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DOI: 10.1055/s-0029-1219203
Dual Electrophilic Trapping-Negishi Coupling with Dilithiothiophenes in a Three-Component, One-Pot Process
Publication History
Publication Date:
15 January 2010 (online)
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Abstract
Based upon a twofold bromine-lithium exchange with 2,5-dibromo thiophene and sequential trapping of the dilithio intermediate, organo zinc halides were generated in situ and subsequently transformed by Negishi cross-coupling to unsymmetrically substituted thiophenes in a one-pot fashion. Application of this novel sequence to diiodo(hetero)arenes quickly furnishes highly interesting building blocks for materials science applications.
Key words
arenes - C-C coupling - heterocycles - lithiation - multicomponent reactions
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References and Notes
Representive Procedure: Synthesis of 3b (Table 1, Entry 2) In a flame-dried Schlenk flask under argon atmosphere n-BuLi (1.6 M in n-hexane, 2.5 mL, 4.0 mmol) and TMEDA (0.6 mL, 4.0 mmol) were dissolved in anhyd THF (80 mL) at -78 ˚C. 2,5-Dibromothiophene (1, 484 mg, 2.0 mmol) was added slowly to the solution, and the mixture was stirred for 30 min. Then, TMSCl (217 mg, 2.0 mmol) in anhyd THF (20 mL) was added dropwise to the stirred solution over a period of 3 h. The reaction mixture was stirred for another 30 min, and ZnBr2 (496 mg, 2.2 mmol) in anhyd THF (10 mL) was added. After stirring for 15 min the reaction mixture was allowed to warm to r.t. and stirred for another 20 min. 1-Iodo-3,5-dimethylbenzene (510 mg, 2.2 mmol) in anhyd THF (5 mL) and Pd(PPh3)4 (5 mol%) were added. The solution was stirred at r.t. for 16 h. The solvent was removed under reduced pressure and the residue purified by flash chromatography on silica gel (n-hexane) yielding 280 mg (54%) of 3b as a colorless oil. ¹H NMR (500 MHz, CDCl3): δ = 0.32 (s, 9 H), 2.33 (s, 6 H), 6.90 (s, 1 H), 7.18 (d, ³ J = 3.3 Hz, 1 H), 7.23 (s, 2 H), 7.31 (d, ³ J = 3.3 Hz, 1 H). ¹³C NMR (125 MHz, CDCl3): δ = 0.1 (CH3), 21.5 (CH3), 124.2 (CH), 129.4 (CH), 134.5 (Cq), 135.1 (Cq), 138.5 (CH), 139.8 (Cq), 150.2 (Cq). MS (EI, 70 eV): m/z (%) = 260 (44) [M]+, 245 (100) [C14H17SSi]+, 215 (5) [C12H11SSi]+, 123 (9), 115 (43). IR (KBr): ν = 544 (w), 561 (w), 608 (w), 623 (w), 652 (w), 692 (m), 756 (m), 802 (s), 842 (s), 947 (w), 990 (s), 1055 (m), 1182 (w), 1212 (m), 1250 (s), 1323 (w), 1377 (w), 1438 (m), 1526 (w), 1601 (m), 1760 (w), 2858 (m), 2925 (m), 2956 (m) cm-¹. UV/Vis (CH2Cl2): λmax (ε) = 294 (12700), 314 (21800) nm. Anal. Calcd for C15H20SSi (260.5): C, 69.17; H, 7.74. Found: C, 69.34; H, 7.60.
7Representive Procedure: Synthesis of Terthiophene 4a In a flame-dried Schlenk flask under argon atmosphere n-BuLi (1.6 M in n-hexane, 2.5 mL, 4.0 mmol) and TMEDA (0.6 mL, 4.0 mmol) were dissolved in anhyd THF (80 mL) at -78 ˚C. 2,5-Dibromothiophene (1, 484 mg, 2.0 mmol) was added slowly to the solution, and the mixture was stirred for 30 min. Then, TMSCl (217 mg, 2.0 mmol) in anhyd THF (20 mL) was added dropwise to the stirred solution over a period of 3 h. The reaction mixture was stirred for another 30 min, and ZnBr2 (496 mg, 2.2 mmol) in anhyd THF (10 mL) was added. After stirring for 15 min the reaction mixture was allowed to warm to r.t. and stirred for another 20 min. Finally, 2,5-diiodothiophene (269 mg, 0.8 mmol) and Pd(PPh3)4 (5 mol%) were added. The solution was stirred at r.t. for 16 h and afterwards the solvent removed under reduced pressure and the residue purified by flash chromatography on silica gel (n-hexane) yielding 200 mg (67%) of 3a as a light yellow solid. ¹H NMR (500 MHz, CDCl3): δ = 0.32 (s, 18 H), 7.06 (s, 2 H), 7.12 (d, ³ J = 3.4 Hz, 2 H), 7.20 (d, ³ J = 3.4 Hz, 2 H). ¹³C NMR (125 MHz, CDCl3): δ = 0.1 (CH3), 124.6 (CH), 125.1 (CH), 135.0 (CH), 136.5 (Cq), 140.2 (Cq), 142.4 (Cq). MS (EI, 70 eV): m/z (%) = 393 (2.5) [M]+, 320 (47), 305 (46), 261 (47), 215 (49), 203 (12), 184 (12), 171 (36), 137 (17), 115 (100), 109 (10).
12
Synthesis of 3b
Starting from Thiophene
In a flame-dried, three-neck
flask under argon atmosphere
n-BuLi
(1.6 M in n-hexane, 6 mL, 8.8 mmol),
TMEDA (1.2 mL, 8.0 mmol), and thiophene (340 mg, 4.0 mmol) were dissolved
in n-hexane (20 mL). The reaction mixture
was heated to reflux for 1.5 h. After complete deprotonation, the mixture
was allowed to cool to r.t. and was then cooled to
-78 ˚C.
THF (130 mL) was given to the content of the flask. Then TMSCl (430
mg, 4.0 mmol) in anhyd THF (20 mL) was added dropwise to the stirred
solution over a period of 3 h. The reaction mixture was stirred
for another 30 min, and ZnBr2 (496 mg, 2.2 mmol) in anhyd
THF (10 mL) was added. After stirring for 15 min the reaction mixture
was allowed to warm to r.t. and stirred for another 20 min. Finally,
1-iodo-3,5-dimethylbenzene (1029 mg, 4.4 mmol) in anhyd THF (10
mL) and Pd(PPh3)4 (5 mol%) were added. The
solution was stirred at r.t. for 16 h and afterwards the solvent
removed under reduced pressure and the residue purified by flash
chromatography on silica gel (n-hexane) yielding
406 mg (39%) of 3b as a colorless
oil.