Asymmetric synthesis of spiro-structural 2,3-dihydrobenzofurans via the bifunctional phosphonium salt-promoted [4+1] cyclization of ortho-quinone methides with alpha-bromoketones

摘要

We report a practical and scalable method for the highly diastereo- and enantio-selective construction of 2,3-dihydrobenzofurans bearing spiro-structures by means of cyclization reactions between ortho-quinone methides and alpha-bromoketones through bifunctional phosphonium salt catalysis under mild conditions. A variety of spiro-fused 2,3-dihydrobenzofuran derivatives were readily synthesized in high yields with excellent diastereo- and enantio-selectivities (up to >20 : 1 dr and 97% ee). This protocol represents an alternative facile way for preparing biologically important chiral 2,3-dihydrobenzofurans. Moreover, mechanistic observations indicated that the hydrogen bonding interaction between the Bronsted acid moiety of the phosphonium catalyst and the "C O" unit of the quinone is crucial for stereoinduction.