A recent JOC article by Prof. Pirrung and coworkers describes synthesis and use of fluorous tagged isonitriles in multi-component reactions. Previously, they reported synthesis of unsaturated isonitriles from oxazole and benzoxazole (J. Am. Chem. Soc. 2006, 128, 11772). For example, as shown below, metallation of benzoxazole by BuLi followed by O-acylation the ring-opened intermediate with toluoyl chloride gave an isonitrile 1. It was used in a Ugi reaction to give dipeptide 2. Upon treatment with HCl-MeOH, the product gave dipeptide 3 and benzoxazole 4.
The JOC full paper includes use of 4-perfluorooctylbenzoyl chloride and perfluorooctylsulfonyl fluoride to obtain fluorous tagged isonitriles 5 and 6, respectively. Those isonitriles were used in Ugi reactions, and the desired products were isolated by F-SPE. The fluorous benzoate derivative 7 was treated with HCl-MeOH to give dipeptide 3 and fluorous benzoxazole 8, and those were separated by F-SPE. The fluorous sulfonate product 9 was further derivatized by Suzuki, Sonogashira, and Stille reactions.
The examples shown in Prof. Pirrung’s paper is another example of how the introduction of a fluorous tag in multi-component reactions significantly simplifies the isolation of the desired products. If you are interested in employing the power of fluorous in your chemistry, please contact us and we’ll provide you with the tools and guidance needed.