Olefination of 3-phenyl indene
SyntheticPage 698
DOI:
Submitted: October 14, 2013, published: October 22, 2013
Authors
A contribution from
Chemicals
1-Phenylindene (Prepared in House, See Synthetic Page 696 DOI: 10.1039/SP697
n-Butyllithium (2.5 M in hexanes, Acros Organics)
Heptane (99.0%, anhydrous, Sigma Aldrich; prepared as air-free in House)
p-Tolualdehyde (97%, Sigma-Aldrich)
2-Methyltetrahydrofuran (≥99.0%, Inhibitor-free, Sigma-Aldrich)
Diethyl Ether (≥99.0%, anhydrous, ACS reagent, contains BHT as inhibitor, Sigma-Aldrich)
Hexanes, mixture of isomers (≥99.0%, anhydrous, Sigma-Aldrich)
Toluene (99.8%, anhydrous, Sigma-Aldrich)
Saturated Ammonium Chloride (Prepared in House)
Brine Solution (NaCl and deionized water, Prepared in House)
MgSO4 (≥99.5%, anhydrous, ReagentPlus®, Sigma-Aldrich)
Procedure
The synthesis was conducted under a nitrogen atmosphere using standard Schlenk techniques. To a 15 mL scintillation vial was added: 3-phenylindene (0.150 g, 7.80 x 10-4 mol), heptane (8.0 mL, 0.1 M) and a stir bar. The reaction was stirred at 0 °C for approximately 10 minutes. Dropwise1, n-Butyllithium (0.330 mL, 8.19 x 10-4 mol) was added and the flask was allowed to return to room temperature and stirred overnight (~20 hours).
Heptane was removed under reduced pressure. To the remaining precipitate was added: 2-methyltetrahydrofuran (8.0 mL, 0.1 M) and the reaction was cooled to 0 °C and stirred2 for approximately 10 minutes at which point p-Tolualdehyde (0.100 mL, 8.58 x 10-4 mol) was added dropwise and the reaction was stirred overnight at room temperature (≈ 20 h).
The reaction was quenched with 3 mL of aqueous NH4Cl. The sample was washed with brine solution (3 x 5 mL) and extracted with diethyl ether (3 x 5 mL)3. The organic layer was dried over MgSO4 and then gravity filtered. The solvent was removed under reduced pressure and the crude product was purified via preparatory plate (90:10 Hexane:Toluene) yielding a highly colored yellow/orange solid (130 mg, 57% yield).
Author Comments
- To ensure the lithium anion product forms, it is imperative to add the n-BuLi base drop wise after the solution has equilibrated to 0 °C in the ice bath. This will help control for reaction selectivity since this base is very reactive. After adding the reaction will turn from a clear, colorless solution to a cloudy, yellow color.
- Upon re-dissolving the yellow precipitate in 2-MeTHF, the solution will turn to a deep red color.
- Additional washes may need to be done in order to reduce the emulsion layer if present.
- Allowing the product to run overnight under high vacuum will remove any excess solvent remaining.
- Reaction has been performed multiple times and resulting yields have shown method is reproducible.
- We would like to thank Dr. Lev Zakharov (University of Oregon) for providing crystal structure analysis.
Data
1H NMR (CDCl3, 500 MHz): δ ppm 2.39 (s, 3H), 7.15 (s, 1H), 7.25 (d, J = 7.88 Hz, 2H), 7.29 - 7.31 (m, 2H), 7.38 (t, J = 6.62 Hz, 1H), 7.46 (t, J = 7.25 Hz, 2H), 7.50 (s, 1H), 7.57 - 7.60 (m, 3H), 7.70 (d, J = 8.20 Hz, 2H), 7.76 (d, J = 6.94 Hz, 1H)
13C NMR (CDCl3, 500 MHz): δ ppm 21.4, 119.2, 120.3, 123.2, 125.4, 127.2, 127.6, 128.1, 128.4, 128.6, 129.5, 130.2, 134.3, 135.8, 138.4, 138.6, 139.0, 140.6, 147.1
GC-MS M.+ EI calculated 294.397, found 294
Other References
Alcalde, E., Mesquida, N., Frigola, J., López-Pérez, S., Mercè, R. Indene-based scaffolds. Design and synthesis of novel serotonin 5-HT6 receptor ligands. Org. Biomol. Chem., 2008, 6, 3795-3810
http://dx.doi.org/10.1039/b808641a
Lu, W., Zhu, Q., Yan C. KF-Al2O3 Induced condensations of indene with aromatic aldehydes. Synthetic Commun, 1997, 27, 3985-3990.
http://dx.doi.org/10.1080/00397919708005920
Pace, V., Castoldi, L., Hoyos, P., Sinisterra, J.V., Pregnolato, M., Sánchez-Montero, J.M. Highly regioselective control of 1,2-addition of organolithiums to α,β-unsaturated compounds promoted by lithium bromide in 2-methyltetrahydrofuran: a facile and eco-friendly access to allylic alcohols and amines. Tetrahedron, 2011, 67, 2670-2675.
http://dx.doi.org/10.1016/j.tet.2011.01.067
Supplementary Information
Keywords
aldehydes, alkenes, aromatics/arenes, nucleophilic, organometallics