Palladium-catalyzed formylation of aryl bromides: elucidation of the catalytic cycle of an industrially applied coupling reaction.

The first comprehensive study of the catalytic cycle of the palladium-catalyzed formylation of aryl bromides with synthesis gas (CO/H2, 1:1) is presented. The formylation in the presence of efficient (Pd/PR2(n)Bu, R = 1-Ad, (t)Bu) and nonefficient (Pd/P(t)Bu3) catalysts was investigated. The main organometallic complexes involved in the catalytic cycle were synthesized and characterized, and their solution chemistry was studied in detail. Comparison of stoichiometric and catalytic reactions using P(1-Ad)2(n)Bu, the most efficient ligand known for the formylation of aryl halides, led to two pivotal results: (1) The corresponding carbonylpalladium(0) complex [Pd(n)(CO)(m)L(n)] and the respective hydrobromide complex [Pd(Br)(H)L2] are resting states of the active catalyst, and they are not directly involved in the catalytic cycle. These complexes maintain the concentration of most active [PdL] species at a low level throughout the reaction, making oxidative addition the rate-determining step, and provide high catalyst longevity. (2) The product-forming step proceeds via base-mediated hydrogenolysis of the corresponding acyl complex, e.g., [Pd(Br)(p-CF3C6H4CO){P(1-Ad)2(n)Bu}]2 (8), under mild conditions (25-50 degrees C, 5 bar). Stoichiometric studies using the less efficient Pd/P(t)Bu3 catalyst resulted in the isolation and characterization of the first stable three-coordinated neutral acylpalladium complex, [Pd(Br)(p-CF3C6H4CO)(P(t)Bu3)] (10). Hydrogenolysis of 10 needed significantly more drastic conditions compared to that of dimeric 8. In the presence of amine base, complex 10 gave a catalytically inactive diamino acyl complex, which explains the low activity of the Pd/P(t)Bu3 catalyst formylation of aryl bromides.