Tris(2,4,6-trimethoxyphenyl)phosphine (TTMPP) as Potent Organocatalyst for Group Transfer Polymerization of Alkyl (Meth)acrylates

Several commercial trialkyl phosphines were tested as organic catalysts for the group transfer polymerization (GTP) of methyl methacrylate (MMA) and <i>tert</i>-butyl acrylate (<i>t</i>BA). Among them, only tris­(2,4,6-trimethoxyphenyl)­phosphine (TTMPP) was able to bring about the “controlled/living” GTP of both monomers at room temperature, in bulk and/or in THF solution, using 1-methoxy-2-methyl-1-[(trimethylsilyl)­oxy]­prop-1-ene (MTS) as initiator. However, control of the polymerization appeared to be more difficult in the case of <i>t</i>BA compared to MMA. Poly­[alkyl­(meth)­acrylate]­s exhibiting dispersities <1.37 in bulk and <1.45 in THF, and molar masses in good accordance with the initial [monomer]₀/[MTS]₀ molar ratio could thus be obtained in quantitative yields. Poly­(methyl methacrylate)-<i>b</i>-poly­(<i>tert</i>-butyl acrylate) block copolymers, with final dispersity <1.2 and controlled molar masses, were also synthesized by sequential TTMPP-catalyzed GTP. First order kinetics plot of the GTP of MMA revealed an induction period of a few hours, which strongly depended on the initial polymerization conditions. The tacticity of the final PMMA’s (<i>mm</i>/<i>mr</i>/<i>rr</i> = 0.06/0.42/0.52) were very similar to that of an anionically derived PMMA. These data are in favor of the occurrence of a dissociative mechanism, forming minute amounts of true enolate-type propagating species, during the TTMPP-catalyzed GTP of MMA in THF. Analyses by ¹³C and ²⁹Si NMR spectroscopy at room temperature of 1/1 molar MTS/TTMPP mixtures did not show the formation of enolate-type species

Enzyme-Degradable Self-Assembled Nanostructures from Polymer–Peptide Hybrids

The peptide PVGLIG, which is known to be selectively cleaved by the tumor-associated enzyme matrix metalloproteinase-2 (MMP-2), was conjugated to α-alkene poly­(trimethylene carbonate) (PTMC) blocks of varying sizes via UV-initiated thiol-ene “click” chemistry. The PTMC precursor was synthesized by metal-free ring-opening polymerization using allyl alcohol as an initiator and an <i>N</i>-heterocyclic carbene as an organic catalyst. The unprecedented PVGLIG-<i>b</i>-PTMC hybrids were self-assembled in aqueous solution and various submicrometer-sized morphologies obtained by a nanoprecipitation process. Characterization of particle morphology was carried out by multiangle dynamic light scattering (DLS) and static light scattering (SLS) evidencing spherical nanoparticles with different morphologies and narrow size distributions. Microstructure details were also observed on transmission electron micrographs and were in good agreement with light scattering measurements showing the assembly of core–shell, large compound micelles, and vesicle morphologies, the particle morphology varying with the hydrophilic weight fractions (<i>f</i>) of the hybrids. These nanostructures displayed selective degradation in the presence of the cancer-associated enzyme MMP-2, as probed by the morphological change both by TEM and DLS. All these results demonstrated that PVGLIG-<i>b</i>-PTMC hybrids were suitable to target the tumor microenvironment

Imidazolium Hydrogen Carbonates versus Imidazolium Carboxylates as Organic Precatalysts for N‑Heterocyclic Carbene Catalyzed Reactions

