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Directed ortho ‐lithiation of chloroquinolines. Application to synthesis of 2,3‐disubstituted quinolines
Author(s) -
Marsais F.,
Godard A.,
Queguiner G.
Publication year - 1989
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570260615
Subject(s) - chemistry , synthon , lithium diisopropylamide , electrophile , moiety , quinoline , nucleophile , aldehyde , ketone , trimethylsilyl , indole test , organic chemistry , surface modification , reactivity (psychology) , medicinal chemistry , combinatorial chemistry , medicine , ion , alternative medicine , pathology , deprotonation , catalysis
2‐, 3‐ and 4‐Chloroquinolines were selectively lithiated at low temperature by lithium diisopropylamide at the more acidic C‐3, C‐4 and C‐3 positions respectively. Reaction of 2‐chloro‐3‐lithioquinoline with electrophiles led to various 2,3‐disubsthuted quinolines. The versatility of this functionalization methodology is enhanced by the C‐2 halogen reactivity towards oxygen or nitrogen nucleophiles. So, a great variety of 2,3‐di‐substituted quinolines were synthesized, such as 2‐chloro, 2‐alkoxy, 2‐aminoquinolines or 2‐quinolones bearing an hydroxy, carbonyl (aldehyde, ketone or carboxylic acid), iodo, trimethylsilyl or boronic acid moiety at the C‐3. Some of the resulting 2,3‐disubstituted synthons were annelated to tetracyclic polyaromatics, which possess the xanthone or indole structure. This could be achieved via further functionalization of the quinoline ring either by SNAr2 or heteroaromatic cross‐coupling reactions, after the first directed‐lithiation step.