Copolyesters of ε-caprolactone and l-lactide catalyzed by a tetrabutylammonium phthalimide-N-oxyl organocatalyst

Aliphatic polyesters are biocompatible materials that can be used in biomedical applications. We report here the use of tetrabutylammonium phthalimide-N-oxyl catalyst (TBAPINO), as a thermally stable organocatalyst for the ring-opening polymerization (ROP) of cyclic esters under mild conditions. In the solution ROP of ε-caprolactone (ε-CL), quantitative conversion and M_n of ∼20 000 g mol⁻¹ are achieved in a wide temperature range from −15 to 60 °C. Under bulk condition, the conversion of ε-CL reaches over 85% at 120 °C within 2 h. The living ROP character of l-lactide (l-LA) catalyzed over TBAPINO is proved by multiple additions of monomer in the bulk polymerization. The catalyst shows comparable selectivity towards the ring-opening polymerization of l-LA and ε-CL. Their copolymerization over TBAPINO is carried out in one-pot bulk condition in terms of the reaction time, monomer feed ratio, and sequence of addition. The colorless poly(ε-caprolactone-co-lactide) (PCLA) is obtained with considerable conversion of both monomers with the M_n over 22 000 g mol⁻¹.

By utilizing tetrabutylammonium phthalimide-N-oxyl organocatalyst, copolymer PCLA with M_n over 20 000 g mol⁻¹ was synthesized by sequential ring-opening polymerization of ε-caprolactone and l-lactide under bulk conditions.     

Synthesis of new polyesters by acyclic diene metathesis polymerization of bio-based α,ω-dienes prepared from eugenol and castor oil (undecenoate)

Synthesis of new polyesters by acyclic diene metathesis (ADMET) polymerization of α,ω-diene, 4-allyl-2-methoxyphenyl 10-undecenoate (M1), prepared from bio-renewable eugenol and castor oil (undecenoate), have been demonstrated. Ruthenium-carbene (called second generation Grubbs) catalyst afforded polymers with unimodal molecular weight distributions (M_n = 12 700, M_w/M_n = 1.85). The polymerization in the presence of a triarm cross-linker, 5-formylbenzene-1,2,3-triyl tris(undec-10-enoate), also afforded polymers with certain uniform network structures.

Synthesis of high molecular weight polymers by acyclic diene metathesis (ADMET) polymerization of α,ω-diene prepared from bio-renewable eugenol and castor oil (undecenoate) has been demonstrated.     

Halide-free neodymium phosphate based catalyst for highly cis-1,4 selective polymerization of dienes

Neodymium-based Ziegler–Natta type catalytic systems are known to produce polydienes with high cis-1,4 content. It is generally believed that in Ziegler–Natta catalytic systems, a halide or pseudohalide, whether in the catalyst itself or a separate source, is required for the success of the polymerization. In this work, we have synthesized an unusual halide-free neodymium diethyl phosphate catalyst for diene polymerization. This neodymium complex combined with triisobutylaluminum (TIBA), formed a binary catalytic system and was used to polymerize β-myrcene. The catalytic system displays high stereospecificity and produces poly(β-myrcene) with 96% cis-1,4 content and a relatively narrow molecular weight distribution (M_w/M_n = 1.80). Also, kinetic studies indicated the catalytic system gives a pseudo-living polymerization. The block copolymer poly(β-myrcene)-b-poly(isoprene) was successfully synthesized by sequential monomer addition, further demonstrating the pseudo-living nature of polymerization with the neodymium diethyl phosphate catalyst.

[Nd(μ-DEP)₃]_x/TIBA stereospecifically polymerizes myrcene in a pseudo-living Ziegler–Natta like catalytic system despite the absence of a halide.     

Binary catalytic system for homo- and block copolymerization of ε-caprolactone with δ-valerolactone

The combined interaction of 2,3,6,7-tetrahydro-5H-thiazolo[3,2-a] pyrimidine (ITU) as the organocatalytic nucleophile with YCl₃ as Lewis acid cocatalyst, generating ITU/YCl₃, was employed for homo- and copolymerization of ε-caprolactone (CL) with δ-valerolactone (VL). Poly(caprolactone) (PCL) and poly(caprolactone)–poly(ethylene glycol)–poly(caprolactone) (PCL–PEG–PCL) triblock copolymer and poly(valerolactone)–poly(caprolactone)–poly(ethylene glycol)–poly(caprolactone)–poly(valerolactone) (PVL–PCL–PEG–PCL–PVL) pentablock copolymer were successfully prepared by ring-opening polymerization (ROP) of CL employing ITU/YCl₃ as catalyst in the presence of benzyl alcohol (BnOH) or poly(ethylene glycol) (PEG) as initiator, respectively. The reaction was systematically optimized, and the architecture, molecular weight and thermal properties of the polymers were characterized by NMR, FTIR, SEC and DSC analyses. Finally, a plausible polymerization mechanism was proposed.

