Question

When the \(\mathrm{Pd}(0)\)-catalyzed reactions covered in this chapter are run with a slight pressure of carbon monoxide, a ketone is often created as the product. For example, the following Stille coupling conditions with added CO give the product shown. Write a mechanism for how this reaction could occur using the organometallic mechanistic steps introduced in this chapter, along with new steps that would be required in this transformation. Hint: CO can coordinate to \(\mathrm{Pd}\) and insert into \(\mathrm{Pd}-\mathrm{C}\) bonds.

Short answer

Answer: The five main steps of the proposed mechanism are: 1) Formation of a Pd-Carbon Monoxide Complex, 2) Oxidative Addition, 3) Transmetalation, 4) CO Insertion, and 5) Reductive Elimination.

Step-by-step solution

Formation of Pd-Carbon Monoxide Complex

Begin by coordinating the CO molecule to the Pd(0) catalyst, forming a transient \(\mathrm{Pd}(0)(\mathrm{CO})\) complex.

Oxidative Addition

Now, the oxidative addition of the aryl halide will take place, where the transient \(\mathrm{Pd}(0)(\mathrm{CO})\) complex will insert itself between the carbon-halogen bond. This will form a \(\mathrm{Pd}(II)(\mathrm{CO}-\mathrm{Ar})(\mathrm{X})\) intermediate, where \(\mathrm{Ar}\) is the aryl group and \(\mathrm{X}\) is the halogen.

Transmetalation

During the transmetalation step, the \(\mathrm{Pd}(II)\) complex will undergo a ligand exchange with the organotin reagent. The organotin reagent will coordinate to the \(\mathrm{Pd}(II)\) center, causing the halogen to leave and form a new \(\mathrm{Sn}-\mathrm{X}\) bond. This results in the formation of a \(\mathrm{Pd}(II)(\mathrm{CO}-\mathrm{Ar})(\mathrm{R}-\mathrm{SnX})\) intermediate, where \(\mathrm{R}\) represents the organotin group.

CO Insertion

The CO will then undergo migratory insertion into the \(\mathrm{Pd-C}\) bond of the intermediate, forming a \(\mathrm{Pd}(II)(\mathrm{SnX})(\mathrm{CO}-\mathrm{Ar}-(\mathrm{C})-\mathrm{R})\) complex. Here, the carbonyl carbon of CO is now directly connected to the aryl group and the side chain, forming a bond with the organotin group.

Reductive Elimination

Finally, the reductive elimination will occur, in which the \(\mathrm{Pd}(II)\) will release the ketone product and regenerate the \(\mathrm{Pd}(0)\) catalyst. The ketone product is formed by the elimination of the ligands attached to the \(\mathrm{Pd}(II)\) complex, and the organotin halide complex is released as a byproduct. The final mechanism consists of the following steps: Formation of Pd-CO complex, oxidative addition, transmetalation, CO insertion, and reductive elimination.