Asymmetric Synthesis of Spiro-structural 2, 3-Dihydrobenzofurans via Bifunctional Phosphonium Salt-promoted [4 + 1] Cyclization of ortho-Quinone Methides with -Bromoketones
We report a practical and scalable method for the highly diastereo- and enantioselective construction of 2,3-dihydrobenzofurans bearing spiro-structures by means of cyclization reactions between ortho-quinone methides and-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 enantioselectivities (up to > 20:1 dr and 96% ee). This protocol represents an alternatively facile way for preparing biologically important chiral 2,3-dihydrobenzofurans. Moreover, mechanistic observations indicated that the hydrogen bonding interaction between the Brønsted acid moiety of the phosphonium catalyst and the “C=O” unit of the quinone must be crucial for stereoinduction.