The combined interaction of 2,3,6,7-tetrahydro-5H-thiazolo[3,2-a] pyrimidine (ITU) as the organocatalytic nucleophile with YCl₃ as Lewis acid cocatalyst, generating ITU/YCl₃, was employed for homo- and copolymerization of CL with VL.     

Synthesis,characterization and chemical degradation of poly(ester-triazole)s derived from d-galactose

α-Azide-ω-alkynyl ester monomers were designed and synthesized in order to obtain hydrolytically degradable polymers. The monomers were prepared from d-galactose, as a renewable resource. Environmentally benign azido–alkyne cycloaddition polymerizations were conducted to afford poly(ester-triazole)s, with complete atom economy. Although polymer formation prevailed under optimized polymerization conditions, variable proportions of cyclic oligomer byproducts were detected. The Cu-catalyzed click polymerization led regioselectively to 1,4-disubstituted triazole linkages, while the thermal, metal-free polymerization produced a random distribution of 1,4- and 1,5-disubstituted triazoles in the polymer backbone. The poly(ester-triazole)s exhibited high molecular weights (M_w in the range 35–85 kDa). They were soluble in organic solvents but highly insoluble in water, thus removal of the Cu(i) catalyst was simplified. The polymers were stable up to 300 °C, and had T_g values in the range 90–100 °C. The materials were hydrolysed under either basic or strong acid conditions, and the degradation products have been characterized.

Carbohydrate-derived poly(ester-triazoles), soluble in organic solvents and degradable in aqueous media, have been synthesized by CuAAC or thermal polymerization.     

Glycol-functionalized ionic liquids for high-temperature enzymatic ring-opening polymerization

Enzymatic ring-opening polymerization (ROP) is a benign method for preparing polyesters, such as polylactides and other polylactones. These reactions are typically carried out at relatively high temperatures (60–130 °C), however, there is a deficiency of enzyme-compatible solvents for such thermally-demanding biocatalytic processes. In this study, we have prepared a series of short-chained glycol-grafted ionic liquids (ILs) based on a phosphonium, imidazolium, pyridinium, ammonium, or piperidinium cationic headgroup. Most of these glycol-grafted ILs exhibit relatively low dynamic viscosities (33–123 mPa s at 30 °C), coupled with excellent short-term thermal stabilities with decomposition temperatures (T_dcp) in the 318–403 °C range. Significantly, the long-term thermal stability under conditions matching those for enzymatic ROP synthesis (130 °C for 7 days) is excellent for several of these task-specific ILs. Using Novozym 435-catalyzed ROP, these ILs are demonstrated to be viable solvents for the enzymatic production of reasonable yields (30–48%) of high molecular mass (M_w ∼20 kDa) poly(l-lactide) and poly(ε-caprolactone) compared to solventless conditions (12–14 kDa).

New glycol-functionalized ionic liquids exhibit high thermal stability and are lipase-compatible, leading to a high molecular weight of polyester in the enzymatic ring-opening polymerization reaction.     

Phosphorus pentoxide as a cost-effective,metal-free catalyst for ring opening polymerization of ε-caprolactone

The ring-opening polymerization (ROP) of ε-caprolactone (ε-CL) using phosphorus pentoxide (P₂O₅) as a metal-free catalyst and isopropanol (iPrOH) as initiator resulted in the preparation of poly(ε-caprolactone) with narrow weight distribution. NMR spectroscopy analyses of the prepared PCL indicated the presence of the initiator residue at the end of the polymer chain, implying the occurrence of the ε-CL-catalysis ROP through a monomer activation mechanism. Kinetic experiments confirmed the controlled/living nature of ε-CL ring-opening catalyzed by phosphorus pentoxide. The commercial availability of phosphorus pentoxide and its easy-handling provide additional opportunities for polymer synthesis and nanocomposite manufacturing.

The ring-opening polymerization (ROP) of ε-caprolactone (ε-CL) using phosphorus pentoxide (P₂O₅) as a metal-free catalyst and isopropanol (iPrOH) as initiator resulted in the preparation of poly(ε-caprolactone) with narrow weight distribution.     

