Highly Selective Radical Relay 1,4-Oxyimination of Two Electronically Differentiated Olefins

Abstract

Radical addition reactions of olefins have emerged as an attractive tool for the rapid assembly of complex structures, and have plentiful applications in organic synthesis, however, such reactions are often limited to polymerization or 1,2-difunctionalization. Herein, we disclose an unprecedented radical relay 1,4oxyimination of two electronically differentiated olefins with a class of bifunctional oxime carbonate reagents via an energy transfer strategy. The protocol is highly chemo-and regioselective, and three different chemical bonds (C−O, C−C, and C−N bonds) were formed in a single operation in an orchestrated manner. Notably, this reaction provides rapid access to a large variety of structurally diverse 1,4-oxyimination products, and the obtained products could be easily converted into valuable biologically relevant δ-hydroxyl-α-amino acids. With a combination of experimental and theoretical methods, the mechanism for this 1,4-oxyimination reaction has been investigated. Theoretical calculations reveal that a radical chain mechanism might operate in the reaction.

Metal-free photosensitized radical relay 1,4-carboimination across two distinct olefins

“…Alternatively, due to low concentrations of the radical species and a relatively high concentration of oxime ester 1a , IM2 can form product 4 via radical attack to oxime ester 1a and subsequent fragmentation, representing a radical chain mechanism. 15 c ,18…”

“…This mechanism is therefore related to our previous work, in which we used oxime carbonates as a source for electrophilic oxygen-centered radicals to achieve a three-component 1,4-oxyimination. 18 In both cases, the desired regioselectivity was achieved by rational reaction design based on the philicity of the generated radicals and the polarity of the olefins. Notably, the different philicities of carbon- and oxygen-centered radicals cause a different order of building block assembly depending on the selected reagent.…”

“…oxyimination. 18 In both cases, the desired regioselectivity was achieved by rational reaction design based on the philicity of the generated radicals and the polarity of the olens. Notably, the different philicities of carbon-and oxygen-centered radicals cause a different order of building block assembly depending on the selected reagent.…”

Photochemical Alkene Trifluoromethylimination Enabled by Trifluoromethylsulfonylamide as a Bifunctional Reagent

“…In addition to 1,2-difunctionalization of alkene, remote alkene difunctionalizations across a long distance were also evaluated on specific substrates, in which an intramolecular distal radical migration was involved . Thus, a range of alkenes with specific structural features was chosen and subjected to the standard reaction conditions.…”

Photosensitized Vicinal Sulfonylamination of Alkenes with Oxime Ester and DABCO·(SO2)2

“…Considering the weak stability of the alkyl carbonyloxyl radical, CO 2 release or subsequent extrusion of another small molecule could be expected . Very recently, Glorius, Molander, Xia, and our group independently employed this strategy to accomplish a variety of difunctionalizations of alkenes by the rational design of bifunctional reagents. Despite these encouraging advances, modulating the reaction pathway by inserting another linker moiety after CO 2 extrusion in the process has been rarely explored.…”