Imidazolium-2-carboxylates (NHC–CO₂ adducts, <b>3</b>) and (benz)­imidazolium hydrogen carbonates ([NHC­(H)]­[HCO₃], <b>4</b>) were independently employed as organic precatalysts for various molecular N-heterocyclic carbene (NHC) catalyzed reactions. NHC–CO₂ adducts were obtained by carboxylation in THF of related free NHCs (<b>2</b>), while the synthesis of [NHC­(H)]­[HCO₃] precursors was directly achieved by anion metathesis of imidazolium halides (<b>1</b>) using potassium hydrogen carbonate (KHCO₃) in methanolic solution, without the need for the prior preparation of free carbenes. Thermogravimetric analysis (TGA) and TGA coupled with mass spectrometry (TGA-MS) of most [NHC­(H)]­[HCO₃] precursors <b>4</b> showed a degradation profile in stages, with either a concomitant or a stepwise release of H₂O and CO₂, between 108 and 280 °C, depending on the nature of the azolium and substituents. In solution, NHC generation from both [NHC­(H)]­[HCO₃] salts and NHC–CO₂ adducts could be achieved at room temperature, most likely by a simple solvation effect. Both types of precursors proved efficient for organocatalyzed molecular reactions, including cyanosilylation, benzoin condensation, and transesterification reactions. The catalytic efficiencies of NHC–CO₂ adducts <b>3</b> were found to be approximately 3 times higher than those of their [NHC­(H)]­[HCO₃] counterparts <b>4</b>

One-Pot Synthesis and PEGylation of Hyperbranched Polyacetals with a Degree of Branching of 100%

The Brønsted acid-catalyzed polytransacetalization of hydroxymethylbenzaldehyde dimethylacetal (<b>1</b>), a commercially available AB₂-type monomer, led to hyperbranched polyacetals (HBPA’s) with a degree of branching (DB) around 0.5 by forming methanol as byproduct. In sharp contrast, the polyacetalization of the nonprotected homologue, namely, hydroxymethylbenzaldehyde (<b>2</b>), yielded HBPA’s with DB = 1, by forming water as byproduct, under the same acidic conditions. This major difference arises from the instability of the initially formed hemiacetal intermediates, which react faster than aldehyde moieties, driving the polyacetalization toward the quantitative formation of dendritic acetal units. This represents a rare example of defect-free hyperbranched polymer synthesis utilizing a very simple AB₂-type monomer. Brønsted acid catalysts included <i>p</i>-toluenesulfonic, camphorsulfonic, and pyridinium camphorsulfonic acids. Trapping of the water generated during polyacetalization of <b>2</b> was accomplished using molecular sieves regularly renewed, which allowed achieving polymers of relatively high molar masses. These HBPA’s with DB = 1 featuring multiple aldehyde functions at their periphery were further derivatized into PEGylated HBPA’s, using linear amino-terminated poly­(ethylene oxide)­s of different molar masses. This led to submicrometric sized HBPA’s with a core–shell architecture. Finally, HBPA derivatives could be readily hydrolyzed under acidic conditions (e.g., pH = 4), owing to the acid sensitivity of their constitutive acetal linkages

All Poly(ionic liquid)-Based Block Copolymers by Sequential Controlled Radical Copolymerization of Vinylimidazolium Monomers

The organometallic-mediated radical polymerization (OMRP) of <i>N</i>-vinyl-3-alkyl­imidazolium-type monomers, featuring the bis­(trifluoromethyl­sulfonyl)­imide counteranion (Tf₂N^–), in the presence of Co­(acac)₂ as controlling agent, is reported. Polymerizations of monomers with methyl, ethyl, and butyl substituents are fast, reaching high monomer conversion in ethyl acetate as solvent at 30 °C, and afford structurally well-defined hydrophobic poly­(ionic liquid)­s (PILs) of <i>N</i>-vinyl type. Block copolymer synthesis is also achieved by sequential OMRP of <i>N</i>-vinyl-3-alkylimidazolium salts carrying different alkyl chains and different counteranions (Tf₂N^– or Br^–). These block copolymerizations are carried out at 30 °C, either under homogeneous solution in methanol or in a biphasic medium consisting of a mixture of ethyl acetate and water. Unprecedented PIL-<i>b</i>-PIL block copolymers are thus prepared under these conditions. However, anion exchange occurs at the early stage of the growth of the second block. Finally, diblock copolymers generated in the biphasic medium can be readily coupled by addition of isoprene, forming all PIL-based and symmetrical ABA-type triblock copolymers in a one-pot process. Such a direct block copolymerization method, involving vinylimidazolium monomers bearing different alkyl chains, thus opens new opportunities in the precision synthesis of all PIL-based block copolymers of tunable properties