Pressure-assisted solvent- and catalyst-free production of well-defined poly(1-vinyl-2-pyrrolidone) for biomedical applications

In this work, we developed a fast, highly efficient, and environmentally friendly catalytic system for classical free-radical polymerization (FRP) utilizing a high-pressure (HP) approach. The application of HP for thermally-induced, bulk FRP of 1-vinyl-2-pyrrolidone (VP) allowed to eliminate the current limitation of ambient-pressure polymerization of ‘less-activated’ monomer (LAM), characterized by the lack of temporal control yielding polymers of unacceptably large disperisites and poor result reproducibility. By a simple manipulation of thermodynamic conditions (p = 125–500 MPa, T = 323–333 K) and reaction composition (two-component system: monomer and low content of thermoinitiator) well-defined poly(1-vinyl-2-pyrrolidone)s (PVP) in a wide range of molecular weights and low/moderate dispersities (M_n = 16.2–280.5 kg mol⁻¹, Đ = 1.27–1.45) have been produced. We have found that HP can act as an ‘external’ controlling factor that warrants the first-order polymerization kinetics for classical FRP, something that was possible so far only for reversible deactivation radical polymerization (RDRP) systems. Importantly, our synthetic strategy adopted for VP FRP enabled us to obtain polymers of very high M_n in a very short time-frame (0.5 h). It has also been confirmed that VP bulk polymerization yields polymers with significantly lower glass transition temperatures (T_g) and different solubility properties in comparison to macromolecules obtained during the solvent-assisted reaction.

High-pressure classical free-radical polymerization allowed to eliminate the current limitation of the ambient-pressure synthesis of 1-vinyl-2-pyrrolidone and production of well-defined polymers.     

One-pot synthesis of end-functionalised soluble star-shaped polymers by living ring-opening metathesis polymerisation using a molybdenum-alkylidene catalyst

Precise synthesis of soluble star-shaped polymers has been achieved by adopting living ring-opening metathesis polymerisation (ROMP) using a molybdenum-alkylidene catalyst with sequential addition of norbornene and cross-linking agent; the method provides efficient one-pot synthesis of high molecular weight end-functionalised star-shaped polymers (M_n = >1.37 × 10⁵) with more arms (branching) with rather low PDI values (M_w/M_n = 1.17–1.37) under the optimised conditions.

Precise synthesis of star-shaped polymers has been achieved by living ROMP using a molybdenum catalyst with sequential addition of norbornene and cross-linker.     

Bismuth subsalicylate,a low-toxicity catalyst for the ring-opening polymerization (ROP) of l-lactide (l-LA) with aliphatic diol initiators: synthesis,characterization, and mechanism of initiation

The ring-opening polymerization (ROP) of l-lactide (l-LA) was induced by the catalytic action of bismuth subsalicylate (BiSS) using linear aliphatic diols [HO(CH₂)_nOH, where n = 2, 3, 4, 5, 6, and 8] as initiators and chain transfer agents. The theoretical and experimental degree of polymerization (DP) in all samples of α,ω-hydroxy telechelic poly(l-lactide) (HOPLLAOH) had a good agreement in all samples, an effect attributed to the interaction of BiSS with HO(CH₂)_nOH inducing a transfer reaction. HOPLLAOH was synthesized and characterized by a range of analytical techniques, confirming the insertion of methylene groups from the initiator into the main chain of the polyester. The glass-transition temperature (T_g) of HOPLLAOH was found to be proportional to the number of methylene groups present in the diol. Various parameters regarding the ROP of l-LA were studied, such as temperature, time of reaction, amount of catalyst, and the nature of the diols. A kinetic study of the reaction allowed the determination of the rate constants (k) and activation energy (E_a). A mechanism of initiation is proposed based on a computational study using density functional theory (DFT), evidencing the role of the alkyl diol as an initiator, producing an alkoxide (Bi–OROH). This species then acts as a nucleophile, attacking the carbonyl group, inducing its insertion, and ultimately completing the ring-opening of l-LA.

Bismuth subsalicylate (BiSS) acted as a catalyst in the ring-opening polymerization of l-lactide (l-LA) in the presence of alkyl diols as initiators.     

