A General Approach to Creating Soluble Catalytic Polymers Heterogenized in Microcapsules Brian P. Mason, Andrew R. Bogdan, Anandarup Goswami, and D. Tyler McQuade* Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell UniVersity, Ithaca, New York 14853 dtm25@cornell.edu Received June 25, 2007 ABSTRACT A general method for preparing site-isolated polymeric catalysts is presented. Linear chloromethyl and azide polymers have been sequestered within polyurea microcapsules and small molecule catalysts soaked through the shell walls to functionalize the soluble polymers. Reaction onto each type of support is quantitative and MacMillan, DMAP, and TEMPO test catalysts are shown to have faster reaction rates than the analogous resin-supported catalysts. We recently reported the preparation of encapsulated catalytic linear polymers. 1 When the capsules were swollen in the reaction solvent, polymeric catalysts bound within remained active and in a solution-like environment. 2 We demonstrated that reaction rates were directly dependent on capsule wall thickness, and that the encapsulated catalyst showed greater activity than the same catalyst on cross-linked polystyrene support. This approach may not be widely adopted, however, because a linear polymer-bound catalyst must first be synthesized and then encapsulated within a polymeric shell. This requires that the catalyst be robust enough to survive the encapsulation conditions. Also, differences in the mo- lecular weight and functionality of the polymer-bound catalyst change the nature of the polyurea shell. Herein, we report general approaches to overcome these barriers by demonstrating that polyurea capsules containing chloromethyl- and azide-functionalized linear polymers can be directly functionalized with small molecule catalysts (Scheme 1). From these premade supports, we prepared three encapsulated catalysts: a MacMillan-type catalyst for Diels- Alder reactions, a 4-(N,N-dimethylamino)pyridine (DMAP) acylation catalyst, and a 2,2,6,6-tetramethylpiperidinyloxy (TEMPO) oxidation catalyst. Rates for the catalysts were compared to those of analogous resin-supported catalysts. We first investigated capsules directly analogous to Merrifield resin. 3,4 Poly(chloromethylstyrene-co-styrene) was generated by using well-known methods 5,6 and microencap- sulated in polyurea shells. 1,7 To determine if an active catalyst could be made from these microcapsules, an imidazolidinone (1) Price, K. E.; Mason, B. P.; Bogdan, A. R.; Broadwater, S. J.; Stein- bacher, J. L.; McQuade, D. T. J. Am. Chem. Soc. 2006, 128, 10376-10377. (2) Price, K. E.; Broadwater, S. J.; Bogdan, A. R.; Keresztes, I.; Steinbacher, J. L.; McQuade, D. T. Macromolecules 2006, 39, 7681-7685. (3) Merrifield, R. B. J. Am. Chem. Soc. 1963, 85, 2149-2154. (4) Benaglia, M.; Puglisi, A.; Cozzi, F. Chem. ReV. 2003, 103, 3401- 3429. Cozzi, F. AdV. Synth. Catal. 2006, 348, 1367-1390. (5) Chen, S. Q.; Janda, K. D. J. Am. Chem. Soc. 1997, 119, 8724- 8725. (6) Malagu, K.; Guerin, P.; Guillemin, J. C. Synlett 2002, 316-318. (7) Scher, H. B. Encapsulation Process and Capsules Produced Thereby. U.S. Patent 4285720, Aug 25, 1981. ORGANIC LETTERS 2007 Vol. 9, No. 17 3449-3451 10.1021/ol071360v CCC: $37.00 © 2007 American Chemical Society Published on Web 07/24/2007