Computational Study of the Palladium‐Catalyzed Carbonylative Synthesis of Aromatic Acid Chlorides: The Synergistic Effect of PtBu₃ and CO on Reductive Elimination

Abstract

We describe herein computational studies on the unusual ability of Pd(PtBu ) to catalyze formation of highly reactive acid chlorides from aryl halides and carbon monoxide. These show a synergistic role of carbon monoxide in concert with the large cone angle PtBu that dramatically lowers the barrier to reductive elimination. The tertiary structure of the phosphine is found to be critical in allowing CO association and the generation of a high energy, four coordinate (CO)(PR )Pd(COAr)Cl intermediate. The stability of this complex, and the barrier to elimination, is highly dependent upon phosphine structure, with the tertiary steric bulk of PtBu favoring product formation over other ligands. These data suggest that even difficult reductive eliminations can be rapid with CO association and ligand manipulation. This study also represents the first detailed exploration of all the steps involved in palladium-catalyzed carbonylation reactions with simple phosphine ligands, including the key rate-determining steps and palladium(0) catalyst resting state in carbonylations.

Mechanism of copper-free Sonogashira reaction operates through palladium-palladium transmetallation

“…13 ). The accessibility of three-coordinated T-shaped Pd II intermediates, like 4-PPh3 , has been assessed computationally 44 and such species have already been considered explicitly in mechanistic studies 45 . The extrusion of bulky phosphines is mostly driven to ease steric strain leading to such short-lived three-coordinate palladium centres, which, implied by our findings, might play a hitherto unrevealed, critical role in other transformations as well.…”

Palladium catalyzed carbonylative generation of potent, pyridine-based acylating electrophiles for the functionalization of arenes to ketones

“…8e We considered using steric effects to balance the electronic needs of oxidative addition with the ultimate reductive elimination of a reactive acyl electrophile. 8 Aer examining various sterically encumbered bidentate ligands, we were pleased to nd that the large bite angle, moderate donor Xantphos allowed the intermolecular functionalization of N-benzyl pyrrole to afford ketone 2a in low yield (13%). 15 In probing approaches to enhance the yield of the reaction, one simple modication was to change the base employed.…”

“…The reactivity observed with the Xantphos ligand is presumably related in part to its ability to associate in a bidentate fashion to palladium and better activate the relatively strong C(sp 2 )-OTf bond towards carbonylation, in concert with its large bite angle, which can favor the reductive elimination. 8,19 The combination of these features offers an avenue to build-up kinetically reactive acylating agents from C(sp 2 )-triates. 20 The importance of pyridine, and the specic pyridine structure, in catalysis is tied to its ability to stabilize the reductive elimination product relative to a highly reactive acid triate.…”

“…6 Recent studies by a number of labs including our own have described how carbonylations can offer an efficient alternative approach to the generation of potent acylating electrophiles. [7][8][9][10] The reactivity of these products has allowed the application of carbonylation reactions to a range of challenging substrates, including the direct functionalization of arenes with acyl tri-ates. 8e However, as with classical Friedel-Cras chemistry, the reaction here also requires the use of stoichiometric metal additives: in this case silver triate salts, in concert with reactive aryl iodides.…”

Catalytic Carbochlorocarbonylation of Unsaturated Hydrocarbons via C−COCl Bond Cleavage**

“…Notably,t he retention of the highly electrophilic acid chloride moiety allows awide variety of synthetic modifications of the product. [14,16,19]…”