Internal azomethine ylide cycloaddition methodology for access to the substitution pattern of aziridinomitosene A.
Highly substituted, tethered alkyne dipolarophiles participate in the internal 2 + 3 cycloaddition with azomethine ylides generated by treatment of oxazolium salts with cyanide ion. Starting from oxazole 26, a sequence of N-methylation, cyanide addition, and electrocyclic ring opening of a 4-oxazoline intermediate affords the indoloquinone 31 in a one-pot process. A similar reaction from the protected alkynol derivative 25 affords the sensitive, but isolable, enone 32, and subsequent oxidation affords 31 and the deprotected quinone alcohol 34. Related azomethine cycloaddition methodology via intramolecular oxazolium salt formation from 43 or 46 is also demonstrated and allows the synthesis of quinone 45 and derived structures having the substitution pattern of aziridinomitosene A. Removal of the N-trityl protecting group could not be achieved without aziridine cleavage.
Bobeck
Drew R
DR
Chemistry Department, University of Michigan, Ann Arbor, Michigan 48109, USA.
Warner
Don L
DL
Vedejs
Edwin
E
D001388:Aziridines / Q000138:chemical synthesis* / Q000737:chemistry; D001391:Azo Compounds / Q000737:chemistry*; D003500:Cyclization; D008968:Molecular Conformation; D013237:Stereoisomerism; D013882:Thiosemicarbazones / Q000737:chemistry*
D001388:Aziridines; D001391:Azo Compounds; D013882:Thiosemicarbazones; C525407:aziridinomitosene A; C512188:azomethine