Boosting the Reactivity of Bis-Lactones to Enable Step-Growth Polymerization at Room Temperature.

The development of new sustainable polymeric materials endowed with improved performances but minimal environmental impact is a major concern, with polyesters as primary targets. Lactones are key monomers thanks to ring-opening polymerization, but their use in step-growth polymerization has remained scarce and challenging. Herein, we report a powerful bis(γ-lactone) (γSL) that was efficiently prepared on a gram scale from malonic acid by Pd-catalyzed cycloisomerization. The γ-exomethylene moieties and the spiro structure greatly enhance its reactivity toward ring-opening and enable step-growth polymerization under mild conditions. Using diols, dithiols, or diamines as comonomers, a variety of regioregular (AB)n copolymers with diverse linkages and functional groups (from oxo-ester to ß-thioether lactone and ß-hydroxy-lactame) have been readily prepared. Reaction modeling and monitoring revealed the occurrence of an original trans-lactonization process following the first ring-opening of γSL. This peculiar reactivity opens the way to regioregular (ABAC)n terpolymers, as illustrated by the successive step-growth polymerization of γSL with a diol and a diamine.

Development of an Efficient Thionolactone for Radical Ring-Opening Polymerization by a Combined Theoretical/Experimental Approach.

The environmental impact of plastic waste has been a real problem for the past decades. The incorporation of cleavable bonds in the polymer backbone is a solution to making a commodity polymer degradable. When radical polymerization is used, this approach is made possible by radical ring-opening polymerization (rROP) of a cyclic monomer that allows for the introduction of a weak bond into the polymer backbone. Among the various cyclic monomers that could be used in rROP, thionolactones are promising structures due to the efficiency of the C═S bond to act as a radical acceptor. Nevertheless, only a few structures were reported to be efficient. In this work, we used DFT calculations to gain a better understanding of the radical reactivity of thionolactones, and in particular, we focused on the transfer rate constant ktr value and its ratio with the propagation rate constant kp of the vinyl monomer. The closer to 1, the better is the statistical incorporation of the two comonomers into the backbone. These theoretical results were in good agreement with all of the experimental data reported in the literature. We thus used this approach to understand the key parameters to tune the reactivity of thionolactone to prepare random copolymers. We identified and prepared the 7-phenyloxepane-2-thione (POT) thionolactone that led to statistical copolymers with styrene and acrylate derivatives that were efficiently degraded under accelerated conditions (KOH in THF/MeOH, TBD in THF, or mCPBA in THF), confirming the theoretical approach. The compatibility with RAFT polymerization as well as the homopolymerization behavior of POT was established. This theoretical approach paves the way for the in-silico design of new efficient thionolactones for rROP.

(P,C)-cyclometalated complexes derived from naphthyl phosphines: versatile and powerful tools in organometallic chemistry.

The chemistry of (P,C)-cyclometalated complexes derived from naphthyl phosphines [Np(P,C)M] is presented and analysed in this review. The three main synthetic approaches, namely P-chelation assisted C-H activation, oxidative addition and transmetalation, are described and compared. If a naphthyl framework inherently predisposes a phosphorus atom and transition metal to interact, a rigid metallacycle may induce some strain and distortion, as apparent from the survey of the single-crystal X-ray diffraction structures deposited in the Cambridge Structural Database (77 entries with metals from groups 7 to 11). Generally, the Np(P,C)-cyclometalation imparts high thermal and chemical robustness to the complexes, and a variety of stoichiometric reactions have been reported. In most cases, the metalacyclic structure is retained, but protodecyclometalation and ring-expansion have been sparingly observed. [Np(P,C)M] complexes have also proved to be competent and actually competitive catalysts in several transformations, and they act as key intermediates in some others. In addition, interesting phosphorescence properties have been occasionally pointed out.

Base-Triggered Oxidative Addition to Gold.

