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. 2011 Jun 17;13(12):3138-41.
doi: 10.1021/ol2010424. Epub 2011 May 25.

The Davis-Beirut reaction: N1,N2-disubstituted-1H-indazolones via 1,6-electrophilic addition to 3-alkoxy-2H-indazoles

Wayne E Conrad  1 , Ryo Fukazawa, Makhluf J Haddadin, Mark J Kurth
Affiliations

The Davis-Beirut reaction: N1,N2-disubstituted-1H-indazolones via 1,6-electrophilic addition to 3-alkoxy-2H-indazoles

Wayne E Conrad et al. Org Lett. .

Abstract

A variety of electrophiles (anhydrides, acid chlorides, carbonochloridates, sulfonyl chlorides, and alkyl bromides) react with 3-methoxy-2H-indazole (1a), benzoxazin[3,2-b]indazole (1d), and oxazolino[3,2-b]indazole (1e) - substrates available by the Davis-Beirut reaction - to yield a diverse set of N(1),N(2)-disubstituted-1H-indazolones. With certain electrophiles, an AERORC (Addition of the Electrophile, Ring Opening, and Ring Closure) process on indazole 1d results in indazoloindazolone formation. An intriguing aspect of these N(1),N(2)-disubstituted-1H-indazolones is that they are poised for diversification through, for example, azide-alkyne cycloaddition chemistry reported here.

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Figures

Schcme 7
Schcme 7
CuAAC reactions on indazolone 19
Scheme 1
Scheme 1
Nucleophilic ring-opening of 3-alkoxy-2H-indazoles
Scheme 2
Scheme 2
Davis-Beirut recation → 1a → 2
Scheme 3
Scheme 3
1,6-Electrophilic addition to 3-methoxy-2H-indazole 1a
Scheme 4
Scheme 4
1,6-Electrophilic addition to oxazolino[3,2-b]-indazole 1e
Scheme 5
Scheme 5
1,6-Electrophilic addition (→ 20) vs. AERORC (→ 22)
Scheme 6
Scheme 6
CuAAC reactions on indazolone 7
See this image and copyright information in PMC

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