AMIDE-DIRECTED HYDROCARBONYLATION OF N-ALKENYLAMIDES AND ALPHA-ALKENYLLACTAMS

The amide-directed Rh-catalyzed hydroformylation and Pd-catalyzed hydroesterification of N-allylamides give the iso-aldehyde and ester, respectively, with good regioselectivity. The Rh- and Co2Rh2(CO)12-catalyzed reactions of N-methallylamide give an 1-acyl-2-formylpyrrolidine through a novel double carbonylation and an 1-acylpyrrolidine through reductive annulation, respectively, with excellent selectivity. A cyclic hemiamidal, N-benzoyl-2-hydroxy-4-methylpyrrolidine, the key intermediate for the double carbonylation and the reductive annulation, is obtained selectively in a Rh4(CO)12-catalyzed reaction of N-methallylamide. The hydrocarbonylations of this cyclic hemiamidal catalyzed by RhCl(PPh3)3, Co2Rh2(CO)12, and Co2(CO)8 give the corresponding double carbonylation product (2-formylpyrrolidine), reductive annulation product (pyrrolidine), and amidocarbonylation product (proline), respectively, in excellent yield and selectivity. The mechanisms of the novel double carbonylation and the reductive annulation is studied on the basis of deuterium-labeling experiments, and it is found that these reactions proceed via enamide intermediate followed by extremely regioselective metal hydride addition to the enamide. The Rh-catalyzed hydrocarbonylations of the alpha-methallyl-gamma- and delta-lactams in triethyl orthoformate followed by treatment with TFA give the corresponding 1-azabicyclo[4.n.0]alkenones via bicyclic hemiamidals through annulation in excellent overall yields. The Co2Rh2(CO)12-catalyzed reactions of these alpha-methallyl lactams give the corresponding 1-azabicyclo[4.n.0]alkanones as the sole isolable products in high yields. The RhCl(PPh3)3-catalyzed hydrocarbonylation of 6-allylpiperidin-2-one gives a mixture of 1-azabicyclo[4.4.0] and 1-azabicyclo[4.3.0] products. However, the addition of phosphines to the Rh catalyst remarkably improves the normal selectivity (n/iso = 9) to give 1-azabicyclo[4.4.0]dec-2-en-10-one as the predominant product.