The coordination of secondary phosphine oxides (SPO) was shown to efficiently promote the activation of C(sp2 )-I bonds by gold, as long as a base is added (NEt3 , K2 CO3 ). These transformations stand as a new type of chelation-assisted oxidative addition to gold. The role of the base and the influence of the electronic properties of the P-ligand were analyzed computationally. Accordingly, the oxidative addition was found to be dominated by Au→(Ar-I) backdonation. In this case, gold behaves similarly to palladium, suggesting that the inverse electron flow reported previously (with prevailing (Ar-I)→Au donation, resulting in faster reactions of electron-enriched substrates) is a specific feature of electron-deficient cationic gold(I) complexes. The reaction gives straightforward access to (P=O,C)-cyclometallated Au(III) complexes. The possibility to chemically derivatize the SPO moiety at Au(III) was substantiated by protonation and silylation reactions.

pH Effect on Particle Aggregation of Vanillin End-Capped Polylactides Bearing a Hydrophilic Group Connected by a Cyclic Acetal Moiety.

To enhance the pH-responsiveness of poly(lactic acid) (PLA) particles, desired vanillin acetal-based initiators were synthesized and functional PLA was initiated at the chain end. PLLA-V6-OEG3 particles were prepared using polymers with various Mn values of 2400-4800 g/mol. PLLA-V6-OEG3 was appropriated to achieve a pH-responsive behavior under physiological conditions within 3 min via the six-membered ring diol-ketone acetal. Moreover, it was found that the polymer chain length (Mn) influenced the aggregation rate. TiO2 was selected as the blending agent to improve the aggregation rate. The PLLA-V6-OEG3 blended with TiO2 was found to accelerate the aggregation rate compared with that without TiO2, and the best ratio of polymer/TiO2 was 1:1. To study the effect of the chain end for stereocomplex polylactide (SC-PLA) particles, PLLA-V6-OEG4 and PDLA-V6-OEG4 were successfully synthesized. The obtained results of SC-PLA particle aggregation implied that the types of chain end and the molecular weight of polymer could influence the aggregation rate. The SC-V6-OEG4 blended with TiO2 could not make our target to aggregate under physiological conditions within 3 min. This study motivated us to control the particle aggregation rate under physiological conditions for applying as a target drug carrier which is significantly influenced by not only the molecular weight but also the hydrophilicity of the chain-end as well as the number of acetal bonds.

Crystal structure of a dicationic PdII dimer containing a 2-[(diisopropylphosphanyl)methyl]quinoline-8-thiolate pincer ligand.

A dicationic PdII dimer, bis{2-[(diisopropylphosphanyl)methyl]quinoline-8-thiolato}palladium(II) bis(hexafluoridoantimonate) dichloromethane monosolvate, [Pd2(C32H42N2P2S2)](SbF6)2·CH2Cl2, containing a 2-[(diisopropylphos-phanyl)methyl]quinoline-8-thiolate pincer ligand, was isolated and its crystal structure determined. The title compound crystallizes in the ortho-rhom-bic space group Pbca. A dimeric structure is formed by bridging coordination of the S atoms. The geometry of the butterfly-shaped Pd2S2 core is bent, with a hinge angle of 108.0 (1)° and a short Pd⋯Pd distance of 2.8425 (7) Å. These values are the lowest measured compared to ten dicationic dimers with a Pd2S2 core featuring sulfur atoms embedded in a chelating ligand. One of the two hexa-fluorido-anti-monate anions is disordered over two sets of positions with site-occupancy factors of 0.711 (5) and 0.289 (5). The crystal structure is stabilized by many C-H⋯F and C-H⋯π inter-actions, forming a supra-molecular network.

Metal-ligand-Lewis acid multi-cooperative catalysis: a step forward in the Conia-ene reaction.

An original multi-cooperative catalytic approach was developed by combining metal-ligand cooperation and Lewis acid activation. The [(SCS)Pd]2 complex featuring a non-innocent indenediide-based ligand was found to be a very efficient and versatile catalyst for the Conia-ene reaction, when associated with Mg(OTf)2. The reaction operates at low catalytic loadings under mild conditions with HFIP as a co-solvent. It works with a variety of substrates, including those bearing internal alkynes. It displays complete 5-exo vs. 6-endo regio-selectivity. In addition, except for the highly congested t Bu-substituent, the reaction occurs with high Z vs. E stereo-selectivity, making it synthetically useful and complementary to known catalysts.

Palladium pincer complexes featuring an unsymmetrical SCN indene-based ligand with a hemilabile pyridine sidearm.

