PhIO/Et₃N ⋅ 3HF‐Mediated Formation of Fluorinated 2H‐Azirines via Domino Fluorination/Azirination Reaction of Enamines

Abstract

A variety of enamine carboxylic esters and enaminones were converted to the biologically interesting fluorinated 2H-azirines through reactions with PhIF 2 generated in situ by PhIO and Et 3 N · 3HF in 1,2-dichroloethane, which features the hypervalent iodine reagents-mediated introduction of fluorine atom and formation of the 2H-azirine skeleton under metal-free conditions. The domino reaction is postulated to proceed via a PhIF 2mediated oxidative fluorination and a subsequent azirination of the fluorinated enamine intermediates.

Fluorination and Fluoroalkylation Reactions Mediated by Hypervalent Iodine Reagents

“…[53] Construction of the biologically interesting fluorinated 2H-azirines (152) from a variety of enamine carboxylic esters and enaminones (151) was accomplished by reaction with PhIO and Et 3 N • 3HF in 1,2dichroloethane (Scheme 30). [54] This PhIO/Et 3 N • 3HFmediated transformation might involve a transition- iodine(III) reagent and TEA • 3HF in the presence of phthalimide as a nitrogen source allowed the fluorination and amination of alkynes in a similar manner, affording the corresponding fluoroalkene phthalimide derivatives in good yields. [55a] Very recently, α-fluoroketones were readily synthesized from terminal and internal alkynes via I(I)/I(III) catalysis utilizing p-TolI as an organocatalyst with selectfluor, water, and amine • HF mixtures.…”

“…Construction of the biologically interesting fluorinated 2 H ‐azirines ( 152 ) from a variety of enamine carboxylic esters and enaminones ( 151 ) was accomplished by reaction with PhIO and Et 3 N ⋅ 3HF in 1,2‐dichroloethane (Scheme ) . This PhIO/Et 3 N ⋅ 3HF‐mediated transformation might involve a transition‐metal‐free hypervalent‐iodine(III)‐mediated intermolecular oxidative C−F bond formation and a subsequent intramolecular oxidative azirination (Scheme ).…”

Easy Access to 2-Fluoro- and 2-Iodo-2H-azirines via the Halex Reaction

“…All the newly synthesized haloazirines 1, 2, and 7 were characterized based of 1 H, 13 C NMR spectroscopic and HRMS data.…”

“…Yield: 619 mg (93%) (from isoxazole 6f); colorless solid; mp 83-84 °C. Fluoro-3-(p-tolyl)-2H-azirine-2-carboxylate (2b) 13 Yield: 170 mg (82%) (from azirine 1b); colorless solid; mp 44-45 °C.…”

“…12 The reaction of -carbonyl-substituted enamines with PhIF 2 generated in situ from PhIO and Et 3 N•3HF was used for the preparation of 2-fluoroazirines, containing a carbonyl substituent at the С2 atom (reaction 4). 13 Another strategy for the synthesis of 2-fluoro-and 2-iodoazirine-2carbonyls is based on the metal-catalyzed ring contraction of 4-fluoro-and 4-iodoisoxazoles (reactions 2 and 3). 14,15 Unfortunately, the methods noted above require either po-…”