Citation: JILKA, P. ... et al, 2010. The selective mono and difunctionalization of carbocyclic cleft molecules with pyridyl groups and X-ray crystallographic analysis. Tetrahedron, 66 (48) --- IntroductionMolecular recognition relies on the ability to design and synthesize appropriate substrates with predictable geometries and binding sites. 1 Towards this end Tröger's base 2 1 has been used to great effect by a number groups within the context of molecular recognition because it contains a rigid predictable structure, heteroatoms capable of binding events and importantly a chiral cavity.3,4 While Tröger's base has proved effective as a chiral cleft molecule, a number of carbocyclic and heterocyclic analogues have also been also investigated as possible surrogates.5 The carbocyclic cleft molecule 2 was initially reported in 1960 by Stetter 6 but was fully characterized and resolved in 1975 by Tatemitsu et al. 7 Significant advances in the functionalization of 2 have been developed by the Harding group 8 and an excellent review on its development/ uses has been published (Figure 1). Of particular interest to our group is the reduced version of 2. Treatment of 2 with excess reducing agent results in the formation of the bis-hydroxyl carbocycle 3, where both hydroxyl groups are directed into the chiral cavity. This potentially gives a ligand which can bind substrates via metal or Brønsted base / acid binding interactions within a chiral cavity (Scheme 1). Scheme 1. Reduction of 2 to give diol 3.To date the only reported functionalization of these hydroxyl groups has been the attachment of simple esters (bromobenzoate, acetate and menthoxy acetyl) and the synthesis of cyclic ethers.7,10 The dibromobenzoate and diacetate derivatives were synthesized for characterization reasons, the dimenthoxy acetate was synthesized for separation purposes and the cyclic ethers A R T I C L E I N F O A B S T R A C TArticle history: Received Received in revised form Accepted Available onlineThe diesterification and selective mono and dialkylation of carbocyclic analogues of Tröger's base with pyridyl groups has been achieved in high yield and good selectivity giving access to a novel range of cleft molecules capable of binding events. Reaction conditions for the selective functionalization of this carbocyclic cleft molecule are discussed as well as the solid state structures of these newly synthesized ligands.