Enantioselective polymerization of lactide for stereoregular and stereocomplex poly(lactic acid)

Abstract

Poly(lactic acid) (PLA) is the leading degradable, biocompatible polymer in the plastics industry. Stereocomplex PLA, i.e., a mixture of poly(L-lactic acid) and poly(D-lactic acid), exhibits enhanced mechanical toughness and elevated melting temperature compared to other PLA stereoisomers. However, because highly enantioselective polymerization catalysts for the resolution of racemic lactide do not exist, stereocomplex PLA has not been produced from commercially available racemic lactide. Herein, the discovery of chiral aluminum catalysts that are highly active for enantioselective lactide polymerization is reported. Using a racemic mixture of the catalysts allowed for the single-step production of highly isotactic stereocomplex PLA from racemic lactide

Description

VTTP 24-050(103418-002PCT)ENANTIOSELECTIVE POLYMERIZATION OF LACTIDE FOR STEREOREGULAR AND STEREOCOMPLEX POLY(LACTIC ACID)CROSS REFERENCE TO RELATED APPLICATIONThis application claims priority to U. S. Provisional Patent Application No. 63 / 733,855, filed on December 13, 2024, the contents of which are hereby incorporated by reference in their entirety.FEDERAL RESEARCH STATEMENT

[0001] This invention was made with government support under Grant no. CHE2404069 awarded by the National Science Foundation. The government has certain rights in the invention.BACKGROUND

[0002] The mass production and uncontrolled disposal of several hundred million metric tons of synthetic nondurable polymers have come with significant economic and environmental costs. To decrease these costs, various strategies have been investigated, including upcycling (using plastic waste as a feedstock for producing value-added materials) and recycling of polymers to their monomers. Alternatively, improving both the material properties of and synthetic methods for existing commercial bioplastics can be equally important because such improvements offer an immediate industrial solution for producing recyclable plastics with properties comparable to widely-used non-degradable commodity polyolefins.

[0003] Poly(lactic acid) (PLA) is a leading sustainable polymer produced by ring-opening polymerization (ROP) of lactide, which is prepared via depolymerization of a low-molecular-weight (MW) condensed prepolymer of biosourced lactic acid (FIG. 1). However, key bottlenecks remain for broader PLA applications because the material properties of PLA are less satisfactory than those of commodity polyolefins. For example, PLA has a low heat-distortion temperature and poor thermal stability, and it is brittle. These issues can be addressed by preparing PLA analogues with pendant functional groups, but a straightforward method for improving PLA’s materials properties without changing the monomer is needed.

[0004] Accordingly, there is a continuing need for improved methods capable of providing PLA with improved material properties. It would be particularly advantageous to provide PLA having controlled stereochemistry.SUMMARY

[0005] An aspect of the present disclosure is an aluminum complex having structure (I) or structure (II)VTTP 24-050(103418-002PCT)wherein in the foregoing structures, each occurrence of R1is independently selected from hydrogen, methyl, t-butyl, bromine, fluorine, chlorine, nitro, ethoxy, and trifluoromethyl; each occurrence of R2is independently selected from hydrogen, methyl, ethyl, t-butyl, bromine, fluorine, chlorine, iodine, nitro, methoxy, and trifluoromethyl; each occurrence of R3is independently selected from a fused unsubstituted phenyl ring, a fused unsubstituted cyclohexyl ring, a fused 6,6’-bromine substituted phenyl ring, and a fused 6,6’-phenyl substituted phenyl ring; and each occurrence of R4is independently selected from a methyl, ethyl, phenyl, t-butyl, fluorine, bromine, iodine, and trifluoromethyl.

[0006] Another aspect is a method for the manufacture of poly(L-lactic acid) from a racemic mixture of lactide, the method comprising: contacting the racemic mixture of lactide with an aluminum complex according to an aspect of the present disclosure under conditions effective to provide the poly(L-lactic acid).

[0007] Another aspect is a method for the manufacture of poly(lactic acid) from a racemic mixture of lactide, the method comprising: contacting the racemic mixture of lactide with an aluminum complex according structure (11) having an R configuration under conditions effective to provide poly(D-lactic acid); or contacting the racemic mixture of lactide with an aluminum according structure (II) having an S configuration under conditions effective to provide poly(L-lactic acid).

[0008] Another aspect is a method for the manufacture of syndiotactic poly(lactic acid), the method comprising: contacting zweso-lactide with the aluminum complex according to an aspect of the present disclosure under conditions effective to provide the syndiotactic poly(lactic acid).

[0009] Another aspect is a method for the manufacture of stereocomplex poly(lactic acid) from a racemic mixture of lactide, the method comprising: contacting the racemic mixture of lactide with a bimetallic aluminum complex according to structure (I) and a monometallic aluminum complex according to structure (II) having an R configuration, wherein the bimetallic aluminum complex and the monometallic aluminum complex are according to the present disclosure, under conditions effective to provide the stereocomplex poly(lactic acid).

[0010] Another aspect is a stereocomplex poly(lactic acid) made by the method of the present disclosure, wherein the stereocomplex poly(lactic acid) exhibits one or both of increasedVTTP 24-050(103418-002PCT)solubility in organic solvent relative to a comparative stereocomplex poly(lactic acid) prepared by blending poly(L-lactic acid) and poly(D-lactic acid); and increased toughness relative to a comparative stereocomplex poly(lactic acid) prepared by blending poly(L-lactic acid) and poly(D-lactic acid).

[0011] Another aspect is a method for the bulk polymerization of a racemic mixture of lactide, the method comprising: contacting the racemic mixture of lactide with an aluminum complex according to structure (II) having an R configuration, wherein the contacting is at a temperature of at least 130 °C and in the absence of a solvent to provide poly(D-lactic acid); or contacting the racemic mixture of lactide with an aluminum complex according to structure (II) having an S' configuration, wherein the contacting is at a temperature of at least 130 °C and in the absence of a solvent to provide poly(L-lactic acid).

[0012] The above described and other features are exemplified by the following figures and detailed description.BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The following figures are exemplary embodiments.

[0014] FIG. 1 illustrates challenges posed by the production of stereocomplex PLA (sc-PLA), which shows superior properties to poly(L-lactic acid) (PLLA), from readily available racemic lactide (rac-LA).

[0015] FIG. 2 illustrates development of enantioselective chiral aluminum complexes that can catalyze polymerization of either enantiomer of rac-LA (left) via the enantiomorphic-site control (ESC) mechanism and that, in racemic form, allow for one-step scalable synthesis of sc-PLA (right).

[0016] FIG. 3 shows a comparison of L-LA / D-LA conversion ratios for ring-opening polymerization (ROP) catalyzed by (S,-AmBn)A12Me4 (m = 1 to 30, n = 1 or 2).

[0017] FIG. 4 shows representative1H NMR spectra obtained when (S-A29B2)Al2Me4 was used for ROP of L-LA (top) and D-LA (bottom), suggesting the possible enantioselectivity of this complex. BnOH, benzyl alcohol; PLLA, poly(L-lactic acid).

[0018] FIG. 5 shows generation of PLLA by (S-L1)Al2Me4- or (S-L2)AhMe4-catalyzed enantioselective polymerization of L-LA from rac-LA.

[0019] FIG. 6 shows homodecoupled1H and13C NMR spectra of PLA generated with (S-L1)Al2Me4([rac-LA] / [(S)-bi-Al] / [BnOH] = 100 / 1 / 1 at 70 °C for 6 h in toluene.

[0020] FIG. 7 shows generation of poly(D-lactic acid) (PDLA) by enantioselective polymerization of D-LA from rac-LA with catalysis by (R-Ll)AlMe and (7?-L2)AlMe.

[0021] FIG. 8 shows homodecoupled1H and13C NMR spectra of PLA generated with (R-L1)AlMe ([rac-LA] / [( / ?)-Al] / [1PrOH] = 100 / 1 / 1 at 70 °C for 6 h in toluene.VTTP 24-050(103418-002PCT)

[0022] FIG. 9 shows representative13C NMR spectra of PLA generated by (S'-L2)A12Me4-and (7?-L2)AlMe-catalyzed polymerization of zneso-LA to afford srf-PLA.

[0023] FIG. 10 shows synthesis of sc-PLA via ring-opening polymerization of rac-lactide (rac-LA) with catalysis by (S)-bi-Al and (7?)-Al complexes.

[0024] FIG. 11 shows homodecoupled1H and13C NMR spectra of sc-PLA (Table 2, entry 1).

[0025] FIG. 12 shows kinetics of the reaction that produced the sc-PLA whose spectra are shown in FIG. 11, and temporal dependence of the site-control selectivity (a) during the polymerization.

[0026] FIG. 13 shows differential scanning calorimetry overlay of poly(L-lactic acid) (PLLA), stereoblock PLA (sZ>-PLA), sc-PLA prepared by blending PLLA and poly(D-lactic acid) (PDLA), and sc-PLA prepared with catalysis by rac-LA-A.

[0027] FIG. 14 shows representative stress-strain curves obtained by means of uniaxial tensile tests of the polymers shown in FIG. 13 and syndiotactic PLA (stf-PLA). Inset: Image of transparent sc-PLA film prepared with catalysis by rac-Ll-Al before and after the uniaxial tensile test, which shows improved ductility and toughness compared to conventionally blended sc-PLA.

[0028] FIG. 15 shows the structures of (S-AmBn)AlMe derivatives bearing different Amand Bnsubstituents.DETAILED DESCRIPTION

[0029] One strategy for improving PLA’s materials properties would be to produce stereoregular polymers, which have enhanced thermomechanical properties relative to those of atactic polymers. Semicrystalline isotactic poly(L-lactic acid) (PLLA), which is produced by ROP of (S, ^-lactide (L-LA), shows higher fracture strength (o) than atactic PLA made from racemic lactide (rac-LA). Moreover, simply blending enantiopure PLLA and poly(D-lactic acid) (PDLA) - which makes stereocomplex PLA (sc-PLA) - is a straightforward, robust strategy to reinforce PLA. sc-PLA is highly crystalline, with a melting temperature (Tm) that is ~40 °C higher than that of PLLA, and it reportedly exhibits higher o, fracture strain (E), and thermal stability than the homopolymer.

[0030] Although sc-PLA has desirable properties among the existing PLA stereoisomers, its manufacture has never been realized on an industrial scale because of the difficulty in producing PDLA. Unlike enantiopure L-lactic acid, which is sourced from bacterial fermentation, enantiopure D-lactic acid could only be produced in limited quantities in the laboratory. In contrast, rac-lactic acid and rac-LA can easily be produced (FIG. 1). To date, only a few chiral aluminum complexes and organocatalysts have been shown to catalyze stereoselective polymerization of one LA enantiomer preferentially over the other at low LA conversions, but all these catalysts eventuallyVTTP 24-050(103418-002PCT)produce gradient stereoblock PLA (sZ>-PLA) at high LA conversions. Synthetic methods for preparing sc-PLA directly from rac-LA are undeniably needed.

[0031] An additional layer of difficulty stems from the challenge of identifying enantioselective catalysts exhibiting intrinsic activity for mediating enchainment via a specific pathway. Ideally, highly enantioselective catalysts should selectively polymerize one enantiomer to give an isotactic polymer via the enantiomorphic-site control (ESC) mechanism, in which stereoerrors are automatically corrected by the chiral catalysts, leaving the other enantiomer unchanged. Nevertheless, known stereoselective catalysts for PLA formation mediate polymerization via the chain-end control (CEC) mechanism, which cannot correct stereoerrors. The preparation of stereocomplex polymers from racemic monomers could be achieved by using a pair of enantioselective catalysts with opposite chirality, as shown schematically in FIG. 2. Enantioselective polymerizations of racemic a-olefins and epoxides have been achieved via the ESC mechanism, as has enantioselective copolymerization of racemic epoxides / anhydrides; however, such polymerization of rac-LA has not.

[0032] The present inventors have discovered highly active enantioselective chiral aluminum complexes that can catalyze the polymerization of either one of the enantiomers of rac-LA via the ESC mechanism. In addition, the racemic catalysts efficiently catalyze the production of highly isotactic sc-PLA from rac-LA in one step, a transformation for which no direct chemical alternative strategy exists. In a further advantageous feature, the present inventors have found that the catalysts may be useful in bulk polymerization processes, whereby a solvent can be excluded. A significant improvement is therefore provided by the present disclosure.

[0033] Accordingly, an aspect of the present disclosure is an aluminum complex which can be particularly useful in producing poly(lactic acid) having controlled stereochemistry. The aluminum complex according to the present disclosure has the structure (I) or (II)wherein in the foregoing structures, each occurrence of R1is independently selected from hydrogen, methyl, t-butyl, bromine, fluorine, chlorine, nitro, ethoxy, and trifluoromethyl; each occurrence of R2is independently selected from hydrogen, methyl, ethyl, t-butyl, bromine, fluorine, chlorine, iodine, nitro, methoxy, and trifluoromethyl; each occurrence of R3is independently selected from a fusedVTTP 24-050(103418-002PCT)unsubstituted phenyl ring, a fused unsubstituted cyclohexyl ring, a fused 6,6’-bromine substituted phenyl ring, and a fused 6,6’-phenyl substituted phenyl ring; andeach occurrence of R4is independently selected from a methyl, ethyl, phenyl, t-butyl, fluorine, bromine, iodine, and trifluoromethyl. For simplicity, the aluminum complex according to structure (I) may also be referred to herein as a “bimetallic aluminum complex” and the aluminum complex according to structure (II) may also be referred to herein as a “monometallic aluminum complex”. It will also be understood that the compound according to structure (II) explicitly includes both the R or S configurations at the indicated bond. The R configuration is shown as structure (IIA) and the S' configuration is shown as structure (IIB) for clarity.