β-Myrcene/isobornyl methacrylate SG1 nitroxide-mediated controlled radical polymerization: synthesis and characterization of gradient,diblock and triblock copolymers

β-Myrcene (My), a natural 1,3-diene, and isobornyl methacrylate (IBOMA), from partially bio-based raw materials sources, were copolymerized by nitroxide-mediated polymerization (NMP) in bulk using the SG1-based BlocBuilder™ alkoxyamine functionalized with an N-succinimidyl ester group, NHS-BlocBuilder, at T = 100 °C with initial IBOMA molar feed compositions f_IBOMA,0 = 0.10–0.90. Copolymer reactivity ratios were r_My = 1.90–2.16 and r_IBOMA = 0.02–0.07 using Fineman–Ross, Kelen–Tudos and non-linear least-squares fitting to the Mayo–Lewis terminal model and indicated the possibility of gradient My/IBOMA copolymers. A linear increase in molecular weight versus conversion and a low dispersity (Đ ≤ 1.41) were exhibited by My/IBOMA copolymerization with f_IBOMA,0 ≤ 0.80. My-rich and IBOMA-rich copolymers were shown to have a high degree of chain-end fidelity by performing subsequent chain-extensions with IBOMA and/or My, and by ³¹P NMR analysis. The preparation by NMP of My/IBOMA thermoplastic elastomers (TPEs), mostly bio-sourced, was then attempted. IBOMA-My-IBOMA triblock copolymers containing a minor fraction of My or styrene (S) units in the outer hard segments (M_n = 51–95 kg mol⁻¹, Đ = 1.91–2.23 and F_IBOMA = 0.28–0.36) were synthesized using SG1-terminated poly(ethylene-stat-butylene) dialkoxyamine. The micro-phase separation was suggested by the detection of two distinct T_gs at about −60 °C and +180 °C and confirmed by atomic force microscopy (AFM). A plastic stress–strain behavior (stress at break σ_B = 3.90 ± 0.22 MPa, elongation at break ε_B = 490 ± 31%) associated to an upper service temperature of about 140 °C were also highlighted for these triblock polymers.

β-Myrcene (My), a natural 1,3-diene, and isobornyl methacrylate (IBOMA), from partially bio-based raw materials sources, were copolymerized by nitroxide-mediated polymerization (NMP) in bulk.     

Synthesis of copolyesters based on substituted and non-substituted lactones towards the control of their crystallinity and their potential effect on hydrolytic degradation in the design of soft medical devices

A series of copolymers based on ε-caprolactone (ε-CL) in combination with lactone monomers substituted with alkyl groups (4 and 6 carbon atoms), specifically δ-decalactone (δ-DL), ε-decalactone (ε-DL) and δ-dodecalactone (δ-DD), as well as a copolymer using two substituted lactone monomers with alkyl groups (ε-DL and δ-DD) were synthesized in different molar ratios. The objective of the synthesis of these copolymers was to evaluate the effects of branching in the polymer backbone on the crystallinity and the thermal properties of the synthesized materials. All copolymers were obtained via ring-opening polymerization with high conversion values for both comonomers using neodymium isopropoxide (Nd(i-Pr)₃) as the initiator, and their compositions were determined by ¹H NMR and ¹³C NMR. The molar masses (M_n and M_w) and distributions were obtained by GPC measurements. Such measurements showed that a majority of the copolymers exhibited dispersities (Ɖ) in the range of 1.2–1.6 and M_n in the range of 15–40 kDa. First- and second-order transitions such as melting, crystallization and glass transition, as well as the crystallization degree (melting enthalpy), were determined by DSC analysis. Copolymers based on ε-CL developed interesting behaviors, wherein the copolymers with higher percentages of this monomer exhibited semicrystalline behavior, while the copolymers with a higher percentage of the comonomers ε-DL, δ-DL or δ-DD showed amorphous behavior. In contrast, the copolymers synthesized using both monomers from the alkyl group-substituted lactone developed fully amorphous features, regardless of their composition. These changes in the crystalline features of the synthesized copolymers suggest that the content of short branchings on the copolymer backbone will significantly modify their rates of hydrolytic degradation and their potential use in the development of different soft medical devices.

ROP synthesis of polyesters at different molar ratios of monomers ε-caprolactone (ε-CL) in combination with alkyl substituted lactones δ-decalactone (δ-DL), ε-decalactone (ε-DL) and δ-dodecalactone (δ-DD), as well copolymers based on ε-DL and δ-DD.     

pH-responsive polymeric vesicles from branched copolymers

A new type of branched copolymer, poly(l-lactide)₂-b-poly(l-glutamic acid) (PLLA₂–PLGA), based on polypeptide PLGA is synthesized by the ring-opening polymerization (ROP) of N-carboxyanhydride of γ-benzyl-l-glutamate (BLG–NCA) with amino-terminated PLLA₂–NH₂ and subsequent deprotection. The branched copolymer is characterized by ¹H NMR, FTIR and GPC measurements. The self-assembly of the copolymers in aqueous media has been systematically discussed. A pyrene probe has been used to demonstrate the aggregated formation of PLLA₂–PLGA in solution by measuring the critical micelle concentration (cmc). The morphology and size of the micelles have further been studied by transmission electron microscopy (TEM), dynamic light scattering (DLS) and field emission scanning electron microscopy (ESEM). We demonstrated that the Rh of the vesicle is depending on solution pH and salt concentration. The vesicles show good stability with remained shapes and sizes during the lyophilizing process. These vesicles have great potential in the application of drug delivery.

