Multifunctionalization of Polymers by Strain-Promoted Cycloadditions

Abstract

We report here a synthetic route to oxime, azide and nitrone-bearing copolymers via reversible addition-fragmentation chain transfer copolymerization of 4-vinylbenzaldehyde and 1-(chloromethyl)-4-vinylbenzene with styrene. The azide and nitrone moieties could be employed in strain-promoted 1,3-dipolar cycloadditions with various functionalized dibenzocyclooctynols (DIBO) for metal-free post-functionalization of the polymers. In situ oxidation of the oximes with hypervalent iodine gave nitrile oxides, which could also be employed as 1,3-dipoles for facile cycloadditions with DIBO derivatives. Kinetic measurements demonstrated that the pendant nitrile oxides reacted approximately twenty times faster compared to similar cycloadditions with azides. A block copolymer, containing azide and oxime groups in segregated blocks, served as a scaffold for attachment of hydrophobic and hydrophilic moieties by sequential strain-promoted alkyne-azide and strain-promoted alkyne-nitrile oxide cycloadditions. This sequential bi-functionalization approach made it possible to prepare in a controlled manner multi-functional polymers that could self-assemble into well-defined nanostructures.

Oxidative cyclizations of oximes using hypervalent iodine reagents

“…[17][18][19] In particular, the reaction of various aldoximes with alkynes in the presence of organohypervalent iodine(III) reagents such as DIB, 48,51,[54][55][56][57] BTI, 46,58,59 Koser's reagent, 49,60 or PhIO, 27,61 leads to oxidative heterocyclization yielding the corresponding isoxazoles. This procedure is applicable to various internal or terminal alkynes under mild condition.…”

“…46,54,60 The reactions of strained cyclic alkynes such as cyclooctyne derivatives with nitrile oxides generated from aldoximes and iodine(III) reagents are especially important in bioorthogonal chemistry. [55][56][57][58] For example, the reaction of lactose oxime with dibenzocyclooctyne derivatives using DIB gives the corresponding isoxazoles in good yields. 56 The obtained compound can be modified with the biotin tag, and can then be useful for an immobilization reaction to the surface of Streptavidin.…”

“…Boons and co-workers reported the preparation of amphiphilic polymeric compounds 39 by using strain-promoted heterocyclization of polymer-supported aldoxime 37 and cyclooctyne derivatives 38 using DIB (Scheme 11). 57 The polymers produced can form stable molecular assemblies in aqueous solution because of their hydrophilic-hydrophobic balance. These self-assembled products can further form nanoparticles potentially useful in materials or biomaterials sciences.…”

Catalyst-free site-specific surface modifications of nanocrystalline diamond films via microchannel cantilever spotting

“…67 Thus, a DBCO-presenting a primary amine group was chosen in this work for the nucleophilic attack to the epoxide ring (Fig. 1).…”

New insights into copper-mediated polymerization and polymer topologies

“…The scope of "click" reactions is further extended by thiol-ene/yne reactions, 100 Diels-Alder addition, 101 strain promoted addition of aziridines and epoxydes, 102 oxime ligation, 103 and nitroxide radical coupling (NRC). 104,105 It is generally desirable for a "click" reaction to require no catalyst, for example strainedpromoted CuAAC 106 and Diels-Alder addition of triazolinediones. 107 However, often moderate stimulus is applied to stimulate the reaction; including physical processes such as irradiation 108 The mechanism of the reaction was revised by Bertrand"s group in 2015 (Scheme 1.4) after the isolation of intermediate compounds.…”