ABSTRACT
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.
Subject(s)
Aziridines/chemical synthesis , Deuterium/chemistry , Lithium/chemistry , Organometallic Compounds/chemistry , Cyclization , Indoles/chemistry , Isotope Labeling , Organoselenium Compounds/chemistry , Oxidation-Reduction , Pyrroles/chemistry , Stereoisomerism , Tin/chemistryABSTRACT
The bicyclic pyrrole ketone 16 has been prepared by using an oxaza-Claisen rearrangement, followed by nitrogen deprotection. Coupling with the stannylaziridine mesylate 15a or nosylate 15b affords 17. Conversion to 40 provides a substrate for generation of an alpha-lithioaziridine 41 by tin lithium exchange. An intramolecular Michael addition pathway for 41 has been demonstrated by the isolation of 46 in 20% yield under conditions where the intermediate enolate 43 is trapped by selenenylation, but competing proton transfer gives 42. The synthetic potential of the process is limited by stability problems at the stage of the enolate 43 or the protonated product 44.