A new type of branched copolymer, poly(l-lactide)₂-b-poly(l-glutamic acid), based on polypeptide PLGA is synthesized by the ring-opening polymerization of N-carboxyanhydride of γ-benzyl-l-glutamate with amino-terminated PLLA₂–NH₂ and subsequent deprotection.     

Chemical grafting of cholesterol on monomer and PDMMLA polymers,a step towards the development of new polymers for biomedical applications

Racemic α,α,β-trisubstituted β-lactones are the monomer units of poly((R,S)-3,3-dimethylmalic acid) (PDMMLA) derivatives, new biopolyesters showing great potential for biomedical applications. Using different groups during the synthesis of these β-lactones allows a tailored synthesis of PDMMLA copolymers with adjustable hydrophilic/phobic ratio. The degradation kinetics of the employed material is one of the most important criteria in the development of bioresorbable implants. The degradation time of PDMMLA derivatives can be controlled using different β-lactones of different hydrophilicity levels during the polymerization stage. Furthermore, PDMMLA has chemically available groups on its side chain allowing to graft functional groups on the polymer via covalent bonds. In this work, following a Steglich esterification protocol, the chemical grafting of cholesterol was carried out on a PDMMLA monomer derived β-lactone as well as on homopolymer PDMMLA–H, and copolymer PDMMLAH₄₀-co-Hex₆₀ (PDMMLA 40/60). Nuclear magnetic resonance (NMR) analyses of the products confirm and quantify the grafting ratio. 100% of cholesterol grafting has been realized on the homopolymer PDMMLA–H giving PDMMLA–Chol, and 10% on the copolymer PDMMLA 40/60, giving PDMMLAH₃₀-ter-Chol₁₀-ter-Hex₆₀ (PDMMLA–Chol 30/10/60) as wished. Fourier-transform infrared (FT-IR) spectra, elemental analysis on the β-lactones and thermogravimetric analyses on the polymers also confirm the chemical modification of the products.

PDMMLAs are synthetic biopolyesters synthesized from tri-substituted β-lactones with available hydroxyl groups. We grafted cholesterol on both monomer and polymers following the Steglich esterification protocol.     

Aromatic fluorocopolymers based on α-(difluoromethyl)styrene and styrene: synthesis,characterization, and thermal and surface properties

A study on the α-(difluoromethyl)styrene (DFMST) reactivity under conventional radical copolymerization conditions is presented. Although the homopolymerization of DFMST failed, its radical bulk copolymerization with styrene (ST) led to the synthesis of fluorinated aromatic polymers (FAPs). The resulting novel poly(DFMST-co-ST) copolymers were characterized by ¹H, ¹⁹F and ¹³C NMR spectroscopies that evidenced the successful incorporation of DFMST units into copolymers and enabled the assessment of their respective molar percentages (10.4–48.2 mol%). The molar masses were in the range of 1900–17 200 g mol⁻¹. The bulkier CF₂H group in the α-position induced the lower reactivity of the DFMST comonomer. ST and DFMST monomer reactivity ratios (r_DFMST = 0.0 and r_ST = 0.70 ± 0.05 at 70 °C) were determined based on linear least-square methods. These values indicate that DFMST monomer is less reactive than ST, retards the polymerization rate, and thus reduces the molar masses. Moreover, the thermal properties (T_g, T_d) of the resulting copolymers indicate that the presence of DFMST units incorporated into poly(ST) structure promotes an increase of the T_g values up to 109 °C and a slightly better thermal stability than that of poly(ST). Additionally, the thermal decomposition of poly(DFMST-co-ST) copolymer (10.4/89.6) was assessed by simultaneous thermal analysis coupled with Fourier-transform infrared spectroscopy and thermogravimetric analysis coupled with mass spectrometry showing that H₂O, CO₂, CO and styrene were released. The surface analysis was focused on the effects of the –CF₂H group at the α-position of styrene comonomers on surface free energy of the copolymer films. Water and diiodomethane contact angle (CA) measurements confirmed that these copolymers (M_n = 2300–17 200 g mol⁻¹) are not exactly the same as polystyrenes (M_n = 2100–21 600 g mol⁻¹) in the solid state. The CA hysteresis for poly(ST) (6–8°) and poly(DFMST-co-ST) copolymers (3–5°) reflected these differences even more accurately.

