Template-directed synthesis employing reversible imine bond formation

Abstract

The imine bond – formed by the reversible condensation of an amine and an aldehyde – and its applications as a dynamic covalent bond in the template-directed synthesis of molecular compounds, will be the focus of this tutorial review. Template-directed synthesis – or expressed another way, supramolecular assistance to covalent synthesis – relies on the use of reversible noncovalent bonding interactions between molecular building blocks in order to preorganise them into a certain relative geometry as a prelude to covalent bond formation to afford the thermodynamically preferred product. The use of this so-called dynamic covalent chemistry (DCC) in templated reactions allows for an additional amount of reversibility, further eliminating potential kinetic products by allowing the covalent bonds that are formed during the template-directed reaction to be ‘proofread for errors’, thus making it possible for the reaction to search out its thermodynamic minimum. The marriage of template-directed synthesis with DCC has allowed chemists to construct an increasingly complex collection of compounds from relatively simple precursors. This new paradigm in organic synthesis requires that each individual piece in the molecular self-assembly process is preprogrammed so that the multiple recognition events expressed between the pieces are optimised in a highly cooperative manner in the desired product. It offers an extremely simple way of making complex mechanically interlocked compounds – e.g., catenanes, rotaxanes, suitanes, Borromean rings and Solomon knots – from relatively simple precursors.