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U. Azzena et al. / Tetrahedron 62 (2006) 1557–1563
(9H, s, 3!CH3); second diastereomer, dH 7.32–7.24 (4H,
m, ArH), 4.41 (1H, s, ArCHOH), 4.13 (1H, d, JZ6.0 Hz,
CHOCH3), 3.52 (1H, d, JZ6.0 Hz, CHOH), 3.14 (3H, s,
OCH3), 2.85 (1H, br s, OH), 0.92 (9H, s, 3!CH3), 0.91
(9H, s, 3!CH3); diastereomeric mixture, dC 141.2,
141.8, 139.7, 138.1, 127.8, 127.6, 126.5, 82.2, 82.1,
80.7, 56.2, 56.0, 35.6, 34.8, 34.5, 26.5, 25.9; diaster-
eomeric mixture, MS (E.I., 70 eV) m/z 237 (MCKt-Bu,
2), 208 (31), 207 (100), 190 (56), 175 (20), 151 (89),
122 (37), 91 (16), 57 (31%); HRMS: found 237.1488.
C14H21O3 requires 238.1491.
Acknowledgements
`
U.A., G.D. and G.S. thank the Universita di Sassari
(Fondo di Ateneo, ex 60%) for financial support. F.B.
and M.Y. thank the Spanish Ministerio de Educacion y
Ciencia (grant no. CTQ2004-01261) for financial
support.
References and notes
4.3.10. 1-Methoxy-3,3-dimethyl-1-phenylbutan-2-ol (6).
Diastereomeric mixture, purified by column chromato-
graphy (hexane/AcOEtZ40:1), colourless oil; first dia-
stereomer, Rf 0.39 (hexane/AcOEtZ10:1); second
diastereomer, Rf 0.38 (hexane/AcOEtZ10:1); nmax (liquid
film) 3514, 3088, 3063, 3033, 2958, 2903, 1481, 1451,
1401, 1371, 1075, 1015 cmK1; first diastereomer, dH
7.37–7.24 (5H, m, ArH), 4.17 (1H, d, JZ3.9 Hz,
CHOCH3), 3.30 (1H, dd, JZ5.8, 3.9 Hz, CHOH), 3.22
(3H, s, OCH3), 2.92 (1H, d, JZ5.8 Hz, OH), 0.90 (9H, s,
3!CH3); second diastereomer, dH 7.37–7.24 (5H, m,
ArH), 4.11 (1H, d, JZ6.2 Hz, CHOCH3), 3.57–3.51 (1H,
m, CHOH) 3.14 (3H, s, OCH3), 2.84 (1H, br s, OH),
0.93 (9H, s, 3!CH3); diastereomeric mixture, dC 140.7,
139.9, 128.6, 128.5, 128.4, 127.8, 127.3, 82.3, 82.0, 80.6,
80.5, 56.2, 56.0, 34.8, 34.5, 26.5; first diastereomer, MS
(E.I., 70 eV) m/z 176 (MCKMeOH, 0.5%), 122 (74),
121 (100), 91 (27), 77 (13%); second diastereomer, MS
(E.I., 70 eV) m/z 176 (MCKMeOH, 0.5%), 122 (75),
121 (100), 91 (29), 77 (13%); first diastereomer, HRMS:
found 176.1183. C12H16O requires 176.1201; second
diastereomer, HRMS: found 176.1201. C12H16O requires
176.1201.
1. For a recent review, see: Yus, M. In The Chemistry of
Orgonolithium Compounds; Rappoport, Z., Marek, I., Eds.;
Wiley: Chichester, 2004; Vol. 1 Part 2, Chapter 11.
2. For a mechanistic study, see: Yus, M.; Herrera, R. P.;
Guijarro, A. Chem. Eur. J. 2002, 8, 2574–2584.
3. Reductive lithiation of arylmethyl ethers: (a) Azzena, U.;
Carta, S.; Melloni, G.; Sechi, A. Tetrahedron 1997, 47,
´
1605–1612. (b) Alonso, E.; Ramon, D. J.; Yus, M. J. Org.
Chem. 1997, 62, 417–421. (c) Azzena, U.; Dettori, G.; Idini,
M. V.; Pisano, L.; Sechi, G. Appl. Organomet. Chem. 2003, 17,
851–855.
