STEREO AND ELECTRONIC EFFECTS IN THE RHODIUM(II)-MEDIATED SYNTHESIS OF POLYCYCLIC LACTONES AND LACTAMS FROM ALPHA-DIAZO ESTER AND AMIDE PRECURSORS

The rhodium(II) carboxylate catalyzed decomposition of several alpha-diazo esters and amides has been studied. A series of 5-keto-1-diazo acetates were prepared by acylation of alpha-hydroxy ketones using the (p-toluenesulfonyl)hydrazone of glyoxylic acid chloride. Treatment of these compounds with Rh(II) acetate afforded products derived from carbenoid insertion into solvent. When the hydrogen atom of the diazo carbon was replaced with an electron-withdrawing substituent, smooth cyclization occurred to produce a carbonyl ylide dipole which was subsequently trapped with different dipolarophiles. A series of N-alkyl-2-diazo-3-oxobutylamides, when treated with a catalytic quantity of rhodium(II) acetate, gave furo[3,4-c]furans in good yield. The reaction proceeds via addition of a rhodium-stabilized carbenoid onto the acetylenic pi-bond to give a vinyl carbenoid which subsequently cyclizes onto the neighboring carbonyl group to produce the furan ring. N-Alkynyl-substituted 2-diazoacetamides were also found to cyclize onto the tethered alkyne unit. The resulting rhodium carbenoid can undergo intramolecular and bimolecular cyclopropanation depending on both electronic and conformational factors. Rotamer population of the starting diazoamide was also found to influence product distribution.