Sequential Electrophilic Trapping Reactions for the Desymmetrization of Dilithio(hetero)arenes

Christian Muschelknautz; Markus Sailer; Thomas J. J. Müller

doi:10.1055/s-2008-1042911

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Synlett 2008(6): 845-848
DOI: 10.1055/s-2008-1042911

LETTER

Sequential Electrophilic Trapping Reactions for the Desymmetrization of Dilithio(hetero)arenes

Christian Muschelknautz, Markus Sailer, Thomas J. J. Müller*
Institut für Organische Chemie und Makromolekulare Chemie, Lehrstuhl für Organische Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany
Fax: +49(211)8114324; e-Mail: ThomasJJ.Mueller@uni-duesseldorf.de;

Further Information

Publication History

Received 19 December 2007
Publication Date:
11 March 2008 (online)

Abstract
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Abstract

Double bromine-lithium exchange and sequential trapping of the dilithio intermediate with different electrophiles gives rise to the formation of unsymmetrically substituted (hetero)arenes in a one-pot fashion.

Key words

arenes - bromine-lithium exchange - dianions - heterocycles - one-pot reactions

References and Notes

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8

Representative Procedure - Synthesis of Trimethyl[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophen-2-yl]silane (3b; Table 1, Entry 2)
In a flame-dried Schlenk flask under N₂ atmosphere n-BuLi (2.5 M in n-hexane, 0.83 mL, 2.00 mmol) and TMEDA (0.3 mL, 2.0 mmol) were dissolved in anhyd THF (30 mL) at
-78 °C. 2,5-Dibromothiophene (1a, 242 mg, 1.00 mmol) was added slowly to the solution, and the mixture was stirred for 30 min. Then, TMSCl (2a, 0.11 g, 1.00 mmol) in anhyd THF (10 mL) was added dropwise to the stirred solution over a period of 3 h. The reaction mixture was stirred for another 30 min and B(OMe)₃ (2c, 208 mg, 1.00 mmol) was added. After stirring for 40 min pinacol (130 mg, 1.10 mmol) in anhyd THF (5 mL) was added to the mixture. The solution was allowed to warm to r.t., a few drops of AcOH were added, and the solution was stirred for 14 h. After aqueous workup and extraction with Et₂O the combined organic layers were dried with MgSO₄. The solvent was removed under reduced pressure and the residue purified by flash chromatography on silica gel (hexane-EtOAc, 10:1) gives 156 mg (55%) of 3b as a colorless solid.
¹H NMR (300 MHz, CDCl₃): δ = 0.30 (s, 9 H), 1.33 (s, 12 H), 7.31 (d, ³ J = 3.3 Hz, 1 H), 7.67 (d, ³ J = 3.3 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = -0.1, 24.8, 84.1, 135.0, 137.9, 148.5. MS (EI): m/z (%) = 282(21) [M]⁺, 267(100) [C₁₂H₂₀BO₂SSi]⁺, 233(4), 209(5), 183(7), 167(11). HRMS (EI): m/z calcd for C₁₃H₂₃BO₂SSi [M]⁺: 282.1281; found: 282.1274.
5-(Trimethylsilyl)thiophene-2-carbaldehyde (3a) ¹H NMR (300 MHz, CDCl₃): δ = 0.34 (s, 9 H), 7.29 (d, ^³ J = 3.6 Hz, 1 H), 7.77 (d, ^³ J = 3.6 Hz, 1 H), 9.92, (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = -0.5, 134.5, 136.7, 148.2, 152.7, 182.6. MS (EI): m/z (%) = 184(19) [M]⁺, 189(100) [C₇H₉OSSi]⁺. HRMS (EI): m/z calcd. for C₈H₁₂OSSi [M]⁺: 184.0378; found: 184.0368.
5-(Trimethylsilyl)-1 H -pyrrole-2-carbaldehyde (3c) ¹H NMR (300 MHz, CDCl₃): δ = 0.24 (s, 9 H), 6.37-6.48 (m, 1 H), 6.91-6.93 (m, 1 H), 9.46 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 0.02, 120.5, 122.8, 137.4, 143.1, 180.4. MS (EI): m/z (%) = 167(36) [M]⁺, 152(100) [C₇H₁₀NOSi]⁺.
