Mechanistic Insight into the Stereochemical Control of Lactide Polymerization by Salan–Aluminum Catalysts

Alkyl aluminum complexes of chiral salan ligands assembled around the 2,2′‐bipyrrolidine core form as single diastereomers that have identical configurations of the N donors. Active catalysts for the polymerization of lactide were formed upon the addition of benzyl alcohol. Polymeryl exchange between enantiomorphous aluminum species had a dramatic effect on the tacticity of the poly(lactic acid) (PLA) in the polymerization of racemic lactide (rac‐LA): The enantiomerically pure catalyst of the nonsubstituted salan ligand led to isotactic PLA, and the racemic catalyst exhibited lower stereocontrol. The enantiomerically pure catalyst of the chloro‐substituted salan ligand led to PLA with a slight tendency toward heterotacticity, whereas the racemic catalyst led to PLA of almost perfect heterotacticity following an insertion/auto‐inhibition/exchange mechanism.     

丙交酯开环聚合反应的新型有机催化剂

作为生物高分子降解材料,聚乳酸具有良好的生物相容性和生物降解性,已经广泛应用于包装材料、农用薄膜等环境领域和药物控制释放体系、医用缝合线、组织工程支架等医学领域。丙交酯开环聚合是制备聚乳酸的理想之选,其催化体系目前以金属催化剂为主,但金属离子在聚合物中的痕量残留和细胞毒性限制了聚乳酸在生物医学及微电子领域的应用,而有机催化剂能够克服这些缺点,是目前聚乳酸合成领域的研究热点。本文从不同的活化机理角度,阐述了近年来有机催化剂在合成聚乳酸中的研究进展,总结了各种催化体系在活性、结构可控性及选择性方面的特点,同时展望有机催化剂在开环聚合反应中所面临的机遇与挑战。     

Undiscovered Potential: Ge Catalysts for Lactide Polymerization

Polylactide (PLA) is a high potential bioplastic that can replace oil-based plastics in a number of applications. To date, in spite of its known toxicity, a tin catalyst is used on industrial scale which should be replaced by a benign catalyst in the long run. Germanium is known to be unharmful while having similar properties as tin. Only few germylene catalysts are known so far and none has shown the potential for industrial application. We herein present Ge complexes in combination with zinc and copper, which show amazingly high polymerization activities for lactide in bulk at 150 °C. By systematical variation of the complex structure, proven by single-crystal XRD and DFT calculations, structure–property relationships are found regarding the polymerization activity. Even in the presence of zinc and copper, germanium acts as the active site for polymerizing probably through the coordination–insertion mechanism to high molar mass polymers.     

Synthesis and Application of New Salan Titanium Complexes in the Catalytic Reduction of Aldehydes

Complexes of formula [(H₂N₂O₂)TiCl₂] and [(H₂N₂O₂)Ti(OⁱPr)₂] (H₂N₂O₂H₂ = HOPh’CH₂NH(CH₂)₂NHCH₂Ph’OH, where Ph’ = 2,4-(CMe₂Ph)C₆H₂) were synthesized by the reaction of the salan ligand precursor H₂N₂O₂H₂ with TiCl₄ and Ti(OⁱPr)₄, respectively, in high yields. The dichlorido complex [(H₂N₂O₂)TiCl₂] revealed to be an efficient catalyst for the reduction of benzaldehyde in toluene. Full conversion was observed after 24 h at 55 °C in THF. The same catalyst also converted phenylacetaldehyde and hydrocinnamaldehyde into the corresponding alkanes quantitatively.     

Isotactic rac‐Lactide Polymerization with Copper Complexes: The Influence of Complex Nuclearity

Diiminopyrrolide copper alkoxide complexes, LCuOR (OR¹=N,N‐dimethylamino ethoxide, OR²=2‐pyridyl methoxide), are active for the polymerization of rac‐lactide at ambient temperature in benzene to yield polymers with M_w/M_n=1.0–1.2. X‐ray diffraction studies showed bridged dinuclear complexes in the solid state for both complexes. While LCuOR¹ provided only atactic polylactide, LCuOR² produced partially isotactic polylactide (P_m=0.7). The difference in stereocontrol is attributed to a dinuclear active species for LCuOR² in contrast to a mononuclear species for LCuOR¹.     

Cytotoxic Titanium Salan Complexes: Surprising Interaction of Salan and Alkoxy Ligands

