Ring-opening Polymerization Of rac-LA Research Articles

Block Copolymer Synthesis by a Sequential Addition Strategy from the Organocatalytic Group Transfer Polymerization of Methyl Methacrylate to the Ring‐Opening Polymerization of Lactide

Sequential block copolymerization involving comonomers belonging to different classes, e.g., a vinyl-type monomer and a heterocycle, is a challenging task in macromolecular chemistry, as corresponding propagating species do not interconvert easily from one to the other by crossover reactions. Here, it is first evidenced that 1-methoxy 2-methyl 1-trimethylsilyloxypropene (MTS), i.e., a silyl ketene acetal (SKA)-containing initiator, can be used in presence of the P4 -t-Bu phosphazene organic base to control the ring-opening polymerization (ROP) of racemic lactide (rac-LA). The elementary reaction, which rapidly transforms SKA groups into propagating alkoxides, can be leveraged to directly synthesize well-defined poly(methyl methacrylate)-b-polylactide block copolymers. This is achieved using P4 -t-Bu as the single organic catalyst and MTS as the initiator for the group transfer polymerization of methyl methacrylate, followed by the ROP of rac-LA. Both polymerization methods are implemented under selective and controlled/living conditions at room temperature in THF. This sequential addition strategy further expands the scope of organic catalysis of polymerizations for macromolecular engineering of block copolymers involving propagating species of disparate reactivity.

The Effect of Symmetric and Asymmetric NHCs on the Structure and Catalytic Properties of Dialkylgallium Alkoxides in the Ring-Opening Polymerization of rac-Lactide—Linking the Structure, Activity, and Stereoselectivity

Manipulating the structure of alkylgallium alkoxides with asymmetric N-heterocyclic carbenes (NHCs) has led to the formation of essentially “on” and “off” states of catalytic gallium centers in the ring-opening polymerization (ROP) of rac-lactide (rac-LA), and has allowed to rationalize the effect of the NHC on the activity and stereoselectivity of Me2GaOR(NHC) complexes. The reactions of dimethylgallium alkoxides with asymmetric NHCs, due to differently substituted nitrogens, resulted in the formation of Me2GaOR(SI(Dipp-Mes)) (OR = OMe (1), OCH2CH2OMe (2), OCH(Me)CO2Me (3)) and Me2GaOR(SI(Me-Mes)) (OR = OMe (4), OCPh2Me (5)) complexes (SI(Dipp-Mes) = 1-(diisopropylphenyl)-3-(mesityl)-imidazolin-2-ylidene, SI(Me-Mes) = 1-(methyl)-3-(mesityl)-imidazolin-2-ylidene). The X-ray analysis of 1, 2, 4, and 5 revealed a strong effect of NHCs on their structure, manifested by the orientation of NHC with respect to Ga–CMe and Ga–O bonds, and OR alkoxide group. The latter, represented by a dihedral O–Ga–CNHC–N angle, have allowed to define the cavity required for the interaction of lactide with gallium and alkoxide groups, and subsequent insertion of lactide into the Ga–Oalkoxide bond. Despite small differences between the cavities of 1 and Me2GaOMe(SIMes) (SIMes = 1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene), the structures of NHCs were responsible for their isoselectivities, of Pm-max = 0.83 and Pm-max = 0.78, respectively, in the ROP of rac-LA at −20 °C. The much smaller cavity of 4 led to a minor activity and lower isoselectivity (Pm-max = 0.56 at −20 °C). Further decrease of the activity of Me(O,CNHC)GaOR (6), possessing both small cavity and, in contrast to 4, restrained rotation of Ga–CNHC bond of the chelate ligand, has supported the effect of NHC on the structure and activity of Me2GaOR(NHC) complexes. DFT calculations of the energy profile of the consecutive ring-opening of two lactide molecules into Ga–Oalkoxide bonds of 1, 4, and Me2GaOMe(SIMes) have confirmed the effect of NHC on their stereoselectivity.

