Nitro-olefin bicycloannulation: one-step synthesis of tricyclo[3.2.1.02,7]octan-6-ones from cyclohexenones and of tricyclo[2.2.1.02,6]heptan-3-ones from cyclopentenones

Abstract

Nitro-olefins bicycloannulate the α′-enolates of α-cyclohexenones and α-cyclopentenones by initial addition at −78 °C, followed by further reaction insitu in the presence of hexamethylphosphoramide in refluxing tetrahydrofuran to give tricyclo[3.2.1.02,7]octan-6-ones and tricyclo[2.2.1.02,6]heptan-3-ones in a single synthetic step. The reactions with 1-nitropropene and with a nitro-olefin having a more complex β-substituent are stereoselective, forming predominantly the tricyclic diastereomer in which the group derived from the β-substituent of the nitro-olefin is syn to the carbonyl bridge. Based on the isolation of intermediates and side products, the mechanism of the bicycloannulation is shown to proceed via sequential kinetically controlled conjugate addition of the enolate to the nitro-olefin at low temperatures, thermodynamically controlled intramolecular Michael addition at higher temperatures to give a bicyclo[2.2.2]octanone intermediate, and hexamethylphosphoramide-assisted expulsion of the nitro group as nitrite ion with formation of the cyclopropane ring. For the first time this type of bicycloannulation has been applied to cyclopentenones, and a one-step synthesis of tricyclenone has been carried out to demonstrate the synthetic utility of this new reaction.