Completely Stereoselective Synthesis of Sulfonated 1,3-Dihydroisobenzofurans via Radical Multicomponent Reactions

Article abstract of DOI:10.1021/acs.joc.9b01918

Two types of new oxidant-free radical multicomponent reactions of β-alkynyl ketones, aryldiazonium salts, and DABCO·(SO₂)₂ (DABSO) were established, leading to the tunable generation of two class of sulfonated 1,3-dihydroisobenzofurans with moderate to good yields and complete stereoselectivity under the mild conditions. The radical-induced scission/recombination of the C(sp³)-C(sp³) bond enabled direct 1,8-halosulfonylation of β-alkynyl ketones, giving 1,3-dimethylene-substituted (1Z,3Z)-1,3-dihydroisobenzofurans with substituent diversity by p-nitrobenzyl bromide (PNBB) or p-nitrobenzyl chloride (PNBC) as the halo source. Fine-tuning substituents to strong electron-withdrawing ones, such as nitro, cyano, and trifluoromethyl, linked to aryldiazonium tetrafluoroborates allowed a different annulation/1,5-azosulfonylation process to access sulfonated (Z)-1,3-dihydroisobenzofurans with one quaternary carbon-amino functionality.