Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jul 6;20(13):3943-3947.
doi: 10.1021/acs.orglett.8b01520. Epub 2018 Jun 11.

Sulfonamide Synthesis via Calcium Triflimide Activation of Sulfonyl Fluorides

Paramita Mukherjee  1 , Cristian P Woroch  2 , Leah Cleary  1 , Mark Rusznak  2 , Ryan W Franzese  2 , Matthew R Reese  1 , Joseph W Tucker  1 , John M Humphrey  1 , Sarah M Etuk  2 , Sabrina C Kwan  2 , Christopher W Am Ende  1 , Nicholas D Ball  2
Affiliations

Sulfonamide Synthesis via Calcium Triflimide Activation of Sulfonyl Fluorides

Paramita Mukherjee et al. Org Lett. .

Abstract

A method using calcium triflimide [Ca(NTf2)2] as a Lewis acid to activate sulfonyl fluorides toward nucleophilic addition with amines is described. The reaction converts a wide array of sterically and electronically diverse sulfonyl fluorides and amines into the corresponding sulfonamides in good yield.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
(a) Current methods toward converting sulfonyl fluorides to sulfonamides, (b) proposed modes of Lewis acid activation sulfonyl fluoride for nucleophilic addition of amines, and (c) our method using Ca(NTf2)2 in tert-amyl alcohol.
Scheme 1.
Scheme 1.
Substrate Scope Reacting Aryl, Heteroaryl, and Aliphatic Amines with PhSO2F* *Reaction conditions: PhSO2F (1 equiv), amine (2 equiv), Ca(NTf2)2 (1 equiv), t-amylOH (0.20 M), 60 °C, 24 h. Isolated yields for Ca(NTf2)2 reactions are averages of two independent trials. Reactions without Ca were conducted as a single reaction. Mass balance is unreacted starting material. aPhSO2F (1 equiv), aniline (1 equiv), Ca(NTf2)2 (1 equiv), Et3N (1 equiv), t-amylOH (0.20 M), 60 °C, 24 h. bN/R denotes no reaction. cTrace product was detected by LC/MS; however, it could not be isolated. dYield of sulfonamide 14 on 6.2 mmol scale.
Scheme 2.
Scheme 2.
Substrate Scope Reacting Aryl- and Alkylsulfonyl Fluorides with Amine 15* *Reaction conditions: RSO2F (1 equiv), 1-(5-trifluoromethyl)-2-pyrdinyl piperazine, 18 (2 equiv), Ca(NTf2)2 (1 equiv), t-amylOH (0.20 M), 60 °C, 24 h. Isolated yields for Ca(NTf2)2 reactions are averages of two independent trials. Reactions without Ca where conducted as a single reaction. aN/R denotes no reaction.
Scheme 3.
Scheme 3.
Comparing the Reactivity of Electron-Deficient Sulfonyl Fluorides with Amines 2 and 15* *Reaction conditions: RSO2F (1 equiv), amine, 15 or 2 (2 equiv), Ca(NTf2)2 (1 equiv), t-amylOH (0.20 M), 60 °C, 24 h. Isolated yields for Ca(NTf2)2 reactions are averages of independent trials. Reactions without Ca weere conducted as a single reaction. aN/R denotes no reaction. bTrace product was detected by LC/MS; however, it could not be isolated.
Scheme 4.
Scheme 4.
Sulfonyl Fluoride as a Latent Electrophile
See this image and copyright information in PMC

References

    1. McGrath NA; Brichacek M; Njardarson JT J. Chem. Educ 2010, 87, 1348.
    1. Devendar P; Yang G-F Top. Curr. Chem 2017, 375, 1. - PubMed
    1. Wright SW; Hallstrom KN J. Org. Chem 2006, 71, 1080. - PubMed
    2. Bahrami K; Khodaei MM; Abbasi J Tetrahedron 2012, 68, 5095.
    3. Goldberg FW; Kettle JG; Kogej T; Perry MWD; Tomkinson NP Drug Discovery Today 2015, 20, 11. - PubMed
    1. Dong J; Krasnova L; Finn MG; Sharpless KB Angew. Chem., Int. Ed 2014, 53, 9430 and references cited therein. - PubMed
    2. Bogolubsky AV; Moroz YS; Mykhailiuk PK; Pipko SE; Konovets AI; Sadkova IV; Tolmachev A ACS Comb. Sci 2014, 16, 192. - PubMed
    1. Kiang T; Zare RNJ Chem. Soc., Chem. Commun 1980, 24, 1228.
    2. Wray KL; Feldman EV J. Chem. Phys 1971, 54, 3445.

Publication types

LinkOut - more resources