SYNTHESIS OF BRIDGED AZABICYCLIC COMPOUNDS USING RADICAL TRANSLOCATION REACTIONS OF 1-(O-BROMOBENZOYL)-2-(PROP-2-ENYL)PYRROLIDINES

A new synthesis of the 7-azabicyclo[2.2.1]heptane and 8-azabicyclo[3.2.1]octane systems is described in which alpha-acylamino radicals generated from 1-(0-bromobenzoyl)-2-(prop-2-enyl)pyrrolidines by a Bu(3)SnH-mediated radical translocation reaction are cyclised. Treatment of methyl 1-(0-bromobenzoyl)-2-(prop-2-enyl)pyrrolidine-2-carboxylate 3a with Bu(3)SnH in the presence of a catalytic amount of azoisobutyronitrile in boiling toluene gave the 7-azabicyclo[2.2.1]heptane 4a (a 5-exo cyclisation product) [42% yield as a diastereoisomeric mixture (66:34)] and the 8-azabicyclo[3.2.1]octane 5a (a 6-endo product) (30%), together with the reduction product 6a (12%). The regiochemistry (5-exo/6-endo) of this cyclisation could be controlled by the introduction of a substituent on the prop-2-enyl group. The substituent(s) at the 2- and/or 4-position(s) of the pyrrolidine ring were found to play an important role in this cyclisation.