[0034] In an aspect, the aluminum complex is the bimetallic aluminum complex according to structure (I). In a specific aspect, R3can be a fused unsubstituted phenyl ring, and the bimetallic aluminum complex can be of the structure

[0035] In another specific aspect, each occurrence of R3can be a fused unsubstituted cyclohexyl ring, and the bimetallic aluminum complex can be of the structure

[0036] Various combinations of the aforementioned R1and R2substituents can be present inVTTP 24-050(103418-002PCT)the bimetallic aluminum complex of structure (I). For example, in some aspects, each occurrence of R1can be hydrogen and each occurrence of R2can be hydrogen; or each occurrence of R1can be hydrogen and each occurrence of R2can be t-butyl; or each occurrence of R1can be hydrogen and each occurrence of R2can be methoxy; or each occurrence of R1can be hydrogen and each occurrence of R2can be chlorine; or each occurrence of R1can be bromine and each occurrence of R2can be bromine; or each occurrence of R1can be methyl and each occurrence of R2can be hydrogen; or each occurrence of R1can be t-butyl and each occurrence of R2can be t-butyl; or each occurrence of R1can be t-butyl and each occurrence of R2can be hydrogen; or each occurrence of R1can be hydrogen and each occurrence of R2can be nitro; or each occurrence of R1can be hydrogen and each occurrence of R2can be fluorine; or each occurrence of R1can be fluorine and each occurrence of R2can be hydrogen; or each occurrence of R1can be bromine and each occurrence of R2can be nitro; or each occurrence of R1can be hydrogen and each occurrence of R2can be bromine; or each occurrence of R1can be hydrogen and each occurrence of R2can be methyl; or each occurrence of R1can be ethoxy and each occurrence of R2can be hydrogen; or each occurrence of R1can be chlorine and each occurrence of R2can be hydrogen; or each occurrence of R1can be chlorine and each occurrence of R2can be chlorine; or each occurrence of R1can be methyl and each occurrence of R2can be chlorine; or each occurrence of R1can be nitro and each occurrence of R2can be chlorine; or each occurrence of R1can be nitro and each occurrence of R2can be hydrogen; or each occurrence of R1can be chlorine and each occurrence of R2can be fluorine; or each occurrence of R1can be hydrogen and each occurrence of R2can be trifluoromethyl; or each occurrence of R1can be fluorine and each occurrence of R2can be fluorine; or each occurrence of R1can be methyl and each occurrence of R2can be fluorine; or each occurrence of R1can be trifluoromethyl and each occurrence of R2can be hydrogen; or each occurrence of R1can be fluorine and each occurrence of R2can be nitro; or each occurrence of R1can be methyl and each occurrence of R2can be methyl; or each occurrence of R1can be fluorine and each occurrence of R2can be methyl; or each occurrence of R1can be hydrogen and each occurrence of R2can be iodine; or each occurrence of R1can be hydrogen and each occurrence of R2can be ethyl. In an aspect, each occurrence of R1can be hydrogen, each occurrence of R2can be selected from methyl or iodine, and each occurrence of R4can be hydrogen.

[0037] In an aspect, the aluminum complex can be a bimetallic aluminum complex according to structure (I), and each occurrence of R1can be hydrogen; each occurrence of R2can be methyl; and each occurrence of R3can be a fused unsubstituted phenyl ring; each occurrence of R4can be hydrogen; and the aluminum complex can be of the structureVTTP 24-050(103418-002PCT)

[0038] In an aspect, the aluminum complex can be a bimetallic aluminum complex according to structure (I), and each occurrence of R1can be hydrogen; each occurrence of R2can be iodine; and each occurrence of R3can be a fused unsubstituted cyclohexyl ring; each occurrence of R4can be hydrogen; and the aluminum complex can be of the structure

[0039] In some aspects, the aluminum complex can be the monometallic complex according to structure (II). In an aspect, each occurrence of R3can be a fused unsubstituted phenyl ring, and the monometallic aluminum complex can be of the structure

[0040] In an aspect, each occurrence of R3can be a fused unsubstituted cyclohexyl ring, and the monometallic aluminum complex can be of the structureVTTP 24-050(103418-002PCT)2

[0041] In an aspect, each occurrence of R3can be a fused 6,6’-bromine substituted phenyl ring, and the monometallic aluminum complex can be of the structure

[0042] In an aspect, each occurrence of R3can be a fused 6,6’-phenyl substituted phenyl ring, and the monometallic aluminum complex can be of the structure

[0043] Various combinations of the aforementioned R1and R2substituents can be present in the monometallic aluminum complex of structure (II). For example, in some aspects, each occurrence of R1can be hydrogen and each occurrence of R2can be hydrogen; or each occurrence of R1can be hydrogen and each occurrence of R2can be t-butyl; or each occurrence of R1can be hydrogen and each occurrence of R2can be methoxy; or each occurrence of R1can be hydrogen and each occurrence of R2can be chlorine; or each occurrence of R1can be bromine and each occurrence of R2can be bromine; or each occurrence of R1can be methyl and each occurrence of R2can be hydrogen; or each occurrence of R1can be t-butyl and each occurrence of R2can be t-butyl; or eachVTTP 24-050(103418-002PCT)occurrence of R1can be t-butyl and each occurrence of R2can be hydrogen; or each occurrence of R1can be hydrogen and each occurrence of R2can be nitro; or each occurrence of R1can be hydrogen and each occurrence of R2can be fluorine; or each occurrence of R1can be fluorine and each occurrence of R2can be hydrogen; or each occurrence of R1can be bromine and each occurrence of R2can be nitro; or each occurrence of R1can be hydrogen and each occurrence of R2can be bromine; or each occurrence of R1can be hydrogen and each occurrence of R2can be methyl; or each occurrence of R1can be ethoxy and each occurrence of R2can be hydrogen; or each occurrence of R1can be chlorine and each occurrence of R2can be hydrogen; or each occurrence of R1can be chlorine and each occurrence of R2can be chlorine; or each occurrence of R1can be methyl and each occurrence of R2can be chlorine; or each occurrence of R1can be nitro and each occurrence of R2can be chlorine; or each occurrence of R1can be nitro and each occurrence of R2can be hydrogen; or each occurrence of R1can be chlorine and each occurrence of R2can be fluorine; or each occurrence of R1can be hydrogen and each occurrence of R2can be trifluoromethyl; or each occurrence of R1can be fluorine and each occurrence of R2can be fluorine; or each occurrence of R1can be methyl and each occurrence of R2can be fluorine; or each occurrence of R1can be trifluoromethyl and each occurrence of R2can be hydrogen; or each occurrence of R1can be fluorine and each occurrence of R2can be nitro; or each occurrence of R1can be methyl and each occurrence of R2can be methyl; or each occurrence of R1can be fluorine and each occurrence of R2can be methyl; or each occurrence of R1can be hydrogen and each occurrence of R2can be iodine; or each occurrence of R1can be hydrogen and each occurrence of R2can be ethyl. In an aspect, each occurrence of R1can be hydrogen, each occurrence of R2can be selected from methyl, ethyl, or iodine, and each occurrence of R4can be methyl or hydrogen

[0044] In a specific aspect, the aluminum complex can be a monometallic aluminum complex according to structure (II), and each occurrence of R1can be hydrogen; each occurrence of R2can be methyl; each occurrence of R3can be a fused unsubstituted phenyl ring; and each occurrence of R4can be hydrogen; and the monometallic aluminum composition can be of the structure

[0045] In a specific aspect, the aluminum complex can be a monometallic aluminumVTTP 24-050(103418-002PCT)complex according to structure (II), and each occurrence of R1can be hydrogen; each occurrence of R2can be iodine; each occurrence of R3can be a fused unsubstituted cyclohexyl ring; and each occurrence of R4can be hydrogen; and the monometallic aluminum composition can be of the structure

[0046] In a specific aspect, the aluminum complex can be a monometallic aluminum complex according to structure (II), and each occurrence of R1can be hydrogen; each occurrence of R2can be methyl; each occurrence of R3can be a fused unsubstituted phenyl ring; and each occurrence of R4can be methyl; and the monometallic aluminum composition can be of the structure

[0047] In a specific aspect, the aluminum complex can be a monometallic aluminum complex according to structure (II), and each occurrence of R1can be hydrogen; each occurrence of R2can be methyl; each occurrence of R3can be a fused unsubstituted cyclohexyl ring; and each occurrence of R4can be methyl; and the monometallic aluminum composition can be of the structureH3CVTTP 24-050(103418-002PCT)

[0048] In a specific aspect, the aluminum complex can be a monometallic aluminum complex according to structure (II), and each occurrence of R1can be hydrogen; each occurrence of R2can be methyl; each occurrence of R3can be a fused 6,6’-bromine substituted phenyl ring; and each occurrence of R4can be methyl; and the monometallic aluminum composition can be of the structureBr

[0049] In a specific aspect, the aluminum complex can be a monometallic aluminum complex according to structure (II), and each occurrence of R1can be hydrogen; each occurrence of R2can be methyl; each occurrence of R3can be a fused 6,6’-phenyl substituted phenyl ring; and each occurrence of R4can be methyl; and the monometallic aluminum composition can be of the structure

[0050] The aluminum complexes described herein can be well suited for use in methods for preparing poly(lactic acid), particularly when a desired stereochemistry is preferred.

[0051] For example, an aspect of the present disclosure is a method for the manufacture of poly(lactic acid) from a racemic mixture of lactide. The term “racemic mixture of lactide” as used herein refers to a composition comprising an approximately equimolar mixture of the two optical isomers (also referred to as enantiomers) of lactide, namely D-lactide and L-lactide. In such a mixture, the molar ratio of D-lactide to L-lactide is substantially 1:1 (e.g., 0.95:1.05 to 1.05:0.95), resulting in an overall composition that is optically inactive due to internal compensation of the optical rotations of the individual enantiomers. The racemic mixture may also be referred to as rac-lactide, and may be obtained by depolymerization of racemic polylactic acid (PLA).

[0052] The method comprises contacting the racemic mixture of lactide with an aluminumVTTP 24-050(103418-002PCT)complex according to the present disclosure under conditions effective to provide the poly(lactic acid). As will be further described herein, the stereochemistry of the resulting poly(lactic acid) can be controlled based on the aluminum complex selected for the polymerization.

[0053] In an aspect, the aluminum complex can be according to structure (I), including all structural variations discussed herein, and the resulting poly(lactic acid) can be poly(L-lactic acid). In an aspect, the aluminum complex can be according to structure (II), including all structural variations discussed herein, and having the R configuration, and the resulting poly(lactic acid) can be a poly(D-lactic acid). In an aspect, the aluminum complex can be according to structure (II), including all structural variations discussed herein, and having the S configuration, and the resulting poly(lactic acid) can be a poly(L-lactic acid).

[0054] Polymerization of the racemic mixture of lactide proceeds by ring opening polymerization (ROP), which may be conducted under bulk or solution conditions using the aluminum complex described herein and, optionally, an initiator. The polymerization can be carried out under anhydrous and inert atmosphere conditions (e.g., under nitrogen or argon) to minimize moisture- or oxygen-induced side reactions. Exemplary conditions can include a temperature of 60 to 200 °C, for example 60 to 100°C depending on the catalyst system and desired molecular weight. The catalyst concentration can be 0.1 to 10 mole percent, based on total moles of lactide, for example 0.5 to 5 mole percent, or 0.5 to 2 mole percent. An initiator such as an aliphatic alcohol, diol, or multifunctional hydroxyl compound may be included to control polymer chain length and architecture. Exemplary initiators can include, but are not limited to, benzyl alcohol, isopropanol, L-methyl lactate, and the like. The molar ratio of lactide to initiator typically ranges from 10:1 to 10,000: 1. When conducted in solution, any suitable organic solvent can be used provided that it is inert to reaction conditions. Exemplary solvents can include, but are not limited to, toluene, xylene, dichloromethane, or the like. Reaction progress can be monitored by nuclear magnetic resonance (NMR) spectroscopy. Upon completion, the polymerization reaction mixture can be cooled and the resulting poly(lactic acid) can be isolated, for example, by precipitation in a suitable nonsolvent, for example an aliphatic alcohol solvent such as methanol, ethanol, or the like. The isolated poly(lactic acid) can be dried under reduced pressure.

