Rac-lactide

Lactide (LA), the cyclic diester of lactic acid, has two stereogenic centers and hence exists as three stereoisomers L-lactide (S,S), D-lactide (R,R), and meso-lactide (R,S). In addition, rac-lactide, a commercially available racemic mixture of the (R,R) and (S,S) forms, is also frequently studied. PLA may exhibit several stereoregular architectures (in addition to the non-stereoregular atactic form), namely isotactic, syndiotactic, and heterotactic (Scheme 15). The purely isotactic form may be readily prepared from the ROP of L-LA (or D-LA), assuming that epimerization does not occur during ring opening. The physical properties, and hence medical uses, of the different stereoisomers of PLA and their copolymers vary widely and the reader is directed to several recent reviews for more information.736 740-743... 

Ma H, MefiUo G, OUva L et al. (2005) Aluminum alkyl complexes supported by [OSSO] type bisphenolato ligands synthesis, characterization and living polymerization of rac-lactide. Dalton Trans 721-727... 

The successful utilization of alkoxo Zn- and Mg-tris(pyrazolyl) borate initiators in the lactide polymerization inspired the synthesis of sterically bulky B-diketiminates (BDls) (Fig. 5) and their zinc and magnesium derivatives [60-62]. Replacing the ancillary ligands resulted in the production of several mono- and dinuclear complexes of Mg" and Zn" 24-39 (Fig. 6), which demonstrated excellent catalytic activity for the polymerization of l- and rac-lactide [62-66]. 

Dizinc-monoethoxide complex 58 (Fig. 11) reported by Hillmyer and coworkers [81] displayed rapid polymerization of rac-lactide in CH2CI2 at room temperature with a [LA]o/[l]o ratio of 300 and [LA]q = 1 M greater than 90% conversion to PLA occurred within 30 min. PLA derived from L-LA was isotactic, lactide, signifying an absence of epimerization of stereogenic centers during the polymerization. In a similar study, zinc alkyl complexes (59a, b) and the alkoxo bridged... 

It has been found that magnesium complexes supported with bidentate p-diketiminate are more active in the ROP of l- and rac-lactide than their structurally analogous zinc complexes. Faster rate of polymerization of magnesium complexes were such that an almost complete conversion (97%) occurred in 1 min at 20 °C for a p-diketiminate magnesium complex [(BDI-l)Mg(0 Pr)]2 31 (O Pr = isopropoxide) whereas the zinc analog needed 33 min for a similar conversion at the same temperature [64] (Table 3, entry 1). Similarly a higher... 

In addition to these, amide complexes 68, 71, and 72 bearing bulkier trispyrazolyl borate (Tp) were allowed to react with 200 equiv. of rac-lactide in THF, and a similar reaction ran using the chiral 9-BBN-Bp(+)-Cam-supported complex 75. In all cases, polymerization was rapid (90% conversion within 5 min), with complex 68 displaying an extremely rapid >90% conversion of lactide in less than 1 min with a PDI of 1.74 and = 37.8 kg moP of the PLA. The complex (Tp Bu)Ca(OC6H3-2,6- Pr2)(THF) 70 was very active in the polymerization of rac-lactide in THF, with stereoselectivity and rate of polymerization similar to those observed for the amide complex 68. 

Darensbourg and coworkers reported a systematic investigation of ROP catalyst performance along with kinetic and mechanistic studies for the polymerization of L- and rac-lactide using calcium complexes derived from tridentate Schiff base ligands (Fig. 13) [90, 91]. With calcium catalysts 77a-d, used in melt and solution polymerization of L-lactide, it was found that calcium salen catalyst 77d with bis (phosphoranylidene)ammonium azide as a co-catalyst is much less active than the calcium complexes with tridentate Schiff base ligands, as reflected in the monomer L-lactide conversions of 59-80% for 77a-c but only 35% for 77d as initiator. 

Fig. 13 Calcium complexes supported by N,0-donor Schiff base ligands Table 4 Ca complexes in rac-lactide and L-lactide polymerization...

Similarly, a turn-over frequency (TON) of 227 of the polymerization process was distinctly low for 77d with [M]/[I] = 350, at 110 °C for 6 h, using in the melt polymerization conditions. Biocompatible calcium complex 77a used as catalyst at 110 °C produced in 30 min PLAs with high molecular weight (65,000-110,600) and narrow polydispersities (1.02-1.05) using [M]/[I] = 350-700. It is worthy of note that complex 77a displayed a notable heteroselectivity (probability of racemic linkages between monomers, = 0.73, see Sect. 4.2) in polymerization of rac-lactide in THF at 33 °C. Data on the aforementioned calcium initiators and their lactide polymerization are listed in Table 4. 

Lanthanide-based catalysts, despite finding a lot of application in homogeneous catalysis, can be rather problematic due to the lability of some ligand types and the versatility of their coordination chemistry in the -1-3 oxidation state this makes the controlled synthesis of single-site Ln complexes a quite ambitious goal [92]. McLain and coworkers first demonstrated the high potential of a homoleptic yttrium complex Y(OCH2CH2NMe2)3 as ROP catalyst for the preparation of PLA from rac-lactide and that it promotes a rapid and controlled polymerization... 

