THEORETICAL INSIGHTS REGARDING THE CYCLOADDITION BEHAVIOR OF PUSH-PULL STABILIZED CARBONYL YLIDES

A series of diazoamido keto eaters were prepared by the reaction of N- substituted 3-carbethoxy-2-piperidone with n-butylmagnesium chloride f ollowed by the addition of ethyl 2-diazomalonyl chloride. Treatment of these diazo amides with rhodium(II) acetate afforded transient push-p ull carbonyl ylide dipoles which could be readily trapped with electro n deficient dipolarophiles. All attempts to induce the dipolar cycload dition to occur across tethered alkenyl pi-bonds failed to give intern al cycloadducts. However, placing a sp(2) center on the tethered side chain was found to result in the formation of a tricyclic adduct in 95 % yield. The stereochemistry of the cycloadduct was firmly established by an X-ray crystallographic study and occurred endo with respect to the amido carbonyl ylide dipole. A detailed computational study was un dertaken to provide better insight into the factors that influence the intramolecular cycloaddition process. The calculations indicate that a severe cross-ring 1,3-diaxial interaction caused by the bridgehead m ethyl group promotes a boat or twist-boat conformation in the piperidi ne ring fused to the newly forming one. The presence of a carbonyl gro up in the dipolarophile tether helps to relieve the steric congestion by virtue of favoring a second boat in the latter ring. Without the C= O group, both nascent and piperidine rings are in the chair conformati on at lowest energy, and the reaction barrier is disadvantaged by 5.6 kcal/mol, allowing other competing processes to intervene.