10-Hexyl-7-iodo-10 H -phenothiazine-3-carbaldehyde (3d) ¹H NMR (300 MHz, acetone-d ₆): δ = 0.82-0.86 (m, 3 H), 1.27-1.30 (m, 4 H), 1.43-1.48 (m, 2 H), 1.74-1.84 (m, 2 H), 4.00 (t, J = 7.0 Hz, 2 H), 6.89 (d, J = 8.5 Hz, 1 H), 7.17 (d, J = 8.5 Hz, 1 H), 7.45 (d, J = 1.8 Hz, 1 H), 7.47 (dd, J = 8.5, 1.8 Hz, 1 H), 7.52 (dd, J = 8.5, 1.9 Hz, 1 H), 7.60 (d, J = 2.2 Hz, 1 H). ¹³C NMR (75 MHz, acetone-d ₆): δ = 14.1, 23.1, 26.8, 27.1, 31.9, 48.2, 85.8, 116.5, 119.1, 124.9, 127.0, 128.5, 130.8, 132.6, 135.8, 137.3, 144.6, 150.9, 190.3. MS (EI): m/z (%) = 437(100) [M]⁺, 366(42), 352(76), 239(14), 255(20), 196(22).
10-Hexyl-7-iodo-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-10 H -phenothiazine-3-carbaldehyde (3e) ¹H NMR (300 MHz, acetone-d ₆): δ = 0.82-0.86 (m, 3 H), 1.27-1.28 (m, 16 H), 1.40-1.46 (m, 2 H), 1.71-1.81 (m, J = 6.9 Hz, 2 H), 3.93 (t, J = 7.0 Hz, 2 H), 6.83 (d, J = 8.4 Hz, 1 H), 7.02 (d, J = 8.1 Hz, 1 H), 7.42-7.44 (m, 2 H), 7.48 (dd, J = 2.2, 8.5 Hz, 1 H), 7.56 (dd, J = 1.5, 8.1 Hz, 1 H). ¹³C NMR (75 MHz, acetone-d ₆]): δ = 14.1, 23.1, 25.0, 26.9, 27.2, 32.0, 48.7, 84.4, 84.8, 116.1, 123.7, 127.9, 134.1, 135.2, 135.6, 135.8, 136.9, 145.6, 148.3. MS (EI): m/z (%) = 535(100) [M]⁺, 450(24), 409(2). Anal. Calcd for C₂₄H₃₁BINO₂S (535.3): C, 53.85; H, 5.84; N, 2.62; S, 5.99. Found: C, 57.84; H, 8.13; N, 1.97.
2-(4′-Iodobiphenyl-4-yl)-4,4,5,5-tetramethyl-1,3-dioxaborolane (3f) ¹H NMR (300 MHz, CDCl₃): δ = 1.35 (s, 12 H), 7.34 (d, ^³ J = 8.50 Hz, 2 H), 7.55 (d, ^³ J = 8.23 Hz, 2 H), 7.75 (d, ^³ J = 8.50 Hz, 2 H), 7.90 (d, ^³ J = 8.23 Hz, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 24.9, 83.9, 93.4, 126.2, 128.8, 129.0, 135.4, 137.9, 140.5, 142.6. MS (EI): m/z (%) = 406(100) [M]⁺, 306(48) [C₁₂H₈BOI]⁺, 179(23) [C₁₂H₈BO]⁺, 152(15). HRMS (EI): m/z calcd for C₁₈H₂₀BIO₂ [M]⁺: 406.0601; found: 406.0556.
9-Octyl-6-(trimethylsilyl)-9 H -carbazole-3-carbaldehyde (3g) ¹H NMR (300 MHz, CDCl₃): δ = 0.35 (s, 9 H), 0.84 (t, ^³ J = 6.7 Hz, 3 H), 1.16-1.47 (m, 10 H), 1.80-1.94 (m, 2 H), 4.30 (t, ^³ J = 7.2 Hz, 2 H), 7.45 (dd, J = 8.3, 1.9 Hz, 1 H), 7.66 (dd, ^³ J = 1.0, 0.4 Hz, 1 H), 7.99 (dd, J = 8.3, 1.3 Hz, 1 H), 8.32 (s, 1 H), 8.64 (d, ^³ J = 1.3 Hz, 1 H), 10.09 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = -0.7, 0.7, 14.1, 22.6, 27.2, 28.9, 29.1, 29.3, 31.8, 43.4, 108.9, 122.8, 123.9, 125.6, 127.1, 131.0, 131.5, 141.7, 144.1, 191.8. MS (EI): m/z (%) = 379(100) [M]⁺, 364(84) [C₂₃H₃₀NOSi]⁺, 280(28) [C₁₇H₁₈NOSi]⁺, 150(11). HRMS (EI): m/z calcd for C₂₄H₃₃NOSi [M]⁺: 379.2331; found: 379.2358. Anal. Calcd for C₂₄H₃₃NOSi: C, 75.94; H, 8.76; N, 3.69. Found: C, 76.37; H, 8.79; N, 3.61.
Trimethyl(5- p -tolylthiophen-2-yl)silane (4) ¹H NMR (300 MHz, CDCl₃): δ = 0.33 (s, 9 H), 2.35 (s, 3 H), 7.18 (m, 3 H), 7.31 (d, ^³ J = 3.4 Hz, 1 H), 7.51 (d, ^³ J = 8.2 Hz, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = -0.4, 21.2, 123.9, 126.0, 129.5, 131.7, 133.8, 134.9, 137.3, 139.4. MS (EI):
m/z (%) = 246(61) [M]⁺, 231(100) [C₁₃H₁₅SSi]⁺. HRMS (EI): m/z calcd for C₁₄H₁₈SSi [M]⁺: 246.0898; found: 246.0920.

9

Interestingly, the expected byproducts, i.e. symmetrical disubstitution with the first electrophile and monosubstitution with the first electrophile followed by proton quenching are only found in minor quantities and were identified by GC-MS analysis in the crude ethereal extract during workup.