Accelerating effect of meta substituents in the ester-mediated nucleophilic aromatic substitution reaction

Tetsutaro Hattori, Ayanobu Takeda, Kenji Suzuki, Nobuyuki Koike, Eiji Koshiishi, Sotaro Miyano

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

The ester-mediated nucleophilic aromatic substitution (SNAr) reaction of 2-methoxybenzoic ester 1 with Grignard reagents 11 is greatly accelerated by introduction of a methoxy or halo substituent at the 3-position of the benzoate ring (7-10). The substituent effects of these groups at the 3-position are compared with those at the 5-position to suggest that the activation mechanism of the methoxy substituent is different from that of the halo substituent; the ligating ability of the 3-methoxy group plays a crucial role in enhancing the reactivity of the 2-methoxy moiety, while the electron-withdrawing ability is more important in the case of the halo groups. It has also been found that introduction of an additional methoxy substituent at the meta-position (33, 34) enables the SNAr methoxy-displacement reaction even at the para-position to the ester activator. The accelerating effect of the 3-bromo substituent is advantageously utilized for regioselective allylation of 3-bromo-2,6-dimethoxybenzoic ester 55 at the 2-position to provide an easy access to a multisubstituted naphthol 59, which is a key compound for the syntheses of michellamines A-C and the related naphthylisoquinoline alkaloids.

Original languageEnglish
Pages (from-to)3661-3671
Number of pages11
JournalJournal of the Chemical Society - Perkin Transactions 1
Issue number22
DOIs
Publication statusPublished - 1998 Nov 21

ASJC Scopus subject areas

  • Chemistry(all)

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