Tetranuclear complexes of group 12 and 13 supported on a polynucleating ligand and activity studies in the ROP of rac-lactide

A polynucleating ligand (L-H4) containing four N,O bidentate sites was cleanly metallated by four equivalents of AlMe3, GaMe3 and ZnEt2 resulting in tetranuclear complexes L(MMe2)4 (M = Al (1), Ga (2)) and L(ZnEt(CH3CN)0.5)4 (3). The Al complex shows the best catalytic activity for the ring-opening polymerization (ROP) of rac-lactide (rac-LA) in the present family of tetranuclear compounds. Polymerization studies indicate the lack of cooperativity between metal centers in the ROP of rac-LA, despite having a ligand platform which binds to four metal centers.

Highly active rare-earth metal catalysts for heteroselective ring-opening polymerization of racemic lactide

Rare-earth metal complexes usually exhibit high activities in the ring-opening polymerization (ROP) of lactide, yet only a few scandium complexes have shown satisfactory activity. Herein, we report the synthesis of a series of chiral anilido-oxazoline-supported scandium and yttrium complexes that exhibit high activity in the ROP of racemic lactide (rac-LA). Complexes La-f-Ln(CH2SiMe3)2THF (La-f = 2-(2,6-R2PhN)-phenyl-4-(S)-R'-oxazoline; for 1a-f: L = La-f, Ln = Sc; for 2a-d: L = La-d, Ln = Y) were synthesized via the convenient one-pot reaction of Ln(CH2SiMe3)3(THF)2 (Ln = Sc, Y) with the corresponding proligands. The crystal structures of 1a, 1d, 1e, and 1f were isostructural, adopting a distorted trigonal bipyramidal configuration. Sc complexes 1 showed outstanding activity in the ROP of rac-LA with heteroselectivity. TOFs of up to 720 h-1 and 2910 h-1 were obtained in THF at room temperature and toluene at 60 °C, respectively. To our knowledge, these are the highest activities reported for Sc systems. Y complexes 2 showed higher activity and heteroselectivity than the Sc complexes, with TOFs of up to 1176 h-1 in THF at room temperature. Compared with the ortho-substituent on the anilido moiety, the bulky substituent at the chiral center of the oxazoline ring had a greater effect on controlling the heteroselectivity.

Enhanced Reactivity of Aluminum Complexes Containing P-Bridged Biphenolate Ligands in Ring-Opening Polymerization Catalysis.

Aluminum complexes containing [RP(O)(2-O-3,5-tBu2C6H2)2]2− [R = tBu (3a), Ph (3b)] have been synthesized, structurally characterized, and their reactivity studied in comparison with those of their [RP(2-O-3,5-tBu2C6H2)2]2− [R = tBu (2a), Ph (2b)] analogs. Treating AlMe3 with one equiv of H2[3a-b] in THF at 0°C affords quantitatively [3a-b]AlMe, subsequent reactions of which with benzyl alcohol in THF at 25°C generate {[3a-b]Al(μ2-OCH2Ph)}2. The methyl [3a-b]AlMe and the benzyloxide {[3a-b]Al(μ2-OCH2Ph)}2 are all active for catalytic ring-opening polymerization (ROP) of ε-caprolactone and rac-lactide (rac-LA). Controlled experiments reveal that {[3a]Al(μ2-OCH2Ph)}2 is competent in living polymerization. Kinetic studies indicate that [3a]AlMe, in the presence of benzyl alcohol, catalyzes ROP of rac-LA at a rate faster than [3b]AlMe and [2a]AlMe(THF) by a factor of 1.8 and 23.6, respectively, highlighting the profound reactivity enhancement in ROP catalysis by varying the P-substituents of these biphenolate complexes of aluminum.

Synthesis of Lewis Acidic, Aromatic Aminotroponiminate Zinc Complexes for the Ring-Opening Polymerization of Cyclic Esters

