Intensive Cycloalkyl-Fused Pyridines for Aminopyridyl–Zinc–Heteroimidazoles Achieving High Efficiency toward the Ring-Opening Polymerization of Lactides

The model precatalyst sp3- and sp2-N dinitrogen-coordinated zinc–heteroimidazole has been used as an efficient catalyst for the ring-opening polymerization of cyclic esters. Subsequent to our exceptional active 5,6,7-trihydroquinolin-8-amine-zinc catalysts for the ring-opening polymerization (ROP) of ε-caprolactone, various pyridine-fused cycloalkanones (ring size from five to eight) are developed for the correspondent fused amine–pyridine derivatives and their zinc–heteroimidazole chloride complexes Zn1–Zn8 (LZnCl2) bearing N-diphenylphosphinoethyl pendants. Activated with two equivalents of LiN(SiMe3)2, the title zinc complexes efficiently promote the ROP of L-lactide (L-LA) in situ; among them, Zn4/2Li(NSiMe3)2 catalyzed 500 equivalent L-LA at 80 °C with 92% conversion in 5 min (TOF: 5520 h−1). Under the same conditions, the catalytic efficiency for the ROP of rac-LA by Zn1–Zn8/2Li(NSiMe3)2 was slightly lower than that for L-LA (highest TOF: 4440 h−1). In both cases, cyclooctyl-fused pyridyl–zinc complexes exhibited higher activity than others, while the cycloheptyl-fused zinc complexes showed the lowest activity. The microstructure analysis of the polymers showed they possessed a linear structure capped with CH3O as major and cyclic structure as minor. In this work, all the ligands and zinc complexes were well characterized by 1H/13C/31P NMR, FT-IR spectroscopy as well as elemental analysis.


Introduction
Aliphatic polyesters, such as polylactide (PLA) and polycaprolactone (PCL), being environment-friendly materials with good biocompatibility and biodegradability, have attracted considerable attention in the past decades [1,2].The polycondensation of lactic acid and the ROP of lactides are two major processes in the formation of PLAs [3].The molecular weights of the PLAs obtained through condensation are generally low, so ROP is extensively investigated for PLA production in order to take advantage of their useful properties [4].Metal-complex precatalysts lead to the ROP of lactides(LA) with not only high efficiency but also the formation of well-defined PLAs [5][6][7].Currently, tin(II) 2-ethylhexanoate is the most popular precatalyst for the industrial production of PLAs via ROP [8]; however, due to the potential cytotoxicity of tin, there are concerns about its use for PLA production, which is a limitation [9,10].Therefore, the development of new metal complex catalysts for the ROP of LA based on non-toxic and environmental-friendly metals is in high demand [11][12][13][14].As an essential element in the human body, as well as having low toxicity for animals and a low cost [15,16], zinc complexes have become a promising candidate for the ROP of cyclic esters.Targeting efficient zinc catalysts for the ROP of LA, various ligands have been explored such as β-diketiminate [17][18][19][20], phenolate [21][22][23][24][25][26], Schiff bases [27][28][29][30][31], bis(pyrazolyl)amide [32,33], N-heterocyclic carbenes [34][35][36] and guanidines [37][38][39].The stereochemical attributes of the ligands are useful factors in controlling the micro-structure and properties of the resultant PLAs [40].
Using the soft donor abilities of phosphorus-based ligands [49,50], a series of zinc complexes containing NˆNˆP ligands (6, Scheme 1) were evaluated for the ROP of ε-CL [51], achieving 90% conversion at high molar ratio of [ε-CL]/[Zn] = 5000:1 within 2 min, indicating a remarkable TOF of 1.35 × 10 5 h −1 ; meanwhile, their iron analogues also performed well for the ROP of ε-CL (TOF up to 8.82 × 10 3 h −1 ), producing high-molecular-weight PCL (Mn up to 2.43 × 10 5 g/mol), demonstrating an exceptional model of iron-complex precatalysts [52].Subsequently, a series of zinc complexes bearing cycloalkyl-fused pyridines with ring sizes tuned from five to eight within their backbones are prepared and achieve good activity for the ROP of lactides (L-LA and rac-LA) under different parameters (time, temperature, solvent or molar ratio of monomer), indicating the significant influence of the ring size of fused cycloalkyls and of the R group on the ortho-position of pyridine on catalytic performance.[53][54][55].The Zn(II) complexes Zn1-Zn8 were obtained by treating the ligands L1-L8 with zinc(II) chloride in ethanol at room temperature for 12 h, respectively.All novel compounds were confirmed by 1 H, 13 C and 31 P NMR (shown in Figures S1-S36), FT-IR spectroscopy and elemental analysis.The 31 P NMR spectrum of ligands showed one signal around −20 ppm, while their corresponding zinc complexes showed a shift around −22 ppm.These little shifts changes in the 31 P NMR spectra indicated little environmental change around phosphine, and also suggesting the possible dissociation of phosphine to zinc.Subsequently, the structures of Zn2, Zn3, Zn7 and Zn8 were further determined by single-crystal X-ray diffraction, which agreed well with their 31 P NMR spectra.

