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.

Figure 1. Application of Carbon Monoxide in Synthesis Made Simple and Safe by Prof. Skrydstrup and Coworkers

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.

Figure 2. The combination of COgen or COgen with the two-chamber system

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.

Figure 3. 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.

Figure 4. CO gen in the COware system is directly comparable to CO

References

1. Hermange P, Lindhardt AT, Taaning RH, Bjerglund K, Lupp D, Skrydstrup T. 2011. Ex SituGeneration of Stoichiometric and Substoichiometric12CO and13CO and Its Efficient Incorporation in Palladium Catalyzed Aminocarbonylations. J. Am. Chem. Soc.. 133(15):6061-6071. https://doi.org/10.1021/ja200818w

2. Nielsen DU, Taaning RH, Lindhardt AT, Gøgsig TM, Skrydstrup T. 2011. Palladium-Catalyzed Approach to Primary Amides Using Nongaseous Precursors. Org. Lett.. 13(16):4454-4457. https://doi.org/10.1021/ol201808y

3. Xin Z, Gøgsig TM, Lindhardt AT, Skrydstrup T. 2012. An Efficient Method for the Preparation of Tertiary Esters by Palladium-Catalyzed Alkoxycarbonylation of Aryl Bromides. Org. Lett.. 14(1):284-287. https://doi.org/10.1021/ol203057w

4. Burhardt MN, Taaning R, Nielsen NC, Skrydstrup T. 2012. Isotope-Labeling of the Fibril Binding Compound FSB via a Pd-Catalyzed Double Alkoxycarbonylation. J. Org. Chem.. 77(12):5357-5363. https://doi.org/10.1021/jo300746x

5. Burhardt MN, Taaning RH, Skrydstrup T. 2013. Pd-Catalyzed Thiocarbonylation with Stoichiometric Carbon Monoxide: Scope and Applications. Org. Lett.. 15(4):948-951. https://doi.org/10.1021/ol400138m

6. Korsager S, Taaning RH, Lindhardt AT, Skrydstrup T. 2013. Reductive Carbonylation of Aryl Halides Employing a Two-Chamber Reactor: A Protocol for the Synthesis of Aryl Aldehydes Including13C- and D-Isotope Labeling. J. Org. Chem.. 78(12):6112-6120. https://doi.org/10.1021/jo400741t

7. Lindhardt AT, Simonssen R, Taaning RH, Gøgsig TM, Nilsson GN, Stenhagen G, Elmore CS, Skrydstrup T. 2012. 14Carbon monoxide made simple - novel approach to the generation, utilization, and scrubbing of14carbon monoxide. J. Label Compd. Radiopharm. 55(11):411-418. https://doi.org/10.1002/jlcr.2962

8. Hermange P, Gøgsig TM, Lindhardt AT, Taaning RH, Skrydstrup T. 2011. Carbonylative Heck Reactions Using CO Generatedex Situin a Two-Chamber System. Org. Lett.. 13(9):2444-2447. https://doi.org/10.1021/ol200686h

9. Gøgsig TM, Taaning RH, Lindhardt AT, Skrydstrup T. 2012. Palladium-Catalyzed Carbonylative ?-Arylation for Accessing 1,3-Diketones. Angew. Chem.. 124(3):822-825. https://doi.org/10.1002/ange.201107494

10. Korsager S, Nielsen DU, Taaning RH, Skrydstrup T. 2013. Access to ?-Keto Esters by Palladium-Catalyzed Carbonylative Coupling of Aryl Halides with Monoester Potassium Malonates. Angew. Chem. Int. Ed.. 52(37):9763-9766. https://doi.org/10.1002/anie.201304072

11. Nielsen DU, Neumann K, Taaning RH, Lindhardt AT, Modvig A, Skrydstrup T. 2012. Palladium-Catalyzed Double Carbonylation Using Near Stoichiometric Carbon Monoxide: Expedient Access to Substituted 13C2-Labeled Phenethylamines. J. Org. Chem.. 77(14):6155-6165. https://doi.org/10.1021/jo3009337

12. Bjerglund K, Lindhardt AT, Skrydstrup T. 2012. Palladium-Catalyzed N-Acylation of Monosubstituted Ureas Using Near-Stoichiometric Carbon Monoxide. J. Org. Chem.. 77(8):3793-3799. https://doi.org/10.1021/jo3000767

13. Gøgsig TM, Nielsen DU, Lindhardt AT, Skrydstrup T. 2012. Palladium Catalyzed Carbonylative Heck Reaction Affording Monoprotected 1,3-Ketoaldehydes. Org. Lett.. 14(10):2536-2539. https://doi.org/10.1021/ol300837d