Palladium-Catalyzed Formylation of Aryl Bromides: Elucidation of the Catalytic Cycle of an Industrially Applied Coupling Reaction

Abstract

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.

Selective Palladium‐Catalyzed Aminocarbonylation of Aryl Halides with CO and Ammonia

“…In agreement with previous studies on the catalytic carbonylation of aryl halides, [21] we suppose that the oxidative addition is the rate determining step at high CO pressure. Hence, aryl chlorides react more slowly than aryl bromides (see Table 2).…”

General and Selective Palladium‐Catalyzed Oxidative Esterification of Alcohols

“…Secondly, such bulky nucleophilic phosphines bind more stably to the palladium center compared to triarylphosphines, thereby preventing agglomeration to palladium particles. To our delight, a highly chemoselective oxidation (88 % yield of methyl benzoate, 2 a) took place in the presence of nBuP(1-adamantyl) 2 (L3, cataCXiumA) [14] and AgPF 6 (Table 1, entry 11). On the other hand, application of the same ligand without AgPF 6 using toluene as solvent gave exclusively benzaldehyde in 84 % yield (> 99 % selectivity).…”

An Improved Protocol for Palladium‐Catalyzed Alkoxycarbonylations of Aryl Chlorides with Alkyl Formates

“…The best activity is found for ligand L1 [n-butylbis(1-adamantyl)-phosphine, cataCXium A], which gave 87% conversion and 52% yield of butyl 3,4-dimethylbenzoate. It should be noted that this ligand induced also improved activities in reductive carbonylations and alkoxycarbonylations of aryl bromides using gaseous CO. [8,9] In addition, in the presence of dppf some activity and excellent selectivity was obtained.…”

“…On further optimization, we discovered that the use of butyl formate as both solvent and reagent considerably improved the yields for electron-poor substrates (see method C in Table 4, entries [5][6][7][8]. Aryl bromides reacted with higher yields than the corresponding chlorides.…”

“…The isopropyl ester was formed in lower yield presumably because of steric reasons. (2) 0 0 [a] Reaction conditions: 1 mmol 3,4-dimethyl-1-chlorobenzene, 1 mL butyl formate, 0.5 mol% PdA C H T U N G T R E N N U N G (OAc) 2 , 0.07 mol% Ru 3 (CO) 12 , ligand as given, 120 mol% DBU (DBU = 2,3,4,6,7,8,9,…”