Stereocontrolled synthesis of functionalized cis-cyclopentapyrazolidines by 1,3-dipolar cycloaddition reactions of azomethine imines.
The reaction of alkene-tethered alpha-ketocarboxylic acid derivatives with monosubstituted hydrazines allows highly substituted cis-cyclopentapyrazolidine ring systems to be constructed rapidly. Successful cyclocondensations are realized under thermal reaction conditions; in some cases, protic or Lewis acids accelerate these reactions. alpha-Methoxy-alpha,beta-unsaturated esters are suitable alkene components, as are alkenes having either electron-withdrawing or electron-donating substituents at the terminal alkene carbon. alpha-Ketoesters, alpha-ketoamides, and alpha-ketothioesters can be employed. Various hydrazines substituted with N-acyl, N-carboalkoxy, or N-carbamothioyl protecting groups are tolerated in these transformations. The rate of intramolecular cycloaddition is found to reflect not only the reactivity and equilibrium concentration of the azomethine imine intermediate, but, also in some cases, the rate at which hydrazone stereoisomers interconvert under the reaction conditions.
Gergely
Joshua
J
Department of Chemistry, 1102 Natural Sciences 2, University of California, Irvine, California 92697-2025, USA.
Morgan
Jeremy B
JB
Overman
Larry E
LE
D001391:Azo Compounds / Q000737:chemistry*; D003500:Cyclization; D007097:Imines / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D011720:Pyrazoles / Q000138:chemical synthesis*; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D013882:Thiosemicarbazones / Q000737:chemistry*
D001391:Azo Compounds; D007097:Imines; D011720:Pyrazoles; D013882:Thiosemicarbazones; C512188:azomethine