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. 2021 Dec 1;27(67):16621-16625.
doi: 10.1002/chem.202103509. Epub 2021 Oct 8.

Remote Radical Desaturation of Unactivated C-H Bonds in Amides

Yong Xia  1   2 , Kalipada Jana  1 , Armido Studer  1
Affiliations

Remote Radical Desaturation of Unactivated C-H Bonds in Amides

Yong Xia et al. Chemistry. .

Abstract

Desaturation of inert aliphatic C-H bonds in alkanes to form the corresponding alkenes is challenging. In this communication, a new and practical strategy for remote site-selective desaturation of amides via radical chemistry is reported. The readily installed N-allylsulfonylamide moiety serves as an N radical precursor. Intramolecular 1,5-hydrogen atom transfer from an inert C-H bond to the N-radical generates a translocated C-radical which is subsequently oxidized and deprotonated to give the corresponding alkene. The commercially available methanesulfonyl chloride is used as reagent and a Cu/Ag-couple as oxidant. The remote desaturation is realized on different types of unactivated sp3 -C-H bonds. The potential synthetic utility of this method is further demonstrated by the dehydrogenation of natural product derivatives and drugs.

Keywords: alkenes; desaturation; oxidation; radical; reaction mechanism.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Different methods for radical desaturation of unactivated sites.
Scheme 2
Scheme 2
Remote desaturation of various amine derivatives. Reaction conditions: 1 (0.2‐0.4 mmol), MeSO2Cl (0.3‐0.6 mmol, 1.50 equiv), CuI (10 mol%) and Ag2CO3 (0.15‐0.30 mmol, 0.75 equiv) in EA (1.0‐2.0 mL) were stirred at 120 °C for 4–16 h. Yields given correspond to isolated yields. Regioselectivity was determined by 1H NMR spectroscopy. [a] Performed on 1.0 mmol scale. [b] 2‐Methylallylsulfonyl‐substituted benzamide was used. Dashed line indicates the double bond position in the minor isomer.
Scheme 3
Scheme 3
Desaturation of various carboxylic acid derivatives. Reaction conditions: 1 (0.2–0.4 mmol), MeSO2Cl (0.3‐0.6 mmol, 1.50 equiv), CuI (10 mol%) and Ag2CO3 (0.15–0.3 mmol, 0.75 equiv) in EA (1.0–2.0 mL) were stirred at 120 °C for 12 h. Yields given correspond to isolated yields. Regioselectivity was determined by 1H NMR. [a] 1.2 Equiv. of 2 e was used instead of 2 c. Dashed line indicates the double bond position in the minor isomer.
Scheme 4
Scheme 4
Mechanistic investigations and proposed reaction mechanism.
See this image and copyright information in PMC

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