Results and Discussion
fused pyridines with ring sizes tuned from five to eight within their backbones are prepared and achieve good activity for the ROP of lactides (L-LA and rac-LA) under different parameters (time, temperature, solvent or molar ratio of monomer), indicating the significant influence of the ring size of fused cycloalkyls and of the R group on the ortho-position of pyridine on catalytic performance.

Synthesis and Characterization of L1-L8 and Their Zn (II) Complexes Zn1-Zn8
A series of ligands L1-L8 of monocycloalkyl (ring size from five to eight)-fused pyridine-bearing pendant N-diphenylphoshinoethyl groups, N- were prepared according to the literature (as shown in Scheme 2) [53][54][55].The Zn(II) complexes Zn1-Zn8 were obtained by treating the ligands L1-L8 with zinc(II) chloride in ethanol at room temperature for 12 h, respectively.All novel compounds were confirmed by 1 H, 13 C and 31 P NMR (shown in Figures S1-S36), FT-IR spectroscopy and elemental analysis.The 31 P NMR spectrum of ligands showed one signal around −20 ppm, while their corresponding zinc complexes showed a shift around −22 ppm.These little shifts changes in the 31 P NMR spectra indicated little environmental change around phosphine, and also suggesting the possible dissociation of phosphine to zinc.Subsequently, the structures of Zn2, Zn3, Zn7 and Zn8 were further determined by single-crystal X-ray diffraction, which agreed well with their 31 P NMR spectra.The single crystals of Zn2, Zn3, Zn7 and Zn8 suitable for X-ray determination were obtained by diffusing diethyl ether into a dichloromethane solution.Their crystal structures are depicted in Figures 1-4, respectively, and the selected bond lengths and angles are summarized in Table 1.The molecular structures of Zn2, Zn3, Zn7 and Zn8 are similar, in which the zinc is four-coordinated by two nitrogen atoms and two chlorine atoms to form a distorted tetrahedral geometry.Similar to our previous reports [51], the phosphorus donor did not coordinate to zinc, which agreed well with the little shift in its 31 P NMR spectra.The bond distances between the Zn (II) and Cl atoms vary between 2.2018(5) 2.230(2) Å and the Zn-N bond lengths vary between 2.0442(13) and 2.1162(16) Å. Nota the bond lengths of the Zn-Cl bond are longer than those of the Zn-N bond, which i accordance with previous reports [56,57].As shown in Table 1, the bond length of the NH bond is longer than that of the Zn-Nquinoline bond in both the Zn2 and Zn8 structu The R substituent and fused ring size also greatly affect the structure.For Zn3, and Zn7, all bearing the same R substituent of phenyl, the dihedral angle between phenyl ring and pyridine plane is 26.49° in Zn3 (five-ring), which is much smaller t that (43.07°) in Zn7 (seven-ring) and that (48.74°) in Zn5 (six-ring) [51], suggesting great influence of cycloalkyl ring size.Another interesting observation is that, due to torsion of different cycloalkyls, the distance from N(H) and P to the pyridine plane var as shown by 0.440 Å and 0.537 Å in Zn3, 0.703 Å and 1.365 Å in Zn5 and 0.471 Å an 3.918 Å in Zn7, respectively, suggesting the increased distortion of the Zn7 structure addition, regarding the distortion of the rings, the carbon C6 atoms of the cycloalkyl viate from the pyridyl-based plane with a distance of 0.408 Å for Zn2, 0.348 Å for Z 1.340 Å for Zn7 and 1.400 Å for Zn8.These different distortions will have an effect on t catalytic activity.

