Notes Exploring the Reversibility of the Ring-Closing Metathesis Mediated Cross-linking of Dendrimers Stephanie L. Elmer, N. Gabriel Lemcoff, † and Steven C. Zimmerman* Department of Chemistry, UniVersity of Illinois at Urbana-Champaign, Urbana, Illinois, 61801 ReceiVed June 3, 2007 ReVised Manuscript ReceiVed July 16, 2007 Introduction The ring closing metathesis reaction has become a powerful and, thus, ubiquitous method for preparing medium and large ring systems. 1 Ruthenium-based catalysts such as 1 and 2 (Figure 1) have been employed to produce a diversity of compounds including natural products, 2 artificial polymers, 3 and mechani- cally interlocked compounds. 4 Macrocyclic systems using the ring-closing metathesis (RCM) reaction such as metallomacro- cycles, 5 nanotubes, 6 monomolecularly imprinted dendrimers (MIDs), 7 and a triply threaded molecular bundle 8 have been described. A monometallic complex has been used as a template to ensure the desired geometry in the synthesis of metallomac- rocycles, 5 catenanes, 9 molecular knots, 10 and molecular wires. 11 Stoddart and Grubbs reported the template-directed olefin metathesis using metal ion templation under thermodynamic control to prepare a rotaxane. 4b-d Here, we analyze the reversibility of the RCM process in a complex macromolecular system related to MIDs. It was suggested previously that the RCM-mediated cross- linking of dendrimers is an excellent approach to MIDs because the reversibility of the ruthenium catalyst allows dynamic molding of the dendritic framework around the template. 7 In prior studies, the rate of cross-linking 12 and the extent of inter- dendron vs intra-dendron cross-linking was investigated, but definitive evidence for reversibility in the RCM was not obtained. 13,14 Herein, we describe a simple test of whether metathesized end groups of a dendrimer are able to open and close again. As shown in Scheme 1 the strategy involves examining whether Grubbs catalyst 1 or 2 is capable of fully cross-linking dendrimer 7 in which two of the three dendrons have already undergone the RCM reaction. If all three dendrons become interconnected, hydrolysis will afford 8; otherwise, 9 and 10 will result. Our previous work used 1 nearly exclu- sively, 6,7,12,13 but we chose additionally to examine 2 because it is more reactive 15 and displays greater functional group tolerance. 1b Results and Discussion The synthesis of 7 began by coupling mono-TBDMS- protected 1,1,1-tris(hydroxymethyl)ethane 16 and [G-3] acid chloride dendron 3 17 to produce dendrimer 4 (Scheme 1). Deprotection of the silyl group followed by cross-linking with first generation Grubbs catalyst 1 at high dilution produced didendron 6, which was fully cross-linked. The RCM product was carefully purified by preparative size exclusion chroma- tography (SEC) and characterized by both 1 H NMR and MALDI-TOF-MS, both techniques indicating complete me- tathesis. Subsequent coupling with excess 3 provided key dendrimer 7 in which two of the three dendritic wedges are fully cross-linked. Using standard conditions, 17 portions of dendrimer 7 were treated in separate reactions with 1.0 equiv (6 mol % per alkene) of Grubbs catalyst 1 and 2 in benzene at a concentration of 10 -5 M at room temperature. An additional 1.0 equiv of catalyst was added on day 2 and 3 for a total of 3.0 equiv. Nearly complete cross-linking was observed by MALDI-TOF-MS * Corresponding author. E-mail: sczimmer@uiuc.edu. † Current address: Department of Chemistry, Ben Gurion University, Beer-Sheva, Israel 84105. Figure 1. Catalysts used for RCM reaction. Scheme 1. Synthesis of Dendrimer 7 and Test for Dynamic Cross-Linking 8114 Macromolecules 2007, 40, 8114-8118 10.1021/ma071233e CCC: $37.00 © 2007 American Chemical Society Published on Web 09/29/2007