A study on the α-(difluoromethyl)styrene (DFMST) reactivity under conventional radical (co)polymerization conditions is presented.     

An efficient enantioselective approach to multifunctionalized γ-butyrolactone: concise synthesis of (+)-nephrosteranic acid

A short, efficient and novel approach for multifunctionalized γ-butyrolactone paraconic acids and its application to the total synthesis of (+)-nephrosteranic acid from readily available PMB (R)-glycidyl ether as a starting material are described. Key transformations include asymmetric Michael addition catalyzed by chiral diphenylprolinol silyl ether and stereoselective α-methylation.

A short, efficient and novel approach for multifunctionalized γ-butyrolactone paraconic acids and its application to the total synthesis of (+)-nephrosteranic acid from readily available PMB (R)-glycidyl ether as a starting material are described.

Bioactive natural products containing a multifunctionalized γ-butyrolactone moiety are found abundantly in nature.¹ The paraconic acids (1–10) containing multifunctionalized γ-butyrolactone were isolated from various species of lichens, fungi, moss and cultures of Penicillium sp.² These acids possess interesting biological activities such as antitumor, antibacterial, antibiotic, antifungal/antiviral and growth regulatory properties.³ The whiskey lactone 11 and cognac lactone 12 have great commercial interest because they are potential key components in the flavor of aged alcoholic beverages.⁴ Architecturally, the paraconic acid family comprises a variable length alkyl chain at the C5 position, a C4 carboxyl group and methyl or methylene substituents at the C3 position, which play an important role in the biological activities of the paraconic acids (Fig. 1).Open in a separate windowFig. 1Representative structures of γ-butyrolactone based paraconic acids and lactones.Intrigued by the unique structural features and biological activities of paraconic acids, hitherto, several total⁵ and formal⁶ synthesis of paraconic acids such as (+)-nephrosteranic acid are documented in literature. More recently, Appayee and co-workers disclosed an elegant approach for the stereodivergent synthesis of chiral paraconic acids via dynamic kinetic resolution of 3-acylsuccinimides.⁷ As part of our research program aimed at developing the asymmetric synthesis of bioactive natural molecules,⁸ we became attentive in developing a flexible and general approach for the synthesis of multifunctionalised γ-butyrolactone paraconic acids. Herein, we are reporting a short, efficient and novel general approach for the synthesis of paraconic acids and its application to the enantioselective synthesis of (+)-nephrosteranic acid 1 using organocatalyzed Michael addition reaction as key step.Our general retrosynthetic route for asymmetric synthesis of γ-butyrolactone based paraconic acids and its application to enantioselective synthesis of (+)-nephrosteranic acid 1 was envisaged via the retrosynthetic approach as displayed Scheme 1. We envisioned that the γ-butyrolactone 13 could be used as a key intermediate from which paraconic acids 1–10 including (+)-nephrosteranic acid 1 would be synthesized via methylenation or stereoselective methylation at the C3 centre. The γ-butyrolactone 13 could be achieved from protected nitro-acid derivative 14via deprotection and in situ lactonization followed by Nef reaction. The nitro-acid derivative 14 in turn could be synthesized from (R)- or (S)-diphenylprolinol silyl ether catalyzed Michael addition of CH₃NO₂ to α,β-unsaturated aldehyde intermediate obtained from the controlled DIBAL-H reduction of olefinic ester derivative 15 followed by oxidation. The α,β-unsaturated ester 15 could be obtained from protected (R)- or (S)-glycidol 16 by treatment with suitable Grignard reagents, secondary alcohol protection, primary alcohol deprotection and oxidation followed by 2C-Wittig olefination reaction. The desired stereochemistry of paraconic acids 1–10 could be achieved by simply altering the (R)- and (S)-configuration of glycidyl ether and/or by using catalyst (R)- or (S)-diphenylprolinol silyl ether during Michael addition reaction. Thus, in principle, C3, C4 and C5 chiral centres in paraconic acids could be easily manipulated and accessed by this approach.Open in a separate windowScheme 1Retrosynthetic general approach of γ-butyrolactone based some paraconic acids and lactones.As depicted in Scheme 2, the synthesis