A new unsymmetrical indene-based pro-ligand featuring thiophosphinoyle and methylpyridine sidearms 2 was prepared. Coordination and cyclometalation in the presence of [PdCl2(PhCN)2] and PS-DIEA afforded three well-defined 2-indenyl SCN pincer complexes 3a-c. The lability of the pyridine moiety has been evidenced upon treatment with triphenylphosphine and 2,6-dimethylphenylisocyanide. In addition, reversible C-Pd bond cleavage has been demonstrated under Brønsted acid/base conditions. The indenediide SCN pincer complex 4 was prepared by deprotonation of 3a in the presence of triphenylphosphine. Preliminary catalytic tests on the cycloisomerization of 4-pentynoic acid have underlined the impact of the pyridine sidearm on the catalytic activity.

A case study of proton shuttling in palladium catalysis.

The mechanism of alkynoic acid cycloisomerization with SCS indenediide Pd pincer complexes has been investigated experimentally and computationally. These studies confirmed the cooperation between the Pd center and the backbone of the pincer ligand, and revealed the involvement of a second molecule of substrate. It acts as a proton shuttle in the activation of the acid, it directs the nucleophilic attack of the carboxylic acid on the π-coordinated alkyne and it relays the protonolysis of the resulting vinyl Pd species. A variety of H-bond donors have been evaluated as external additives, and polyols featuring proximal hydroxyl groups, in particular catechol derivatives, led to significant catalytic enhancement. The impact of 4-nitrocatechol and 1,2,3-benzenetriol is particularly striking on challenging substrates such as internal 4- and 5-alkynoic acids. Endo/exo selectivities up to 7.3/1 and 60-fold increase in reactivity were achieved.

O-Carboxyanhydrides: Useful Tools for the Preparation of Well-Defined Functionalized Polyesters.

Over the last ten years, O-carboxyanhydrides (OCA) have attracted increasing attention as ring-opening polymerization (ROP) monomers. They are readily available from α-hydroxyacids and are significantly more reactive than 1,4-dioxane-2,5-diones. Thus, softer catalysts and milder reaction conditions can be used, allowing for a better control of the polymerization. Most attractive are the functionalized OCA that enable the introduction of functional groups along the polyester backbone and thereby vary and finely tune their physicochemical properties. In this viewpoint, the achievements made over the last years are critically overviewed. Particular attention is paid to the different catalytic approaches that have been reported for the ROP of these heterocycles and to the comparison with lactide ROP. In addition, the most representative examples of functionalized polyesters and polymer conjugates prepared from OCA are discussed.

Bare histidine-serine models: implication and impact of hydrogen bonding on nucleophilicity.

A new family of 2-hydroxyalk(en/yn)ylimidazoles has been evaluated as serine-histidine bare dyad models for the ring-opening reaction of L-lacOCA, a cyclic O-carboxyanhydride. These models were selected to unravel the implication of intramolecular hydrogen bonding and to substantiate its influence on the nucleophilicity of the alcohol moiety, as it is suspected to occur in enzyme active sites. Although designed to exclusively facilitate the preliminary step of proton transfer during the studied ring-opening reaction, these minimalistic models depicted a measureable increase in reactivity relative to the isolated fragments. A couple of reliable experimental and theoretical methods have been developed to readily monitor the strength of the intramolecular hydrogen bond in dilute solution. Results show that the folded conformers are the most nucleophilic species because of the intramolecular hydrogen bond.

Walking metals in d8···d8 hetero-bimetallic complexes: an original dynamic phenomenon.

