Phosphoric Acid-Catalyzed Asymmetric Synthesis of SPINOL Derivatives

Abstract

Axially chiral 1,1'-spirobiindane-7,7'-diol (SPINOL) is the most fundamental and important privileged structure from which other chiral ligands containing a 1,1'-spirobiindane backbone are synthesized. Driven by the development of enantioselective syntheses of axially chiral SPINOL derivatives, we have successfully developed the first phosphoric acid-catalyzed asymmetric approach. This approach is highly convergent and functional group tolerant, efficiently providing SPINOLs in good yield with excellent enantioselectivity, thus delivering a practical and straightforward access to this privileged structure. It should be emphasized that the catalyst loading could be decreased to only 0.1 mol% for the preparative-scale synthesis. Furthermore, 4,4'-dimethyl-SPINOL-phosphoric acid was synthesized and applied to catalyze the model reaction for synthesis of enantioenriched SPINOL derivatives.