Adaptive dynamic kinetic resolution enables alteration of chiral induction with ring sizes.

Dynamic kinetic resolution (DKR) is an efficient chiral induction strategy that transforms both enantiomers of the substrate racemates into the same optically enriched product. Typically, the absolute configurations of the products should be determined by the chiral catalyst. Here we report an adaptive DKR strategy that forges diverse azapolycycles with high stereochemical selectivities by taking full advantage of the dynamic interconversion of diastereomeric aminoalkyl cyclopalladated complexes. Notably, this innovative adaptive DKR model achieves alterations of absolute configurations at the contiguous stereocentres with the same chiral diphosphine-ligated palladium catalyst by changing the ring sizes of the annulation products. Moreover, a concise and efficient total synthesis of martinellic acid was carried out by using the adaptive DKR process as the key chirality forging and scaffold establishment step, which further demonstrated the efficacy of this strategy.