Visible Light‐Promoted Synthesis of Spiroepoxy Chromanone Derivatives via a Tandem Oxidation/Radical Cyclization/Epoxidation Process

Abstract

A highly efficient and straightforward approach for the synthesis of spiroepoxy chroman‐4‐one derivatives was developed using a visible light‐enabled tandem radical strategy. The reaction is initiated by the formation of an acyl radical that undergoes intramolecular radical cyclization and epoxidation. The optimal result was obtained with 1 mol% of Ru(bpy)3Cl2⋅6H2O, TBHP, and K2CO3 in i‐PrOAc at room temperature with irradiation from a blue LED. This unprecedented tandem approach utilizes a broad range of substrates, and provides a convenient and powerful synthetic tool for accessing the synthetically useful spiroepoxy chroman‐4‐ones and their nitrogen‐containing derivatives.magnified image

Acyl Radical Chemistry via Visible-Light Photoredox Catalysis

“…Intramolecular acyl radical addition/epoxidation. 29 a Yields in parentheses were obtained by the reaction of benzyl alcohol substrates using 8 equiv of TBHP.…”

“…In 2017, Hong et al reported an intramolecular cyclization and epoxidation (Scheme 11), developed in analogy to the intermolecular method reported by Wang et al ., using TBHP as the HAT reagent. 29 The reaction conditions were applicable to both allyloxy and allylamino substrates to produce the desired spiroepoxy chroman-4-ones and enaminones. Interestingly, a three-step tandem process starting from benzyl alcohol and using the 8.00 equivalents of TBHP also occurred, albeit with lower yields.…”

Radical Reactions for the Synthesis of 3‐Substituted Chroman‐4‐ones

“…[106][107][108][109][110][111][112][113][114][115][116][117][118] In 2017, Hong's group reported a visible-light-enabled radical strategy to synthesize spiroepoxy chroman-4-one derivatives 74 via a tandem oxidation/radical cyclization/epoxidation process (Scheme 14). [119] The optimal conditions involving the use of Ru(bpy) 3 Cl 2 ·6H 2 O, TBHP, and K 2 CO 3 in iPrOAc at room temperature with irradiation of blue LEDs demonstrated broad substrate scope and good functional group tolerance with respect to both 2-(allyloxy)arylaldehydes 72 and (2-(allyloxy)aryl)methanols 73. In the control experiment without base, the -peroxy ketone 78 was isolated, which could further be converted into the target product α-carbonyl epoxide 74 in the presence of K 2 CO 3 as base.…”

“…Particularly, visible‐light photoredox catalysis is an ideal tool to initiate radical cascade reactions for the synthesis of heterocycles . In 2017, Hong's group reported a visible‐light‐enabled radical strategy to synthesize spiroepoxy chroman‐4‐one derivatives 74 via a tandem oxidation/radical cyclization/epoxidation process (Scheme ) . The optimal conditions involving the use of Ru(bpy) 3 Cl 2 · 6H 2 O, TBHP, and K 2 CO 3 in i PrOAc at room temperature with irradiation of blue LEDs demonstrated broad substrate scope and good functional group tolerance with respect to both 2‐(allyloxy)arylaldehydes 72 and (2‐(allyloxy)aryl)methanols 73 .…”

Radical Carbonylative Synthesis of Heterocycles by Visible Light Photoredox Catalysis

“…Moreover, Melchiorre et al achieved an asymmetric acylation reaction of enals for the stereocontrolled construction of 1,4-dicarbonyl products [58]. Using the same strategy, in 2017, Hong's group reported an acyl radical-mediated intramolecular epoxyacylation reaction catalyzed by Ru(bpy)3Cl2 (Scheme 13a) [59]. The investigation of optimum reaction conditions revealed that TBHP was the best HAT reagent.…”