Selective Initiation from Unprotected Aminoalcohols for the <i>N</i>‑Heterocyclic Carbene-Organocatalyzed Ring-Opening Polymerization of 2‑Methyl-<i>N-</i>tosyl Aziridine: Telechelic and Block Copolymer Synthesis

Commercial aminoalcohols, namely, 2-(methyl amino)­ethanol (<b>1</b>) and diethanolamine (<b>2</b>), are investigated as direct initiators, i.e., with no need of protection of the hydroxyl groups, for the <i>N</i>-heterocyclic carbene-organocatalyzed ring-opening polymerization (NHC-OROP) of 2-methyl-<i>N</i>-<i>p</i>-toluenesulfonyl aziridine. NHC-OROP’s are performed at 50 °C in tetrahydrofuran, in the presence of 1,3-bis­(isopropyl)-4,5­(dimethyl)­imidazol-2-ylidene (^Me5-IPr) as organocatalyst. Thus, nonprotected and nonactivated aminoalcohol initiators <b>1</b> and <b>2</b> provide a direct access to metal-free α-hydroxy-ω-amino- and α,α′-bis-hydroxy-ω-amino telechelics on the basis of polyaziridine (PAz), respectively. Excellent control over molar masses, narrow dispersities (<i><i>Đ</i></i> ≤ 1.20), and high chain-end fidelity are evidenced by combined analyses, including NMR spectroscopy, size exclusion chromatography, and MALDI ToF mass spectrometry. The amino-initiated NHC-OROP is therefore tolerant to the presence of nonprotected hydroxyl group(s). The as-obtained hydroxyl-ended PAz can be further derivatized in reaction with phenyl isocyanate, highlighting the accessibility of the hydroxyl groups in α-position. Moreover, block copolymer synthesis can be readily achieved by sequential NHC-OROP of 2-methyl-<i>N</i>-<i>p</i>-toluenesulfonyl aziridine and l-lactide, from <b>1</b> used in this case as a double-headed initiator. Remarkably, each of the two NHC-OROP steps proves highly chemoselective, with PAz and poly­(l-lactide) (PLLA) segments being grown from the secondary amino- and the primary hydroxy- function, respectively. In this way, a well-defined PAz-<i>b</i>-PLLA diblock copolymer is synthesized in the presence of the same ^Me5-IPr organocatalyst, i.e., following a completely metal-free strategy

Poly(arylene vinylene) Synthesis via a Precursor Step-Growth Polymerization Route Involving the Ramberg–Bäcklund Reaction as a Key Post-Chemical Modification Step

The synthesis of conjugated copolymers based on poly­(fluorene vinylene) [<b>PFV</b>] and poly­(fluorene vinylene-<i>co</i>-carbazole vinylene) [<b>PFVCV</b>] was achieved via a previously unexplored precursor three-step synthetic route involving the Ramberg–Bäcklund reaction. The resulting π-conjugated (co)­polymers proved highly soluble in common organic solvents, such as DCM, THF, or CHCl₃. The solution step-growth polymerization between 2,7-bis­(bromomethyl)-9,9′-dihexyl-9<i>H-</i>fluorene [<b>F-Br</b>] and 2,7-bis­(mercaptomethyl)-9,9′-dihexyl-9<i>H-</i>fluorene [<b>F-SH</b>] was carried out under basic conditions at 100 °C in a mixture of MeOH and THF. The resulting polysulfides were then subjected to an oxidation reaction using <i>m-</i>CPBA, which was followed by the Ramberg–Bäcklund reaction in the presence of CF₂Br₂/Al₂O₃–KOH, thus achieving the desired <b>PFV</b>. Similarly, <b>PFVCV</b> could be synthesized through the same three-step sequence employing, in this case, 2,7-bis­(mercaptomethyl)-9-(tridecan-7-yl)-9<i>H</i>-carbazole (<b>C-SH</b>) and <b>F-Br</b>. Conjugated polymers with apparent molecular weights up to 15 kg mol^–1 and exhibiting promising optical features were obtained following this convenient synthetic strategy