Ring-Opening Polymerization (ROP) of L-LA by Zn1-Zn8/2LiN(SiMe3)2
In the beginning, Zn6 was tested for the ROP of L-LA without any additional in tor, but there was no activity observed, considered the result of the stability of the Zn bond.According to our previous work [51], a binary system consisting of zinc comple and two equivalents of LiN(SiMe3)2 exhibited extremely high activity toward the r opening polymerization of ɛ-CL in situ; here, a similar system was explored for the R of L-LA.Firstly, the effect of LiN(SiMe3)2 on the ROP of L-LA was investigated by us Zn6 in toluene at a molar ratio of [LA]:[Zn] = 250:1 and within 10 min at 30 °C.The res showed that no polymer was obtained when using one equivalent LiN(SiMe3)2.Howe when increasing the LiN(SiMe3)2 from one to two equivalents, the monomer convers could reach 36% under the same conditions.In addition, the blank experiments show 10% conversion of monomers was achieved using only two equivalents of LiN(SiMe3) catalysts.Therefore, a catalyst system of Zn6/2LiN(SiMe3)2 was employed for the RO L-LA, and the polymerization results are collected in Table 2.The bond distances between the Zn (II) and Cl atoms vary between 2.2018(5) and 2.230(2) Å and the Zn-N bond lengths vary between 2.0442(13) and 2.1162( 16) Å. Notably, the bond lengths of the Zn-Cl bond are longer than those of the Zn-N bond, which is in accordance with previous reports [56,57].As shown in Table 1, the bond length of the Zn-NH bond is longer than that of the Zn-N quinoline bond in both the Zn2 and Zn8 structures [2.1091(15) vs. 2.0777(15); 2.0920( 12) vs. 2.0442( 13) Å], indicating more effective coordination by N quinoline than NH; On the contrary, the bond length of Zn-NH in Zn3 and Zn7 is shorter than that of Zn-N quinoline .The different bond lengths between Zn-NH and Zn-N quinoline indicate that the size of substituents and rings influence the molecular structure of the zinc complexes.
The R substituent and fused ring size also greatly affect the structure.For Zn3, Zn5 and Zn7, all bearing the same R substituent of phenyl, the dihedral angle between the phenyl ring and pyridine plane is 26.49• in Zn3 (five-ring), which is much smaller than that (43.07 • ) in Zn7 (seven-ring) and that (48.74 • ) in Zn5 (six-ring) [51], suggesting the great influence of cycloalkyl ring size.Another interesting observation is that, due to the torsion of different cycloalkyls, the distance from N(H) and P to the pyridine plane varied, as shown by 0.440 Å and 0.537 Å in Zn3, 0.703 Å and 1.365 Å in Zn5 and 0.471 Å and −3.918 Å in Zn7, respectively, suggesting the increased distortion of the Zn7 structure.In addition, regarding the distortion of the rings, the carbon C6 atoms of the cycloalkyl deviate from the pyridyl-based plane with a distance of 0.408 Å for Zn2, 0.348 Å for Zn3, 1.340 Å for Zn7 and 1.400 Å for Zn8.These different distortions will have an effect on their catalytic activity.

