SYNTHESIS OF FUNCTIONALIZED AZOMETHINE YLIDES VIA THE RH(II)-CATALYZED CYCLIZATION OF ALPHA-DIAZO CARBONYLS ONTO IMINO PI-BONDS

alpha-Diazo carbonyl compounds containing an imino group in the gamma- position have been found to undergo a rhodium(II) acetate induced cycl ization reaction to generate cyclic azomethine ylides. The reactive di pole undergoes a subsequent 1,3-dipolar cycloaddition with added dipol arophiles. The imino/oxime nitrogen lone pair of electrons must be pro perly oriented so as to interact with the rhodium carbenoid. Thus, acy clic oxime ethers which exist in the proper E-configuration readily un dergo the tandem cyclization-cycloaddition reaction. In sharp contrast , the isomeric Z-oximino diazo carbonyl system does not cyclize to an azomethine ylide but rather intramolecularly inserts into the oximino C-H bond. Addition of a catalytic amount of rhodium(II) acetate to (E) -2-(diazoacetyl)benzaldehyde O-methyloxime in the presence of DMAD or N-phenylmaleimide affords a dipolar cycloadduct in high yield. When p- quinone was used as the dipolarophile, the initially formed cycloadduc t was treated with acetic anhydride to give a compound containing the basic core dibenzo[a,d]cyclohepten-5,10-imine skeleton found in MK-801 . Cyclic imines such as isoxazolines were particularly effective subst rates for azomethine ylide formation. The rhodium(II) catalyzed reacti on of (4-diazo-3-oxobutyl)-5-phenyl-Delta(2)-isoxazoline with DMAD pro duced a 4:1 mixture of diastereomeric cycloadducts in good yield. Cycl ization of the rhodium carbenoid did not occur with the aromatic isoxa zole system and this is presumably due to the low basicity of the nitr ogen lone pair of electrons.