Synthesis of diverse 2,3-dihydroindoles, 1,2,3,4-tetrahydroquinolines, and benzo-fused azepines by formal radical cyclization onto aromatic rings.
2,3-Dihydroindoles, 1,2,3,4-tetrahydroquinolines, and 2,3,4,5-tetrahydrobenzo[b]azepines are available by a process that represents formal radical cyclization onto aromatic rings. Optically pure benzo-fused heterocycles are also accessible by this method. p-Iodophenols, especially those with the phenolic oxygen protected as a MOM-ether, can be coupled with amino alcohols to produce N-aryl amino alcohols, which can be converted into the corresponding alkyl iodides in which the nitrogen is protected as a carbamate. These compounds give cross-conjugated ketones after removal of the phenolic protecting group and oxidation with PhI(OAc)(2) in the presence of MeOH. The ketones undergo 5-, 6- or 7-exo-trigonal radical cyclization, and then exposure to acid, or sequential treatment with a Grignard reagent and then acid, effects rearomatization to produce the benzo-fused nitrogen heterocycles.
Clive
Derrick L J
DL
Chemistry Department, University of Alberta, Edmonton, Alberta, Canada T6G 2G2. derrick.clive@ualberta.ca
Peng
Jianbiao
J
Fletcher
Stephen P
SP
Ziffle
Vincent E
VE
Wingert
David
D
D000605:Amino Alcohols / Q000737:chemistry; D001381:Azepines / Q000138:chemical synthesis*; D001555:Benzene Derivatives / Q000138:chemical synthesis; D003500:Cyclization; D005609:Free Radicals / Q000737:chemistry; D007211:Indoles / Q000138:chemical synthesis*; D007454:Iodides / Q000737:chemistry; D007659:Ketones / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry; D010636:Phenols / Q000737:chemistry; D011804:Quinolines / Q000138:chemical synthesis*
D000605:Amino Alcohols; D001381:Azepines; D001555:Benzene Derivatives; D005609:Free Radicals; D007211:Indoles; D007454:Iodides; D007659:Ketones; D010636:Phenols; D011804:Quinolines; D009584:Nitrogen