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. 2020 May 15;85(10):6380-6391.
doi: 10.1021/acs.joc.0c00139. Epub 2020 May 4.

Photochemically Mediated Nickel-Catalyzed Synthesis of N-(Hetero)aryl Sulfamides

R Thomas Simons  1 , Georgia E Scott  1 , Anastasia Gant Kanegusuku  1 , Jennifer L Roizen  1
Affiliations

Photochemically Mediated Nickel-Catalyzed Synthesis of N-(Hetero)aryl Sulfamides

R Thomas Simons et al. J Org Chem. .

Abstract

A general method for the N-arylation of sulfamides with aryl bromides is described. The protocol leverages a dual-catalytic system, with [Ir(ppy)2(dtbbpy)]PF6 as a photosensitizer, NiBr2·glyme as a precatalyst, and 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU) as a base, and proceeds at room temperature under visible light irradiation. Using these tactics, aryl boronic esters and aryl chlorides can be carried through the reaction untouched. The developed reactions efficiently engage simple bromoarenes and primary sulfamides in between 66% and quantitative yields. For more challenging substrates, such as secondary sulfamides, the reaction efficiency is documented. Thereby, these methods complement the known Buchwald-Hartwig coupling methods for N-arylation of sulfamides.

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Conflict of interest statement

Conflicts of interest

The authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
N-heteroaryl sulfamides are important FDA-approved drugs and therapeutic targets
Scheme 1.
Scheme 1.
Recent advances allow for diverse and complementary strategies for the synthesis of N-(hetero)aryl sulfamides
Scheme 2.
Scheme 2.
This research extends the development of light-driven dual catalytic C–N bond-forming technologies, first pioneered by Buchwald, MacMillan, and co-workers
Scheme 3.
Scheme 3.
Photochemically-mediated nickel-catalyzed conditions engage a variety of electron-deficient aryl bromides and sulfamides a General conditions: sulfamide 1 (1.0 equiv), (hetero)aryl bromide (1.5 equiv), [Ir(ppy)2(dtbbpy)]PF6 (1 mol %), NiBr2•glyme (5 mol %), and DBU (3.0 equiv unless otherwise specified) in MeCN (0.25 M) with stirring between two 34W blue Kessil lamps for 24–48 h. b Isolated yield through a palladium-mediated cross-coupling reaction.c Isolated yield when prepared from subjecting morpholinyl sulfamoyl chloride following literature conditions.d DBU (0.5 equiv).
Scheme 4.
Scheme 4.
Photochemically-mediated nickel-catalyzed reactions proceed in ethanol a General conditions: sulfamide 1 (1.0 equiv), (hetero)aryl bromide (1.5 equiv), [Ir(ppy)2(dtbbpy)]PF6 (1 mol %), NiBr2•glyme (10 mol %), dtbbpy (4 mol %) and DBU (3.0 equiv) in EtOH (0.25 M) with stirring between two 34 W blue Kessil lamps for 24–96 h. b Isolated yield when prepared from N,N-dichlorosulfamide.c Isolated yield when prepared from sulfamic acid.
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References

    1. For recent reviews that highlight sulfamide-containing therapeutic targets, see:
    2. Reitz AB; Smith GR; Parker MH The role of sulfamide derivatives in medicinal chemistry: a patent review (2006–2008). Expert Opin. Ther. Pat 2009, 19, 1449–1453. - PubMed
    3. Scott KA; Njardarson JT Analysis of US FDA-Approved Drugs Containing Sulfur Atoms. Top. Curr. Chem. (Z), 2018, 376, 5. - PubMed
    1. Devendar P; Yang G-F Sulfur-Containing Agrochemicals. Top. Curr. Chem. (Z), 2017, 375, 82. - PubMed
    1. For SNAr approaches to prepare Macitentan, see:
    2. Bolli M; Boss C; Treiber A 4-PYRIMINIDINESULFAMIDE DERIVATIVE. World IP Org. WO 2009/024906 A1 February 26, 2009.
    3. Bolli MH; Boss C; Binkert C; Buchmann S; Bur D; Hess P; Iglarz M; Meyer S; Rein J; Rey M; Trieber A; Clozel M; Fischli W; Weller T The discovery of N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl-N’-propylsulfamide (Macitentan), an Orally Active, Potent Dual Endothelin Receptor Antagonist. J. Med. Chem 2012, 55, 17, 7849–7861. - PubMed
    1. For palladium-catalyzed cross-coupling approaches to prepare the depicted chemokine receptor modulator, see:
    2. Cheshire DR; Cox RJ; Meghani P; Preston CF; Smith NM; Stonehouse JP PYRIMIDINE SULPHONAMIDE DERIVATIVES AS CHEMOKINE RECEPTOR MODULATORS. World IP Org. WO 2006/024823 A1 March 9, 2006.
    1. Ahn KH; Yoo DJ; Kim JS Asymmetric aldol reactions employing a cyclic sulfamide chiral auxillary.Tetrahedron Lett 1992, 33, 6661–6664.

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