In the course of our investigations on polymetallic complexes derived from 1,3-bis(thiophosphinoyl)indene (Ind(Ph(2)P=S)(2)), we observed original fluxional behavior and report herein a joint experimental/computational study of this dynamic process. Starting from the indenylidene chloropalladate species [Pd{Ind(Ph(2) P=S)(2)}Cl](-) (1), the new Pd(II)···Rh(I) hetero-bimetallic pincer complex [PdCl{Ind(Ph(2) P=S)(2)}Rh(nbd)] (2; nbd=2,5-norbornadiene) was prepared. X-ray crystallography and DFT calculations substantiate the presence of a d(8)···d(8) interaction. According to multinuclear variable-temperature NMR spectroscopic experiments, the pendant {Rh(nbd)} fragment of 2 readily shifts in solution at room temperature between the two edges of the SCS tridentate ligand. To assess the role of the pincer-based polymetallic structure on this fluxional behavior, the related monometallic Rh complex [Rh{IndH(Ph(2) P=S)(2)}(nbd)] (3) was prepared. No evidence for a metal shift was observed in that case, even at high temperature, thus indicating that inplane pincer coordination to the Pd center plays a crucial role. The previously described Pd(II)···Ir(I) bimetallic complex 4 exhibited fluxional behavior in solution, but with a significantly higher activation barrier than 2. This finding demonstrates the generality of this metal-shift process and the strong influence of the involved metal centers on the associated activation barrier. DFT calculations were performed to shed light onto the mechanism of such metal-shift processes and to identify the factors that influence the associated activation barriers. Significantly different pathways were found for bimetallic complexes 2 and 4 on one hand and the monometallic complex 3 on the other hand. The corresponding activation barriers predicted computationally are in very good agreement with the experimental observations.

Original palladium pincer complexes deriving from 1,3-bis(thiophosphinoyl)indene proligands: C(sp3)-H versus C(sp2)-H bond activation.

A series of original 2-indenylidene palladium pincer complexes {PdL[Ind(Ph(2)P==S)(2)]} (L = HNCy(2), PPh(3), Cl(-)) have been prepared by double C-H activation of a 1,3-bis(thiophosphinoyl)indene proligand. Crystallographic analyses and DFT calculations indicate that the bonding situation of the {Pd[Ind(Ph(2)P==S)(2)]} fragment is essentially governed by the conjugated and rigid nature of the dianionic pincer ligand, the nature of the coligand having little influence. The formation of the 2-indenylidene complexes involves either a 2-indenyl pincer or a four-membered cyclometalated complex as an intermediate, suggesting that C(sp(2))-H or C(sp(3))-H bond activation takes place. However, deuterium labelling experiences show that in all cases, C(sp(3))-H bond activation occurs followed eventually by a Pd/H exchange. Nevertheless, evidence for direct C(sp(2))-H bond activation under mild conditions is obtained when a methyl group is introduced at the indene proligand to prevent C(sp(3))-H bond activation. The ensuing dissymmetrical 2-indenyl palladium pincer complex has been fully characterized.

Organo-catalyzed ring opening polymerization of a 1,4-dioxane-2,5-dione deriving from glutamic acid.

The (3S)-[(benzyloxycarbonyl)ethyl]-1,4-dioxan-2,5-dione (BED) was prepared in four steps starting from glutamic acid and bromoacetyl bromide. According to X-ray diffraction analysis, the pendant functional group is located in equatorial position and points away from the six-membered ring. The organo-catalyzed ring-opening polymerization of BED was promoted with 4-dimethylaminopyridine (DMAP) and the combination of thiourea TU(Cy) and (-)-sparteine. PolyBED samples of number-average molar mass M(n) up to 36000 and narrow polydispersity (M(w)/M(n) < 1.25) were thereby prepared in a controlled manner under mild conditions (dichloromethane solution, 30 degrees C), as substantiated by size-exclusion chromatography, matrix-assisted laser desorption ionization time-of-flight-mass spectrometry (MALDI-TOF-MS) and nuclear magnetic resonance (NMR) spectroscopy. The pendant functional group does not interfere with the polymerization and BED was even found to be slightly more reactive than lactide. Despite the strongly dissymmetric substitution pattern of the 1,4-dioxan-2,5-dione core, the ensuing polyBED polymers present a random distribution of glycolic-[(benzyloxycarbonyl)ethyl]glycolic (gly glu) units, as supported by a (1)H-(13)C HMBC 2D NMR experiment. The preparation of 1:1 adducts with n-pentanol confirmed that ring-opening of BED occurs almost indifferently on either of the endocyclic ester groups. Poly(alpha-hydroxyacids) featuring pendant carboxylic acids were finally obtained by acetylation of the terminal OH groups followed by hydrogenolysis.

Ring-opening polymerization of ε-caprolactone catalyzed by sulfonic acids: computational evidence for bifunctional activation.

