Guest-Induced Selective Functionalization of Polyaza[n]paracyclophanes M. Isabel Burguete, † Beatriu Escuder, † Juan C. Frı ´as, † Enrique Garcı ´a-Espan ˜ a,* ,‡ Santiago V. Luis,* ,† and Juan F. Miravet † Laboratory of Organic Chemistry, Department of Inorganic and Organic Chemistry, E.S.T.C.E., University Jaume I, E-12080 Castello ´ n, Spain, and Department of Inorganic Chemistry, University of Valencia, 46100 Burjassot (Valencia), Spain Received July 21, 1997 A new strategy to the preparation of selectively functionalized polyazamacrocycles is presented. Polyaza[n]paracyclophane receptors are able to efficiently direct their own selective functionalization upon interaction with simple guests such as metal cations. This enables the preparation of novel receptors functionalized at one of the benzylic nitrogen atoms with a variety of groups. Selective difunctionalization at both benzylic positions can also be achieved in this way. Introduction One of the most interesting features of aza macrocyclic receptors is the possibility of introducing additional groups by functionalization of the nitrogen atoms. As a matter of fact, development of monoaza- and diaza-crown ethers has been associated with their central role as starting materials for the preparation, via N-substitution, of lariat and bibrachial crown ethers, as well as receptors with tridimensional cavities (cryptands). 1 The introduction of sidearms in a macrocyclic ligand can greatly affect its properties, 2 in particular when the additional functional groups modify the number and nature of the donor atoms or change the lipophilic/ lipophobic balance of the receptor. 3 In this sense, N- functionalized polyaza macrocycles represent an impor- tant class of synthetic hosts, in particular when devel- opment of ligands for biomedical applications is consid- ered. Different N-substituted polyaza macrocycles have been synthesized in order to obtain novel contrast agents in magnetic resonance imaging, or for the preparation of labeled recombinant antibodies and related systems. 4 Introduction of a variety of chromophoric and photoactive subunits in the ligand has been also accomplished is this way. 5 Additionally, selective N-functionalization repre- sents an interesting approach for the preparation of enzyme mimics and catalytic models. 6 In this context, selective functionalization of polyaza- macrocyclic receptors is an important goal in order to obtain more elaborate and selective receptors and to prepare what has been called polyamines with intelligent functions. 7 Accordingly, much effort has been devoted to this end, and different methodologies have been developed recently. For the selective monofunctional- ization of symmetrical macrocycles, commonly triaza and tetraaza macrocycles, two different approaches have been used. 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