Synthesis of Halomethyl Isoxazoles/Cyclic Nitrones via Cascade Sequence: 1,2-Halogen Radical Shift as a Key Link

Abstract

A novel iminoxyl radical-promoted dichotomous regioselective 5-exo-trig cyclization onto vinylic halogen/1,2-halogen radical shift sequence is developed for the synthesis of halomethyl isoxazoles/cyclic nitrones using β-halo-β,γ- and γ-halo-γ,δ-unsaturated ketoximes as the substrates and PhI(OAc)/TEMPO as the oxidation system. DFT calculations reveal that a halogen-bridged three-membered ring transition state is involved in the 1,2-Cl-/Br-atom shift, while the 1,2-I atom migration can be taken into account with an elimination/readdition mechanism. The migration ability was indicated to be ranked in the following order: I > Br > Cl.

Radical Cascade Reactions of β,γ‐Unsaturated Hydrazones/Oximes

“…In 2018, the group of Han explored a novel and efficient protocol for the synthesis of structurally useful halomethyl isoxazoles/cyclic nitrones by using vinylic halogen‐tethered ketoximes as the starting materials via 1,2‐halogen radical shift process (Scheme 40). [59] Noticeably, this strategy also could extend to γ ‐halo‐ γ , δ ‐unsaturated ketoximes, which underwent a similar process to form TEMPO‐trapped and halomethyl incorporated cyclic nitrones. DFT calculations revealed that the 1,2‐Cl‐/Br‐atom shift process experienced a halogen‐bridged three‐membered ring transition state, while the 1,2‐I atom migration proceeded through an elimination/readdition process.…”

Visible-Light-Induced Catalytic Selective Halogenation with Photocatalyst

“…Halogen derivatives are useful building blocks in organic synthesis for the construction of complicated, high-activity molecules [ 1 , 2 , 3 ]. Moreover, as halogenation can be applied to a wide variety of organic compounds without altering their basic structures, halogen-substituted compounds have become popular intermediates for transformation to create different functional groups [ 4 , 5 , 6 ]. Various areas such as pharmaceuticals, material sciences, industrial chemicals, and bioactive compounds have all benefited from halogen-containing compounds [ 7 , 8 , 9 , 10 ].…”

Efficient and Chemoselective Procedure for Conversion of Rhodanine Derivatives into 1,3‐Thiazolidine‐2,4‐diones via 1,3‐Dipolar Cycloaddition Reaction and Rearrangement Sequences

“…Heterocyclic structures are extremely significant compounds and different synthetic routes to construct heterocyclic structures have attracted the attention of scholars for many years [1–8] . Heterocycles possess a broad spectrum of pharmaceutical and medicinal properties.…”