The synthesis, biochemical evaluation, and hydrolysis studies of a wide selection of alkyl‐ and halogen‐substituted titanium salan alkoxides are presented herein. A systematic change in the employed alkoxides revealed that both the bulk of the salan ligands and the steric demand of the labile ligands are of great importance for the obtained biological activity. Surprisingly, these two factors are not independent from each other; lowering the steric demand of the alkoxide of a hitherto nontoxic complex renders it cytotoxic. Therefore, our data suggest that the overall size of the complex exerts a strong influence on its biological activity. To decide whether the correlation between the cytotoxicity and the steric demand of the whole complex is merely based on an altered hydrolysis or on the interaction with biomolecules, the behavior of selected complexes under hydrolytic conditions and the influence of transferrin were investigated. Complexes differing only in their labile alkoxy ligands gave the same hydrolysis products with similar hydrolysis rates but displayed cytotoxicities that differed in the range of one order of magnitude. Thus, it seems that the hydrolysis product is not the active species but rather that the unhydrolysed complex is important for the first interaction with a biomolecule. This promoted the idea of hydrolysis being a detoxification pathway. In accordance with the above conclusion, chloro‐substituted complex [Ti(Ph^ClN^Me)₂(O^iPr)₂] displayed a high cytotoxicity (IC₅₀≈5 μM ) and surprisingly high hydrolytic stability (t_1/2=108 h). These findings, together with the observed cytotoxicity in a cisplatin‐resistant cell line, make halo‐substituted salan complexes an interesting target for further studies.     

Metal‐Size Influence in Iso‐Selective Lactide Polymerization

Iso‐selective initiators for the ring‐opening polymerization (ROP) of rac‐lactide are rare outside of Group 13. We describe the first examples of highly iso‐selective lutetium initiators. The phosphasalen lutetium ethoxide complex shows excellent iso‐selectivity, with a P_i value of 0.81–0.84 at 298 K, excellent rates, and high degrees of polymerization control. Conversely, the corresponding La derivative exhibits moderate heteroselectivity (P_s=0.74, 298 K). Thus, the choice of metal center is shown to be crucial in determining the level and mode of stereocontrol. The relative order of rates for the series of complexes is inversely related to metallic covalent radius: that is, La>Y>Lu.     

The Dual‐Stereocontrol Mechanism: Heteroselective Polymerization of rac‐Lactide and Syndioselective Polymerization of meso‐Lactide by Chiral Aluminum Salan Catalysts

We describe alkoxo‐aluminum catalysts of chiral bipyrrolidine‐based salan ligands that follow the dual‐stereocontrol mechanism wherein a given combination of stereogeneities at the metal site and the proximal center of the last inserted lactidyl (“match”) is active towards lactide having a proximal stereogenic center of the opposite configuration, while the diastereomeric combination of stereogeneities (“mismatch”) is inactive towards any lactide. Polymerization of rac‐LA by the enantiomerically pure catalysts was sluggish and gave stereoirregular poly(lactic acid) (PLA) because selective insertion to a match diastereomer gives a mismatch diastereomer. The racemic catalysts showed higher activity and led to highly heterotactic PLA following polymeryl exchange between two mismatched catalyst enantiomers. A succession of match diastereomers in selective meso‐LA insertions led to syndiotactic PLAs reaching a syndiotacticity degree of α=0.96. This polymer featured a T_m of 153 °C matching the highest reported value, and the highest crystallinity (ΔH_m=56 J g^?1) ever reported for syndiotactic PLA.     

Ring‐Opening Polymerization of Lactide with Group 3 Metal Complexes Supported by Dianionic Alkoxy‐Amino‐Bisphenolate Ligands: Combining High Activity,Productivity, and Selectivity

A series of new alkoxy‐amino‐bis(phenols) (H₂L 1 – 6 ) has been synthesized by Mannich condensations of substituted phenols, formaldehyde, and amino ethers or diamines. The coordination properties of these dianionic ligands towards yttrium, lanthanum, and neodymium have been studied. The resulting Group 3 metal complexes have been used as initiators for the ring‐opening polymerization of rac‐lactide to provide poly(lactic acid)s (PLAs). The polymerizations are living, as evidenced by the narrow polydispersities of the isolated polymers, together with the linear natures of number average molecular weight versus conversion plots and monomer‐to‐catalyst ratios. Complex [Y(L 6 ){N(SiHMe₂)₂}(THF)] ( 17 ) polymerized rac‐lactide to heterotactic PLA (P_r = 0.90 at 20 °C) and meso‐lactide to syndiotactic PLA (P_r = 0.75 at 20 °C). The in situ formation of [Y(L 6 )(OiPr)(THF)] ( 18 ) from 17 and 2‐propanol resulted in narrower molecular weight distributions (PDI = 1.06). With complex 18 , highly heterotactic PLAs with narrow molecular weight distributions were obtained with high activities and productivities at room temperature. The natures of the ligand substituents were shown to have a significant influence on the degree of control of the polymerizations, and in particular on the tacticity of the polymer.     

Rapid Ring‐Opening Polymerization of D,L‐Lactide by Microwaves

Summary: Poly(D ,L ‐lactide) with a molar mass of 10⁵ g · mol⁻¹ and a yield over 90% was produced in 10 min by the ring‐opening polymerization of D ,L ‐lactide under microwave irradiation with forward power of 255 W. A degradation of the poly(D ,L ‐lactide) was also induced by microwaves with a power level over 340 W. The molar mass of poly(D ,L ‐lactide) was dependent upon the competition between the polymerization of D ,L ‐lactide and the degradation of the resulting polymer.

Profiles of molar mass versus microwave irradiation time (1.8 g DLLA, 0.1% Sn(Oct)₂).     