of (+)-nephrosteranic acid 1 as a representative target compound of paraconic acids was commenced from readily available PMB (R)-glycidyl ether 16a⁹ which was subjected to copper-catalyzed (CuI) regioselective ring opening with the Grignard reagent, derived from decyl bromide to furnish the alcohol derivative 17 in 85% yield. The alcohol derivative 17 on silyl protection with tert-butyldiphenylsilyl chloride (TBDPSCl) and imidazole with DMAP in catalytic amount afforded the silyl ether derivative 18 in 95% yield which on PMB ether cleavage using CAN (ceric ammonium nitrate) at 0 °C to rt furnished the terminal alcohol derivative 19 in 91% yield. The alcohol derivative 19 on oxidation under Swern conditions¹⁰ followed by treatment with (ethoxycarbonylmethylene)triphenylphosphorane in THF afforded the trans-olefinic ester derivative 20 in 92% yield. Our next goal was to carry out the synthesis of multifunctionalized γ-butyrolactone. Towards this end, trans-olefinic ester 20 on controlled reduction with DIBAL-H at −78 °C to α,β-unsaturated aldehyde intermediate and successive conjugate Michael addition¹¹ of nitromethane in the presence of (S)-diphenylprolinol silyl ether (10 mol%) afforded the nitroaldehyde adduct which on subsequent oxidation with oxone¹² furnished the nitro-acid derivative 21 in excellent yield.Open in a separate windowScheme 2Reagents and conditions: (a) C₁₀H₂₁MgBr, CuI, dry THF, −30 °C, 6 h, 85%; (b) TBDPSCl, imidazole, cat. DMAP, CH₂Cl₂, 0 °C-rt, 8 h, 95%; (c) CAN, CH₃CN : H₂O (4 : 1, v/v), 0 °C-rt, 2 h, 91%; (d) (i) (COCl)₂, DMSO, Et₃N, CH₂Cl₂, −78 °C to −60 °C, 3 h; (ii) PPh₃CHCOOEt, THF, rt, 20 h, 92% (over two steps); (e) (i) DIBAL-H, CH₂Cl₂, −78 °C, 1 h; (ii) (S)-diphenylprolinol silyl ether (10 mol%), CH₃NO₂, benzoic acid, MeOH, rt, 16 h; (iii) oxone, DMF, rt, 12 h, 84% (over 3 steps); (f) TBAF, dry THF, rt, 2 h, 95%; (g) NaNO₂, acetic acid, DMSO, rt, 24 h, 94%; (h) NaHMDS, CH₃I, dry THF, −78 °C, 3 h, 93%.Further to demonstrate the stereochemistry during the conjugate Michael addition of nitromethane to α,β-unsaturated aldehyde intermediate we carried out the reaction with racemic catalyst (±)-diphenylprolinol silyl ether to get the nitro-aldehyde adduct which on subsequent oxidation with oxone afforded the anti-/syn-nitro acid diastereomers (dr, 1 : 1) in 83% combined yield. However, on the other hand, in presence of (S)-diphenylprolinol silyl ether catalyst the conjugate addition of nitromethane on α,β-unsaturated aldehyde intermediate obtained from 20 followed by oxidation with oxone furnished the anti-nitro acid derivative 21 as a single diastereomer¹³ in 84% yield.The anti-nitro acid derivative 21 on TPS deprotection and concomitant cyclisation with TBAF (tetra-n-butylammonium fluoride) furnished the γ-butyrolactone derivative 22 in 95% yield. The nitro-γ-butyrolactone derivative 22 was subjected to treatment with sodium nitrite and acetic acid under Nef reaction conditions¹⁴ to afford the γ-butyrolactone acid derivative 23 in 94% yield. Finally, stereoselective methylation at α-position of acid derivative 23 was carried out with methyl iodide and NaHMDS in dry THF to furnish the target compound (+)-nephrosteranic acid 1 in 93% yield ([α]²⁵_D + 27.18 (c 1.50, CHCl₃), {lit.^5s [α]²⁷_D + 27.2 (c 1.45, CHCl₃)}. The spectral and physical properties of the (+)-nephrosteranic acid 1 were in full agreement with reported values.^5a     

A more sustainable isothiocyanate synthesis by amine catalyzed sulfurization of isocyanides with elemental sulfur

Isothiocyanates (ITCs) are typically prepared using amines and highly toxic reagents such as thiophosgene, its derivatives, or CS₂. In this work, an investigation of a multicomponent reaction (MCR) using isocyanides, elemental sulfur and amines revealed that isocyanides can be converted to isothiocyanates using sulfur and catalytic amounts of amine bases, especially DBU (down to 2 mol%). This new catalytic reaction was optimized in terms of sustainability, especially considering benign solvents such as Cyrene™ or γ-butyrolactone (GBL) under moderate heating (40 °C). Purification by column chromatography was further optimized to generate less waste by maintaining high purity of the product. Thus, E-factors as low as 0.989 were achieved and the versatility of this straightforward procedure was shown by converting 20 different isocyanides under catalytic conditions, while obtaining moderate to high yields (34–95%).

