DOI: 10.1002/chem.200800094 A Materials Approach to Site-Isolation of Grubbs Catalysts from Incompatible Solvents and m-Chloroperoxybenzoic Acid Martin T. Mwangi, M. Brett Runge, Kevin M. Hoak, Michael D. Schulz, and Ned B. Bowden* [a] Introduction The capability to carry out multiple reactions in one flask is an important goal in chemistry because of the need to speed the synthesis of molecules while producing less waste and requiring fewer hours of effort. [1–38] These reactions are often called cascade or domino reactions; their names refer to how several reactions occur in a predicted sequence in the same reaction vessel. These reactions are terrific exam- ples of green chemistry because they require less solvent and produce less waste than the traditional method of isolat- ing and characterizing products after each reaction. [5, 30, 39] Numerous cascade reactions have been developed, and many of them use one catalyst that catalyzes multiple steps, such as in a recent report in Nature of a catalytic reaction with a proline derivative to form four stereocenters in one pot. [1] The use of single catalysts to carry out multiple reac- tions has been very successful, but these cascade reactions typically require the development of new catalysts and cannot be integrated with numerous homogeneous catalysts that are often commercially available and are excellent cata- lysts for one reaction. [3] The main reason for this limitation is that these catalysts often poison one another or are pois- oned by reagents required by a second catalyst. Thus, only one can be added to a reaction vessel, and no cascade se- quence is possible. What is needed to advance the field of cascade reactions is a new method to integrate multiple cat- alysts and reagents to take advantage of mature homogene- ous catalysts that catalyze one reaction very well. Because many catalysts and reagents poison one another, they must be site-isolated from each other, such that multi- ple catalysts or reagents can be integrated into one reaction vessel for cascade reactions. [28, 40–42] Site-isolation involves Abstract: The development of a method for site-isolation of Grubbs second-generation catalyst from MCPBA is described. In these reac- tions, Grubbs catalyst was dissolved in a solvent consisting of a mixture (1:1 v/v) of 1-butyl-3-methylimidazolium hexafluorophosphate and methylene chloride and completely encapsulated within a thimble fabricated from poly- dimethylsiloxane (PDMS). A series of molecules that react by cross metathe- sis or ring-closing metathesis were added to the interior of the thimble and allowed to react. In the last step, m-chloroperoxybenzoic acid (MCPBA) dissolved in MeOH/H 2 O (1:1 v/v) was added to the exterior of the PDMS thimble. Small organic molecules dif- fused through the PDMS to react with MCPBA to form epoxides, but the Grubbs catalyst remained encapsulat- ed. This result is important because Grubbs catalyst catalytically decompos- es MCPBA at ratios of MCPBA to Grubbs of 3000 to 1. The yields for this two-step cascade sequence ranged from 67 to 83%. The concept behind this se- quence is that small organic molecules have high flux through PDMS but large molecules—such as Grubbs cata- lyst—and ionic reagents—such as MCPBA—have much lower flux through PDMS. Small molecules can thus react both outside and inside PDMS thimbles, whereas incompatible catalysts and reagents remain site-iso- lated from each other. This method does not require alteration of struc- tures of the catalysts or reagents, so it may be applied to a wide range of ho- mogeneous catalysts and reagents. To demonstrate further that the catalyst was encapsulated, the Grubbs catalyst was successfully recycled within the cascade sequence. Keywords: cascade reactions · epoxidation · metathesis · recycling [a] M. T. Mwangi, M. B. Runge, K. M. Hoak, M. D. Schulz, Prof. N. B. Bowden Department of Chemistry, University of Iowa Iowa City, IA 52242 (USA) Fax: (+ 1) 319-335-1270 E-mail : ned-bowden@uiowa.edu Supporting information for this article is available on the WWW under http://www.chemeurj.org/ or from the author. # 2008 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim Chem. Eur. J. 2008, 14, 6780 – 6788 6780