Ring-Opening Polymerization (ROP) of L-LA by Zn1-Zn8/2LiN(SiMe 3 ) 2
In the beginning, Zn6 was tested for the ROP of L-LA without any additional initiator, but there was no activity observed, considered the result of the stability of the Zn-Cl bond.According to our previous work [51], a binary system consisting of zinc complexes and two equivalents of LiN(SiMe 3 ) 2 exhibited extremely high activity toward the ring-opening polymerization of ε-CL in situ; here, a similar system was explored for the ROP of L-LA.Firstly, the effect of LiN(SiMe 3 ) 2 on the ROP of L-LA was investigated by using Zn6 in toluene at a molar ratio of [LA]:[Zn] = 250:1 and within 10 min at 30 • C. The results showed that no polymer was obtained when using one equivalent LiN(SiMe 3 ) 2 .However, when increasing the LiN(SiMe 3 ) 2 from one to two equivalents, the monomer conversion could reach 36% under the same conditions.In addition, the blank experiments showed 10% conversion of monomers was achieved using only two equivalents of LiN(SiMe 3 ) 2 as catalysts.Therefore, a catalyst system of Zn6/2LiN(SiMe 3 ) 2 was employed for the ROP of L-LA, and the polymerization results are collected in Table 2. × 144 × conv.%;d 10 4 g/mol, GPC data were recorded from THF vs. polystyrene standards using a correcting factor of 0.58 [58]; e 1 equiv.BnOH; f 3 equiv.BnOH; g 3 mL toluene; h 5 mL toluene.
In the first instance, the effect of benzyl alcohol (BnOH) on polymerization was investigated with the molar ratio of [L-LA]:[Zn] = 250:1 at a temperature kept at 30 • C (runs 1-3, Table 2).The results indicated that the monomer conversion decreased from 36% to 11% when one equivalent benzyl alcohol was added.Then, the amount of benzyl alcohol was further increased to three equivalents, and the monomer conversion continued to decrease to only 8%.These results revealed that benzyl alcohol could not improve the monomer conversion in this catalytic system.In order to enhance the monomer conversion, the polymerization was screened from 10 min to 60 min under the same conditions (runs 1 and 4-6, Table 2).The results showed that monomer conversion greatly increased from 36% in 10 min to 86% in 60 min with the extension of time, but the molecular weight decreased from 3.99 × 10 4 to 1.65 × 10 4 g/mol and the polydispersity became broader, suggesting the increased side reaction of transesterification during longer times.The comparison of the M n values with the calculated values [M n(calcd) ] shows large differences, which indicates that the polymerizations are not well controlled [59].The kinetics of polymerization by Zn6, shown as a semilogarithmic plot, slightly deviates from the first order with the polymerization rate constant k app as 0.03177 min −1 (LA/Zn = 250:1) or 0.02294 min −1 (LA/Zn = 250:0.5)(Figure S37 in Supplementary Materials).
Secondly, the molar ratio of [L-LA]:[Zn] was fixed at 250:1 and the run time at 10 min, and the influence of temperature on polymerization was also investigated (runs 1 and 7-10, Table 2).As the reaction temperature increased from 30 • C to 80 • C, the monomer conversion rate also increased gradually from 36% to 100%, indicating that higher temperatures favored the increase in the polymerization rate.At the same time, the polymer obtained from 50 • C and 80 • C possessed similar M n values (M n = 2.66-2.83× 10 4 g/mol) and molecular weight distributions (M w /M n = 1.87-2.08);within this temperature range, the M n values were all lower than the M n(calcd) values.This may be explained by the efficiency of active species and the effect of transesterification during polymerization [60].Moreover, the molecular weight distribution of all obtained polymers was broad, suggesting more side reactions of transesterification at higher temperatures [61][62][63].
Subsequently, in order to explore the role of various solvents for the ROP of L-LA, the polymerizations were carried out in dichloromethane at 30 • C with THF and 60 • C with nhexane (runs 11-13, Table 2).When THF was used, high monomer conversion of up to 92% was achieved at [L-LA]:[Zn] = 250:1 within 10 min.However, when dichloromethane and n-hexane were used, the monomer conversion was extremely low, at 0 and 8%, respectively.The reason for this may be related to the coordination competition between the monomer and solvent for the active zinc centers [64,65].
Fixing the temperature at 80 • C and run time at 10 min, increasing the molar ratio of [L-LA]:[Zn] from 250:1 to 1000:1 led to a slightly decrease in monomer conversion from 100% to 89% (runs 10, 14, 15, Table 2), but the molecular weights of the polymer were very similar (from 2.46 to 2.66 × 10 4 g/mol), which were much lower than M n(calcd) .Furthermore, the effect of the amount of toluene was also explored at a high molar ratio of [L-LA]:[Zn] = 1000:1 in 10 min at 80 • C (runs 15-17, Table 2).When increasing the toluene volume from 1 mL to 5 mL, the monomer conversion gradually decreased from 89% to 65% and the molecular weight of the polymer slightly decreased from 2.61 × 10 4 g/mol to 2.02 × 10 4 g/mol.This may be attributed to the deactivation of some active species caused by more impurities in toluene [66].Moreover, the reaction time was reduced from 10 min to 5 min at 80 • C with the molar ratio of [L-LA]:[Zn] = 500:1, and the monomer conversion also decreased from 96% to 63% (runs 15 vs. 18, Table 2).The average molecular weight of the obtained polymer decreased from 2.61 × 10 4 g/mol to 1.86 × 10 4 g/mol.
With the [L-LA]:[Zn] ratio kept at 500:1 and temperature and time at 80 • C and 5 min, respectively, all zinc complexes Zn1-Zn8 were evaluated for the ROP of L-LA by using pretreatment with two equivalents of LiN(SiMe 3 ) 2 , and the results are shown in runs 18, 19-25 (Table 2).The data revealed that the catalytic system Zn1-Zn8/2LiN(SiMe 3 ) 2 can efficiently catalyze the ROP of L-LA, in which the catalytic efficiency is related with the size of the substituent group (R) and the size of the pyridyl-fused ring (shown in Figure 5).
tained from 50 °C and 80 °C possessed similar Mn values (Mn = 2.66-2.83× 10 4 g/mol) and molecular weight distributions (Mw/Mn = 1.87-2.08);within this temperature range, the Mn values were all lower than the Mn(calcd) values.This may be explained by the efficiency of active species and the effect of transesterification during polymerization [60].Moreover, the molecular weight distribution of all obtained polymers was broad, suggesting more side reactions of transesterification at higher temperatures [61][62][63].
Subsequently, in order to explore the role of various solvents for the ROP of L-LA, the polymerizations were carried out in dichloromethane at 30 °C with THF and 60 °C with n-hexane (runs 11-13, Table 2).When THF was used, high monomer conversion of up to 92% was achieved at [L-LA]:[Zn] = 250:1 within 10 min.However, when dichloromethane and n-hexane were used, the monomer conversion was extremely low, at 0 and 8%, respectively.The reason for this may be related to the coordination competition between the monomer and solvent for the active zinc centers [64,65].
Fixing the temperature at 80 °C and run time at 10 min, increasing the molar ratio of [L-LA]:[Zn] from 250:1 to 1000:1 led to a slightly decrease in monomer conversion from 100% to 89% (runs 10, 14, 15, Table 2), but the molecular weights of the polymer were very similar (from 2.46 to 2.66 × 10 4 g/mol), which were much lower than Mn(calcd).Furthermore, the effect of the amount of toluene was also explored at a high molar ratio of [L-LA]:[Zn] = 1000:1 in 10 min at 80 °C (runs 15-17, Table 2).When increasing the toluene volume from 1 mL to 5 mL, the monomer conversion gradually decreased from 89% to 65% and the molecular weight of the polymer slightly decreased from 2.61 × 10 4 g/mol to 2.02 × 10 4 g/mol.This may be attributed to the deactivation of some active species caused by more impurities in toluene [66].Moreover, the reaction time was reduced from 10 min to 5 min at 80 °C with the molar ratio of [L-LA]:[Zn] = 500:1, and the monomer conversion also decreased from 96% to 63% (runs 15 vs. 18, Table 2).The average molecular weight of the obtained polymer decreased from 2.61 × 10 4 g/mol to 1.86 × 10 4 g/mol.
With the [L-LA]:[Zn] ratio kept at 500:1 and temperature and time at 80 °C and 5 min, respectively, all zinc complexes Zn1-Zn8 were evaluated for the ROP of L-LA by using pre-treatment with two equivalents of LiN(SiMe3)2, and the results are shown in runs 18, 19-25 (Table 2).The data revealed that the catalytic system Zn1-Zn8/2LiN(SiMe3)2 can efficiently catalyze the ROP of L-LA, in which the catalytic efficiency is related with the size of the substituent group (R) and the size of the pyridyl-fused ring (shown in Figure 5).2).
In order to gather more information about the mechanism of the ROP of L-LA, the obtained PLLA (run 18, Table 2) was characterized by a 1 H NMR and MALDI-TOF spectrum.The MALDI-TOF mass spectrum revealed two families of peaks (as shown in Figure 6): both A/A* and B/B* were separated by an m/z of 72, in which the major peaks A/A* can be ascribed to CH 3 OH + (C 3 H 4 O 2 ) n + Na + /K + and the minor peaks B/B* are assignable to (C 3 H 4 O 2 ) n + Na+/K+.The 1 H NMR spectrum clearly showed the presence of CH 3 O protons around δ 3.75 ppm (shown in Figure 7), which may come from the methanolysis of the polymer chain during the quenching process [60,67,68].In addition, there was no signal of -N(SiMe 3 ) 2 in either the 1 H NMR or MALDI-TOF spectra, which was consistent with a previous report in the literature [51].
In order to gather more information about the mechanism of the ROP of L-LA, the obtained PLLA (run 18, Table 2) was characterized by a 1 H NMR and MALDI-TOF spectrum.The MALDI-TOF mass spectrum revealed two families of peaks (as shown in Figure 6): both A/A* and B/B* were separated by an m/z of 72, in which the major peaks A/A* can be ascribed to CH3OH + (C3H4O2)n + Na + /K + and the minor peaks B/B* are assignable to (C3H4O2)n + Na+/K+.The 1 H NMR spectrum clearly showed the presence of CH3O protons around δ 3.75 ppm (shown in Figure 7), which may come from the methanolysis of the polymer chain during the quenching process [60,67,68].In addition, there was no signal of -N(SiMe3)2 in either the 1 H NMR or MALDI-TOF spectra, which was consistent with a previous report in the literature [51].2).2).
Based on the above results, the mechanism of the ROP of L-LA catalyzed by Zn1-Zn8/2LiN(SiMe3)2 was proposed, as shown in Scheme 3. It is assumed that a Lewis pair  2).
In order to gather more information about the mechanism of the ROP of L-LA, the obtained PLLA (run 18, Table 2) was characterized by a 1 H NMR and MALDI-TOF spectrum.The MALDI-TOF mass spectrum revealed two families of peaks (as shown in Figure 6): both A/A* and B/B* were separated by an m/z of 72, in which the major peaks A/A* can be ascribed to CH3OH + (C3H4O2)n + Na + /K + and the minor peaks B/B* are assignable to (C3H4O2)n + Na+/K+.The 1 H NMR spectrum clearly showed the presence of CH3O protons around δ 3.75 ppm (shown in Figure 7), which may come from the methanolysis of the polymer chain during the quenching process [60,67,68].In addition, there was no signal of -N(SiMe3)2 in either the 1 H NMR or MALDI-TOF spectra, which was consistent with a previous report in the literature [51].2).
Based on the above results, the mechanism of the ROP of L-LA catalyzed by Zn1-Zn8/2LiN(SiMe3)2 was proposed, as shown in Scheme 3. It is assumed that a Lewis pair  2).
Based on the above results, the mechanism of the ROP of L-LA catalyzed by Zn1-Zn8/2LiN(SiMe 3 ) 2 was proposed, as shown in Scheme 3. It is assumed that a Lewis pair will form during the ROP process and can be 'loosened up' at higher temperatures to form a zwitterionic intermediate.Subsequently, this 'loose' pair can initiate the polymerization, causing the ring to expand to form the cyclic macrolactone metal ring; this mechanism has also been reported in the literature [51,69,70].Finally, methanol was added to terminate the polymerization reaction, and a linear polymer capped with a methoxyl group was obtained [71].Furthermore, its minor cyclic structure may be due to intramolecular transesterification. a zwitterionic intermediate.Subsequently, this 'loose' pair can initiate the polymerization, causing the ring to expand to form the cyclic macrolactone metal ring; this mechanism has also been reported in the literature [51,69,70].Finally, methanol was added to terminate the polymerization reaction, and a linear polymer capped with a methoxyl group was obtained [71].Furthermore, its minor cyclic structure may be due to intramolecular transesterification.Scheme 3. Possible mechanistic pathways for the ROP of L-LA using Zn6/2LiN(SiMe3)2.

