Liu loosens CO from renewable thiocarbonate platform

 Citation:

 Rajabimoghadam, K.; Faialaga, N.H.; Naito, N.; Li, Y.; Liu, R.Y. Photochemical CO Release from a Bench-Stable, Recyclable Organic Platform: Applications to Carbonylative Cross-Coupling. Org. Lett. 2025, ASAP. 

Summary figure:

 

Background: 

Carbonylation reactions are really nice 3 component reactions that usually form ketones. I've posted about one of them previously (https://alwaysbecoupling.blogspot.com/2025/03/palladium-promotes-precise-conversions.html) if you want to see an example. The general idea is you can do migratory addition with a metal carbonyl to form a C-C bond, and then eventually reductively eliminate from the metal acyl complex to form another C-C bond.

 

Usually, there are two difficulties. First, you have to get the relative rates right, or else you can directly couple your R groups. This is also a common issue with other three-component coupling reactions like dicarbofunctionalizations.  Second, you need to find a way to introduce CO into the reaction mixture.

Carbon monoxide (CO) is a highly toxic gas. If you breathe it in, it will begin to bind irreversibly to the hemoglobin in your bloodstream and cut off the oxygen supply, leading you to pass out and eventually die. About 500 people a year accidentally die from this in the US, usually because they leave an engine or heating generator running in a closed space and it slowly generated CO from burning fuel. If you 

The other major hazard with carbon monoxide comes specifically with metal carbonyls, and particularly with nickel carbonyl. If you get metal carbonyls into your body, they tend to shed the carbonyls over time and deposit heavy metals deep into your body. Nickel tetracarbonyl Ni(CO)4 is a gas, which means you can inhale it and then end up depositing toxic nickel metal into your lungs, which is immediately fatal. 

All this is to say that we really don't want to use carbon monoxide gas if we can help it! There are some other alternatives to straight CO- the authors mention a couple:

 

I'll briefly mention the paper I wrote about a few months ago used W(CO)6 as a carbon monoxide releasing molecule (CORM) for similar reasons. 

In this paper, the authors describe a CORM designed to be reusable. 

How it works:

 The authors designed a strained dithiocarbonate which is light sensitive. Upon irradiation with ~400 nm light, one of the C-S bonds is homolytically cleaved to form a thiol radical and an acyl radical. This diradical quickly rotates so that the carbonyl ends up on the other side of the sulfur, enabling an SH2 reaction to form a disulfide and liberate CO gas.

What makes this special is that you can regenerate the reagent through a two step sequence. First, the disulfide is reduced with sodium borohydride to form the dithiol. Then, CDI can be used to reform the dithiocarbonate. In a sense, you are using CDI as the carbonyl source, so you never need to use CO gas. 

Initial Questions and Key findings

1. Can you use light to slowly release CO from a reagent?

A. Yes, the dithiocarbonate fragments upon exposure to light, releasing CO. 

2.  Can you recycle the reagent to make it renewable?

A. Yes, by tethering the two sulfur atoms together, you form a strained disulfide that can be reduced and then reacted with a carbonate derivative to reform the thiocarbonate

3. Is this compatible with conditions required for cross-coupling reactions involving carbonyls?

A. With a slightly different set up. Instead of mixing this reagent in with the cross-coupling reaction, they use something that looks somewhat like an H-cell

 

This takes advantage of CO being a gas, so only CO is able to travel out of solution from one chamber to the other.