Competition-driven selection in covalent dynamic networks and implementation in organic reactional selectivity

Abstract

Competition among reagents in dynamic combinatorial libraries of increased complexity leads to reactional self-sorting (improved regioselectivity) in mixtures of aldehydes and oligoamines. High selectivity of a given library component is transferred to a different reacting component of low selectivity through a network of underlying equilibrating reactions which provide component exchange between all species. The selectivity of various carbonyl compounds in reactions with amines was also assessed towards the formation of defined sequences of residues along oligoamine chains. The approach was further exploited for defining selective dynamic protecting groups (DPGs), based on the reversible linkage between the substrate and the protecting group. They represent an intermediate approach between the conventional protecting groups and the protecting-group-free approach in organic synthesis. Removal of the protecting group is effected via dynamic exchange trapping by formation of a more stable product. The establishment of equilibrium eliminates the need for isolation and purification of the dynamically protected intermediate(s) and enables as well the selective sequential derivatisation of oligoamines. The DPG concept can be generalised to other reversible reactions and can thus represent a valuable alternative in the design of total synthesis of complex molecules.