Dual C(sp³)–H Functionalization of Cyclic Ethers via Singlet Oxygen-Mediated Ring Opening and Ring Closing

Abstract

A metal-free dual C­(sp3)–H bond functionalization of saturated cyclic ethers via photooxidative singlet oxygen-mediated ring opening and ring closing has been developed, providing a method for generating hydrobenzofurans/pyrans/dioxins. Mechanistic studies have confirmed that ring-opening intermediates were effectively generated by singlet oxygen-mediated C­(sp3)–H activation and efficiently reacted with aldehydes and activated methylene compounds to form a wide array of products with high diastereoselectivities (up to >95:5 dr). This study is a rare example of α,β-dual C­(sp3)–H bond functionalization of ethers.

Visible-Light-Induced α-C(sp3)–H Phosphinylation of Unactivated Ethers under Photocatalyst- and Additive-Free Conditions

“…According to the above experimental evidence and literatures precedents, , a plausible reaction mechanism for the formation of product 3aa is outlined in Scheme . Initially, an α-alkoxyalkyl radical I is generated from THF 2a via a single electron oxidation by O 2 with the assistance of blue LED light in the reaction system . Next, I combines with O 2 to produce peroxyl radical II , which generates hydroperoxide III via abstraction of a hydrogen atom from 2a , together with a regeneration of radical I .…”

“…According to the above experimental evidence and literatures precedents, , a plausible reaction mechanism for the formation of product 3aa is outlined in Scheme . Initially, an α-alkoxyalkyl radical I is generated from THF 2a via a single electron oxidation by O 2 with the assistance of blue LED light in the reaction system .…”

Oxidative [2 + 1 + 1 + 1] Annulation of Aldehydes and Methylene Nitriles: Synthesis of Diastereoselective Polysubstituted Cyclopentenes

“…4a reacted with acetyl chloride to form 6a with good yield (91%) (Scheme b path a). Under an air atmosphere, 4a reacted with NaOAc in EtOH solvent to form 6b with good yield (Scheme b path b). Under alkaline water conditions, 4a underwent hydrolysis and a condensation annulation cascade to form cyclopenta­[ c ]­isoxazole 6c (Scheme b path c), whereas, under the same conditions, if the reaction is heated, the aromatization product 6d can be obtained (Scheme b path d).…”

“…Under an air atmosphere, 4a reacted with NaOAc in EtOH solvent to form 6b with good yield (Scheme b path b). Under alkaline water conditions, 4a underwent hydrolysis and a condensation annulation cascade to form cyclopenta­[ c ]­isoxazole 6c (Scheme b path c), whereas, under the same conditions, if the reaction is heated, the aromatization product 6d can be obtained (Scheme b path d). Interestingly, cyclopenta­[ c ]­pyrimidine derivatives 6e and 6f can be easily prepared by the thermal condensation reaction of 4a and formamide or formic acid (Scheme b paths e and f).…”

Synthesis of 2-Aminofurans and 2-Aminothiophenes through Elemental Sulfur-Promoted Switchable Redox Condensation Reaction of Enaminones with Methylene Nitriles

“…In a heated aqueous solution of sodium hydroxide, 5a underwent intramolecular condensation to obtain the bicyclic compound 7d. 22 Finally, compound 3a reacted with formic acid solution at 110 °C to produce pyranone derivative 7e, which was confirmed by X-ray crystallography.…”