The mechanism of ring-opening of ε-caprolactone by methanol catalyzed by trifluoromethane and methane sulfonic acids has been studied computationally at the DFT level of theory. For both elementary steps, the sulfonic acid was predicted to behave as a bifunctional catalyst. The nucleophilic addition proceeds via activation of both the monomer and the alcohol. The ring-opening involves the cleavage of the endo C-O bond of the tetrahedral intermediate with concomitant proton transfer. In both cases, the sulfonic acid acts as a proton shuttle via its acidic hydrogen atom and basic oxygen atoms. The computed activation barriers are consistent with the relatively fast polymerizations observed experimentally at room temperature with both catalysts.

Lipase-catalyzed ring-opening polymerization of the O-carboxylic anhydride derived from lactic acid.

Both lipase PS and Novozym 435 promote the ring-opening polymerization of lacOCA, the O-carboxylic anhydride derived from lactic acid. Accordingly, PLA of relatively high molecular weights (M(n) up to 38400 g/mol) and low polydispersities (M(w)/M(n) < 1.4) are obtained in high yields within a few hours at 80 degrees C. Slight preference for l-lacOCA over d-lacOCA is observed, and with Novozym 435, the molecular weight of the obtained PLA can be controlled by varying the lipase loading.

2-Indenylidene pincer complexes of zirconium and palladium.

[IndH(2)(Ph(2)P=X)(2)] derivatives (1, X = NMes; 4, X = S) react with [Zr(NMe(2))(4)] and [PdCl(2)(cod)] to afford the complexes {[Ind(Ph(2)PNMes)(2)]Zr(NMe(2))(2)} (3), {[Ind(Ph(2)PS)(2)]Zr(NMe(2))(2)} (5), and {[Ind(Ph(2)PS)(2)]Pd(HNc-Hex(2))} (7). The ability of the phosphazene and thiophosphinoyl side arms to support the coordination of the indenyl ring as 2-indenylidene was evidenced by NMR spectroscopy and X-ray diffraction studies. Analysis of the bonding situation by density functional theory calculations revealed a strong sigma interaction but a negligible (if any) pi interaction between C2 and the metal.

(1-Naphthyl)(trifluoromethyl) O-carboxy anhydride as a chiral derivatizing agent: eclipsed conformation enforced by hydrogen bonding.

The preparation of the (1-naphthyl)(trifluoromethyl) O-carboxy-anhydride 1 and its use as a chiral derivatizing agent with several alpha-chiral primary amines are reported. The very large Delta delta(RS) values observed in (1)H NMR have been correlated with a marked preference of the corresponding alpha-hydroxy-amides for the eclipsed conformation. In comparison, the related O-methylated amides are shown to adopt staggered conformations, which substantiates the critical role of intramolecular hydrogen bonding in maximizing the anisotropic effect.

Monomer versus alcohol activation in the 4-dimethylaminopyridine-catalyzed ring-opening polymerization of lactide and lactic O-carboxylic anhydride.

Model reactions for the 4-dimethylaminopyridine (DMAP)-catalyzed ring-opening polymerization of lactide and the corresponding lactic O-carboxylic anhydride (lacOCA) have been studied computationally at the B3LYP/6-31G(d) level of theory. The solvent effect of dichloromethane was taken into account through PCM/SCRF single-point calculations at the B3LYP/6-31G(d) level of theory. In marked contrast with that predicted for the reaction of alcohols with acetic anhydride, the mechanism in which nucleophilic activation of the monomer involving acylpyridinium intermediates was found to be energetically less favorable than the base activation of the alcohol through hydrogen bonding. The concerted pathway for the ring-opening of lactide and lacOCA was shown to compete with the traditional stepwise mechanism involving tetrahedral intermediates. Furthermore, DMAP is proposed to act as a bifunctional catalyst through its basic nitrogen center and an acidic ortho-hydrogen atom.

Functionalized polyesters from organocatalyzed ROP of gluOCA, the O-carboxyanhydride derived from glutamic acid.

Well-controlled poly(alpha-hydroxyacids) featuring pendant carboxylic acid groups were prepared under mild conditions via DMAP-catalyzed ROP of the O-carboxyanhydrides derived from glutamic and lactic acids.