Ring-Opening Polymerization of rac-LA by Zn1-Zn8/2LiN(SiMe3)2
Under the conditions of the molar ratio of the monomer to the catalyst of 500:1, polymerization temperature of 80 °C and reaction time of 5 min, the catalytic performance of Zn1-Zn8/2LiN(SiMe3)2 for the ROP of rac-LA was also investigated.The polymerization results are shown in Table 3.The results showed that Zn1-Zn8/2LiN(SiMe3)2 also displayed good efficiency for the ROP of rac-LA but without stereoselectivity and all the resultant polymers were amorphous.Both the substituent and ring size of the ligand greatly influenced the activity, and the order of activity is as follows: Zn8, bearing a small substituent group with an eight-membered ring, exhibited the highest activity (TOF = 4.44 × 10 3 h −1 ), higher than Zn1-Zn7 (TOF range: 1.08-4.26× 10 3 h −1 ).Additionally, the catalytic efficiency of the Zn/2LiN(SiMe3)2 catalytic system for the ROP of rac-LA was generally lower than that for the ROP of L-LA (Figure 8).Under the conditions of the molar ratio of the monomer to the catalyst of 500:1, polymerization temperature of 80 • C and reaction time of 5 min, the catalytic performance of Zn1-Zn8/2LiN(SiMe 3 ) 2 for the ROP of rac-LA was also investigated.The polymerization results are shown in Table 3.The results showed that Zn1-Zn8/2LiN(SiMe 3 ) 2 also displayed good efficiency for the ROP of rac-LA but without stereoselectivity and all the resultant polymers were amorphous.Both the substituent and ring size of the ligand greatly influenced the activity, and the order of activity is as follows: Zn1 (59%, R = H) > Zn2 (53%, R = Me) > Zn3 (52%, R = Ph); Zn4 (71%, R = H) > Zn5 (53%, R = Ph); Zn6 (46%, R = H) > Zn5 (18%, R = Ph).Zn8, bearing a small substituent group with an eight-membered ring, exhibited the highest activity (TOF = 4.44 × 10 3 h −1 ), higher than Zn1-Zn7 (TOF range: 1.08-4.26× 10 3 h −1 ).Additionally, the catalytic efficiency of the Zn/2LiN(SiMe 3 ) 2 catalytic system for the ROP of rac-LA was generally lower than that for the ROP of L-LA (Figure 8).
The microstructure of poly(rac-LA) (run 1, Table 3) was also studied by MALDI-TOF and 1 H NMR spectra.The MALDI-TOF mass spectrometry showed two families of A/A* and B/B* (as shown in Figure S38), in which the major family peaks A/A* were attributed to CH 3 OH + (C 3 H 4 O 2 ) n + Na + /K + , as the visible linear structure with a methoxy end group, while the minor family peaks B/B* were assigned as the cyclic structure (C 3 H 4 O 2 ) n + Na + /K + .According to the 1 H NMR spectrum (as shown in Figure S39), the signal at around 3.75 ppm of the CH 3 O protons appeared to further confirm the MALDI-TOF analysis.Therefore, the mechanism is similar to that for the ROP of L-LA.All the obtained polymers were sticky.In order to exemplify their stereoselectivity, they were further characterized by using decoupling 1 H NMR (shown in Figure S40) and results showed that their Pm values varied approximately between 0.30 and 0.35.The microstructure of poly(rac-LA) (run 1, Table 3) was also studied by MALDI-TOF and 1 H NMR spectra.The MALDI-TOF mass spectrometry showed two families of A/A* and B/B* (as shown in Figure S38), in which the major family peaks A/A* were attributed to CH3OH + (C3H4O2)n + Na + /K + , as the visible linear structure with a methoxy end group, while the minor family peaks B/B* were assigned as the cyclic structure (C3H4O2)n + Na + /K + .According to the 1 H NMR spectrum (as shown in Figure S39), the signal at around 3.75 ppm of the CH3O protons appeared to further confirm the MALDI-TOF analysis.Therefore, the mechanism is similar to that for the ROP of L-LA.All the obtained polymers were sticky.In order to exemplify their stereoselectivity, they were further characterized by using decoupling 1 H NMR (shown in Figure S40) and results showed that their Pm values varied approximately between 0.30 and 0.35.

