Mechanism of Amidocarbonylation: A Stereochemical Approach

The mechanism of Co₂(CO)₈-catalyzed amidocarbonylation of aldehyde is studied on the basis of a stereochemical approach. This study is focused on the distinction of the “azlactone pathway”, which has been proposed for some time, and the “direct hydrolysis of an acylcobalt species pathway” in order to account for the selective formation of carboxylic acid instead of aldehyde under a high pressure of hydrogen. Three α-methallyllactams, 4-(2-methyl-2-propenyl)azetidin-2-one (1), 5-(2-methyl-2-propenyl)pyrrolidin-2-one (2), and 6-(2-methyl-2-propenyl)piperidin-2-one (3), have been chosen as the substrates for the study. The MMX calculations of the key intermediates, bicyclic (α-amidoalkanoyl)cobalt species, reveal that (i) if the azlactone formation were the requisite, only 3 (or its hemiamidal intermediate 6) would give the amidocarbonylation product, the bicyclic N-acyl amino acid (15), (ii) if the coordination of amide carbonyl to the cobalt metal center were the essential factor, both 3 and 2 (or their hemiamidal intermediates, 6 and 5) would give the corresponding bicyclic α-acylamino acids (15 and 14), and (iii) as far as either the azlactone formation or the coordination of amide carbonyl to the cobalt metal center is indispensable, 1 (or its hemiamidal intermediate 4) would not give any bicyclic α-acyl amino acid (13). In fact, the attempted amidocarbonylation of 1 and its O-ethyl hemiamidal (19) obtained in the RhCl(PPh₃)₃-catalyzed hydro-carbonylation does not give any acid or ester product (13 or 13-OEt) but affords a bicyclic enamide (16). In sharp contrast to this, the reactions of 2 and 3 and their O-ethyl hemiamidals (20, 21) afford the corresponding bicyclic a-acyl amino acids and their esters (14, 15; 14-OEt, 15-OEt). The results clearly indicate that the direct hydrolysis of acylcobalt species pathway is the actual mechanism of amidocarbonylation, and thus, the coordination of the amide carbonyl to the cobalt metal center bearing a water molecule as an aquo ligand is crucial for the suppression of hydrogenolysis and promotes the unique hydrolysis even under a high pressure of hydrogen.