Synthesis of bridged azabicyclic compounds using radical translocation reactions of 1-(o-halogenobenzoyl)-2-(prop-2-enyl)- and -(prop-2-ynyl)-piperidines

Abstract

Methyl 1-(o-bromobenzoyl)-2-(prop-2-enyl)piperidine-2-carboxylate 8a, upon treatment with tributyltin hydride in the presence of azoisobutyronitrile in boiling toluene gave regioselectively the 8-azabicyclo[3.2.1]octane 14a (a 5-exo cyclisation product) in quantitative yield as a diastereomeric mixture (66:34). 1-(o-Bromobenzoyl)-2-(prop-2-enyl)piperidine 13 also gave the 8-azabicyclo[3.2.1]octane 16(75% as a diastereomeric mixture), along with the pyrido[2,1-a]isoindolone 17(10%) and the simple reduction product 18(5%). 1-(o-Iodobenzoyl)-2-[3-(trimethylsilyl)prop-2-ynyl]piperidine 23 afforded, in addition to the pyrido[2,1-a]isoindolone 25(18%), the 8-azabicyclo[3.2.1]octane 24(75%) which was converted into the 6-oxo derivative 27. For comparison, the behaviour of the azetidine congener 31 was also examined.