Internal Azomethine Ylide Cycloaddition Methodology for Access to the Substitution Pattern of Aziridinomitosene A

摘要

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 quinine 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.