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 \(\mathrm{CO}\) 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

Question: Outline the step-by-step mechanism for a Pd(0)-catalyzed reaction with added carbon monoxide that leads to the formation of a ketone product.

Step-by-step solution

Oxidative Addition to Pd(0)

Start with the oxidative addition of the Pd(0) catalyst to the aryl halide to form the Pd(II) species with the aryl group and the halogen (X) ligands coordinated to the palladium metal.

CO Coordination

Carbon monoxide (CO) coordinates to the Pd(II) species from the prior step, which will incorporate CO into the new complex.

Transmetalation

Proceed with the transmetalation step where the tin-containing organometallic reagent bonds with the halogen (X) ligand and the aryl group attached to the Pd(II) species. This results in transferring the aryl group from the tin-containing reagent to the Pd(II) species.

CO Insertion

At this stage, the insertion of CO into the Pd-C bond takes place (as mentioned in the hint), which results in a new complex with Pd(II) metal bound to both aryl and acyl groups.

Reductive Elimination

Finally, conclude the mechanism with the reductive elimination step, where the aryl and acyl groups combine and dissociate from the Pd(II) species forming the ketone product. This step also regenerates the Pd(0) catalyst, allowing the cycle to continue. Throughout the steps, remember to take into account proper arrow-pushing mechanisms and electron movement to ensure the correct formation and dissociation of bonds.

Key concepts

Oxidative Addition

One of the key steps in Pd(0)-catalyzed reactions is oxidative addition. Simply put, this is when a palladium(0) catalyst adds to a molecule, like an aryl halide, increasing its oxidation state to Pd(II). During this process, the palladium inserts itself between, let's say, a carbon-halogen bond, leading to a complex where the palladium is now bonded to both the aryl group and the halogen.
Think of this as palladium playing a game of 'break and enter' where it breaks the original bond and then promptly attaches to the pieces. This step sets the stage for a cascade of further reactions, creating a Pd(II) species ready to undergo a series of transformations, eventually leading to complex organic products like ketones.

CO Coordination

After palladium has undergone oxidative addition, the journey continues with CO coordination. Here, a carbon monoxide molecule approaches the Pd(II) species and 'holds hands' with the palladium atom, creating a new bonded unit. It's crucial to understand that CO is like a magnet for transition metals; they find each other quite attractive.
This coordination serves as a prelude to a transformative event where CO will get even cozier with palladium, setting the scene for the following step. Remember, CO coordination requires some open sites on palladium, which is why this cozy dance can only happen after palladium has bulked up through oxidative addition.

Transmetalation

The next sequence in our Pd-catalyzed reaction is transmetalation. This is where things get a bit 'tradey'. The Pd(II) complex, now with a CO and aryl group attached, meets an organometallic reagent, typically containing tin. The aryl group is then politely handed over from the tin reagent to palladium in exchange for the halogen.
This switcheroo is a pivotal moment, as it rearranges the players without adding or removing atoms but simply by swapping partners. It essentially prepares the Pd(II) complex for the exciting event of CO insertion, ensuring that the palladium is properly partnered up for the next dance move.

CO Insertion

Following transmetalation, CO insertion takes place. It might sound simple, but it's a bit like threading a needle while wearing boxing gloves. During this maneuver, the CO that was lovingly coordinated to palladium slides into the pivotal position between the palladium and the aryl group.
This results in the formation of an acyl palladium complex, a crucial intermediate that gets us one step closer to the ultimate goal: the ketone product. Inserting CO is like inserting a plot twist in a novel, changing the direction of our story and leading to new possibilities.

Reductive Elimination

Finally, we reach the grand finale: reductive elimination. After all that bonding and rearranging, the palladium complex decides it's time to let go, allowing the aryl and acyl groups to come together to form the desired ketone. This parting of ways effectively reduces the palladium back to its original Pd(0) state.
Reductive elimination is not just an elegant exit but also a recycle sign, regenerating the palladium catalyst so it can jump back into the cycle to create more complex molecules. It's the green aspect of Pd-catalyzed reactions, ensuring that the precious palladium is not wasted and can be used over and over again.