Click-binol-phosphoric acid catalysts in intramolecular enantioselective oxidative CH-bond functionalization

- Synthesis of a new family of C2-symmetric triazole-phosphoric acid catalysts.
- Intramolecular asymmetric CH bond functionalization of N-aryl substituted tetrahydroisoquinolines.
- Important effects of the triazoles and the regiomeric structures for optimal enantioselectivity.
- π-π vs. cooperative π-π and triazole-substrate interactions.

Counteranion-catalysis represents an appealing but challenging approach for the development of enantioselective oxidative CH bond functionalization reactions. In this work, a new family of 3,3′-triazolyl BINOL-derived phosphoric acids was synthesized and employed in the intramolecular asymmetric CH bond functionalization of N-aryl substituted tetrahydroisoquinolines. As previously reported with related structures, the presence of the triazole groups on the catalysts was key to attain enantioselectivity. Our study also shows the importance of choosing the appropriate regioisomeric triazole groups at the BINOL backbone to achieve a more efficient chirality transfer. Moderate enantiomeric ratios were obtained with the N-benzamide substrates, whereas the change of the nature of the nucleophile fragment was translated to a dramatic loss of the enantioselectivity. Therefore, it can be foreseen that there is a need for designing further superior catalyst structures to develop future counter-anion organocatalyzed asymmetric CH bond functionalization reactions.

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