Anomalous Substituent Effects in the Bischler−Napieralski Reaction of 2-Aryl Aromatic Formamides

• Published in: Journal of organic chemistry Vol. 65; no. 26; pp. 9143 - 9151
• Main Authors: Ishikawa, Tsutomu, Shimooka, Kazunari, Narioka, Tomoko, Noguchi, Shigeru, Saito, Tatsuru, Ishikawa, Akiko, Yamazaki, Emi, Harayama, Takashi, Seki, Hiroko, Yamaguchi, Kentaro
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 29.12.2000; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; RUTACEOUS PLANTS; STRUCTURAL ESTABLISHMENT; TRANSFORMATION; METHODOLOGY; CHEMICAL-CONSTITUENTS; BENZOPHENANTHRIDINE ALKALOIDS; STEREOCONTROL; ISOARNOTTIANAMIDE; DERIVATIVES; INTRAMOLECULAR BUCHNER REACTION
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo0012849

Treatment of some 1-naphthylformamides (or formanilides) possessing a 2,4,5-trioxygenated phenyl substituent at the 2-position with POCl3 caused an unprecedented carbon insertion reaction into a benzene ring, producing 7-5 ring (azaazulene) systems as valence isomers of isoquinoline skeletons. Precise examination of this abnormal Bischler−Napieralski reaction (BNR) using various substrates led to the following scope and limitations:  (i) the 7-5 ring systems were constructed when either 2-alkoxy-4,5-methylenedioxyphenyl- or 4,5-dialkoxy-2-hydroxyphenyl-substituted formamides were used as a starting substrate; (ii) in the former case the formyl carbon was inserted into the C1−C6 bond of the 2-phenyl group, and normal isoquinoline cyclization competed with an abnormal carbon insertion reaction; (iii) the presence of a hydroxy group at the 2‘-position as in the latter cases caused exclusive carbon insertion, in which alternative C1−C2 insertion products were quantitatively formed; (iv) 3,6-dimethoxy-2-hydroxyphenyl-substituted formanilide electronically equivalent to 4,5-dialkoxy-2-hydroxy derivatives produced an indole−pyrone as an abnormal BNR product. Theoretical approaches using the PM-3 method indicated that these abnormal BNRs could be triggered by ipso attack at the 1‘-position yielding spiro intermediates. Ring cleavege of the six-membered ring in the spiro intermediates to a ketene function followed by recyclization was proposed for the 2‘-hydroxy-directed abnormal BNRs leading to the C1−C2 insertion product or the indole−pyrone derivative.