Rapid Metal -free Macromolecular Coupling via in situ Nitrile Oxide-Activated Alkene Cycloaddition

Abstract

Nitrile oxide 1,3 dipolar cycloaddition is a simple and powerful coupling methodology. However, the self-dimerization of nitrile oxides has prevented the widespread use of this strategy for macromolecular coupling. By combining an in situ nitrile oxide generation with a highly reactive activated dipolarophile, we have overcome these obstacles and present a metal-free macromolecular coupling strategy for the modular synthesis of several ABA triblock copolymers. Nitrile oxides were generated in situ from chloroxime terminated poly(dimethylsiloxane) B-blocks and coupled with several distinct hydrophilic (poly(2-methyloxazoline) and poly(ethylene glycol)), and poly(N-isopropylacrylamide) or hydrophobic (poly(L-lactide) A-blocks terminated in activated dipolarophiles in a rapid fashion with high yield. This methodology overcomes many drawbacks of previously reported metal-free methods due to its rapid kinetics, versatility, scalability, and ease of introduction of necessary functionality. Nitrile oxide cycloaddition should find use as an attractive macromolecular coupling strategy for the synthesis of biocompatible polymeric nanostructures.

Keywords: 1,3-dipolar cycloaddition; nitrile oxide; poly(2-methyloxazoline) (PMOXA); poly(L-lactide) (PLA); poly(N-isopropylacrylamide) (PNIPAM); poly(dimethylsiloxane) (PDMS); poly(ethylene glycol) (PEG); triblock copolymers.

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