[0055] The poly(lactic acid) polymerized from a racemic mixture of lactide using the aluminum complex of the present disclosure can have a number average molecular weight of 3,000 to 50,000 grams per mole (g / mol), for example 3,000 to 15,000 g / mol, as determined by gel permeation chromatography (GPC, also referred to as size exclusion chromatography (SEC)), for example using tetrahydrofuran (THF) or chloroform relative to polystyrene or poly(methyl methacrylate) standards. The poly(lactic acid) can have a dispersity of less than 1.2, as determined by gel permeation chromatography.VTTP 24-050(103418-002PCT)

[0056] In some aspects, the poly(lactic acid) can have an enantiotopic site-control selectivity a of greater than or equal to 0.9, or greater than or equal to 0.91, or greater than or equal to 0.92, or greater than or equal to 0.94, or greater than or equal to 0.95. As used herein, the term “enantiotopic site-control selectivity (a)” refers to a measure of the preference of the aluminum complex for one enantiotopic coordination or insertion site over the other during polymerization of the racemic mixture of lactide. In the context of lactide polymerization, a represents the ratio of the rate of insertion of one enantiomeric form of the monomer at a given chain end to that of the opposite enantiomeric form, such that a value of a greater than 0.5 indicates preferential enantiotopic site control, and a value approaching 1.0 indicates nearly complete selectivity for one enantiotopic site, leading to the formation of stereoregular polymer sequences.

[0057] The value of enantiotopic site-control selectivity (a) may be determined by several analytical methods. In one approach, the stereochemical microstructure of the resulting polymer is analyzed by nuclear magnetic resonance (NMR) spectroscopy, typically by13C or 'H NMR, to quantify the relative abundance of stereochemical sequences (e.g., triads, tetrads, or pentads) within the polymer backbone. These distributions are then used to calculate a according to established statistical models of stereocontrol in polymerization. In an alternative or complementary approach, chiral high-performance liquid chromatography (HPLC) may be employed to monitor the enantiomeric composition of the residual monomer or low-molecular-weight oligomers formed during polymerization of racemic lactide. The difference in the rates of consumption or formation of each monomer enantiomer, as determined by chiral HPLC, provides a kinetic measure of enantiotopic site preference. These exemplary analytical techniques enable quantitative evaluation of the degree of stereochemical control imparted by the aluminum complexes described herein.

[0058] The method of preparing poly(lactic acid) from a racemic mixture of lactide is further described in the working examples provided herein.

[0059] Another aspect of the present disclosure is a method for the manufacture of syndiotactic poly(lactic acid). As used herein, the term “syndiotactic poly(lactic acid)” refers to a poly(lactic acid) in which the configuration of successive stereogenic centers along the polymer backbone alternates in a regular fashion, such that the stereochemical sequence follows an alternating R, S, R, S (or S, R, S, R) pattern. This alternating facticity arises from stereoselective enchainment of monomer units during ROP of the lactide monomer mediated by the aluminum complexes described herein. Syndiotactic poly(lactic acid) exhibits a distinct stereochemical microstructure, which can be confirmed by analysis of facticity using, for example,13C NMR spectroscopy (e.g., by identification of characteristic tetrad or pentad resonance patterns). Such a polymer can exhibit thermal and mechanical properties that differ from isotactic or heterotactic forms of polylactide.VTTP 24-050(103418-002PCT)

[0060] The method of preparing syndiotactic poly(lactic acid) comprises contacting mesolactide with the aluminum complex of the present disclosure under conditions effective to provide the syndiotactic poly(lactic acid). As used herein, “meso-lactide” refers to the diastereomer of lactide in which the two stereocenters have opposite configurations, i.e., one is R and the other is S, resulting in a molecule that is achiral despite containing two stereogenic centers. Afeso-lactide is distinct from the enantiomerically pure forms, L-lactide (R, R) and D-lactide (S, S), and can be obtained by depolymerization of racemic lactic acid or via stereoselective synthesis.

[0061] The method can be conducted using the various reaction conditions already described herein, including parameters such as temperature, initiator identity and concentration, presence of solvent, etc. The resulting poly(lactic acid) can be characterized using the techniques described herein.

[0062] The syndiotacticity of the poly(lactic acid) can be confirmed by analysis of the polymer microstructure using spectroscopic and physical methods. Primary confirmation can be obtained byor13C NMR spectroscopy to quantify stereochemical sequence distributions (triads, tetrads or pentads). Syndiotactic sequences give rise to characteristic resonance patterns and intensity ratios in the methine and carbonyl regions that are distinct from isotactic or atactic polymers. These patterns can be compared to reference spectra or simulated distributions to determine the fraction of syndiotactic dyads / tetrads. Secondary, corroborative measurements can include differential scanning calorimetry (DSC) and X-ray diffraction (XRD). For example, syndiotactic PLA may exhibit a thermal profile or crystalline reflections that differ from isotactic PLA, providing supporting evidence of the alternating stereochemistry.

[0063] Another aspect of the present disclosure is a method for the manufacture of stereocomplex pofy(lactic acid) from a racemic mixture of lactide. As used herein, the term “stereocomplex poly(lactic acid)” refers to a blend formed from poly(L-lactic acid) (PLLA) and poly(D-lactic acid) (PDLA), through strong stereochemical interactions such as hydrogen bonding and van der Waals forces. The resulting stereocomplex exhibits a highly ordered crystalline structure distinct from the crystals of the individual enantiomeric polymers. Stereocomplex PLA can exhibit enhanced thermal stability, higher melting temperature, and improved mechanical properties relative to homochiral PLA. The formation and degree of stereocomplexation can be confirmed by techniques including differential scanning calorimetry (DSC), X-ray diffraction (XRD), and NMR spectroscopy.

[0064] The method comprises contacting the racemic mixture of lactide with a bimetallic aluminum complex according to structure (I) and a monometallic aluminum complex according to structure (II). The bimetallic aluminum complex and the monometallic aluminum complex are as already described herein. The monometallic aluminum complex according to structure (II) has the RVTTP 24-050(103418-002PCT)configuration about the noted bond. In an aspect, the molar ratio of the bimetallic aluminum complex of structure (I) to the monometallic aluminum complex of structure (II) can be 0.95:1.05 to 1.05 to 0.95, or 1:1.

[0065] In an aspect, the bimetallic aluminum composition can be of the structure

[0066] In an aspect, the bimetallic aluminum composition can be of the structure\CH3; andthe monometallic aluminum complex can be of the structure

[0067] The racemic mixture of lactide and the aluminum complexes are contacted underVTTP 24-050(103418-002PCT)conditions effective to provide the stereocomplex poly(lactic acid). Suitable reaction conditions can be as already described herein, including parameters such as temperature, initiator identity and concentration, presence of solvent, etc. The resulting stereocomplex poly(lactic acid) can be characterized using the techniques described herein.

[0068] In a specific aspect, the method can comprise contacting a first portion of the racemic mixture of lactide with the bimetallic aluminum complex for a predetermined amount of time to provide a first reaction mixture. A second portion of the racemic mixture of lactide can be contacted with the monometallic aluminum complex for the predetermined amount of time to provide a second reaction mixture. After the predetermined amount of time, the first reaction mixture and the second reaction mixture can be combined to provide the stereocomplex poly(lactic acid).

[0069] The stereocomplex poly(lactic acid) produced by the method described herein can exhibit one or more advantageous properties. For example, the stereocomplex poly(lactic acid) can exhibit increased solubility in organic solvent relative to a comparative stereocomplex poly(lactic acid) prepared by blending poly(L-lactic acid) and poly(D-lactic acid). In an aspect, the stereocomplex poly(lactic acid) can exhibit increased toughness relative to a comparative stereocomplex poly(lactic acid) prepared by blending poly(L-lactic acid) and poly(D-lactic acid).

[0070] Another aspect of the present disclosure is a method for the bulk polymerization of a racemic mixture of lactide. The stereochemistry of the resulting poly(lactic acid) can be controlled based on the selection of the aluminum catalyst complex used. In an aspect, the method comprises contacting the racemic mixture of lactide with an aluminum complex according to structure (II) having an R configuration, wherein the contacting is at a temperature of at least 130 °C and in the absence of a solvent to provide poly(D-lactic acid). In an aspect, the method comprises contacting the racemic mixture of lactide with an aluminum complex according to structure (II) having an S configuration, wherein the contacting is at a temperature of at least 130 °C and in the absence of a solvent to provide poly(L-lactic acid).

[0071] Exemplary conditions can include a catalyst concentration of 0.1 to 10 mole percent, based on total moles of lactide, for example 0.2 to 5 mole percent, or 0.2 to 2 mole percent. An initiator such as an aliphatic alcohol, diol, or multifunctional hydroxyl compound may be included to control polymer chain length and architecture. Exemplary initiators can include, but are not limited to, benzyl alcohol, isopropanol, L-methyl lactate, and the like. The molar ratio of lactide to initiator can be, for example, 10:1 to 10,000:1.

[0072] The resulting poly(lactic acid) can be characterized using various techniques already described herein. The poly(lactic acid) produced from bulk polymerization of lactide using the aluminum complex of the present disclosure can have an enantiotopic site-control selectivity a of greater than or equal to 0.85, or greater than or equal to 0.9, or greater than or equal to 0.92.VTTP 24-050(103418-002PCT)

[0073] The bulk polymerization of racemic lactide using the aluminum complexes described herein is further described in the working examples below.

[0074] This disclosure is further illustrated by the following examples, which are nonlimiting.EXAMPLESBimetallic aluminum complexes enantioselectively polymerized L-LA from rac-LA

[0075] The inability of existing chiral aluminum complexes to catalyze enantioselective ROP of rac-LA necessitates the exploration of methods to improve their enantioselectivity. Initial studies were directed at screening ligands with a chiral biaryl linker (AmBn), which were prepared via a condensation reaction between (S)-biarylamines and salicylaldehydes bearing various substituents. The obtained ligands reacted with 2 equiv. of AlMea to afford the desired (S)-bi-Al complexes ((5-AmBn)A12Me4, FIG. 3). Because measuring the rate of reaction of each complex with each LA enantiomer would have been time-consuming, each (S)-bi-Al complex was mixed with L-LA and D-LA separately and allowed ROP to proceed at 70 °C for 4 h in the presence of benzyl alcohol (BnOH) as an alcohol initiator ([LA] / [(, S -bi-Al] / [BnOH] = 100 / 1 / 1, [LA] = 694 mM in toluene). For each (S)-bi-Al complex, the ratio between L-LA conversion and D-LA conversion was measured usingXH NMR spectroscopy, aiming to identify enantioselective complexes that gave high ratios (FIG. 4). ( )-bi-Al complexes with ligands A9B1, A14B1, A9B2, and A29B2 showed high L-LA / D-LA conversion ratios (>7) and L-LA conversions of >70% over the course of 4 h, indicating their high reactivities and outstanding kinetic preference for L-LA. The Bi and B2 linkers proved to have the greatest beneficial effect on the enantioselectivity, whereas the diformylated binaphthyl linker B3 and tetrahydro- 1,1 ’-spirobi[indene] linker B4 decreased the enantioselectivity. Notably, increasing the amount of BnOH to 2 equiv. resulted in lower L-LA / D-LA conversion ratios, that is, a decrease in enantioselectivity for L-LA. The polymerization did not proceed in the absence of BnOH. These studies regarding BnOH stoichiometry exclude the possibility that enantioselective enchainment occurred on both of the aluminum centers of the (S)-bi-Al complexes.

[0076] Using the four best-performing (S)-bi-Al complexes, ability to enantioselectively produce isotactic PLLA from rac-LA was evaluated. When ROP of rac-LA at 70 °C for 6 h (FIG.5), it was found that the complexes with ligands A14B1 and A29B2 (hereafter referred as LI and L2) exhibited remarkable enantioselectivity for L-LA (Table 1, entries 1 and 2). Reactions involving these ligands showed enantiotopic site-control selectivity (a) values of >0.9, as determined by homodecoupled1H and13C NMR spectroscopy of the obtained PLA (representative spectra are shown in FIG. 6); and percentage enantiomeric excess of D-LA in the unreacted monomer (eemin Table 1) exceeded 70%, as measured by chiral HPLC. The tetrad peaks of the a-methine groups inVTTP 24-050(103418-002PCT)the homodecoupled NMR spectrum of the product obtained from (5-Ll)A12Me4-mediated ROP of rac-LA (FIG. 6) showed an [rmm] / [rmr] ratio of 1.03 / 1, which is close to the theoretical ratio of 1 / 1 for ESC-mediated polymerization. ROP via the CEC mechanism (which would form sZ>-PLA) would give an [mrm l[mmr l[rmm\ ratio of -1 / 1 / 1, which was not observed in the present case. Similar results were observed for (S'-L2)A12Me4-mediated ROP of rac-LA, confirming that the ESC mechanism prevailed in these ROP reactions.

[0077] Additionally, the obtained polymers exhibited number-average MW ( ) values close to the expected MW and had narrow MW distributions (D - 1.1) (Table 1, entries 1 and 2). Switching the alcohol initiator from BnOH to 'PrOH did not substantially affect the a values obtained with ligands LI and L2 (Table 1, entries 3 and 4). Moreover, the chirality of the initiator did not substantially affect a, as indicated by the results of reactions initiated by L- or D-methyl lactate (MeLac) (entries 5 and 6), suggesting that enchainment by the ESC mechanism efficiently corrected stereoerrors. Furthermore, reactions catalyzed by (S)-bi-Al complexes bearing ligand LI or L2 exhibited first-order kinetics, and high a values (>0.9) were maintained over time. Increasing the reaction time to 7 h did not substantially increase the rac-LA conversion values (which were 52% and 53% for LI and L2, respectively), suggesting that sZ>-PLA formation was unlikely (otherwise more D-LA would have been consumed). The present results contrast with the kinetics for previously reported aluminum-complex-catalyzed ROP of rac-LA - those complexes continue to react even after one LA enantiomer is consumed.

