Reaction #77705

Reaction equation

tricyclohexylphosphine

6-bromo-1,2,3,4-tetrahydrocyclopent[b]indole

potassium (triisopropylsilyl)sulfide

→

1,2,3,4-tetrahydro-6-(triisopropylsilyl)thio cyclopent[b]indole

Yield 73.0%

Solvents

tetrahydrofuran

Conditions

Workup

1. 1
   Otherpre-flushed with argon
2. 2
   Othersubsequently flushed with argon for 5 min before dissolution in toluene (20 mL)
3. 3
   workup.STIRRINGwas stirred for 45 min at room temperature
4. 4
   Temperatureheated at 80° C. (bath temp) for 70 min
5. 5
   Temperaturethen cooled to room temperature over 16 h
6. 6
   OtherThe mixture was partitioned between toluene (40 mL) and water (60 mL)
7. 7
   ExtractionThe separated aqueous layer was extracted with toluene (30 mL)
8. 8
   Washthe combined organic extracts were washed with brine (20 mL)
9. 9
   Dryingdried (Na2SO4)
10. 10
    Filtrationfiltered
11. 11
    Concentrationconcentrated in vacuo
12. 12
    OtherThe residue was purified by column chromatography [SiO2; heptane-ethyl acetate (98:2) to (96:4)]

Procedure

Palladium dibenzylidene-acetone (0.155 g, 5 mol %) and tricyclohexylphosphine (0.19 g, 20 mol %), were weighed out into a flask pre-flushed with argon, and subsequently flushed with argon for 5 min before dissolution in toluene (20 mL). The deep red mixture was stirred at room temperature for 5 minutes under argon, then 6-bromo-1,2,3,4-tetrahydrocyclopent[b]indole (0.8 g, 3.4 mmol) was added in one portion. After a further 5 min a solution of potassium (triisopropylsilyl)sulfide (Tetrahedron Letts., 1994, 35(20), 3221-3224 and 3225-6)) in tetrahydrofuran (6 mL) was added via syringe over 4 min The mixture was stirred for 45 min at room temperature, heated at 80° C. (bath temp) for 70 min then cooled to room temperature over 16 h. The mixture was partitioned between toluene (40 mL) and water (60 mL). The separated aqueous layer was extracted with toluene (30 mL) and the combined organic extracts were washed with brine (20 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography [SiO2; heptane-ethyl acetate (98:2) to (96:4)] to yield 1,2,3,4-tetrahydro-6-(triisopropylsilyl)thio cyclopent[b]indole as a pale yellow solid (0.85 g, 73%); NMR (400 MHz, CDCl3) δH 7.76 (1H, br s, NH), 7.43 (1H, d, J 1.5 Hz), 7.27-7.25 (1H, m), 7.18 (1H, dd, J 8.2, 1.5 Hz), 2.85 (2H, obs dt, J 6.9, 1.6 Hz), 2.79 (2H, obs t, J 7.0 Hz), 2.52 (2H, obs quint, J 7.0 Hz), 1.29-1.19 (3H, m), 1.08 (18H, d, J 7.0 Hz); HPLC: [Supelcosil ABZ+; 1.0 ml/min, methanol-10 mM aqueous ammonium acetate solution, (90:10)] 99% (11.1 min).

Source