Alternating Isotactic Polyhydroxyalkanoates via Site- and Stereoselective Polymerization of Unsymmetrical Diolides

Naturally produced, biodegradable polyhydroxyalkanoates (PHAs) promise more sustainable alternatives to nonrenewable/degradable plastics, but biological PHA's stereomicrostructures are strictly confined to isotactic (R)-polymers or copolymers of random sequences. Chemical synthesis via catalyzed ring-opening polymerization (ROP) of cyclic (di)esters offers expedient access to diverse PHA microstructures, including those with defined comonomer sequences and tacticities. However, the synthesis of alternating isotactic PHAs has not been achieved by the existing methodologies. Here, we report the design of unsymmetrically disubstituted eight-membered diolides (rac-8DLR1-R2) and their site- and stereoselective ROP with discrete chiral catalysts, enabling the synthesis of alternating isotactic PHAs, poly(3-hydroxybutyrate-alt-3-hydroxyvalerate) (alt-P3HBV) and poly(3-hydroxybutyrate-alt-3-hydroxyheptanoate) (alt-P3HBHp), with high to quantitative (>99%) alternation and isotacticity and Mn up to 113 kDa and Đ = 1.01. Physical properties of such PHAs are substantially determined by the degree of backbone sequence alternation and tacticity, ranging from amorphous to semi-crystalline materials. The alt-P3HBV shows significantly improved mechanical performance relative to the constituent homopolymers. Intriguingly, enantiomeric (R)-alt-P3HBV and (S)-alt-P3HBV, synthesized by kinetically resolved ROP of rac-8DLMe-Et, form a stereocomplex with a significantly enhanced Tm (by 53 °C), while the enantiomeric homopolymers do not form a stereocomplex.