[0078] Furthermore, the Mnof the PLLA obtained using (S)-bi-Al complexes with ligand LI or L2 increased when the [rac-LA] / [(5)-bi-Al] ratio was elevated to 300 / 1, and all the a values were > 0.89. On the basis of the above-described results, it was concluded that ligands LI and L2 were the best ligands for enantioselective ROP catalyzed by (S)-bi-Al complexes.Table 1rac-LACCm ee? spfactorEntry Ligand Initiator conv. adMWcaie D (kDa)fb(%r (%) (%d f(kDa) )1 5-L1 BnOH 48.5 73.4 0.92 70.7 11.5 6.3 7.0 1.11 2 5-L2 BnOH 44.2 77.8 0.93 75.8 13.3 6.6 6.5 1.15 3 5-L1 'PrOH 49.0 77.1 0.91 67.9 10.1 7.8 7.1 1.15 4 5-L2 'PrOH 45.5 73.3 0.93 75.1 13.3 6.9 6.6 1.12 5 5-L2 L-MeLac 48.8 72.5 0.90 64.2 9.0 7.7 7.5 1.146 5-L2 D-MeLac 47.6 75.5 0.91 68.7 10.1 7.0 6.9 1.11aPolymerization conditions: [rac-LA] / [(S)-bi-Al] / [initiator] = 100 / 1 / 1; [rac-LA]o = 694 mM in toluene. All polymerizations were performed at 70 °C for 6 h. Abbreviations: LA, lactide; bi-Al, bimetallic aluminum; Ln, ligand; conv., conversion; eem, percentage enantiomeric excess of D-LA in the unreacted monomer; eep, percentage enantiomeric excess of the L-LA unit in the polymer;p, selectivity factor of the polymer; a, enantiotopic sitecontrol selectivity; Mn, number-average molecular weight; MWcai, molecular weight calculated from feed ratio and conversion; D, molecular weight distribution; MeLac, methyl lactate.bDetermined by1H NMR spectroscopy.cDetermined by chiral HPLC of the unreacted rac-LA monomer.dDetermined by13C NMR spectroscopy.esp= a / ( 1 - a) = ln[l - conv. x (1 + eep)] / ln[l - conv. x (1 - eep)]. Here spwas calculated from a, and thenpandVTTP 24-050(103418-002PCT)conv. were used to derive eep.fDetermined by size-exclusion chromatography.Monometallic aluminum complexes enantioselectively polymerized D-LA from rac-LA

[0079] Inverting the chirality of the ligands of enantioselective ROP catalysts often reverses the enantioselectivity of reactions of racemic monomer mixtures. Because the leading ( )-bi-Al complexes (i.e., those with ligands LI and L2) required only 1 equiv. of alcohol to initiate the ROP, it was hypothesized that a mononuclear aluminum complex with R ligands might exhibit enantioselectivity toward D-LA in ROP of rac-LA. To test this, ROP of rac-LA was performed using R-Ll and 7?-L2 instead of the corresponding S ligands (FIG. 7). The ROP of rac-LA mediated by (R-Ll)AlMe and (7?-L2)AlMe complexes showed enantioselectivity toward D-LA with remarkable a values (>0.95) (Representative NMR spectra are shown in FIG. 8). The homodecoupled NMR spectra showed [rmm] / [rmr] ratios of ~1 / 1, confirming that an ESC mechanism was operative. The obtained polymers had Mnvalues close to the calculated MWs and had narrow D values (<1.1). Moreover, like the corresponding (S)-bi-Al complexes, the (R-Ll)AlMe and (R-L2)AlMe complexes enantioselectively polymerized rac-LA at feed ratios ([rac-LA] / [Al]) up to 300 / 1, yielding PDLA with a values of > 0.95.Chiral aluminum complexes catalyzed enantioselective polymerization of meso-LA

[0080] Having identified chiral aluminum complexes that mediated enantioselective ROP via the ESC mechanism, whether the complexes could mediate enantioselective ROP of meso-LA was investigated. Chiral (?-AiBi)AlO'Pr complexes have previously been shown to mediate enantioselective ROP of meso-LA to form syndiotactic (sd) PLA. Chiral (S-Ll)AhMe4 and S-L2)AhMe4 were used to polymerize meso-LA in the presence of BnOH, 'PrOH, or L-MeLac as an alcohol initiator, and scZ-PLA was obtained with a values ranging from 0.80 to 0.87.13C NMR spectroscopy showed that for the scZ-PLA obtained from these reactions, the tetrad [rmr\l\mrm}l\rrm\l\mrr\ ratios in the methine region were approximately 2 / 1 / 1 / 1 (representative13C NMR spectra of the ROP of meso-LA by (S-L2)AhMe4 / BnOH in FIG. 9, left panel), confirming that ROP of meso-LA proceeded via ESC enchainment. Noticeably, (7?-Ll)AlMe and (R-L2)AlMe proved to be more enantioselective than the corresponding S isomers in the ROP of meso-LA, affording srf-PLA with a values of 0.93 or 0.94 (representative13C NMR spectra of the ROP of meso-LA by (7?-L2)AlMe / L-MeLac in FIG. 9, right panel). The fact that the a values for (S)-bi-Al-catalyzed ROP of meso-LA were lower than the values for ROP of rac-LA using identical ligands (Table 1) indicates that the sensitivity of the chiral catalytic pockets of the (5)-bi-Al complexes to the subtle chirality difference between rac-LA and meso-LA. In contrast, the (2?)-Al complexes exhibited similar a values for ROP of rac-LA and meso-LA. This differential sensitivity suggests that the bimetallic ligand framework may provide a delicate chiral environment for enantio-VTTP 24-050(103418-002PCT)discrimination between two enantiomers in rac-LA. Note that all the scZ-PLA that was produced had Mnvalues close to the calculated values, and all the £> values were <1.1, suggesting that the polymerization was well-controlled. When the [? Meso-LA] / [(2?-L2)AlMe] / [L-MeLac] ratio was increased to 250 / 1 / 1 (24 h in toluene at 70 °C), the obtained s -PLA displayed a high a value of 0.93, a Mnof 28.0 kDa, and a D of 1.04.Mixtures of enantioselective aluminum complexes catalyzed the formation of stereocomplex PLA

[0081] With highly efficient enantioselective chiral aluminum complexes in hand, preparation of sc-PLA was explored. Although the screened (S)-bi-Al and (R)-A1 complexes were bimetallic and monometallic, respectively, both required just 1 equivalent of an alcohol initiator to mediate enantioselective ROP, indicating that for both catalysts, enchainment proceeded via a single metal center. It was hypothesized that 1 / 1 racemic mixtures of the (S)-bi-Al and (7?)- Al complexes, both with the same substituents on the ligands, would mediate enantioselective ROP of rac-LA to produce sc-PLA. To test this, aluminum complexes bearing racemic LI or L2 ligands were used for the ROP of rac-LA. It was found that the reactions showed <15% monomer conversion within 1 h, likely because initiation in the presence of the racemic mixtures of aluminum complexes was slow. To address this problem, the racemic aluminum complexes were allowed to react with rac-LA in two separate flasks for 1 h and then combined the two reaction mixtures in another flask and stirred the resulting mixture for an additional 7 h (FIG. 10, [rac-LA] / [(S)-bi-Al] / [(R)-Al] / ['PrOH] = 100 / 0.5 / 0.5 / 1, [rac-LA] = 694 mM in toluene at 70 °C). The (S-Ll)A12Me4 / (R-Ll)AlMe racemic mixture (hereafter referred to as rac-Ll-Al) produced highly isotactic PLA from rac-LA with an a value of 0.92 (FIG. 11), and the LA conversion was 93.5% (Table 2, entry 1). The obtained PLA had a Mnof 13.3 kDa, which is close to the calculated MW for sc-PLA (13.5 kDa), and a D of 1.01. The homodecoupled ’H NMR spectrum of the a-methine region of the obtained PLA showed an [rmr] / [rmm] ratio of 1 / 1.07 (FIG. 11), confirming that the ESC mechanism was operative (the theoretical ratio is 1 / 1). Additionally, the use of a racemic mixture rac-L2-Al (i.e., (S-L2)A12Me4 / (?-L2)AlMe) with 'PrOH resulted in slightly lower a values (Table 2, entry 2). Chiral HPLC showed that in the above-described polymerizations, the remaining rac-LA in the reaction (7 h after mixing) was approximately 1 / 1 mixture of L-LA and D-LA, indicating that equal amounts of the two LA enantiomers had been incorporated into the polymer. Furthermore, these polymerizations exhibited first-order kinetics after the two separate reaction mixtures were combined, and there was no obvious change in a during the polymerization (FIG. 12). The obtained sc-PLA exhibited a Tmof 200 °C with a negligible glass transition (Ts) peak (FIG. 13); the Tmvalue was higher than those for sZ>-PLA and pure PLLA. Taken together, the results are consistent with the results of our aforementioned studies of individual enantioselective aluminum complexes, a finding that rules out the possibility that sb-PLA formed via the CEC mechanism in these isoselective polymerizations.VTTP 24-050(103418-002PCT)Using optimized conditions, it was found that the Mnof the obtained sc-PLA increased proportionally to 47.1 kDa with an a of 0.90 as the [rac-LA] / [(5)-bi-Al] / [(7?)-Al] / ['PrOH] ratio was increased to 300 / 0.5 / 0.5 / 1 (Table 2, entries 3-5).

[0082] Given the opposite enantioselectivities exhibited by rac-Ll-Al complexes during the enchainment, it was hypothesized that replacing one chiral aluminum complex in the racemic catalyst mixture with another of the same chirality would not significantly affect the production of sc-PLA. To test this, ROP of rac-LA was performed using the racemic mixture (S’-L2)A12Me4 / (7?-Ll)AlMe with BnOH. The resulting sc-PLA had a Mnof 13.7 kDa, a £> of 1.01, and an a value of 0.91, comparable to sc-PLA produced using rac-Ll-Al (Table 2, entry 1). These results also exclude chain transfer - which often leads to sZ>-PLA - between chiral aluminum catalysts with different enantioselectivities.

[0083] The effects of PLA microstructure on the mechanical properties of the polymers was also explored. Notably, conventional sc-PLA prepared by blending PLLA and PDLA is poorly soluble in organic solvents (<20 g / L in dichloromethane), whereas the sc-PLA prepared by using rac-Ll-Al had excellent solubility in organic solvents (>200 g / L in dichloromethane), enabling convenient preparation of polymer films by means of the solvent-casting method. The sc-PLA (Mn= 47.1 kDa) exhibited a o of 46.2 MPa and an E of 40.0 %; that is, it was 11.3 times as tough as conventionally blended sc-PLA, which has a o of 50.6 MPa and an E of 4.5 % (FIG. 14). The low ratios of stereoerrors (high a values) in our sc-PLA may explain why the ductility and overall toughness were improved without a significant decrease in tensile strength. Notably, the syndiotactic s -PLA Mn= 28.0 kDa, a = 0.93) prepared from meso-LA presented as a soft polymer with a o of 11.5 MPa and an E of 12.5 % (FIG. 14).Table 2[rac-LA] / [(S)-bi- Time rac-LA Mi (kDa)Entry Ligand A1] / [(R)-A1] / a MWcai D (h)pbconv. (%)c dePrOHl (kDa)e1 rac-Ll 100 / 0.5 / 0.5 / 1 8 93.5 0.92 13.3 13.5 1.01 2 rac-L2 100 / 0.5 / 0.5 / 1 8 74.1 0.88 10.1 10.7 1.08 3 rac-Ll 150 / 0.5 / 0.5 / 1 12 91.6 0.91 18.3 19.9 1.07 4 rac-Ll 200 / 0.5 / 0.5 / 1 16f87.7 0.91 24.3 25.3 1.065 rac-Ll 300 / 0.5 / 0.5 / 1 26897.5 0.90 47.1 42.2 1.05aPolymerization conditions: [rac-LA] = 694 mM in toluene. All polymerizations were performed at 70 °C.Abbreviations: sc-PLA, stereocomplex PLA; conv., conversion; a, enantiotopic site-control selectivity; Mn, numberaverage molecular weight; MWcai, molecular weight calculated from feed ratio and conversion; D, molecular weight distribution.bIncludes the 1-h reaction time prior to mixing.cDetermined by *H NMR spectroscopy.dDetermined by13C NMR spectroscopy.eDetermined by size-exclusion chromatography.fIncludes the 4-h reaction time prior to mixing.8Includes the 6-h reaction time prior to mixing.Mechanistic and density functional theory studiesVTTP 24-050(103418-002PCT)

[0084] To unravel the origin of the enantioselectivity of the (S)-bi-Al-catalyzed ROP of rac-LA, density functional theory (DFT) calculations were done with (S-L2)AhMe4 because this complex afforded the polymer with the highest a value (Table 1, entries 2). Note that determining the site selectivity by means of NMR spectroscopy is untenable given the complicated (S)-bi-Al structure. Previous studies of rac-LA ROP mediated by chiral aluminum complexes have suggested that nucleophilic addition of LA to aluminum alkoxide via TS1 is the enantioselectivity-determining step that which LA enantiomer (L- or D-LA) insertion is more favorable. Additionally, the spatial orientation of LA coordination to the (S)-bi-Al complex — occurring at the cleft or at the side of the complex — may also impact the enantioselectivity. DFT calculations (at the SMDtoiuene / coB97M-V / def2-TZVP / / IEFPCMtoiuene / B3LYP-D3 / 6-31G(d)|LANL2DZ(I)] level of theory) showed that with (S, S)-lactate at the chain end ((S-L2)A12(S, S-Lac), mimicking the chain end post-L-LA ringopening), the energy barrier to insertion of L-LA into the cleft of (S-L2)A12(S, S-Lac) via TS-1 (TS-IS-L-c,; here S refers chain-end S, S-Lac, L: L-LA, C: cleft insertion) is 2.5 kcal / mol lower than the barrier to insertion at the side of the aluminum complex (TS-IS-L-S), and is 8.1 kcal / mol lower than the barrier to insertion of D-LA into the cleft (TS-1S-D-C). Interestingly, when the aluminum-attached chain end was replaced with (R, R)-lactate (mimicking the stereoerror of D-LA incorporation), L-LA insertion into the cleft via TS-1 (TS-17?-L-C) still showed a lower energy barrier than that of all the other pathways. The calculations thus corroborate the experimental results indicating that the catalyst chirality dictated the enantioselectivity, whereas the chain-end chirality was irrelevant (Table 1, entries 5 and 6), further confirming the involvement of the ESC enchainment mechanism.

