Radical 1,4/5‐Amino Shift Enables Access to Fluoroalkyl‐Containing Primary β(γ)‐Aminoketones under Metal‐Free Conditions

Abstract

An ovel radical 1,4/5-amino shift from the oxygen center of alkene-tethered diphenyl ketoxime ethers to the carbon center to achieve high value-added fluoroalkyl-containing primary b(g)-amino-ketones is reported. Mechanism studies reveal that the migration is triggered by the alkene addition of fluoroalkyl radical derived from the electron donor-acceptor (EDA) complex of Tognisr eagent II or fluoroalkyl iodides and quinuclidine,a nd involves au nique 5(6)-exo-trig cyclization of the carbon-centered radical onto the N-atom of ketoxime ethers followed by acascade sequence of NÀObond cleavage and dehydrogenation. Notably,besides Tognisreagent II and fluoroalkyl iodides,this protocol is also compatible with other radical precursors to provide various functionalizedprimary aminoketones.

Efficient access to β-amino acid ester/β-amino ketone derivatives via photocatalytic radical alkoxycabonylimidation/carbonylimidation of alkenes

“…18 In 2021, Han and co-workers reported the synthesis of CF 3 -substituted β-amino ketones by the radical method. 19 Hence, radical difunctionalization involving the bifunctional reagent 2a reported here via a radicalradical cross-coupling process was explored. Unexpectedly, α-trifluoromethylstyrenes exhibited excellent reactivity, and different kinds of substituents on the benzene ring such as Ph, MeO, PhO, acetyl, F, and Br, reacted well, affording β-CF 3β-amino acid ester derivatives (3t-3z) with average yields greater than 80%.…”

Updates on hypervalent-iodine reagents: metal-free functionalisation of alkenes, alkynes and heterocycles

“…The substrate scope was extended to an array of oxime ethers containing diverse functionalities at the aryl and alkene positions (Scheme 17). 67…”

“…The substrate scope was extended to an array of oxime ethers containing diverse functionalities at the aryl and alkene positions (Scheme 17). 67 In 2020, the Li group reported a PIDA-mediated synthesis of vinyl sulfones (30) using sulfonyl chlorides and styrenes (29). The metal-free sulfonylation strategy proceeds under mild and neutral conditions without external oxidants or bases.…”

Radical hydrotrifluoromethylation of ynamides: a route toward β-CF3enamides

“…DMF was likely the H-donor in such a simple reaction mixture and a radical process was proposed for the formation of 2a . According to our previous work in which radical trifluoromethylation of alkenes with PhICF 3 Cl could not occur at room temperature without the assistance of a reductant, 9 d ynamide substrate 1a likely acted as a tertiary amine type electron donor 12 for the generation of the CF 3 radical from PhICF 3 Cl. Thus, an additional reductant was used for the above hydrotrifluoromethylation of 1a .…”