Biradicals/Zwitterions from Thermolysis of Enyne−Isocyanates.
Application to the Synthesis of 2(1H)-Pyridones,
Benzofuro[3,2-c]pyridin-1(2H)-ones,
2,5-Dihydro-1H-pyrido[4,3-b]indol-1-ones, and Related Compounds
posted on 2004-06-25, 00:00authored byHongbin Li, Hua Yang, Jeffrey L. Petersen, Kung K. Wang
Thermolysis of benzannulated enyne−isocyanates 13 and enyne−isocyanates 36 and 37 promoted
the cycloaromatization reactions to generate in situ O,4-didehydro-2-hydroxyquinolines and O,4-didehydro-2-hydroxypyridines, respectively, as reactive intermediates. These cycloaromatized
intermediates could be captured either as biradicals and/or as zwitterions depending on the nature
of the substituent at the alkynyl terminus. The intermediate derived from cycloaromatization of
13a bearing a phenyl substituent could be regarded as biradical 14, which then abstracts hydrogen
atoms from γ-terpinene leading to 2(1H)-quinolinone 15. Alternatively, the same intermediate could
also be regarded as zwitterion 14‘, which then undergoes an initial hydride abstraction from
γ-terpinene followed by protonation to produce 15. The presence of a 2-phenylethyl substituent in
13b and 37a or a 2-methylphenyl substituent in 37b also allowed the resulting intermediates to
be captured intramolecularly either as biradicals or as zwitterions, producing 2(1H)-quinolinone
19, 2(1H)-pyridone 39, and benzopyranopyridine 43, respectively. On the other hand, with a
2-methoxyphenyl, a 2-(dimethylamino)phenyl, or a 3-methoxypropyl substituent, the chemical
behavior of the cycloaromatized adduct could be best accounted for in terms of a zwitterionic
intermediate leading to benzofuro[3,2-c]quinolin-6(5H)-one (20), 5,11-dihydro-11-methyl-6H-indolo[3,2-c]quinolin-6-one (25), benzofuro[3,2-c]pyridin-1(2H)-one 44, 2,5-dihydro-2,5-dimethyl-1H-pyrido[4,3-b]indol-1-one 46, and related compounds. Interestingly, thermolysis of 37f bearing a 2-(methoxymethyl)phenyl substituent at the alkynyl terminus produced the unexpected benzopyranopyridine
56 as the major product in a process involving the cleavage of the bond between the methoxyl
oxygen and the adjacent methylene carbon. The efficiency and selectivity of the cycloaromatization
reaction could also be enhanced by the introduction of 1.1 to 10 equiv of dimethylphenylsilyl chloride
to the reaction mixture to capture the resulting zwitterion.