Imidazol(in)ium Hydrogen Carbonates as a Genuine Source of <i>N</i>-Heterocyclic Carbenes (NHCs): Applications to the Facile Preparation of NHC Metal Complexes and to NHC-Organocatalyzed Molecular and Macromolecular Syntheses

Anion metathesis of imidazol­(in)­ium chlorides with KHCO₃ afforded an easy one step access to air stable imidazol­(in)­ium hydrogen carbonates, denoted as [NHC­(H)]­[HCO₃]. In solution, these compounds were found to be in equilibrium with their corresponding imidazol­(in)­ium carboxylates, referred to as <i>N</i>-heterocyclic carbene (NHC)-CO₂ adducts. The [NHC­(H)]­[HCO₃] salts were next shown to behave as masked NHCs, allowing for the NHC moiety to be readily transferred to both organic and organometallic substrates, without the need for dry and oxygen-free conditions. In addition, such [NHC­(H)]­[HCO₃] precursors were successfully investigated as precatalysts in two selected organocatalyzed reactions of molecular chemistry and polymer synthesis, namely, the benzoin condensation reaction and the ring-opening polymerization of d,l-lactide, respectively. The generation of NHCs from [NHC­(H)]­[HCO₃] precursors occurred <i>via</i> the formal loss of H₂CO₃ <i>via</i> a concerted low energy pathway, as substantiated by Density Functional Theory (DFT) calculations

Polyaldol Synthesis by Direct Organocatalyzed Crossed Polymerization of Bis(ketones) and Bis(aldehydes)

Synthesis of polyaldols consisting of β-keto alcohol monomer units is described. These polymers were obtained by direct step-growth polymerization of purposely designed bifunctional enolizable bis­(ketone) monomers playing the role of nucleophilic donors, and activated nonenolizable bis­(aldehyde)­s serving as electrophilic acceptors. Monofunctional ketone and aldehyde homologues were first synthesized as models to establish the aldol reaction conditions using reaction partners at stoichiometry. A bifunctional organocatalytic system consisting of pyrrolidine in conjunction with acetic acid allowed performing polyaldolizations of stoichiometric amounts of the bis­(aldehyde) and the bis­(ketone) in solution in THF, DMSO, or DMF, at room temperature. However, polar solvents and/or prolonged reaction time induced further aldol reactions between aldol units of polymer chains, as indicated by the relatively broad molecular weight distribution of related polyaldols observed by size exclusion chromatography. Analysis by NMR spectroscopy confirmed the formation of β-keto alcohol units, but also evidenced that the latter were also partly dehydrated into conjugated ketones via a crotonization reaction (from 20 to 33% depending on the structure of the initial monomers)

Direct Route to Well-Defined Poly(ionic liquid)s by Controlled Radical Polymerization in Water

The precision synthesis of poly­(ionic liquid)­s (PILs) in water is achieved for the first time by the cobalt-mediated radical polymerization (CMRP) of <i>N</i>-vinyl-3-alkylimidazolium-type monomers following two distinct protocols. The first involves the CMRP of various 1-vinyl-3-alkylimidazolium bromides conducted in water in the presence of an alkyl–cobalt­(III) complex acting as a monocomponent initiator and mediating agent. Excellent control over molar mass and dispersity is achieved at 30 °C. Polymerizations are complete in a few hours, and PIL chain-end fidelity is demonstrated up to high monomer conversions. The second route uses the commercially available bis­(acetylacetonato)­cobalt­(II) (Co­(acac)₂) in conjunction with a simple hydroperoxide initiator (<i>tert</i>-butyl hydroperoxide) at 30, 40, and 50 °C in water, facilitating the scaling-up of the technology. Both routes prove robust and straightforward, opening new perspectives onto the tailored synthesis of PILs under mild experimental conditions in water