Chemistry of Pyrrolizines; Reactions with Cyanogen Bromide and Trifluoroacetic Anhydride

-Interaction of the pyrrolizine 3 with cyanogen bromide in a tetrahydrofuran/water mixture affords addition to the enamine double bond with formation of 5 which can be aromatized to 6 by silica gel. Reaction of 6 with cyanogen bromide in the same solvent mixture yields the indoline 8a which structure is proved in a chemic/d way by conversion of the product into the aldehyde 8(1. The different reaction pathway is discussed in terms of steric hindrance by the ester groups. Treatment of 6 with trifluoroacetic anhydride gives the trifluoroacetylated compound II. Removal of the sterically hindered ester groups in 6, with acetic acid in quinoline at 200 °, is accompanied by the simultaneous decarboxylation to yield the pyrrolo[1, 2-a]indole 13. Recently we reported that the reactions of 3-(1-pyrrolidinyl) thiophenes I and 1-pyrrolidinyl cycloalkenes 2'3 with dimethyl acetylenedicarboxylate in polar solvents give pyrrolizines instead of the cyclobutene derivatives that are formed in apolar solvents. Since the 1Hpyrrolo[1, 2-a]indole system is the chemical backbone of the anti-tumor antibiotic mitomycin 2 we are currently exploring the possibility of modification of our pyrrolizines and the conversion of these into analogues of mitomycins. Since the structures of the mitomycins were first elucidated, 4 several approaches to their synthesis have been reported 5 and a total synthesis was accomplished via compound 1 by Kishi et al: However, the number of steps and the low overall yield renders the synthesis of a large number of derivatives very difficult. OH I OMe 0 ~ e M e O ~