Synthesis of the aziridinomitosene skeleton by intramolecular Michael addition of alpha-lithioaziridines: an aromatic route featuring deuterium as a removable blocking group.
A convergent synthetic route to the 1,2-aziridinopyrrolo(1,2-a)indole 34 has been developed. Key features of this route include the deuterium kinetic isotope effect to block undesired indole lithiation during tin-lithium exchange from 27a to 30a, the intramolecular Michael addition to generate the enolate 31a, and conversion into 34 by trapping with phenylselenenyl chloride. Reductive cleavage of the N-trityl group in 34 allows access to tetracyclic aziridinomitosenes containing the aziridine N-H subunit. Reduction of the C(9) ester in 34 with LAH gives the primary alcohol 35 with the correct C(9), C(9a), C(10) oxidation state corresponding to the aziridinomitosenes, and deprotection of 34 affords 37.
Vedejs
Edwin
E
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. edved@umich.edu
Little
Jeremy D
JD
D001388:Aziridines / Q000138:chemical synthesis*; D003500:Cyclization; D003903:Deuterium / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry; D007553:Isotope Labeling; D008094:Lithium / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D016566:Organoselenium Compounds / Q000737:chemistry; D010084:Oxidation-Reduction; D011758:Pyrroles / Q000737:chemistry; D013237:Stereoisomerism; D014001:Tin / Q000737:chemistry
D001388:Aziridines; D007211:Indoles; D009942:Organometallic Compounds; D016566:Organoselenium Compounds; D011758:Pyrroles; C413848:aziridinomitosene; D014001:Tin; D008094:Lithium; D003903:Deuterium