Efficient catalyst for tandem solvent free enantioselective Knoevenagel-formal [3+3] cycloaddition and Knoevenagel-hetero-Diels–Alder reactions

Abstract

In this study a highly efficient catalyst has been observed for tandem solvent free enantioselective Knoevenagel-formal [3+3] cycloaddition and Knoevenagel-hetero-Diels–Alder reactions. Thus, the synthesis of bicyclic tetrahydro-2H-chromen-5(6H)-one and tricyclic octahydro-2H-benzo[c]-chromen-1(6H)-one derivatives with enantioselectivity up to ee 99% has been achieved in the presence of a chiral Lewis acid assisted Brønsted acid (LBA), titanium-isopropoxy-(S)-BINOLate under solvent free conditions. The stereochemistry of the tricyclic product 10 has been further supported by single crystal X-ray analysis. This domino powerful strategy combines both the economic and environmental aspects of organic chemistry, which are necessary for academic and industrial applications.