Synthesis of 2,2′,6-Trisubstituted
and 2,2′,6,6′-Tetrasubstituted Diaryl Sulfides and
Diaryl Sulfones by Copper-Promoted Coupling and/or Ortholithiation

Jonathan Clayden; James Senior

doi:10.1055/s-0029-1217986

LETTER

Synthesis of 2,2′,6-Trisubstituted and 2,2′,6,6′-Tetrasubstituted Diaryl Sulfides and Diaryl Sulfones by Copper-Promoted Coupling and/or Ortholithiation

Jonathan Clayden*, James Senior
School of Chemistry, University of Manchester, Oxford Rd., Manchester M13 9PL, UK
Fax: +44(161)2754612; e-Mail: clayden@man.ac.uk;

Abstract

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Abstract

Stoichiometric copper(I) iodide, in the presence of potassium carbonate and ethylene glycol, promotes the coupling of even highly sterically encumbered 2,6-disubstituted thiophenols and aryl iodides to form hindered diarylsulfides. Hindered diarylsulfones may be made in a complementary fashion by ortholithiation of the sulfone oxidation products of less hindered diarylsulfides.

Key words

copper - Ullmann - coupling - sulfide - sulfone - lithiation

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References

References and Notes

For examples of atropisomerism and discussions on the conformational properties of non-biaryl systems, see:

<A NAME="RD15909ST-1A">1a</A> Clayden J. Turner H. Helliwell M. Moir E. J. Org. Chem. 2008, 73: 4415

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<A NAME="RD15909ST-1F">1f</A> For an overview of this area, see: Clayden J. Chem. Commun. 2004, 127

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Copper-Promoted Coupling; Typical Procedure for (2,4-Di-tert-butyl-6-bromophenyl)-(2,4-di-tert-butyl-6-methylphenyl)
sulfane (20b) Thiophenol 18a (574 mg), copper(I) iodide (462 mg) and potassium carbonate (560 mg) were charged to a flask fitted with a reflux condenser, which was evacuated/back-filled with nitrogen (×3). A solution of iodide 19c (800 mg) and ethylene glycol (0.23 mL) in tert-amyl alcohol (6 mL) was added via syringe and the reaction mixture was heated to reflux for 24 h. The reaction mixture was allowed to cool to r.t., diluted with ethyl acetate (40 mL) and filtered through a glass sinter. The filtrate was washed with water (3 × 50 mL) and brine (50 mL), dried over MgSO₄ and the solvents were removed under reduced pressure. The crude product was purified by flash chromatography (petroleum ether) to yield the title compound as a white solid that was recrystallised from acetone (1.27 g, 76%); mp 125-129 ˚C(acetone); R _f = 0.69 (petroleum ether); ^¹H NMR (400 MHz, CDCl₃): δ = 7.45 (d, J = 2 Hz, 1 H, ArH), 7.36 (d, J = 2 Hz, 1 H, ArH), 7.33 (d, J = 2 Hz, 1 H, ArH), 6.93 (d, J = 2 Hz, 1 H, ArH), 1.75 (s, 3 H, ArCH ₃), 1.65 (s, 9 H, CMe₃), 1.64 (s, 9 H, CMe₃), 1.30 (s, 9 H, CMe₃), 1.28 (s, 9 H, CMe₃); ^¹³C NMR (100 MHz, CDCl₃): δ = 150.8, 150.2, 149.0, 148.5, 139.0, 133.1, 131.8, 129.7, 127.0, 126.1, 123.6, 122.5, 38.3, 37.5, 34.7, 34.5, 31.3, 31.3, 31.1, 30.9, 23.0; MS (CI): m/z (%) = 502 (40) [⁷⁹Br M]⁺, 504 (40) [^8¹Br M]⁺, 503 (50) [⁷⁹BrM + H]⁺, 505 (50) [^8¹BrM + H]⁺; HRMS: m/z calcd for C₂₉H₄₃BrS: 502.2263; found: 502.2264.