Isothiocyanates were snythesized in a more sustainable manner by sulfurization of isocyanides with elemental sulfur using catalytic amounts of DBU (down to 2 mol%).     

Mechanism and effect of γ-butyrolactone solvent vapor post-annealing on the performance of a mesoporous perovskite solar cell

In this paper, γ-butyrolactone (GBL) solvent vapor post-annealing (SVPA) on CH₃NH₃PbI₃ thin films is reported, aiming to improve the complete transformation of PbI₂ and increase the grain size of the CH₃NH₃PbI₃ crystal, thus boosting the performance of mesoporous CH₃NH₃PbI₃ perovskite solar cells (PSCs). The influence of GBL SVPA on the microstructure of perovskite layers and performance of PSCs was studied. The short circuit current density (J_sc) of the devices significantly increased, yielding a high efficiency of 16.58%, which was 27.05% higher than that of thermally annealed films. A model was derived to explain the effect of GBL SVPA on PSCs. The perovskite films prepared by this method present several advantages such as complete transformation of PbI₂ to CH₃NH₃PbI₃, high crystallinity, large grain size, and fewer grain boundaries than those prepared without GBL SVPA. This improvement is beneficial for charge dissociation and transport in hybrid photovoltaic devices.

γ-Butyrolactone was used to post-anneal perovskite films and better performance of cells was achieved; a mechanism was derived.     

Reverse atom transfer radical polymerization of dimethyl itaconate initiated by a new azo initiator: AIBME

Reverse atom transfer radical polymerization (RATRP) was used to synthesize poly(dimethyl itaconate) (PDMI) using an AIBME/CuBr₂/dNbpy system. The number average molecular weight (M_n) of PDMI was as high as M_n = 15 000 g mol⁻¹, the monomer conversion rate reached up to 70%, and the dispersity remained low (Đ = 1.06–1.38). The first-order kinetics of PDMI are discussed in detail. The AIBME initiator had a higher initiation efficiency than the AIBN initiator. As the ratio of initiator (AIBME) to catalyst (CuBr₂) decreased, the M_n and Đ of PDMI decreased. At 60 °C and 80 °C, the M_n of PDMI was much higher than the theoretical number average (M_n,th), and the Đ of PDMI broadened with the conversion rate. At 100 °C, the Đ of PDMI remained low, and the M_n of PDMI was closer to the M_n,th. As the ratio of monomer (DMI) to initiator (AIBME) increased, the M_n of PDMI changed little over time. These phenomena could be explained by the influence of the initiator and catalyst on polymerization kinetics.

Low-dispersity poly(dimethyl itaconate) (PDMI) was synthesized by RATRP with a new azo initiator: AIBME.     

An efficient access to β-ketosulfones via β-sulfonylvinylamines: metal–organic framework catalysis for the direct C–S coupling of sodium sulfinates with oxime acetates

A copper-based framework Cu₂(OBA)₂(BPY) was synthesized and used as a recyclable heterogeneous catalyst for the synthesis of β-sulfonylvinylamines from sodium sulfinates and oxime acetates via direct C–S coupling reaction. The transformation was remarkably affected by the solvent, and chlorobenzene emerged as the best option. This Cu-MOF displayed higher activity than numerous conventional homogeneous and MOF-based catalysts. The catalyst was reutilized many times in the synthesis of β-sulfonylvinylamines without considerably deteriorating in catalytic efficiency. These β-sulfonylvinylamines were readily converted to the corresponding β-ketosulfones via a hydrolysis step with aqueous HCl solution. To the best of our knowledge, this direct C–S coupling reaction to achieve β-sulfonylvinylamines was not previously conducted with a heterogeneous catalyst.

Cu₂(OBA)₂(BPY) was used as catalyst for the synthesis of β-sulfonylvinylamines from sodium sulfinates and oxime acetates. These β-sulfonylvinylamines were readily converted to corresponding β-ketosulfones via a hydrolysis step.