/id/eprint/81522
DOI: 10.1016/j.tet.2021.132455

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