Oxidative Fluorocyclization of Vinyl Azides Leading to 5‐Azido,5‐fluoro‐1,3‐oxolan‐2‐one

Abstract

Vinyl azides have become versatile building blocks in organic synthesis. Most of their transformations usually undergo a fast release of molecular N2 to generate 2H‐aziridine and vinyl nitrene intermediates. However, retaining the azides group in the final product is quite rare and challenging. Herein, we design and validate a new alkene difunctionalization strategy that involves an oxidative fluorocyclization of vinyl azides for the synthesis of a variety of 5‐azido,5‐fluoro‐1,3‐oxolan‐2‐ones with broad substrate scope and good functional group tolerance in good to excellent yields. The in situ removal of a leaving group in this difunctionalization reaction is a key to retain azide moiety in the final product.

o-Silylaryl Triflates: A Journey of Kobayashi Aryne Precursors

“…This strategy smartly avoided the N 1/ N 2 regioselective problem in conventional alkylation reaction of benzotriazoles. Beside the aforementioned examples, this transition-metal-free aryne-azide [3 + 2] cycloaddition protocol turned out to be quite general and has found a broad spectrum of synthetic applications. − …”

Synthesis of 1,3‐Dioxan‐2‐ones by Photo‐Aerobic Selenium‐π‐Acid Multicatalysis

“…elegantly harnessed this feature of alkenes by treating allylic and homoallylic alcohols with strong bases in the presence CO 2 and elemental iodine to furnish the corresponding iodocarbonates (Scheme 1B) [3a] . A similar concept has been recently reported by Ning et al., who demonstrated the 6‐ endo ‐trig fluoro‐cyclization of allylic carbonates using I , I ‐difluoro(phenyl)‐λ 3 ‐iodane as the terminal oxidant [3b] . Gaunt et al.…”

“… [3a] A similar concept has been recently reported by Ning et al., who demonstrated the 6‐ endo ‐trig fluoro‐cyclization of allylic carbonates using I , I ‐difluoro(phenyl)‐λ 3 ‐iodane as the terminal oxidant. [3b] Gaunt et al. and Kleij et al.…”

New Strategies for the Synthesis of Aliphatic Azides

“…Notably, the in situ removal of a leaving group in this difunctionalization reaction is key to retaining the azide moiety in the final product (Scheme 78a). 304 Under similar conditions, the authors successively achieved the 3-azido saturated O-/N-heterocycles (324/326) α-Fluorinated alkyl azides represent promising building blocks for the synthesis of fluoro alkylated five-membered heterocycles of pharmaceutical interest. 203 But their direct synthesis from fluorinated alkyl halides with nucleophilic azides (for example NaN 3 ) via the nucleophilic substitution process is challenging and needs elevated temperature to afford azides in good yields.…”

“…The reaction enables the direct synthesis of a variety of 5-azido-5-fluoro-1,3-oxolan-2-ones 322 with a broad substrate scope and good functional group tolerance in good to excellent yields. Notably, the in situ removal of a leaving group in this difunctionalization reaction is key to retaining the azide moiety in the final product (Scheme a) . Under similar conditions, the authors successively achieved the 3-azido saturated O-/N-heterocycles ( 324/326 ) via an intramolecular fluorocyclization of vinyl azides bearing appropriately positioned O-/N-nucleophiles ( 323/325 , Scheme b).…”