Organocatalytic asymmetric [4 + 1] annulation of in situ generated ortho-quinomethanes with 4-halo pyrazolones: straightforward access to chiral spiro-benzofuran pyrazolones

Abstract

A highly straightforward route to enantiomerically enriched spiro-benzofuran pyrazolones has been achieved via chiral amine squaramide catalyzed [4 + 1] annulation of in situ generated ortho-quinomethanes with the novel C1 synthons of 4-halo pyrazolones. In oil–water biphases, high yields (up to 95%) and high to excellent stereoselectivities (up to 99 : 1 dr, 99% ee) of the resulting 4-spiropyrazolones with a wide substrate scope could be achieved. Furthermore, the present protocol provided an arbitrary access to all four possible stereoisomers of the spiro-benzofuran pyrazolones via an appropriate choice of C1 synthons and chiral catalysts.