[0085] To gain insight into the origin of the enantiocontrol exhibited by (S-L2)AhMe4, we utilized the independent gradient model based on the Hirshfeld partition to analyze the noncovalent interactions between the inserted LA and (S-L2)Ah in both TS-IS- -C and TS-IS-L-S. Particularly in the favored TS-IS-L-C transition state, L-LA is firmly embedded in an open pocket of (S-L )A12(S, S-Lac), and there are two C-O- -n interactions between the inserted LA and the phenyl rings of salicylaldehyde and the octahydrobinaphthyl groups in (S)-L2, interactions that are almost nonexistent in TS-1S-L-S or TS-IS-D-C. Although dispersion interactions are weaker than hydrogen bonds, more than five pairs of the former may have been sufficient to lead to the excellent enantiocontrol in the reactions listed in Table 1. Furthermore, energy decomposition analysis of the interaction between (S-L2)Ah(S, S-Lac) and LA interactions on enantioselectivity showed a more stabilizing dispersion interaction (i.e., more negative) in TS-IS-L-C (-42.97 kcal / mol) than in TS-IS-L-S (-33.68 kcal / mol), given the electrostatic and orbital interactions rarely varied. These results collectively confirm that the dispersion interactions between L-LA and (S-L2)Ah may have been the predominant factor controlling the enantioselectivity, rendering a delicate chiral environment forVTTP 24-050(103418-002PCT)favoring L-LA from rac-LA isomers and correcting stereoerrors.Enantioselective bulk polymerization of rac-LA

[0086] Bulk (solvent-free) polymerization is industrially attractive because it eliminates solvent handling, reduces cost and environmental burden, and affords high space-time yields.Because rac-LA has a melting point of ~120 °C, bulk polymerizations are typically carried out at >130 °C. At such temperatures, however, many catalysts exhibit diminished or even lost stereocontrol, and epimerization can occur. Stereoblock PLA (sZ>-PLA) produced by stereocontrolled bulk ROP of rac-LA has been demonstrated, however, bulk enantioselective ROP of rac-LA to get stereoregular PLLA or stereocomplex sc-PLA has not yet been reported.

[0087] It was hypothesized that introducing substituents on the aluminum complex’s chiral linkers Bi and B2 may affect enantioselectivity in the ROP of rac-LA.Screening of (1S’-ArnBn)AlMe for enantioselective ROP of rac-LA

[0088] A ligand framework was prepared where the chiral bridging linker (Bn; mostly derived from B1 / B2) and the aryl substituents (Ri, R2) on the phenolate rings were varied, as shown in FIG. 15. The resulting ligands were treated with 1.0 equiv of AlMea to produce monometallic complex (<S,-AmBn)AlMe. It was hypothesized that varying chiral linker Bnand substituents on phenyl group Amin monometallic complexes (1S’-AmBn)AlMe would develop new complex with improved L-LA selectivity in the enchainment from rac-LA. The present inventors sought to identify complexes that exhibit high enantioselectivity, deliver high-molecular-weight, highly isotactic PLLA, and retain this selectivity under bulk polymerization conditions.

[0089] Complexes were screened in the ROP of rac-LA at 70 °C for 6 h using benzyl alcohol (BnOH) as an initiator ([rac-LA / (S-AmBn)AlMe / [BnOH] = 100 / 1 / 1, [LA] = 694 mM in toluene], and conversion of rac-LA, a value and rmmlrmr ratio from homodecoupledNMR were recorded for each complex. For complexes showing low conversion at 70 °C after 6 h, the polymerization was repeated at 100 °C for 3 h. Complexes that (i) exhibit strong enantioselectivity (high a), (ii) afford ~50% conversion of rac-LA, which means reaction stops once L-LA is consumed and (iii) display rmmlrmr ratios ~ 1 which means the complex mediate the polymerization under ESC mechanism were prioritized.

[0090] Table 3 shows ROP of rac-LA mediated by various (S-AmBi)AlMe. As shown in Table 3, introducing substituents at Ri in (1S’-AmBn)AlMe generally diminishes both enantioselectivity and activity. Complexes with bulky Ri groups yield atactic PLA and markedly retard the reaction (entries 4, 6, 7, 11, 14, 15, 16, 17, 21), whereas less-bulky Ri groups still depress enantioselectivity, giving lower a values (entries 5, 10, 19, 20, 22). By contrast, judicious choice of R2 in (S-AmBn)AlMe can enhance both enantioselectivity and activity (entries 2, 3, 27, 28, 29, 30). AVTTP 24-050(103418-002PCT)similar trend was observed for S-AmE^AlMe (Table 4). Notably, (S-A2B2)AlMe exhibited relatively low conversion at 70 °C for 6 h with a high a at 0.971 (Table 4, entry 1), whereas at 100 °C for 3 h the conversion went above 0.6, a decreased to 0.898, and rmm / rmr increased to 1.57 in the ROP of rac-LA (Table 4, entry 1 vs entry 2). This means the complex loses enantioselectivity at higher temperature and may not be suitable for bulk polymerization.Table 3Entry Ligand rac-LA conv.[bIaM rmmlrmi^ 1 5-AiBi 0.578 0.879 1.64 2 S-A2BI 0.481 0.954 1.01 3 S-A3B1 0.532 0.952 1.04 4 5-AsBiM 0.230 ~0.5 0.83 5 5-AsBi 0.229 0.7836 S-A7B1H 0.116 0.690 3.38 7 S-AgBiW 0.107 0.8688 S-A9B1 0.417 0.865 1.00 9 5-AIQBI 0.565 0.934 1.07 10 5-AnBi 0.360 0.864 1.42 11 S-A12B1M 0.132 -0.512 S-A13B1 0.513 0.920 1.06 13 5-A14B1 0.584 0.923 1.54 14 S-AisBiW 0.331 0.649 1.04 15 5-Ai9BiM 0.044516 S-A20B1M 0.0459 - - 17 S-A21B1W 0.410 0.634 1.24 18 5-A22Bl 0.518 0.913 1.00 19 S-A23B1 0.425 0.854 1.52 20 5-A24B1M 0.498 0.711 1.02 21 S-A25B1W 0.086122 S-A28B1 0.485 0.875 1.67 23 S-A29B1 0.521 0.936 1.07 24 S-A30B1 0.571 0.926 1.19 25 S-AgiBl 0.290 0.940 1.01 26 5-A32B1M 0.685 0.867 1.96 27 5-A33B1 0.424 0.944 1.04 28 S-A34B1 0.498 0.947 1.02 29 S-A35B1 0.483 0.947 1.0030 tV-AseBi 0.467 0.947 1.00 a] Polymerization conditions: [rac-LA] / (S-AmB AlMe / [BnOH] = 100 / 1 / 1; [rac-LA] = 694 mM in toluene. All polymerizations were performed at 70 °C for 6 h. Abbreviation: conv., conversion; a, site-control selectivity; [b] Determined by 'H NMR spectroscopy.[c] Determined by homodecoupled 'H NMR or13C NMR spectroscopy.[d] Determined by homodecoupled 'H NMR.[e] Polymerizations were performed at 100 °C for 3 h.Table 4VTTP 24-050(103418-002PCT)Entry Ligand rac-LA conv.[bIaM rmm / rrm^ 1 5-A2B2 0.210 0.971 1.03 2 S-A2B2[el0.621 0.898 1.57 3 JS-A3B2 0.448 0.956 1.00 4 5-A4B2 0.535 0.941 1.02 5 S-A9B2 0.461 0.865 1.00 6 5-A10B2 0.562 0.942 1.02 7 5-AI3B20.513 0.950 1.01 8 5-A14B2 0.575 0.925 1.08 9 S-A26B2 0.12410 S-A29B2 0.589 0.920 1.52 11 5'-A3QB2 0.556 0.941 1.02 12 5’-A3iB2[el0.426 0.783 1.0313 5-A32B2 0.518 0.946 1.01 a] Polymerization conditions: [rac-LA] / [(S-AmB2)AlMe] / [BnOH] = 100 / 1 / 1; [rac-LA] = 694 mM in toluene. All polymerizations were performed at 70 °C for 6 h. Abbreviation: conv., conversion; a, site-control selectivity; [b] Determined by 'H NMR spectroscopy.[c] Determined by homodecoupled 'H NMR or13C NMR spectroscopy.[d] Determined by homodecoupled 'H NMR.[e] Polymerizations were performed at 100 °C for 3 h.

[0091] (S-AmB3)AlMe and (S'-AmB5)AlMe both produce atactic PLAs without stereocontrol in the ROP of rac-LA (Table 5, entry 1-3, 5). Groups on the 3, 3 '-positions of binaphthyl linker (Bi) or hydrogenated binaphthyl linker (B2) were introduced. The (S-AuB^AlMe with chloro group substitute on 3,3'-positions of binaphthyl shows lower activity and lower a value (Table 5, entry 4).Table 5Entry Ligand rac-LA conv.[blal'] rmrn / rmi^ 1 S-A7B3 0.120 - 2 S-A9B3 0.948 ~0.5 0.9 3 S-A14B3 0.985 -0.5 0.9 4 5-Ai4B4[e]0.437 0.861 1.025 5-A14B5 0.987 -0.5 0.98 a] Polymerization conditions: [rac-LA] / [(5-AmBn)AIMe] / [BnOH] = 100 / 1 / 1; [rac-LA] = 694 mM in toluene. All polymerizations were performed at 70 °C for 6 h. Abbreviation: conv., conversion; a, site-control selectivity; [b] Determined by *H NMR spectroscopy.[c] Determined by homodecoupled *H NMR or13C NMR spectroscopy.[d] Determined by homodecoupled *H NMR.[e] Polymerizations were performed at 100 °C for 3 h.

[0092] A smaller substituent (e.g., methyl) was introduced at the 3, 3 ’-positions of the binaphthyl linker to synthesize (1S,-AmBe)AlMe. (S-AuBe^lMe and (S-A3oBe)AlMe exhibited moderate conversion at 70 °C for 6 h with high a values, and they maintained high enantioselectivity (a > 0.92) at 100 °C for 3 h with rmm / rmr ~ 1.0 (Table 6, entries 10-13), suggesting a stable chiral pocket and good prospects for bulk polymerization. By contrast, (S-AsBe^lMe, (S’-A9Be)AlMe, and (S’-Ai3B6)AlMe showed lower a values but still rmmlrmr 1 (Table 6, entries 4 - 9), whereas (S-A2Bs)AlMe exhibited moderate enantioselectivity (Table 6, entries 2-3). These results suggest that an alkyl substituent at Ri benefits the enantioselectivity of (lS’-AmBe)AlMe. It is worth noting that (S-AiBe)AlMe shows improved a and rmm / rmr = 1.01 (Table 6, entry 1) relative to (S-AiBi)AlMe (Table 3, entry 1), indicating that the Be linker enhances enantioselectivity compared to Bi.VTTP 24-050(103418-002PCT)Table 6Entry Ligand rac-LA conv.[bla[c]rmm / rmr^ 1 S-AiB6[e]0.463 0.919 1.01 2 tS-AzBg 0.249 0.940 1.03 3 5-A2B6[el0.481 0.910 1.02 4 jS-AsBfi 0.270 0.962 1.01 5 S-AaBs^ 0.476 0.898 1.02 6 jS-AgBe 0.1527 S-AsBsM 0.327 0.743 1.03 8 iV-AiaBe 0.278 0.9149 S-ABB^J 0.427 0.882 1.02 10 5’-A14B6 0.314 0.964 1.01 11 S-Ai4B6[el0.485 0.925 1.02 12 S-A30B6 0.265 0.955 1.0213 S-AaoB^l 0.513 0.931 1.05 [a] Polymerization conditions: [rac-LA] / [(5-AmBi)AlMe] / [BnOH] = 100 / 1 / 1; [rac-LA] = 694 mM in toluene. All polymerizations were performed at 70 °C for 6 h. Abbreviation: conv., conversion; a, site-control selectivity; [b] Determined by ’H NMR spectroscopy.[c] Determined by homodecoupled 'H NMR or13C NMR spectroscopy.[d] Determined by homodecoupled 'H NMR.[e] Polymerizations were performed at 100 °C for 3 h.