General Considerations
All operations of moisture-and air-sensitive chemicals were carried out under an atmosphere of high-purity nitrogen using standard Schlenk techniques and a N2-filled glovebox.LiN(SiMe3)2 (1.0 M in THF) was purchased from Aldrich (San Diego, CA, USA) and used as received.Toluene, n-hexane, tetrahydrofuran and diethyl ether were dried by refluxing over sodium benzophenone, distilled under N2 and stored over activated molecular sieves (4 Å) for 24 h in a glovebox prior to use.Dichloromethane was dried over CaH2 for 48 h, distilled under N2 and stored over activated molecular sieves (4 Å) in a glovebox prior to use.L-lactide and rac-lactide were purchased from TCI and used as received without further purification.And other reagents were obtained from common commercial suppliers.
All NMR spectra were recorded with Bruker Avance III 400 or Bruker Avance III 400 HD spectrometers (400 MHz for 1 H NMR, 100 MHz for 13 C NMR) at room temperature.The chemical shifts were related to the position of the NMR signal using tetramethylsilane (TMS) as a reference.And 31 P NMR spectra were measured on a Bruker Avance II + 400 instrument.Elemental analyses were performed with a Flash EA 1112 microanalyzer, while IR spectra were conducted using a Perkin-Elmer System 2000 FT-IR spectrometer (Thermo Flash Smart, Beijing, China).MALDI-TOF MS analysis was performed with a Bruker Ultraflex mass spectrometer.For MALDI MS analysis, mass spectra were acquired with a SmartBeam laser (355nm, Bruker, Bremen, Germany) operating at 200 Hz with a laser focus of 50 µm.The device parameters for MALDI MS were chosen as follows: plate offset voltage, 19 kV; deflector detector voltage, 20 kV.Data were processed using Date-Analysis 3.0 (Bruker Daltonics,).GPC analysis was performed using a system composed of a 390-LC multidetector (MDS), a 209-LC pump injection module (PIM) and a PL-GPC

