Macrocyclization of folded diamines in cavitands

Academic Article
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publication date

  • August 2016

abstract

  • Synthetic access to water-soluble cavitands and capsules has moved recognition events from organic solvents into aqueous media. Here we report the binding and reactivity of long-chain α,ω-diamines (C11 to C18) in cavitand hosts. The containers bind the diamines in folded conformations that bury the hydrocarbon chains and expose the amino groups to the aqueous medium. Their acylation with succinic anhydride results in improved yields of monofunctionalized products. The cavitand-bound amino acid products were cyclized to the corresponding macrocyclic dilactams in D2O using water-soluble carbodiimide. Direct reaction of the folded diamines in the cavitand with activated diesters of succinic acid and glutaric acids resulted in 54-96% yields of the 17- to 25-membered dilactams. These cavitand-chaperoned reactions provided 3- to 10-fold improvements over the yields obtained in bulk solution and offer an alternative to high dilution methods. The cavitand induces unlikely conformations in flexible guests and channels their reactivity along otherwise improbable paths.