An Organocatalytic Highly Enantioselective Stereospecific Synthesis of 1,1-Disubstituted-1,3-Dihydroisobenzofurans

Chemistry. 2024 Feb 23:e202303980. doi: 10.1002/chem.202303980. Online ahead of print.ABSTRACTHHerein, we disclosed the asymmetric construction of an oxa-quaternary stereocenter via an intramolecular oxa-Michael (IOM) reaction in β-substituted ortho-hydroxymethyl chalcone by the formation of 1,1-disubstituted-1,3-dihydroisobenzofuran using cinchona alkaloid-based chiral amino-squaramide catalyst. Both the (E- and Z)-β-substituted ortho-hydroxymethyl chalcone provide (S)- and (R)-enantiomers of the 1,1-disubstituted-1,3-dihydroisobenzofuran with excellent stereospecificity. In general, excellent yields (up to 95%) and enantioselectivity (up to 98% ee) were obtained. Furthermore, the resulting 1,1-disubstituted isobenzofuran or phthalan was converted to corresponding chiral 3,3-disubstituted phthalides without losing the enantioselectivity. This methodology provides the core moiety of the (S)-citalopram drug.PMID:38391113 | DOI:10.1002/chem.202303980

Source: Chemistry - February 23, 2024 Category: Chemistry Authors: Chandan Kamilya Sachin S Gorad Prasanta Ghorai Source Type: research