Carbosilane Dendrimeric Carbodiimides: Site Isolation as a Lactamization Tool Alessia Amore, ² Rieko van Heerbeek, ² Niek Zeep, ‡ Jan van Esch, ‡ Joost N. H. Reek, ² Henk Hiemstra, ² and Jan H. van Maarseveen* ,² Van ’t Hoff Institute for Molecular Sciences, UniVersity of Amsterdam, Nieuwe Achtergracht 129, 1018 WS Amsterdam, The Netherlands, and Stratingh Institute, UniVersity of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands jVm@science.uVa.nl ReceiVed September 27, 2005 The convergent syntheses of three generations of carbosilane dendrimeric carbodiimides are described. The wedge-type building blocks were synthesized in a divergent way, starting from allyl chloride and a repetitive sequence of hydrosilylation with HSiCl 3 and a Grignard reaction with allylmagnesium bromide. Hydrogenation of the terminal double bonds led to inert and stable wedges. The chloride substitutent at the focal point was transformed into several functional groups that eventually led to dendrimeric structures with a carbodiimide core. The extent of the site isolation effect of the dendrimers was studied with dilution experiments monitored by FT-IR spectroscopy on the corresponding dendrimeric ureas. These studies showed that only the first generation self-aggregates via hydrogen bonding, while the second and the third do not, implying isolation of core-bound moieties. The dendrimeric carbodiimides mediated lactamization reactions to obtain homodiketopiperazines. Introduction Dendrimers are well-defined macromolecules with a regular and highly branched three-dimensional structure. 1 These mac- romolecules possess internal cavities that can exhibit site- isolation effects, as the branches shield the core to create a distinct nanoenvironment isolated from the bulk solution. 2 This peculiar feature of dendrimers has been explored in different research fields, especially homogeneous catalysis. Properties of dendrimers such as reactivity were, in some cases, different from those of the nondendrimeric analogues. For example, dendritic nickel catalysts used in the oligomerization of ethylene showed higher activity compared with their parent complex due to dendritic site isolation. 3 The ability of dendrimers to alter the local environments has seen application in other research fields, including material science and biology (drug delivery). 4 Surprisingly, only a few applications of dendrimers are known in organic synthesis, 5 none of which utilize core-functionalized dendrimers. For example, Kim and co-workers 6 reported the * To whom correspondence should be addressed. Phone: +31205255671. Fax: +31205255670. ² University of Amsterdam. ‡ University of Groningen. (1) (a) Newkome, G. R.; Moorefield, C. N.; Vo ¨gtle, F. Dendrimers and Wedges: Concept, Synthesis and Application; Wiley-VCH: Weinheim, 2001. (b) Dendrimers and Other Dendritic Polymers; Fre ´chet, J. M. J., Tomalia, D. A., Eds.; Wiley: Chichester, 2001. (2) (a) Hawker, C. J.; Wooley, L. K.; Fre ´chet, J. M. J. J. Am. Chem. Soc. 1993, 115, 4375-4376. (b) Hecht, S.; Fre ´chet, J. M. J. Angew. Chem., Int. Ed. 2001, 40, 74-91. (3) Muller, C.; Ackerman, L.; Reek, J. N. H.; Kamer, P. C. J.; Leeuwen, P. W. N. M. J. Am. Chem. Soc. 2004, 126, 14960-14963. (4) For recent reviews, see: (a) Bosman, A. W.; Janssen, H. M.; Meijer, E. W. Chem. ReV. 1999, 99, 1665-1688. (b) van Heerbeek, R.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Chem. ReV. 2002, 102, 3717-3756. (c) Preston, A. C.; Klein Gebbink, R. J. M.; van Koten, G. J. Organomet. Chem. 2004, 24, 4016-4054. 10.1021/jo052027c CCC: $33.50 © 2006 American Chemical Society J. Org. Chem. 2006, 71, 1851-1860 1851 Published on Web 02/01/2006