Synthesis of Fre´chet-type Tetramethylated Resorcarene Dendrimers MINNA LUOSTARINEN 1 , KIRSI SALORINNE 1 , HEIDI LA ¨ HTEENMA ¨ KI 1 , HEIDI MANSIKKAMA ¨ KI 1 , CHRISTOPH A. SCHALLEY 2 , MAIJA NISSINEN 1, * and KARI RISSANEN 1, * 1 Department of Chemistry, Nanoscience Center, University of Jyva ¨skyla ¨ P.O. Box 35, 40014, University of Jyva ¨skyla ¨, Finland; 2 Institut fu ¨r Chemie und Biochemie À Organische Chemie, Freie Universita ¨t Berlin, Takustr. 3, 14195, Berlin, Germany (Received: 25 April 2006; in final form: 25 May 2006) Key words: Fre´ chet dendrons, mass spectrometry, phase-transfer catalysis, resorcarene, X-ray crystallography Abstract Tetramethylated resorcarenes are good core molecules for the synthesis of Fre´chet-type dendrimers. Fre´chet-type dendron bromides were synthesised on a gram scale, and were easily attached under phase-transfer conditions to the tetramethylated resorcarene core to obtain pure products in high yields. Introduction Resorcarenes have been widely used as starting material for the synthesis of various types of host molecules [1], and studies of their chemical properties and molecular recognition properties have also been reported [2]. Den- drimers are polymers with a well-defined, highly bran- ched molecular architecture, which is characterised by a central multifunctional core, from which one or more shells of branching units extend towards terminating peripheral monomers [3]. Dendrimers can be prepared by the divergent or the convergent method. The former method starts from a central core molecule and proceeds radially outward [4]. In contrast, the latter approach builds the dendrimer from the periphery towards the central core [5]. In this study, the convergent method was used to synthesise the dendritic wedges (see Scheme 3). Resorcarenes and calixarenes are attractive candi- dates for multifunctional cores in dendritic molecules, because these macrocyclic phenols have numerous sites for attaching dendritic wedges. Several research groups have used the phenolic OH functions of calixarenes and resorcarenes as core molecules for the synthesis of dendrimers [6]. This approach is of particular interest, because the dendrons are not equally distributed in space due to the bowl-shaped geometry of the resorca- rene, but rather extend to the open side of the bowl and may thus change its hostÀguest properties. In our earlier studies, we attached Fre´chet-type den- dron amines to the 2-position of each resorcarene ring through Mannich reaction with rather high yields [7]. We now aim at exploring other possibilities to use resorca- renes as core molecules in dendrimers, and for this pur- pose we chose tetramethylated resorcarenes [8] as new core molecules (Scheme 1). As described below, Fre´chet- type dendrons bearing benzylic bromides at their focal points can be easily attached to the resorcarene core with high yields under phase-transfer conditions. Experimental section General 1 H and 13 C, HMQC, HMBC, and variable temperature NMR spectra were measured with Bruker Avance DRX 500 (500 MHz for 1 H and 126 MHz for 13 C) spec- trometer in CDCl 3 solution. ESI mass spectra were re- corded on a Micromass LCT ESI-TOF instrument equipped with a Z geometry electrospray ion source. The samples were introduced into the source as CH 2 Cl 2 :CH 3 CN (2:1) solutions of the dendrimer and ca. 4À5 equivalents of CsCl at flow rates of 34 lL/min. A constant spray and highest intensities were achieved with a capillary voltage of 4700 V at a source temper- ature of 80 °C and a desolvation temperature of 120 °C. Other selected source parameters were as follows: Sample cone voltage: ca. 180 V, extraction cone voltage: 2 V, flow of cone gas: 10 L/h, flow of desolvation gas: 150À200 L/h. Multiple scans (50À200) were recorded and averaged for each spectrum in order to improve the signal-to-noise ratio. The third generation dendrimer has a molecular weight outside the available mass range. All attempts to incorporate a doubly charged cation failed, and no signal was observed at half the molecular * Author for Correspondence. E-mails: maija.nissinen@jyu.fi; kari.rissanen@jyu.fi Journal of Inclusion Phenomena and Macrocyclic Chemistry (2006) Ó Springer 2006 DOI 10.1007/s10847-006-9124-z