Enantioselective Synthesis of Spiropyrazolone-Fused Cyclopenta[c]chromen-4-ones Bearing Five Contiguous Stereocenters via (3+2) Cycloaddition

An enantioselective synthesis of spiropyrazolone-fused cyclopenta[c]chromen-4-ones is demonstrated via a (3+2) cycloaddition reaction. The reactions of 3-homoacylcoumarins and alpha,beta-unsaturated pyrazolones in the presence of the cinchona-alkaloid derived hydrogen-bonding catalyst provide aforementioned spiropyrazolone-chromenone adducts bearing five contiguous stereocenters, of which one is the spiro all-carbon quaternary stereocenter in high yields (up to 98%) with good to excellent stereoselectivities (>25:1 dr and up to 99% ee). This one-pot methodology could also be practically demonstrated on a gram-scale with similar efficacy.

Automated summary

An enantioselective synthesis of spiropyrazolone-fused cyclopenta[c]chromen-4-ones is demonstrated via a (3+2) cycloaddition reaction using cinchona-alkaloid derived hydrogen-bonding catalyst. The method provides high yields of adducts with five contiguous stereocenters, including a spiro all-carbon quaternary stereocenter with good to excellent stereoselectivities. The one-pot methodology can also be scaled up effectively.