Visible-Light-Induced and Diastereoselective Synthesis of Fluorinated Tetrahydrofuran Derivatives

Abstract

The stereocontrolled construction of molecules bearing three contiguous stereocenters is a formidable challenge in synthetic organic chemistry. We report a visible-light-driven, three-component radical cascade that enables the efficient and regioselective formation of fluorinated frameworks containing three consecutive stereocenters. Using trifluoromethyl thianthrenium triflate as a dual-function reagent, the reaction proceeds via in situ generation of CF3••and thianthrene radical cation species under photochemical control. The CF3 radical selectively engages addition to 1,6-dienes to initiate a cascade cyclization/trapping/nucleophilic substitution sequence, forming highly functionalized tetrahydrofuran derivatives in yields up to 85%. This mild and operationally simple protocol exhibits broad nucleophile and substrate scope, including primary, secondary, and tertiary alcohols, as well as water, azide and acetamide sources. Single-crystal X-ray diffraction and NMR analyses confirmed the structures and relative configurations of the products. The observed diastereomeric ratios are attributed to the occurrence of hydrogen bonding interactions as suggested by Density Functional Theory (DFT) calculations.