Three novel aminotroponiminate (ATI) zinc complexes I-III (I = [(Ph2)ATI]Zn-N(SiMe3)2, II = [(C6H3-2,6-C2H5/Ph)ATI]Zn-N(SiMe3)2, and III = [(C6H3-2,6-CH(CH3)2/Ph)ATI]Zn-N(SiMe3)2) were synthesized and tested in the ring-opening polymerization of the lactones β- rac-butyrolactone (BBL) and rac-lactide (LA). The ligands, with two of them literature unknown, were readily obtained via a three-step synthesis from tropolone. Forming a five-membered metallacycle with zinc, the complexes were further structurally examined via single-crystal X-ray analysis and compared with that of the established, 6-ringed β-diiminate (BDI) complex IV ([CH(CMeNPh)2]Zn-N(SiMe3)2). The influence of the varying metallacycle ring size on the polymerization was evaluated. In situ IR measurements indicate a higher catalytic activity of the novel ATI complexes I-III for BBL compared with the BDI system IV. The activity and degree of control were further improved by an in situ generated alkoxy initiating group generated after the addition of 2-propanol. An enhanced initiator efficiency allowed the synthesis of polymers with controlled molecular weights and narrow polydispersities. Furthermore, II and III exhibited a high activity in the ring-opening polymerization of rac-LA. Hereby, reaction time and initiator efficiency could also be optimized at a higher temperature or by the addition of 2-propanol.

Ring Opening Polymerization and Copolymerization of Cyclic Esters Catalyzed by Group 2 Metal Complexes Supported by Functionalized P-N Ligands.

We report the preparation of alkali and alkaline earth (Ae) metal complexes supported by 2-picolylamino-diphenylphosphane chalcogenide [(Ph2P(=E)NHCH2(C5H4N)] [E = S (1-H); Se (2-H)] ligands. The treatment of the protic ligand, 1-H or 2-H, with alkali metal hexamethyldisilazides at room temperature afforded the corresponding alkali metal salts [M(THF)2(Ph2P(=E)NCH2(C5H4N)] [M = Li, E = S (3a), Se (3b)] and [{M(THF) n(Ph2P(=E)NCH2(C5H4N)}2] [M = Na, E = S (4a), Se (4b); M = K, E = Se (5b)] in good yield. The homoleptic Ae metal complexes [κ2-(Ph2P(=Se)NCH2(C5H4N)Mg(THF)] (6b) and [κ3-{(Ph2P(=Se)NCH2(C5H4N)}2M(THF) n] (M = Ca (7b), Sr (8b), Ba (9b)] were synthesized by the one-pot reaction of 2-H with [KN(SiMe3)2] and MI2 in a 2:2:1 molar ratio at room temperature. The molecular structures of the protic-ligands 1-H and 2-H, as well as complexes 3a,b-5a,b and 6b-9b were established using single-crystal X-ray analysis. The Ae metal complexes 6b-9b were tested for ring-opening polymerization (ROP) of racemic lactide ( rac-LA) and copolymerization of rac-LA and ε-caprolactone (ε-CL) at room temperature. In the ROP of rac-LA, the calcium complex 7b exhibited high isoselectivity, with Pi = 0.89, whereas both the barium and strontium complexes showed lower isoselectivity with Pi = 0.78-0.62. In the copolymerization of rac-LA and ε-CL, both barium and strontium complexes proved to be efficient precatalysts for the formation of the block copolymer rac-LA-CL, but the reactivity of 9b was found to be better than that of 8b. All the polymers were fully characterized using differential scanning calorimetry, thermogravimetric analysis, and gel permeation chromatography analyses. Kinetic studies on the ROP reaction of LA confirmed that the rate of polymerization followed the order Ba ≫ Sr ≈ Ca.

Zinc(II) complexes containing N′-aromatic group substituted N,N′,N-bis((1H-pyrazol-1-yl)methyl)amines: Synthesis, characterization, and polymerizations of methyl methacrylate and rac-lactide