[0093] Bulky substituents at the 3,3 ’-positions of the binaphthyl linker or hydrogenated binaphthyl linker in (1S’-AmBn)AlMe greatly decrease the enantioselectivity. For example, (S-Ai4B7)AlMe and (S-AuB^AlMe bearing phenyl groups produced atactic PLAs (Table 7, entries 1, 6, 7); the iodo-substituted (1S’-AmB8)AlMe produced PLA with a values < 0.88 (Table 7, entries 4, 5); and the bromo-substituted derivatives (S-Ai4Bio)AlMe and (S-Ai4Bi2)AlMe exhibited moderate enantioselectivity, affording PLAs with a = 0.88 - 0.92 (Table 7, entries 8-13).

[0094] (5-Ai4Bi3)AlMe, with a methyl substituent at the 3,3’-positions of the hydrogenated binaphthyl linker, showed slightly lower enantioselectivity than (S-AuBe^lMe in the ROP of rac-LA (a > 0.9 at both 70 ° C for 6 h and 100 ° C for 3 h, Table 7, entries 14-15). By contrast, the trifluoromethyl-substituted (S-AuB^AlMe gave a much lower a of 0.78 (Table 7, entry 16), indicating that substituent electronic effects are also operativeTable 7VTTP 24-050(103418-002PCT)Entry Ligand rac-LA conv.[bIaM rmm / rmi^ 1 (S-AuB? 0.295 0.614 0.79 2 S-A3B8[el0.493 0.815 1.01 3 S-A, B8W 0.0941 - - 4 S-A4BSH 0.385 0.735 1.02 5 S-Ai4B8[el0.395 0.880 1.02 6 5-A14B9 0.429 ~0.5 0.65 7 S-Ai4B9[e]0.878 -0.5 0.72 8 (S-AaBio 0.206 0.923 1.03 9 5-A3Bio[el0.455 0.893 1.05 10 5-AI4B10M 0.378 0.928 1.04 11 S-Ai4B12H 0.424 0.862 1.02 12 S-A30B12 0.207 0.90113 5-A30Bi2[e]0.427 0.885 1.03 14 S-A14B13 0.301 0.948 1.01 15 S-Ai4B13H 0.523 0.914 1.0416 S-A14B15 0.372 0.783 1.01 a] Polymerization conditions: [rac-LA] / [(S'-AmBn)AlMe] / [BnOH] = 100 / 1 / 1; [rac-LA] = 694 mM in toluene. All polymerizations were performed at 70 °C for 6 h. Abbreviation: conv., conversion; a, site-control selectivity; [b] Determined by *H NMR spectroscopy.[c] Determined by homodecoupled 'H NMR or13C NMR spectroscopy.[d] Determined by homodecoupled *H NMR.[e] Polymerizations were performed at 100 °C for 3 h.

[0095] The performance of (S-AmBn)AlMe bearing substituents at the 6,6'-positions of the binaphthyl linker was also investigated in the enantioselective ROP of rac-LA. The 6,6’bromo-substituted derivatives, (S-AmBn)AlMe, showed satisfactory conversion and a values at 70 ° C for 6 h (Table 8, entries 1, 3, 4, 5, 8), except for (5-A24Bn)AlMe, which displayed much lower a values (0.791 and 0.729), attributable to the introduction of Ri substituent in the phenyl group of salicylaldehyde. For (S-A2Bn)AlMe, increasing the polymerization temperature to 100 °C decreased a from 0.964 to 0.919 and raised rmmlrmr to 1.34, indicating that — despite its strong performance at 70 °C for 6 h — it is not promising for bulk polymerization. By contrast, (5-Ai4Bi4)AlMe, bearing phenyl groups at the 6,6'-positions of the binaphthyl linker, gave conversion near 0.50 and high alpha at both 70 °C and 100 °C (Table 8, entries 9 and 10).Table 8Entry Ligand rac-LA conv.[blrmm / rmr^ 1 5-A2B 11 0.402 0.964 1.02 2 S-AzBiiW 0.556 0.919 1.34 3 5-A3B11 0.565 0.937 1.03 4 5-A4B11 0.500 0.934 1.01 5 S-A14B11 0.540 0.937 1.00 6 5,-A24BU 0.225 0.791 1.03 7 S,-A24B11[el0.439 0.729 1.04 8 5-A30B11 0.405 0.961 1.01 9 S-A14B14 0.422 0.962 1.0010 5-Ai4Bi4[el0.488 0.940 1.01 a] Polymerization conditions: [rac-LA] / [(5'-AmBn)AlMe] / [BnOH] = 100 / 1 / 1; [rac-LA] = 694 mM in toluene. All polymerizations were performed at 70 °C for 6 h. Abbreviation: conv., conversion; a, site-control selectivity; [b] Determined by *H NMR spectroscopy.[c] Determined by homodecoupled *H NMR or13C NMR spectroscopy.[d] Determined by homodecoupled *H NMR.VTTP 24-050(103418-002PCT)[e] Polymerizations were performed at 100 °C for 3 h.Bulk polymerization of rac-LA by using leading (S’-AmBn)AlMe

[0096] As the top-performing candidates in the 70 °C / 100 °C ROP of rac-LA screening, (S-Ai4B6)AlMe, (5-A3oBe)AlMe, and (S-AuBi4)AlMe were selected for bulk ROP of rac-LA ([rac-LA] / (S-AmBn)AlMe / [BnOH] = 300 / 1 / 1), with (S-Ai4Bi)AlMe used as a control. As shown in Table 9, the complex (S-AuBe^lMe polymerized the rac-LA with high enantioselectivity as the a values > 0.92 and rmmlrmr ~ 1 (entry 2 and 3). The complex (5-A3oB6)AlMe gave a slightly increased rmmlrmr to 1.23 and (S'-Ai4Bi4)AlMe afforded PLA with decreased a of 0.896 (entry 4 and 5). By contrast, the complex (S-AuB^AlMe produced PLA with a much lower a of 0.781 and conversion of rac-LA>0.6 at 0.5 h, indicating the loss of stereocontrol.Table 9Reaction timeEntry Ligand rac-LAconv.[bIaM rmmlrmr^ (h)1 S-A14B1 0.5 0.629 0.781 1.55 2 0.5 0.267 0.948 1.01 3 5-A14B6 1.5 0.413 0.920 1.04 4 iS-AsoBe 1.5 0.541 0.900 1.235 S-A14B14 1.5 0.450 0.896 1.05 a] Polymerization conditions: [rac-LA] / [(S,-AmBn)AlMe] / [BnOH] = 300 / 1 / 1; [rac-LA] = 100 mg. All polymerizations were performed at 130 °C for designated time. Abbreviation: conv., conversion; a, site-control selectivity;[b] Determined by ’H NMR spectroscopy.[c] Determined by homodecoupled 'H NMR or13C NMR spectroscopy.[d] Determined by homodecoupled *H NMR.

[0097] In an industrial setting, enantioselective ROP of rac-LA to generate sc-PLA would be the most direct method for enhancing the thermomechanical properties of PLA. Herein, the present inventors have disclosed the first solution to the longstanding challenge of finding a practical method for mediating ROP of rac-LA via the ESC enchainment mechanism for each enantiomer separately, as well as for mixtures of the enantiomers. The sc-PLA obtained displayed better toughness and ductility than PLLA, sft-PLA, and sc-PLA prepared by blending PLLA and PDLA.

[0098] Experimental details follow.General polymerization procedures of rac-LA by BnOH and (5)-bi-Al complex

[0099] In a glove box, 50 pL BnOH (4.5 mg / mL in toluene, 2.08 pmol) and (S-Ll)ALMe4 or (5-L2)A12Me4 catalyst (2.08 pmol) were mixed first in a 15-mL thick-wall glass vessel equipped with a stirrer bar, followed by adding rac-LA (30 mg, 0.208 mmol) and 250 pL toluene to get a final concentration of rac-LA of 694 mM ([rac-LA] / [(S)-bi-Al] / [BnOH] = 100 / 1 / 1). The reaction was stirred at 70 °C for 6 hours. The reaction was then cooled to room temperature, and an aliquot of the solution was dried for NMR analysis to determine the monomer conversion and stereochemistry. Another aliquot of solution was used for chiral HPLC analysis. The remaining solution was dried, and the obtained solid was washed by excess methanol to remove the residue monomers for SECVTTP 24-050(103418-002PCT)analysis.General polymerization procedures of rac-LA by ‘PrOH and rac-Ll-Al complexes

[0100] In a glove box, (5-Ll)A12Me4 (2.08 pmol) was mixed with isopropanol (‘PrOH, 2.08 pmol in 50 pL toluene) in a 15-mL thick-wall glass vessel with a stirrer bar, followed by adding rac-LA (0.208 mmol) and 250 pL toluene. Separately, (7?-Ll)AlMe (2.08 pmol) was mixed with isopropanol (2.08 pmol in 50 pL toluene) in another 15-mL thick- wall glass vessel with a stirrer bar, and rac-LA (0.208 mmol) and 250 pL toluene were added. Both vessels were heated at 70 °C for 1 hour in the glove box. The solution containing (2?-Ll)AlMe were then quickly transferred to the vessel (5-Ll)A12Me4 in the glove box. The combined solution ([rac-LA] / [(S-Ll)A12Me4] / [(?-L^AlMeJ / PrOH] = 100 / 0.5 / 0.5 / 1) was stirred at 70 °C for additional 7 hours. The reaction was then cooled to room temperature, and an aliquot of the solution was dried for NMR analysis to determine the conversion and stereochemistry. Another aliquot of solution was used for chiral HPLC analysis. The remaining solution was dried, and the obtained solid was washed by excess methanol to remove the residue monomers for SEC analysis.

[0101] This disclosure further encompasses the following aspects.

[0102] Aspect 1: An aluminum complex having structure (I) or structure (II)wherein in the foregoing structures, each occurrence of R1is independently selected from hydrogen, methyl, t-butyl, bromine, fluorine, chlorine, nitro, ethoxy, and trifluoromethyl; each occurrence of R2is independently selected from hydrogen, methyl, ethyl, t-butyl, bromine, fluorine, chlorine, iodine, nitro, methoxy, and trifluoromethyl; each occurrence of R3is independently selected from a fused unsubstituted phenyl ring, a fused unsubstituted cyclohexyl ring, a fused 6,6’-bromine substituted phenyl ring, and a fused 6,6’-phenyl substituted phenyl ring; and each occurrence of R4is independently selected from a methyl, ethyl, phenyl, t-butyl, fluorine, bromine, iodine, and trifluoromethyl.

[0103] Aspect 2: The aluminum complex of claim 1, wherein the aluminum complex is a bimetallic aluminum complex according to structure (I).

[0104] Aspect 3: The aluminum complex of aspect 2, wherein each occurrence of R3is a fused unsubstituted phenyl ring, and the bimetallic aluminum complex is of the structureVTTP 24-050(103418-002PCT)

[0105] Aspect 4: The aluminum complex of aspect 2, wherein each occurrence of R3is a fused unsubstituted cyclohexyl ring, and the bimetallic aluminum complex is of the structure

[0106] Aspect 5: The aluminum complex of any of aspects 1 to 4, wherein each occurrence of R1is hydrogen and each occurrence of R2is hydrogen; or each occurrence of R1is hydrogen and each occurrence of R2is t-butyl; or each occurrence of R1is hydrogen and each occurrence of R2is methoxy; or each occurrence of R1is hydrogen and each occurrence of R2is chlorine; or each occurrence of R1is bromine and each occurrence of R2is bromine; or each occurrence of R1is methyl and each occurrence of R2is hydrogen; or each occurrence of R1is t-butyl and each occurrence of R2is t-butyl; or each occurrence of R1is t-butyl and each occurrence of R2is hydrogen; or each occurrence of R1is hydrogen and each occurrence of R2is nitro; or each occurrence of R1is hydrogen and each occurrence of R2is fluorine; or each occurrence of R1is fluorine and each occurrence of R2is hydrogen; or each occurrence of R1is bromine and each occurrence of R2is nitro; or each occurrence of R1is hydrogen and each occurrence of R2is bromine; or each occurrence of R1is hydrogen and each occurrence of R2is methyl; or each occurrence of R1is ethoxy and each occurrence of R2is hydrogen; or each occurrence of R1is chlorine and each occurrence of R2is hydrogen; or each occurrence of R1is chlorine and each occurrence of R2is chlorine; or each occurrence of R1is methyl and each occurrence of R2is chlorine; or each occurrence of R1is nitro and each occurrence of R2is chlorine; or each occurrence of R1is nitro and each occurrence of R2is hydrogen; or each occurrence of R1is chlorine and each occurrence of R2is fluorine; or each occurrence of R1is hydrogen and each occurrence of R2is trifluoromethyl; or each occurrence of R1is fluorine and each occurrence of R2is fluorine; or each occurrence of R1is methyl and each occurrence of R2is fluorine; or each occurrence of R1is trifluoromethyl and each occurrence of R2is hydrogen; or each occurrence of R1is fluorine and each occurrence of R2is nitro; or each occurrence of R1is methyl and each occurrence of R2is methyl; orVTTP 24-050(103418-002PCT)each occurrence of R1is fluorine and each occurrence of R2is methyl; or each occurrence of R1is hydrogen and each occurrence of R2is iodine; or each occurrence of R1is hydrogen and each occurrence of R2is ethyl.

