Application of Carbon Monoxide in Synthesis Made Simple and Safe by Prof. Skrydstrup and Coworkers

Studies in the field of carbonylation chemistry led to the discovery of a novel carbon monoxide (CO) delivery system.¹ The solid and bench stable CO-precursor, COgen, was found to be a highly efficient and reliable source of gaseous CO. Palladium mediated CO-release from COgen in near quantitative amounts occurs in any aprotic solvent and at a wide temperature range. Furthermore, its carbon-13 labeled counterpart, ¹³COgen, provides the corresponding ¹³C-carbon monoxide under identical conditions.

The combination of COgen or ¹³COgen with the two-chamber system, COware, is a safe and simple method for performing carbonylation chemistry. Release of CO in one chamber and its direct application in the secondary chamber provides a method in which the direct handling of CO is avoided. Substitution of ¹³COgen for COgen yields the labeled product under identical conditions.¹ This versatile method is now available through Sigma Aldrich as laboratory hardware and bench-stable CO precursors.

To date, this CO technique has found application in numerous carbonylation purposes including the classical amino-,^1,2 alkoxy-,³
thio-⁴ and reductive carbonylations.⁵ Furthermore, new conditions were developed providing access to carbonylative versions of the Suzuki-Miyaura coupling,⁶ the Mizoroki-Heck reaction,⁷ the α-arylation⁸ and even access to α-ketoamides⁶ by a double carbonylation was obtained by the COware-COgen combination.^9,10 Again, the carbon-13 labeled compounds were obtained by simple substitution of ¹³COgen for COgen.

CO generated in the COware system is directly comparable to CO delivered from a pressurized canister and does not require setup in a glove box. COware comes with PTFE-stabilizing discs, which ensures the PTFE-silicone seal is resealable. The method fits into any fume hood and allows simple and safe protocols for carrying out chemistry applying CO.