General Considerations
All operations of moisture-and air-sensitive chemicals were carried out under an atmosphere of high-purity nitrogen using standard Schlenk techniques and a N 2 -filled glovebox.LiN(SiMe 3 ) 2 (1.0 M in THF) was purchased from Aldrich (San Diego, CA, USA) and used as received.Toluene, n-hexane, tetrahydrofuran and diethyl ether were dried by refluxing over sodium benzophenone, distilled under N 2 and stored over activated molecular sieves (4 Å) for 24 h in a glovebox prior to use.Dichloromethane was dried over CaH 2 for 48 h, distilled under N 2 and stored over activated molecular sieves (4 Å) in a glovebox prior to use.L-lactide and rac-lactide were purchased from TCI and used as received without further purification.And other reagents were obtained from common commercial suppliers.

General Procedure for Ring-Opening Polymerization of L-lactide or rac-LA
A typical polymerization procedure is outlined as follows using Zn6 as the representative precatalyst.In a Schlenk flask, Zn6 (0.0051 g, 0.010 mmol) and LiN(SiMe 3 ) 2 (0.02 mmol, 2 equiv) were dissolved in 1 mL toluene and the mixture was stirred at room temperature for 30 min under a nitrogen atmosphere.Then, the Zn6/LiN(SiMe 3 ) 2 was immediately injected into the monomer (L-LA, 0.36 g, 2.5 mmol) to react for the designated time at a specified temperature.After the reaction, the resulting viscous solution was transferred to a flask containing 100 mL cold methanol and stirred.The ring-opening polymerization procedure of the rac-lactide is similar to that of the L-lactide above.