A novel series of Zn(II) complexes [LnZnCl2] (Ln = LA − LF) based on N,N′,N-bis((1H-pyrazol-1-yl)methyl)amine bidentate ligands, N,N-bis((1H-pyrazol-1-yl)methyl)-3,5-dimethylaniline [LA], N,N-bis((1H-pyrazol-1-yl)methyl)-2,6-dimethylaniline [LB], N,N-bis((1H-pyrazol-1-yl)methyl)-2,6-diethylaniline [LC], N,N-bis((1H-pyrazol-1-yl)methyl)-2,6-diisopropylaniline [LD], N,N-bis((1H-pyrazol-1-yl)methyl)-4-bromoaniline [LE] and N,N-bis((1H-pyrazol-1-yl)methyl)benzhydrylamine [LF], has been synthesized and characterized. X-ray structures of these Zn(II) complexes showed a distorted tetrahedral geometry. No interaction exists between the Namine and the Zn(II) center in the [LnZnCl2] (Ln = LA − LF) complexes, resulting in formation of an eight-membered chelate ring. [LFZnCl2] exhibited the highest catalytic activity (3.95 × 104 g PMMA/mol·Zn·h) for the polymerization of methyl methacrylate (MMA) in the presence of modified methylaluminoxane (MMAO) at 60 °C and yielded high molecular weight (Mw) (11.0 × 105 g/mol) of poly(methylmethacrylate) (PMMA). All the complexes resulted in syndiotactic enriched PMMA with high Tg (125–131 °C). The steric bulk of ligand architecture plays an influential role in controlling the catalytic activity and stereoregularity of the resultant PMMA. Further, alkyl derivatives [LnZnMe2] (Ln = LA − LF) of synthesized Zn(II) complexes, generated in situ, showed moderate to high activities toward ring opening polymerization (ROP) of rac-lactide (rac-LA) and yielded heterotactic polylactide (PLA) with Pr up to 0.95 at −50 °C. The activity and stereoselectivity toward ROP of rac-LA by these dimethyl Zn(II) complexes should be considered as a combined effect of steric hindrance and electronic density around the metal center.

Polymerization of rac‐Lactide Using Zinc(II) and Copper(II) Complexes of N1,N1‐Dimethyl‐N2‐[(1R)‐Myrtenylmethyl]Ethane‐1,2‐Diamine

Diisoproxide derivatives, generated in situ, of novel enantiopure dichloro Cu(II) and Zn(II) complexes supported by N1,N1-dimethyl-N2-[(1R)-myrtenylmethyl]ethane-1,2-diamine were assessed in ring opening polymerization of rac-LA, which displayed excellent activity and stereoselectivity. (L)Cu(OCHMe2)2 resulted in complete conversion of monomer in 80 s and yielded PLA that gave preference for heterotactic enchainment with Pr = 0.84 at 25 °C.

Efficient Diethylzinc/Gallic Acid and Diethylzinc/Gallic Acid Ester Catalytic Systems for the Ring-Opening Polymerization of rac-Lactide.

Polylactide (PLA) represents one of the most promising biomedical polymers due to its biodegradability, bioresorbability and good biocompatibility. This work highlights the synthesis and characterization of PLAs using novel diethylzinc/gallic acid (ZnEt2/GAc) and diethylzinc/propyl gallate (ZnEt2/PGAc) catalytic systems that are safe for human body. The results of the ring-opening polymerization (ROP) of rac-lactide (rac-LA) in the presence of zinc-based catalytic systems have shown that, depending on the reaction conditions, “predominantly isotactic”, disyndiotactic or atactic PLA can be obtained. Therefore, the controlled and stereoselective ROP of rac-LA is discussed in detail in this paper.

Syntheses and structures of lanthanide borohydrides supported by a bridged bis(amidinate) ligand and their high activity for controlled polymerization of ε-caprolactone, l-lactide and rac-lactide

Metathesis reaction of LLnCl(THF)(2) [L = (Me(3)SiNC(C(6)H(5))N)(2)(CH(2))(3)] with NaBH(4) in a 1 : 1.5 molar ratio in THF (THF = tetrahydrofuran) at 60 °C afforded the monoborohydride LLn(BH(4))(DME) [Ln = Y (1), Nd (2), Sm(3) and Yb(4)] crystallized from DME solution (DME = dimethoxyethane). Crystal structure analyses revealed 1-4 are monomers, in which each metal is ligated by one L ligand, one η(3)-BH(4) group and one DME molecule in a trigonal bipyramid geometry. Complexes 1-4 were found to be very active single-site initiators for the controlled ring opening polymerization of ε-caprolactone (ε-CL) and L-lactide (L-LA) as judged by relatively narrow molecular weight distributions (M(w)/M(n): 1.34-1.50) and experimental values M(n)(exp) were in good agreement with theoretic values M(n)(theo). The highest activity and the best control over the molecular weight for both monomers were found for the system with 2. These monoborohydride complexes can also initiate the ring opening polymerization of rac-LA to gave heterotactically enriched polyLA with Pr (heterotactic enrichment) values in a range of 0.69-0.85 depending on the lanthanide metals and the most effective heterotactic enrichment (Pr) was found for 1 (Pr = 0.85). Moreover, complex 1 initiated the polymerization of rac-LA in a living fashion.

