Enantioselective palladium-catalyzed C(sp2)-C(sp2) σ bond activation of cyclopropenones by merging desymmetrization and (3+2) spiroannulation with cyclic 1,3-diketones

Catalytic asymmetric variants for functional group transformations based on carbon-carbon bond activation still remain elusive. Herein we present an unprecedented palladium-catalyzed (3 + 2) spiro-annulation merging C(sp(2))-C(sp(2)) sigma bond activation and click desymmetrization to form synthetically versatile and value-added oxaspiro products. The operationally straightforward and enantioselective palladium-catalyzed atom-economic annulation process exploits a TADDOL-derived bulky P-ligand bearing a large cavity to control enantioselective spiro-annulation that converts cyclopropenones and cyclic 1,3-diketones into chiral oxaspiro cyclopentenone-lactone scaffolds with good diastereo- and enantio-selectivity. The click-like reaction is a successful methodology with a facile construction of two vicinal carbon quaternary stereocenters and can be used to deliver additional stereocenters during late-state functionalization for the synthesis of highly functionalized or more complex molecules.

Automated summary

Catalytic asymmetric variants for functional group transformations based on carbon-carbon bond activation are still challenging to achieve. Here, a palladium-catalyzed (3 + 2) spiro-annulation process is presented, merging C(sp(2))-C(sp(2)) sigma bond activation and click desymmetrization to form synthetically versatile oxaspiro products. The operationally straightforward and enantioselective process uses a bulky P-ligand to control enantioselective spiro-annulation, converting cyclopropenones and cyclic 1,3-diketones into chiral oxaspiro cyclopentenone-lactone scaffolds.