Natural chiral polymers, such as DNA, proteins, cellulose and poly[(R)-3-hydroxybutyrate] ((R)-P3HB), are prevalent in their enantiopure forms1,2. Existing methods to synthesize enantiopure polymers focus on enantiospecific polymerization, in which only one specific enantiomer is obtained from the corresponding chiral monomer3–6. Here we introduce a catalytic stereodivergent synthetic strategy to access all enantiopure di-isotactic poly(3-hydroxyalkanoate) (PHA) diastereomers from bacterial (R)-P3HB as the single chiral source. A series of enantiopure (R,R)-α-alkylated-β-butyrolactones are obtained from (R)-P3HB and then subjected to the catalyst-controlled diastereodivergent ring-opening polymerization (ROP) to enantiopure di-isotactic α-alkylated PHAs. Metal-catalysed coordination–insertion ROP results in threo-(R,R)-di-isotactic PHAs with chiral retention, whereas anionic ROP catalysed by an organic superbase produces erythro-(R,S)-di-isotactic PHAs with chiral inversion, achieving precision di-isotactic PHAs with exclusive regio- and stereoregularity. This strategy has also enabled the stereodivergent synthesis of all four [(R,R), (S,S), (R,S) and (S,R)] stereoisomers of α,α-dialkylated PHAs from (R)-P3HB, which can be depolymerized to chiral α,α-dialkylated-β-butyrolactones with high stereoselectivity. Overall, this catalyst-controlled regio- and stereoselective, stereodivergent synthetic methodology provides access to 16 enantiopure stereoisomers of α(α)-(di)substituted PHAs and enables the stereochemistry-defined structure–property relationship study of the di-isotactic PHAs, providing insights into the effects of main-chain stereoconfigurations and alkyl side chains on their thermal properties, melt processability, mechanical performance and supramolecular stereocomplexation.