[0107] Aspect 6: The aluminum complex of any of aspects 1 to 5, wherein the aluminum complex is a bimetallic aluminum complex according to structure (I), and each occurrence of R1is hydrogen; each occurrence of R2is methyl; and each occurrence of R3is a fused unsubstituted phenyl ring; each occurrence of R4is hydrogen; and the aluminum complex is of the structure

[0108] Aspect 7: The aluminum complex of any of aspects 1 to 5, wherein the aluminum complex is a bimetallic aluminum complex according to structure (I), and each occurrence of R1is hydrogen; each occurrence of R2is iodine; and each occurrence of R3is a fused unsubstituted cyclohexyl ring; each occurrence of R4is hydrogen; and the aluminum complex is of the structure

[0109] Aspect 8: The aluminum complex of aspect 1, wherein the aluminum complex is a monometallic aluminum complex according to structure (II).

[0110] Aspect 9: The aluminum complex of aspect 8, wherein each occurrence of R3is a fused unsubstituted phenyl ring, and the monometallic aluminum complex is of the structure

[0111] Aspect 10: The aluminum complex of aspect 8, wherein each occurrence of R3is aVTTP 24-050(103418-002PCT)fused unsubstituted cyclohexyl ring, and the monometallic aluminum complex is of the structure

[0112] Aspect 11: The aluminum complex of aspect 8, wherein each occurrence of R3is a fused 6,6’-bromine substituted phenyl ring, and the monometallic aluminum complex is of the structure

[0113] Aspect 12: The aluminum complex of aspect 8, wherein each occurrence of R3is a fused 6,6’-phenyl substituted phenyl ring, and the monometallic aluminum complex is of the structure

[0114] Aspect 13: The aluminum complex of any of aspects 1 or 8 to 12, wherein the aluminum complex is a monometallic aluminum complex according to structure (II), and each occurrence of R1is hydrogen and each occurrence of R2is hydrogen; or each occurrence of R1is hydrogen and each occurrence of R2is t-butyl; or each occurrence of R1is hydrogen and each occurrence of R2is methoxy; or each occurrence of R1is hydrogen and each occurrence of R2isVTTP 24-050(103418-002PCT)chlorine; or each occurrence of R1is bromine and each occurrence of R2is bromine; or each occurrence of R1is methyl and each occurrence of R2is hydrogen; or each occurrence of R1is t-butyl and each occurrence of R2is t-butyl; or each occurrence of R1is t-butyl and each occurrence of R2is hydrogen; or each occurrence of R1is hydrogen and each occurrence of R2is nitro; or each occurrence of R1is hydrogen and each occurrence of R2is fluorine; or each occurrence of R1is fluorine and each occurrence of R2is hydrogen; or each occurrence of R1is bromine and each occurrence of R2is nitro; or each occurrence of R1is hydrogen and each occurrence of R2is bromine; or each occurrence of R1is hydrogen and each occurrence of R2is methyl; or each occurrence of R1is ethoxy and each occurrence of R2is hydrogen; or each occurrence of R1is chlorine and each occurrence of R2is hydrogen; or each occurrence of R1is chlorine and each occurrence of R2is chlorine; or each occurrence of R1is methyl and each occurrence of R2is chlorine; or each occurrence of R1is nitro and each occurrence of R2is chlorine; or each occurrence of R1is nitro and each occurrence of R2is hydrogen; or each occurrence of R1is chlorine and each occurrence of R2is fluorine; or each occurrence of R1is hydrogen and each occurrence of R2is trifluoromethyl; or each occurrence of R1is fluorine and each occurrence of R2is fluorine; or each occurrence of R1is methyl and each occurrence of R2is fluorine; or each occurrence of R1is trifluoromethyl and each occurrence of R2is hydrogen; or each occurrence of R1is fluorine and each occurrence of R2is nitro; or each occurrence of R1is methyl and each occurrence of R2is methyl; or each occurrence of R1is fluorine and each occurrence of R2is methyl; or each occurrence of R1is hydrogen and each occurrence of R2is iodine; or each occurrence of R1is hydrogen and each occurrence of R2is ethyl.

[0115] Aspect 14: The aluminum complex of any of aspects 1 or 8 to 13, wherein the aluminum complex is a monometallic aluminum complex according to structure (II), and each occurrence of R1is hydrogen; each occurrence of R2is methyl; each occurrence of R3is a fused unsubstituted phenyl ring; and each occurrence of R4is hydrogen; and the monometallic aluminum composition is of the structure

[0116] Aspect 15: The aluminum composition of any of aspects 1 or 8 to 13, wherein the aluminum complex is a monometallic aluminum complex according to structure (II), and eachVTTP 24-050(103418-002PCT)occurrence of R1is hydrogen; each occurrence of R2is iodine; each occurrence of R3is a fused unsubstituted cyclohexyl ring; and each occurrence of R4is hydrogen; and the monometallic aluminum composition is of the structure

[0117] Aspect 16: The aluminum complex of any of aspects 1 or 8 to 13, wherein the aluminum complex is a monometallic aluminum complex according to structure (II), and each occurrence of R1is hydrogen; each occurrence of R2is methyl; each occurrence of R3is a fused unsubstituted phenyl ring; and each occurrence of R4is methyl; and the monometallic aluminum composition is of the structure

[0118] Aspect 17: The aluminum complex of any of aspects 1 or 8 to 13, wherein the aluminum complex is a monometallic aluminum complex according to structure (II), and each occurrence of R1is hydrogen; each occurrence of R2is methyl; each occurrence of R3is a fused unsubstituted cyclohexyl ring; and each occurrence of R4is methyl; and the monometallic aluminum composition is of the structureVTTP 24-050(103418-002PCT)

[0119] Aspect 18: The aluminum complex of any of aspects 1 or 8 to 13, wherein the aluminum complex is a monometallic aluminum complex according to structure (II), and each occurrence of R1is hydrogen; each occurrence of R2is methyl; each occurrence of R3is a fused 6,6’-bromine substituted phenyl ring; and each occurrence of R4is methyl; and the monometallic aluminum composition is of the structure

[0120] Aspect 19: The aluminum complex of any of aspects 1 or 8 to 12, wherein the aluminum complex is a monometallic aluminum complex according to structure (II), and each occurrence of R1is hydrogen; each occurrence of R2is methyl; each occurrence of R3is a fused 6,6’-phenyl substituted phenyl ring; and each occurrence of R4is methyl; and the monometallic aluminum composition is of the structure

[0121] Aspect 20: A method for the manufacture of poly(L-lactic acid) from a racemic mixture of lactide, the method comprising: contacting the racemic mixture of lactide with an aluminum complex according to any of aspects 2 to 7 under conditions effective to provide the poly(L-lactic acid).

[0122] Aspect 21: The method of aspect 20, wherein the poly(L-lactic acid) has a number average molecular weight of 3,000 to 50,000 Daltons, preferably 3,000 to 15,000 Daltons, as determined by gel permeation chromatography; a dispersity of less than 1.2, as determined by gel permeation chromatography; and an enantiotopic site-control selectivity a of greater than or equal to 0.9.

[0123] Aspect 22: A method for the manufacture of poly(lactic acid) from a racemic mixtureVTTP 24-050(103418-002PCT)of lactide, the method comprising: contacting the racemic mixture of lactide with an aluminum complex according structure (II) having an R configuration of any of aspects 8 to 19 under conditions effective to provide poly(D-lactic acid); or contacting the racemic mixture of lactide with an aluminum according structure (II) having an S configuration of any of aspects 8 to 19 under conditions effective to provide poly(L-lactic acid).

[0124] Aspect 23: The method of aspect 22, wherein the poly(lactic acid) has a number average molecular weight of 3,000 to 50,000 Daltons, preferably 3,000 to 15,000 Daltons, as determined by gel permeation chromatography; a dispersity of less than 1.2, as determined by gel permeation chromatography; and an enantiotopic site-control selectivity a of greater than or equal to 0.9.

[0125] Aspect 24: A method for the manufacture of syndiotactic poly(lactic acid), the method comprising: contacting / Meso-lactide with the aluminum complex of any of aspects 1 to 19 under conditions effective to provide the syndiotactic poly(lactic acid).

[0126] Aspect 25: A method for the manufacture of stereocomplex poly(lactic acid) from a racemic mixture of lactide, the method comprising: contacting the racemic mixture of lactide with a bimetallic aluminum complex according to structure (I) and a monometallic aluminum complex according to structure (II), wherein the bimetallic aluminum complex and the monometallic aluminum complex are according to any of aspects 1 to 19 under conditions effective to provide the stereocomplex poly(lactic acid).

[0127] Aspect 26: The method of aspect 25, wherein a molar ratio of the bimetallic aluminum complex of structure (I) to the monometallic aluminum complex of structure (II) is 0.95:1.05 to 1.05 to 0.95, or 1:1.

[0128] Aspect 27: The method of aspect 25 or 26, wherein the bimetallic aluminum composition is of the structureAl'O / \ H3C CH3; and the monometallic aluminum complex is of the structureVTTP 24-050(103418-002PCT)

[0129] Aspect 28: The method of any of aspects 25 to 27, comprising: contacting a first portion of the racemic mixture of lactide with the bimetallic aluminum complex for a predetermined amount of time to provide a first reaction mixture; contacting a second portion of the racemic mixture of lactide with the monometallic aluminum complex for the predetermined amount of time to provide a second reaction mixture; and combining the first reaction mixture and the second reaction mixture to provide the stereocomplex poly(lactic acid).

[0130] Aspect 29: A stereocomplex poly(lactic acid) made by the method of any of aspects 25 to 28, wherein the stereocomplex poly(lactic acid) exhibits one or both of increased solubility in organic solvent relative to a comparative stereocomplex poly(lactic acid) prepared by blending poly(L-lactic acid) and poly(D-lactic acid); and increased toughness relative to a comparative stereocomplex poly(lactic acid) prepared by blending poly(L-lactic acid) and poly(D-lactic acid).

[0131] Aspect 30: A method for the bulk polymerization of a racemic mixture of lactide, the method comprising: contacting the racemic mixture of lactide with an aluminum complex according to structure (II) having an R configuration of any of aspects 8 to 19, wherein the contacting is at aVTTP 24-050(103418-002PCT)temperature of at least 130 °C and in the absence of a solvent to provide poly(D-lactic acid); or contacting the racemic mixture of lactide with an aluminum complex according to structure (II) having an S configuration of any of aspects 8 to 19, wherein the contacting is at a temperature of at least 130 °C and in the absence of a solvent to provide poly(L-lactic acid).

[0132] The compositions, methods, and articles can alternatively comprise, consist of, or consist essentially of, any appropriate materials, steps, or components herein disclosed. The compositions, methods, and articles can additionally, or alternatively, be formulated so as to be devoid, or substantially free, of any materials (or species), steps, or components, that are otherwise not necessary to the achievement of the function or objectives of the compositions, methods, and articles.

[0133] Unless defined otherwise, technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this application belongs. All cited patents, patent applications, and other references are incorporated herein by reference in their entirety. However, if a term in the present application contradicts or conflicts with a term in the incorporated reference, the term from the present application takes precedence over the conflicting term from the incorporated reference.

[0134] Compounds are described using standard nomenclature. For example, any position not substituted by any indicated group is understood to have its valency filled by a bond as indicated, or a hydrogen atom. A dash ("-") that is not between two letters or symbols is used to indicate a point of attachment for a substituent. For example, -CHO is attached through carbon of the carbonyl group.

[0135] Unless substituents are otherwise specifically indicated, each of the foregoing groups can be unsubstituted or substituted, provided that the substitution does not significantly adversely affect synthesis, stability, or use of the compound. “Substituted” means that the compound, group, or atom is substituted with at least one (e.g., 1, 2, 3, or 4) substituents instead of hydrogen, where each substituent is independently nitro (-NO2), cyano (-CN), hydroxy (-OH), halogen, thiol (-SH), thiocyano (-SCN), Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1.9 alkoxy, Ci-6 haloalkoxy, C3-12 cycloalkyl, Cs-is cycloalkenyl, Ce-i2 aryl, C7-13 arylalkylene (e.g., benzyl), C7-12 alkylarylene (e.g, toluyl), C4-12 heterocycloalkyl, C3-12 heteroaryl, Ci-6 alkyl sulfonyl (-S(=O)2-alkyl), C6.12 aiylsulfonyl (-S(=O)2-aryl), or tosyl (CH3C6H4SO2-), provided that the substituted atom’s normal valence is not exceeded, and that the substitution does not significantly adversely affect the manufacture, stability, or desired property of the compound. When a compound is substituted, the indicated number of carbon atoms is the total number of carbon atoms in the compound or group, including those of any substituents.

[0136] While particular embodiments have been described, alternatives, modifications,VTTP 24-050(103418-002PCT)variations, improvements, and substantial equivalents that are or may be presently unforeseen may arise to applicants or others skilled in the art. Accordingly, the appended claims as filed and as they may be amended are intended to embrace all such alternatives, modifications variations, improvements, and substantial equivalents.