Optically Active Helical Vinylterphenyl Polymers: Chiral Teleinduction in Radical Polymerization and Tunable Stereomutation

Helical vinyl aromatic polymers are emerging as interesting chiral materials due to their dynamic tailorability, synthetic simplicity, and outstanding chemical and physical stabilities. This Personal Account discusses long‐range chirality transfer in the radical polymerization of vinylterphenyl monomers and tunable stereomutation of the resultant polymers. It begins with a general introduction to the design, synthesis, and characterization of helical poly{(+)‐2,5‐bis[4′‐((S)‐2‐methylbutyloxy)phenyl]styrene}, the first one of this series of polymers. Then, long‐range chirality transfer during radical polymerization of terphenyl‐based vinyl monomers is explained. After that, the chiroptical property control of the resultant polymers by means of the transition from kinetically controlled conformation to thermodynamically controlled conformation and external stimulus is described. This Personal Account concludes by discussing the advantages and disadvantages of the strategy of using vinylterphenyls to obtain optically active helical polymers and providing a short outlook, especially emphasizing the importance of tacticity on the chiroptical properties of polymers.     

二(2,6-二叔丁基-4-个甲基苯氧基)钐催化丙交酯开环聚合

聚丙交酯（PLA）可以生物降解，产物无毒，可用于外科手术的缝合线、人造器官以及药物缓释等方面，因此引起了人们的广泛注意．丙交酯的开环聚合是合成聚丙交酯的一种方便方法，所用的催化剂主要是主族及副族金属的配合物，如双金属氧桥配合物［‘j，烷基金属有机化合物［‘j，异丙氧基铝［’‘以及叶琳铝「“等．最近，关于三价烷氧基稀土化合物作为单组份催化剂催化丙交酯开环聚会已有报道［’·’‘．我们发现两价芳氧基稀土化合物（ArO）。Sin（THF）。（ArO一2，已二叔丁基一个甲基苯氧基）也可以有效地催化丙文酯的开环聚合．本…     

Yttrium Complexes as Catalysts for Living and Immortal Polymerization of Lactide to Highly Heterotactic PLA

Amino‐alkoxy‐bis(phenolate) yttrium complexes act in the presence of an excess of alcohol (up to 50 equiv. vs. Y) as highly active and stereoselective catalysts for rac‐lactide and rac‐β‐butyrolactone polymerizations. These versatile systems enable the production of large quantities of polymer with small amounts of catalyst, optimizing productivity, and also allow the preparation of polymers with functional end groups, which may be employed as intermediates for macromolecular engineering applications.

     

Living Polymerization of Lactide Using Titanium Alkoxide Catalysts

Several titanium isopropoxides have facilitated the ring opening polymerization of l-lactide (LA) and rac-lactide in toluene solution at various polymerization temperatures via a coordination insertion mechanism. Depending on catalysts, the controlled/living poly(l-lactide), or the heterotactic-biased poly(rac-lactide) were obtained. The stereochemical microstructure of polylactide (PLA) was determined from homonuclear decoupled ¹H NMR spectral studies. Such spectra of PLA derived from rac-LA featured the characteristic five-methine resonance pattern, whereas corresponding spectra derived from l-LA exhibited only one methine peak.     

Zinc Complexes of Sequential Tetradentate Monoanionic Ligands in the Isoselective Polymerization of rac‐Lactide

Zinc complexes of {ONNN}‐type sequential tetradentate monoanionic ligands reacted with diethylzinc to give the mononuclear ethylzinc complexes. The benzyloxy complexes were formed readily and were found to be highly active as well as living/immortal catalysts for ring‐opening polymerization of rac‐lactic acid with a clear isospecific inclination. Chiral gas chromatography analysis revealed a mild preference for a given lactide enantiomer by the chiral catalysts.     

Ring‐opening Polymerization of L‐Lactide by an Anionic Cobalt(II) Aryloxide

The reaction of anhydrous CoCl₂ with NaOAr (ArO=2,4,6‐tri‐tert‐butylphenoxo) in THF at room temperature in 1:3 molar ratio afforded anionic cobalt aryloxide [Na(THF)₆][Co(OAr)₃] ( 1 ). The definite structure of this complex was characterized by X‐ray single crystal diffraction. It was found that this anionic aryloxo cobalt(II) complex could effectively initiate the ring‐opening polymerization of L‐lactide both in solution and in bulk, leading to high molecular weight poly(L‐lactide).     

己内酯和丙交酯的微波辅助开环聚合反应

己内酯和丙交酯在异辛酸亚锡存在下经微波辐照 5min可分别获得分子量 1 2 0kg·mol- 1的聚己内酯和 2 2 5kg·mol- 1 的聚乳酸。苯甲酸可作为己内酯微波辅助开环聚合的引发剂 ,所得聚己内酯的分子量达到 44 8kg·mol- 1 。通过混有布洛芬的己内酯的微波开环聚合可直接制备以聚己内酯为基质的药物控释系统。己内酯和丙交酯在微波辐照下的热行为对它们的开环聚合反应有重要影响。