Cinchona Alkaloids as Stereoselective Organocatalysts for the Partial Kinetic Resolution Polymerization of rac-Lactide

This work investigates, for the first time, cinchona alkaloids such as cinchonidine (CD) and β-isocupreidine (ICD) consisting of both a chiral nucleophilic amine catalyst site and an electrophilic hydroxy moiety, as bifunctional, stereoselective organocatalysts for the ring-opening polymerization (ROP) of l-lactide (l-LA) and rac-lactide (rac-LA). While the ROP of l-LA by CD is ineffective, the ROP of l-LA by ICD proceeds without noticeable epimerization, thus affording polylactide (PLA) with a quantitative isotacticity. The measured number-average molecular weight (Mn) is much higher than the expected Mn due to sluggish initiation by ICD, but when benzyl alcohol is added as an external protic initiator, the ROP is highly efficient and proceeds to high conversions without undesired transesterification reactions, thus producing PLA with a controlled Mn and a narrow molecular weight distribution of 1.12. More significantly, the ROP of rac-LA by ICD/alcohol affords crystalline isotactic-rich, stereogradient PLA that exhibits multiple melting-transition temperatures as a result of a partial kinetic resolution polymerization that preferentially polymerizes l-LA and kinetically resolves d-LA. Overall, this study uncovers the first kinetic resolution polymerization of rac-LA by an organocatalyst.

Exploring Electronic versus Steric Effects in Stereoselective Ring‐Opening Polymerization of Lactide and β‐Butyrolactone with Amino‐alkoxy‐bis(phenolate)–Yttrium Complexes

A series of methoxy-amino-bis(phenol)s (ONOO(R(1),R(2)))H(2) possessing on the phenol rings R(1) ortho substituents with variable steric and electronic properties (R(1)=CMe(2)Ph, 1; CMe(2)tBu, 3; CMe(2)(4-CF(3)C(6)H(4)), 5; CPh(3), 9; Cl, 10) has been synthesized and further reacted with [Y{N(SiHMe(2))(2)}(3)](THF)(2) to give cleanly the corresponding yttrium compounds [Y(ONOO(R(1),R(2))){N(SiHMe(2))(2)}(thf)(n)] (Y-x); the solid-state structures of Y-3 and Y-10 have been determined. These amido complexes have been used as initiators for the ring-opening polymerization (ROP) of rac-lactide (LA) and rac-β-butyrolactone (BBL) to provide heterotactically enriched poly(lactic acid)s (PLAs) and syndiotactically enriched poly(3-hydroxybutyrate)s (PHBs), respectively, by means of a chain-end control mechanism. Most of these polymerizations proceeded in a controlled fashion, giving polymers with narrow polydispersities and experimental molecular weights in good agreement with calculated values. The nature of the R(1) ortho substituents has a profound impact on the rates and, more spectacularly, on the stereocontrol of the polymerizations. The heterotactic stereocontrol in the ROP of rac-LA appears to be governed essentially by steric considerations; the larger the substituent, the higher the heterotacticity: R(1)=Cl (P(r)=0.56)≪CMe(3) (P(r)=0.80)≪CMe(2)Ph (P(r)=0.90)<CMe(2)(4 CF(3)-Ph) (P(r)=0.93-0.94)≤CMe(2)tBu (P(r)=0.94-0.95)≤CPh(3) (P(r)=0.95-0.96). On the other hand, the syndiotactic stereocontrol in the polymerization of rac-BBL follows a quite different trend: R(1)=Cl (P(r)=0.42-0.45)≪CMe(2)tBu (P(r)=0.62-0.70)<CMe(3) (P(r)=0.80)≤CMe(2) (4 CF(3)-Ph) (P(r)=0.82-0.84)<CMe(2)Ph (P(r)=0.89)<CPh(3) (P(r)=0.94), which suggests the involvement of electronic interactions. DFT computations on model intermediates confirmed a stabilizing C-H···π interaction between a methylene C-H of the ring-opened BBL unit and the π system of one of the ortho-aryl substituents of the ONOO(R(1)) ligand; by contrast, for model intermediates in the ROP of LA, no such C-H···π interaction involving the methyl group of lactate was observed.