Nitro-olefin bicycloannulation: one-step synthesis of tricyclo[3.2.1.0^2,7]octan-6-ones from cyclohexenones and of tricyclo[2.2.1.0^2,6]heptan-3-ones from cyclopentenones

Abstract

. Can. J. Chem. 63, 2618Chem. 63, (1985. Nitro-olefins bicycloannulate the a'-enolates of a-cyclohexenones and a-cyclopentenones by initial addition at -7S°C, followed by further reaction in situ in the presence of hexamethylphosphoramide in refluxing tetrahydrofuran to give tricyclor3.2.1 .0Z,7]octan-6-ones and tricyclo[2.2.1 .02.6]heptan-3-ones in a single synthetic step. The reactions with I-nitropropene and with a nitro-olefin having a more complex P-substituent are stereoselective, forming predominantly the tricyclic diastereomer in which the group derived from the P-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 hexamethylphosphoramideassisted 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. [Traduit par le journal] Introduction The development of new methodology for the efficient construction of polycyclic systems has long been a major emphasis of research in organic synthesis. Our own contributions to this work have focussed on the discovery of new bicycloannulation reactions, in which tricyclic structures are formed in a single synthetic operation from monocyclic precursors.' In particular, we have reported a series of methods for the bicycloannulation of cyclohexenes (1 b, 2) and cyclohexenones (la, 3) to give tricyclo[3.2.1 .02.7]octanes (1). This tricyclic system is a salient

Synthetic Access to Poly-Substituted 6-Alkoxyindoles from 1,3-Cyclohexanediones and Nitroolefins through Facile Aromatization Reaction

“…Having succeeded in aromatization of cyclohexane-1,3-dione enol ether moiety, we extended this aromatization reaction to the nitrones 8a − c (Scheme ), bearing H, PhS, and Bn(Boc)N at the C3 position of 9-azabicyclo[4.3.0]-nonadiene core. These nitrones 8a − c were prepared in a similar manner as described above from the respective precursor 2-cyclohexenones by Michael addition of regioselectively generated kinetic Li enolates to the nitroolefin 2 , followed by Zn reduction of the nitroketones 7a − c . Thus, the treatment of 8a with acetic anhydride (3 equiv) produced the corresponding indoline 9a in lesser yield (35%), compared with the case of the 3-methoxy derivative 4a .…”