X-ray Crystallographic Analyses
Single-crystal X-ray diffraction data for Zn2, Zn3, Zn7 and Zn8 were conducted on an XtaLAB Synergy-R HyPix diffractometer with graphite-monochromated Cu-Kα radiation (λ = 1.54184 (Å)) at 169.98(10) K.The cell parameters were obtained through global optimization of the positions of all the reflected signals collected.Intensities were corrected for Lorentz and polarization effects and empirical absorption.The structures were solved by direct methods and refined by full-matrix least squares on F 2 .All hydrogen atoms were placed in calculated positions.Structure solution and refinement were performed using the SHELXTL-97 package [72][73][74].Crystal data and structure refinements for Zn2, Zn3, Zn7 and Zn8 are summarized in Table 4.

Conclusions
In summary, the finely tuned ring sizes of the cycloalkyl-fused pyridine-bearing pendant N-diphenylphosphinoethyl groups are developed as ligands L1-L8 for their zinc chloride complexes Zn1-Zn8.The catalytic systems, Zn1-Zn8/2Li(NSiMe 3 ) 2 , display good activities toward the ROP of L-LA and rac-LA in situ without BnOH.In general, the cyclohexyl-or cyclooctyl-fused pyridyl-zinc catalysts demonstrate competitively higher activities.For L-LA, 92% monomer conversion was achieved with the [L-LA]: [Zn] molar ratio of 500:1 in only 5 min and at 80 • C. By comparison, the activity for the ROP of rac-LA were generally observed to be much lower than that seen for L-LA, in which the highest monomer conversion could only reach 74% under the same polymerization conditions and all of the obtained poly(rac-LA) product was amorphous.The microstructures of PLAs indicate the linear structures capped with a CH 3 O-end group were the major and the zwitterionic species was proposed as the intermediate in the polymerization.

Data Availability Statement:
The original contributions presented in the study are included in the article/Supplementary Materials, further inquiries can be directed to the corresponding authors.

Scheme 1 .
Scheme 1. Zinc complexes containing phosphorus atoms for the ROP of lactides.

Figure 1 .
Figure 1.An ORTEP drawing of Zn2 with thermal ellipsoids of 30% probability.All hydrogen ato are omitted for clarity.

Figure 2 .
Figure 2.An ORTEP drawing of Zn3 with thermal ellipsoids of 30% probability.All hydrogen ato are omitted for clarity.

Figure 3 .
Figure 3.An ORTEP drawing of Zn7 with thermal ellipsoids of 30% probability.All hydrogen ato are omitted for clarity.

Figure 1 .Figure 1 .
Figure 1.An ORTEP drawing of Zn2 with thermal ellipsoids of 30% probability.All hydrogen atoms are omitted for clarity.

Figure 2 .
Figure 2.An ORTEP drawing of Zn3 with thermal ellipsoids of 30% probability.All hydrogen a are omitted for clarity.

Figure 3 .
Figure 3.An ORTEP drawing of Zn7 with thermal ellipsoids of 30% probability.All hydrogen a are omitted for clarity.

Figure 2 .
Figure 2.An ORTEP drawing of Zn3 with thermal ellipsoids of 30% probability.All hydrogen atoms are omitted for clarity.

Figure 1 .
Figure 1.An ORTEP drawing of Zn2 with thermal ellipsoids of 30% probability.All h are omitted for clarity.

Figure 2 .
Figure 2.An ORTEP drawing of Zn3 with thermal ellipsoids of 30% probability.All h are omitted for clarity.

Figure 3 .
Figure 3.An ORTEP drawing of Zn7 with thermal ellipsoids of 30% probability.All h are omitted for clarity.

Figure 3 .
Figure 3.An ORTEP drawing of Zn7 with thermal ellipsoids of 30% probability.All hydrogen atoms are omitted for clarity.

Figure 4 .
Figure 4.An ORTEP drawing of Zn8 with thermal ellipsoids of 30% probability.All hydrogen at are omitted for clarity.
[2.1091(15) vs. 2.0777(15); 2.0920(12) vs. 2.0442(13) Å], indicating more effective coord tion by Nquinoline than NH; On the contrary, the bond length of Zn-NH in Zn3 and Zn shorter than that of Zn-Nquinoline.The different bond lengths between Zn-NH and Zn-N oline indicate that the size of substituents and rings influence the molecular structure of zinc complexes.

Figure 4 .
Figure 4.An ORTEP drawing of Zn8 with thermal ellipsoids of 30% probability.All hydrogen atoms are omitted for clarity.

Table 3 .
Ring-opening polymerization of rac-LA by Zn1

Table 3 .
Ring-opening polymerization of rac-LA by Zn1