Titanium alkoxides are also effective and sought-after initiators for the ROP of lactides due to a low toxicity, which minimizes the problems linked to the presence of catalyst residues in commercial PLA products [18, 19]. Despite impressive advancements in the use of Lewis acidic metal initiators in the preparation of PLAs, surprisingly little attention has been paid to the group 4 metal (Ti, Zr, Hf) initiators, probably due to the highly oxophilic nature of M(1V) which has a natural tendency to form aUcoxy-bridged multinuclear complexes. Verkade and coworkers previously demonstrated a series of titanium aUcoxide complexes 118-122 (Fig. 17) that function as moderately efficient initiators in bulk homopolymeization of L-lactide and rac-lactide, some of these initiators displaying a well-controlled polymerization behavior [119]. 

Recently, dithio-diolate ligands have been employed for construction of group 4 metal catalysts for the ROP of lactide. These metal dithiolate complexes form mononuclear species of the type [(OSSO)M(OR)2] with an octahedrally coordinated metal center. These fluxional compounds acted as highly active catalysts in the ROP of L- and rac-lactide. Hafnium complexes were also introduced as initiators for the ROP of L-lactide and rac-lactide (vide infra) in very limited cases. To our knowledge, the hafnium derivative 146 displayed the highest activity among the group 4 catalysts reported to date (complete conversion of 300 equiv. of... 

Fig. 25 Homonuclear decoupled NMR spectrum of the methine (—C//(CH3)-) region of heterotactic PLA P = 87%) obtained from ROP of rac-lactide with [L2Mg2(p-OBn)2]2 (L = (Z)-4- [2-(dimethylamino)ethylamino](phenyl)methylene -3-methyl-l-phenyl-pyrazol-5-one) at 0 °C for 48 h (600 MHz, CDCI3) [70]...

Spassky and coworkers discovered a remarkable stereocontrol of an enantiomerically pure A1 complex (7 )-161a for the ROP of rac-lactide resulting in a tapered stereoblock PLA microstructure with high melting point =187 °C) (Fig. 26) [160]. Structurally analogous, racemic salen-Al complex 162 resulted in highly isotactic PLA [161]. Feijen s enantiopure chiral complex (RJ )-163 (Fig. 26) exhibited an excellent reverse stereocontrol by preferential polymerization of L-lactide over D-lactide monomer (Kss/Krr = 14) that resulted in PLA with... 

A series of pseudo-C or pseudo-C2 symmetric complexes 168-171 (Fig. 27) exhibited isotactic predominance P = 0.50-0.75) however, the isotacticity is compromised in solvent-free bulk polymerization at 130 °C [129]. Fluorous tertiary alcohol ligands with electron-withdrawing CF3 group are weakly basic and thus expected to reduce the possibility of catalyst deactivation by bridged species formation. Al complexes 172 and 173 offered highly isotactic-enriched stereoblock PLA (Pm = 0.87) from ROP of rac-lactide [168]. 

Fig. 29 Rare-earth complexes with heteroselective rac-lactide ROP...

Bachmann and Seebach [159] have reported the preparation and characterization of cyclic lactones (MeCHCH2C(0)0)n, where n = 4 and 8. The reaction product between butyl lithium in benzene and the solid polystyrene support PS-C6H4CH2NH2 leads to a lithiated species that can be represented as PS-Cfd bCI 12N11 Li(BuI i)x, where x 4 is active in the ring-opening of the cyclic esters L-lactide, rac-lactide, and 2,5-morpholinediones, leading to their respective cyclic oligoesters and cyclodepsipeptides (Fig. 49) [160]. The... 

The tacticity of PLA influences the physical properties of the polymer, including the degree of crystallinity which impacts both thermo-mechanical performance and degradation properties. Heterotactic PLA is amorphous, whereas isotactic PLA (poly(AA-lactide) or poly (55-lac tide)) is crystalline with a melting point of 170-180°C [26]. The co-crystallization of poly (RR-lactide) and poly(55-lactide) results in the formation of a stereocomplex of PLA, which actually shows an elevated, and highly desirable, melting point at 220-230°C. Another interesting possibility is the formation of stereoblock PLA, by polymerization of rac-lactide, which can show enhanced properties compared to isotactic PLA and is more easily prepared than stereocomplex PLA [21]. 

There are two forms of PLA with alternating stereochemistry along the polymer backbone heterotactic PLA (disyndiotactic), obtained from rac-lactide, and syndiotactic PLA, obtained from mc.vo-lactide (Fig. 5c, d, respectively). 

Fig. 8 Methine region (homonuclear decoupled 1H NMR spectrum) of moderately isotactic PLA (Pi = 0.69) Table 2 rac-Lactide tetrad probabilities based on Bemoullian statistics ...

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