Stereoselective polymerization of a racemic monomer with a racemic catalyst: Direct preparation of the polylactic acid stereocomplex from racemic lactide

PLA is prepared by the ring opening polymerization (ROP) of lactide, the cyclic dimer of lactic acid. Commercial polylactides usually are synthesized from lactide monomers prepared from a single lactic acid enantiomer, and because the resulting polymers are stereoregular, they have high degrees of crystallinity. 2 The mechanical properties of crystalline polymers are stable to near the polymer melting point, and thus they have higher use temperatures than their amorphous analogues. For example, polymerization ofL-lactide gives a semicrystalline polymer with a melting transition near 180 °C andTg ∼ 67 °C,3 properties that make it useful for applications ranging from degradable packaging to surgical implants and matrices for drug delivery. 4 In contrast, the polymer derived fromrac-lactide, a 1:1 mixture ofDand L-lactide, yields amorphous polymers with glass transitions near room temperature. AlthoughL-lactide can be prepared with relatively high enantiopurity from corn fermentation, the requirement for an enantiopure monomer places restrictions on the polymer synthesis. As shown in Scheme 1, chiral catalysts have been employed to effect kinetic resolution of racemic lactide. Spassky et al. have reported kinetic resolutions of rac-lactide by employing a chiral Schiff’s base complex of aluminum, ( -)1.5 At low conversions high enantiomeric enrichment in the polymer is observed. 6 This finding is significant because the catalyst overrides the tendency for syndiotactic placements that are typically favored by chainend control. 7 At higher conversions the enantiomeric enrichment in the polymer decreases. The drop in selectivity can be attributed to the fact that the relative concentration of the “wrong” isomer increases in the monomer pool as the desired enantiomer is incorporated in the polylactide. In a recent report, Coates et al. effected the syndiotactic polymerization of meso-lactide by using the isopropoxide catalyst ( -)-2.8 Sincemeso-lactide possesses two stereocenters of opposite configuration, the concentration of D andL stereocenters remains constant and the intrinsic selectivity of the catalyst is not diminished by statistical depletion of the preferred stereocenter. An interesting effect of stereoregularity on lactide properties was first reported by Tsuji and co-workers. 9-11 As shown in Scheme 1,L-PLA and D-PLA form a stereocomplex that has a Tm 50 °C higher than theTm for the homochiral polymers. Preparation of this stereocomplex presently requires parallel ROP of Dand L-lactide with subsequent combination of the chiral polylactide chains. Despite its improved mechanical properties, practical applications of the stereocomplex are prohibited by the requirement that separate pools of enantiopure lactide monomers must be polymerized to enantiopure polymers. If the same material could be prepared from the rac-lactide, it is conceivable that applications of the stereocomplex could be realized. Spassky’s and Coates’ results in stereoselective ROP of lactides suggests a strategy for the direct preparation of the polylactide stereocomplex fromrac-lactide. Specifically, the racemic catalyst, rac-2, should lead to parallel syntheses of isotactic D-PLA and L-PLA chains since ( -)-2 preferentially polymerizes D-lactide and (+)-2 preferentially polymerizesL-lactide. In contrast to kinetic resolution ofrac-lactide with (-)-1, theD:L ratio in the monomer pool should remain constant at high conversion since polymerization by the racemic catalyst will remove D and L isomers at equal rates. Thus, the high enantioselectivity that is realized at low conversion in kinetic resolutions using chiral 1 should be maintained at high conversion with rac-1 to give a 1:1 mixture of isotactic chains (Scheme 2). Polymerization ofrac-lactide withrac-2 yields nearly monodisperse chains ( Mw/Mn ) 1.05) consistent with a “living” polymerization and the absence of transesterification. This is supported by the linear relationship between the monomer conversion to polymer andMn. More importantly, the1H NMR spectrum (Figure 1a) is consistent with formation of chains