OSMIUM-PROMOTED DIPOLAR CYCLOADDITIONS WITH PYRROLES - AN EFFICIENT, STEREOSELECTIVE SYNTHESIS OF 7-AZANORBORNANES

A series of 7-azabicyclo[2.2.1]hept-5-ene complexes are prepared from [Os(NH3)5(eta(2)-L)](2+) (L = pyrrole, 1-methylpyrrole 2,5-dimethylpyr role. 1,2,5-trimethylpyrrole, or l-(trimethylsilyl)pyrrole) and variou s dipolarophiles (e.g., acrylonitrile, methyl acrylate, alpha-methylen e-gamma-butyrolactone, dimethyl maleate, dimethyl fumarate, N-phenyl m aleimide, cyclopentene-1,2-dicarboxylic acid anhydride and (E)- and (Z )- methyl 3-(3'-pyridyl)acrylate). The cycloaddition is promoted by co ordination of the pyrrole with [Os(NH3)(5)](2+) across C3 and C4, tran sforming the uncoordinated portion of the pyrrole nucleus into an azom ethine ylide capable of undergoing 1,3-dipolar cycloadditions. The met al serves not only to activate the pyrrole ring but also to stabilize the resulting 7-azabicyclo[2.2.1] heptene ligands. A number of organic 7-azabicyclo[2.2.1]heptanes, including analogs of the alkaloid epibat idine, have been synthesized by this methodology. For the cases examin ed, the cycloaddition favors exo stereochemistry of the electron-withd rawing substituent when the pyrrole nitrogen is unsubstituted. Crystal structures have been determined for the complexes obtained from the r eactions of pyrrole with N-phenylmaleimide (8a), 2,5-dimethylpyrrole w ith dimethyl maleate (13a), and 2,5-dimethylpyrrole with alpha-methyle ne-gamma-butyrolactone (22a).