Claims

VTTP 24-050(103418-002PCT)CLAIMS1. An aluminum complex having structure (I) or structure (II)wherein in the foregoing structures,each occurrence of R1is independently selected from hydrogen, methyl, t-butyl, bromine, fluorine, chlorine, nitro, ethoxy, and trifluoromethyl;each occurrence of R2is independently selected from hydrogen, methyl, ethyl, t-butyl, bromine, fluorine, chlorine, iodine, nitro, methoxy, and trifluoromethyl;each occurrence of R3is independently selected from a fused unsubstituted phenyl ring, a fused unsubstituted cyclohexyl ring, a fused 6,6’-bromine substituted phenyl ring, and a fused 6,6’-phenyl substituted phenyl ring; andeach occurrence of R4is independently selected from a methyl, ethyl, phenyl, t-butyl, fluorine, bromine, iodine, and trifluoromethyl.

2. The aluminum complex of claim 1, wherein the aluminum complex is a bimetallic aluminum complex according to structure (I).

3. The aluminum complex of claim 2, wherein each occurrence of R3is a fused unsubstituted phenyl ring, and the bimetallic aluminum complex is of the structure4. The aluminum complex of claim 2, wherein each occurrence of R3is a fused unsubstituted cyclohexyl ring, and the bimetallic aluminum complex is of the structureVTTP 24-050(103418-002PCT)5. The aluminum complex of claim 1, wherein the aluminum complex is a bimetallic aluminum complex according to structure (I), andeach occurrence of R1is hydrogen and each occurrence of R2is hydrogen; oreach occurrence of R1is hydrogen and each occurrence of R2is t-butyl; oreach occurrence of R1is hydrogen and each occurrence of R2is methoxy; oreach occurrence of R1is hydrogen and each occurrence of R2is chlorine; oreach occurrence of R1is bromine and each occurrence of R2is bromine; oreach occurrence of R1is methyl and each occurrence of R2is hydrogen; oreach occurrence of R1is t-butyl and each occurrence of R2is t-butyl; oreach occurrence of R1is t-butyl and each occurrence of R2is hydrogen; oreach occurrence of R1is hydrogen and each occurrence of R2is nitro; oreach occurrence of R1is hydrogen and each occurrence of R2is fluorine; oreach occurrence of R1is fluorine and each occurrence of R2is hydrogen; oreach occurrence of R1is bromine and each occurrence of R2is nitro; oreach occurrence of R1is hydrogen and each occurrence of R2is bromine; oreach occurrence of R1is hydrogen and each occurrence of R2is methyl; oreach occurrence of R1is ethoxy and each occurrence of R2is hydrogen; oreach occurrence of R1is chlorine and each occurrence of R2is hydrogen; oreach occurrence of R1is chlorine and each occurrence of R2is chlorine; oreach occurrence of R1is methyl and each occurrence of R2is chlorine; oreach occurrence of R1is nitro and each occurrence of R2is chlorine; oreach occurrence of R1is nitro and each occurrence of R2is hydrogen; oreach occurrence of R1is chlorine and each occurrence of R2is fluorine; oreach occurrence of R1is hydrogen and each occurrence of R2is trifluoromethyl; or each occurrence of R1is fluorine and each occurrence of R2is fluorine; oreach occurrence of R1is methyl and each occurrence of R2is fluorine; oreach occurrence of R1is trifluoromethyl and each occurrence of R2is hydrogen; or each occurrence of R1is fluorine and each occurrence of R2is nitro; oreach occurrence of R1is methyl and each occurrence of R2is methyl; orVTTP 24-050(103418-002PCT)each occurrence of R1is fluorine and each occurrence of R2is methyl; oreach occurrence of R1is hydrogen and each occurrence of R2is iodine; oreach occurrence of R1is hydrogen and each occurrence of R2is ethyl.

6. The aluminum complex of claim 1, wherein the aluminum complex is a bimetallic aluminum complex according to structure (I), andeach occurrence of R1is hydrogen;each occurrence of R2is methyl; andeach occurrence of R3is a fused unsubstituted phenyl ring;each occurrence of R4is hydrogen;and the aluminum complex is of the structure7. The aluminum complex of claim 1, wherein the aluminum complex is a bimetallic aluminum complex according to structure (I), andeach occurrence of R1is hydrogen;each occurrence of R2is iodine; andeach occurrence of R3is a fused unsubstituted cyclohexyl ring;each occurrence of R4is hydrogen;and the aluminum complex is of the structure8. The aluminum complex of claim 1, wherein the aluminum complex is a monometallic aluminum complex according to structure (II).

9. The aluminum complex of claim 8, wherein each occurrence of R3is a fused unsubstitutedVTTP 24-050(103418-002PCT)phenyl ring, and the monometallic aluminum complex is of the structure10. The aluminum complex of claim 8, wherein each occurrence of R3is a fused unsubstituted cyclohexyl ring, and the monometallic aluminum complex is of the structure11. The aluminum complex of claim 8, wherein each occurrence of R3is a fused 6,6’-bromine substituted phenyl ring, and the monometallic aluminum complex is of the structureBr12. The aluminum complex of claim 8, wherein each occurrence of R3is a fused 6,6’-phenyl substituted phenyl ring, and the monometallic aluminum complex is of the structureVTTP 24-050(103418-002PCT)13. The aluminum complex of claim 8, wherein the aluminum complex is a monometallic aluminum complex according to structure (II), andeach occurrence of R1is hydrogen and each occurrence of R2is hydrogen; or each occurrence of R1is hydrogen and each occurrence of R2is t-butyl; or each occurrence of R1is hydrogen and each occurrence of R2is methoxy; or each occurrence of R1is hydrogen and each occurrence of R2is chlorine; or each occurrence of R1is bromine and each occurrence of R2is bromine; or each occurrence of R1is methyl and each occurrence of R2is hydrogen; or each occurrence of R1is t-butyl and each occurrence of R2is t-butyl; oreach occurrence of R1is t-butyl and each occurrence of R2is hydrogen; or each occurrence of R1is hydrogen and each occurrence of R2is nitro; or each occurrence of R1is hydrogen and each occurrence of R2is fluorine; or each occurrence of R1is fluorine and each occurrence of R2is hydrogen; or each occurrence of R1is bromine and each occurrence of R2is nitro; oreach occurrence of R1is hydrogen and each occurrence of R2is bromine; or each occurrence of R1is hydrogen and each occurrence of R2is methyl; or each occurrence of R1is ethoxy and each occurrence of R2is hydrogen; or each occurrence of R1is chlorine and each occurrence of R2is hydrogen; or each occurrence of R1is chlorine and each occurrence of R2is chlorine; or each occurrence of R1is methyl and each occurrence of R2is chlorine; or each occurrence of R1is nitro and each occurrence of R2is chlorine; oreach occurrence of R1is nitro and each occurrence of R2is hydrogen; or each occurrence of R1is chlorine and each occurrence of R2is fluorine; or each occurrence of R1is hydrogen and each occurrence of R2is trifluoromethyl; or each occurrence of R1is fluorine and each occurrence of R2is fluorine; or each occurrence of R1is methyl and each occurrence of R2is fluorine; or each occurrence of R1is trifluoromethyl and each occurrence of R2is hydrogen; orVTTP 24-050(103418-002PCT)each occurrence of R1is fluorine and each occurrence of R2is nitro; oreach occurrence of R1is methyl and each occurrence of R2is methyl; oreach occurrence of R1is fluorine and each occurrence of R2is methyl; oreach occurrence of R1is hydrogen and each occurrence of R2is iodine; oreach occurrence of R1is hydrogen and each occurrence of R2is ethyl.

14. The aluminum complex of claim 8, wherein the aluminum complex is a monometallic aluminum complex according to structure (II), andeach occurrence of R1is hydrogen;each occurrence of R2is methyl;each occurrence of R3is a fused unsubstituted phenyl ring; andeach occurrence of R4is hydrogen;and the monometallic aluminum composition is of the structure15. The aluminum composition of claim 8, wherein the aluminum complex is a monometallic aluminum complex according to structure (II), andeach occurrence of R1is hydrogen;each occurrence of R2is iodine;each occurrence of R3is a fused unsubstituted cyclohexyl ring; andeach occurrence of R4is hydrogen;and the monometallic aluminum composition is of the structureVTTP 24-050(103418-002PCT)16. The aluminum complex of claim 8, wherein the aluminum complex is a monometallic aluminum complex according to structure (II), andeach occurrence of R1is hydrogen;each occurrence of R2is methyl;each occurrence of R3is a fused unsubstituted phenyl ring; andeach occurrence of R4is methyl;and the monometallic aluminum composition is of the structure17. The aluminum complex of claim 8, wherein the aluminum complex is a monometallic aluminum complex according to structure (II), andeach occurrence of R1is hydrogen;each occurrence of R2is methyl;each occurrence of R3is a fused unsubstituted cyclohexyl ring; andeach occurrence of R4is methyl;and the monometallic aluminum composition is of the structure18. The aluminum complex of claim 8, wherein the aluminum complex is a monometallic aluminum complex according to structure (II), andVTTP 24-050(103418-002PCT)each occurrence of R1is hydrogen;each occurrence of R2is methyl;each occurrence of R3is a fused 6,6 ’-bromine substituted phenyl ring; andeach occurrence of R4is methyl;and the monometallic aluminum composition is of the structureBr19. The aluminum complex of claim 8, wherein the aluminum complex is a monometallic aluminum complex according to structure (II), andeach occurrence of R1is hydrogen;each occurrence of R2is methyl;each occurrence of R3is a fused 6,6 ’-phenyl substituted phenyl ring; andeach occurrence of R4is methyl;and the monometallic aluminum composition is of the structure20. A method for the manufacture of poly(L-lactic acid) from a racemic mixture of lactide, the method comprising:contacting the racemic mixture of lactide with an aluminum complex according to claim 2 under conditions effective to provide the poly(L-lactic acid).VTTP 24-050(103418-002PCT)21. The method of claim 20, wherein the poly(L-lactic acid) hasa number average molecular weight of 3,000 to 50,000 Daltons, preferably 3,000 to 15,000 Daltons, as determined by gel permeation chromatography;a dispersity of less than 1.2, as determined by gel permeation chromatography; and an enantiotopic site-control selectivity a of greater than or equal to 0.9.

22. A method for the manufacture of poly(lactic acid) from a racemic mixture of lactide, the method comprising:contacting the racemic mixture of lactide with an aluminum complex according structure (II) having an R configuration of claim 8 under conditions effective to provide poly(D-lactic acid); or contacting the racemic mixture of lactide with an aluminum according structure (II) having an S configuration of claim 8 under conditions effective to provide poly(L-lactic acid).

23. The method of claim 22, wherein the poly(lactic acid) hasa number average molecular weight of 3,000 to 50,000 Daltons, preferably 3,000 to 15,000 Daltons, as determined by gel permeation chromatography;a dispersity of less than 1.2, as determined by gel permeation chromatography; and an enantiotopic site-control selectivity a of greater than or equal to 0.9.

24. A method for the manufacture of syndiotactic poly(lactic acid), the method comprising: contacting meso-lactide with the aluminum complex of claim 1 under conditions effective to provide the syndiotactic poly(lactic acid).

25. A method for the manufacture of stereocomplex poly(lactic acid) from a racemic mixture of lactide, the method comprising:contacting the racemic mixture of lactide with a bimetallic aluminum complex according to structure (I) and a monometallic aluminum complex according to structure (II), wherein the bimetallic aluminum complex and the monometallic aluminum complex are according to claim 1 under conditions effective to provide the stereocomplex poly(lactic acid).

26. The method of claim 25, wherein a molar ratio of the bimetallic aluminum complex of structure (I) to the monometallic aluminum complex of structure (II) is 0.95:1.05 to 1.05 to 0.95, or 1:1.

27. The method of claim 25, whereinVTTP 24-050(103418-002PCT)the bimetallic aluminum composition is of the structurethe monometallic aluminum complex is of the structurethe monometallic aluminum complex is of the structure28. The method of claim 25, comprising:contacting a first portion of the racemic mixture of lactide with the bimetallic aluminum complex for a predetermined amount of time to provide a first reaction mixture;contacting a second portion of the racemic mixture of lactide with the monometallic aluminum complex for the predetermined amount of time to provide a second reaction mixture; and combining the first reaction mixture and the second reaction mixture to provide the stereocomplex poly(lactic acid).VTTP 24-050(103418-002PCT)29. A stereocomplex poly(lactic acid) made by the method of claim 25, wherein the stereocomplex poly(lactic acid) exhibits one or both ofincreased solubility in organic solvent relative to a comparative stereocomplex poly(lactic acid) prepared by blending poly(L-lactic acid) and poly(D-lactic acid); andincreased toughness relative to a comparative stereocomplex poly(lactic acid) prepared by blending poly(L-lactic acid) and poly(D-lactic acid).

30. A method for the bulk polymerization of a racemic mixture of lactide, the method comprising:contacting the racemic mixture of lactide with an aluminum complex according to structure (II) having an R configuration of claim 8, wherein the contacting is at a temperature of at least 130 °C and in the absence of a solvent to provide poly(D-lactic acid); orcontacting the racemic mixture of lactide with an aluminum complex according to structure (II) having an S configuration of claim 8, wherein the contacting is at a temperature of at least 130 °C and in the absence of a solvent to provide poly(L-lactic acid).

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