4. Reductive lithiation of a-N,N-dialkylammino-substituted
benzyl butyl ethers and 2-aryl-3-methyl-1,3-oxazolidines: (a)
Azzena, U.; Pilo, L.; Piras, E. Tetrahedron 2000, 56,
3775–3780. (b) Azzena, U. J. Chem. Soc., Perkin Trans. 1
2002, 360–365.
5. Reductive lithiation of 2-aryl-sustituted oxygen hetero-
cycles: (a) Bartmann, E. Angew. Chem., Int. Ed. Engl.
1986, 25, 653–654. (b) Almena, J.; Foubelo, F.; Yus, M.
Tetrahedron 1995, 51, 3351–3364. (c) Almena, J.;
Foubelo, F.; Yus, M. Tetrahedron 1995, 51, 3365–3374. (d)
Azzena, U.; Demartis, S.; Melloni, G. J. Org. Chem. 1996, 61,
4913–4919. (e) Azzena, U.; Pilo, L. Synthesis 1999, 664–668.
(f) Azzena, U.; Demartis, S.; Pilo, L.; Piras, E. Tetrahedron
2000, 56, 8375–8382. (g) Foubelo, F.; Moreno, B.; Yus, M.
Tetrahedron 2004, 60, 4655–4662. For recent reviews on
reductive lithiation of oxygen-, nitrogen- and sulfur-containing
heterocycles, see: (h) Yus, M. Pure Appl. Chem. 2003, 75,
1453–1475. (i) Yus, M.; Foubelo, F. Targets Heterocycl. Syst.
2002, 6, 136–171.
4.3.11. 3,3-Diisopropyl-1,3-dihydro-isobenzofuran-1-ol
(8). Acetal 1d (500 mg, 2.7 mmol) was lithiated as
described in the Section 4.3. To this mixture, chilled to
K80 8C, a solution of 2,4-dimethylpentan-3-one (620 mg,
5.4 mmol) dissolved in THF (2 mL) was added dropwise.
After stirring at the same temperature until almost
complete decolouration, the reaction mixture was
quenched and elaborated as described in the Section
4.3. The crude reaction product was dissolved in a
mixture of THF/1 M H2SO4Z1:1 (5 mL) and stirred at rt
for 8 h. The resulting mixture was extracted with Et2O
(3!10 mL), the organic phases were collected, washed
with saturated NaHCO3 (20 mL), dried (K2CO3) and the
solvent evaporated. Purification by flash chromatography
(petroleum ether/AcOEt/Et3NZ7:3:1), afforded a colour-
less oil (310 mg, 1.4 mmol, 52%), which solidifies upon
standing, and was characterized as following: [Found: C,
76.1; H, 9.5. C14H20O2 requires C, 76.33; H, 9.15]; Rf
0.66 (petroleum ether/AcOEt/Et3NZ7:3:1); nmax (liquid
film) 3342 cmK1; dH 7.30–7.12 (3H, m, 3!ArH),
7.17–7.09 (1H, m, ArH), 6.44 (1H, s, OCHO), 3.10
(1H, br s, OH), 2.38–2.16 (2H, m, 2!CH), 0.95 (3H, d,
JZ6.9 Hz, CH3), 0.82 (3H, d, JZ6.9 Hz, CH3), 0.82
(3H, d, JZ6.9 Hz, CH3), 0.73 (3H, d, JZ6.9 Hz, CH3);
dC 142.6, 140.5, 129.0, 127.9, 122.8, 121.7, 100.5, 96.7,
34.2, 32.6, 18.1, 17.2.
6. Gil, J. F.; Ramon, D. J.; Yus, M. Tetrahedron 1993, 49,
9535–9546.
7. Azzena, U.; Melloni, G.; Pisano, L.; Sechi, B. Tetrahedron
Lett. 1994, 35, 6759–6762.
8. von Schrader, T.; Woodward, S. Eur. J. Org. Chem. 2002,
3833–3836.
9. Siwek, M. J.; Green, J. R. Synlett 1996, 560–562.
´
10. Huerta, F. F.; Gomez, C.; Yus, M. Tetrahedron 1999, 55,
4043–4050.
11. Azzena, U.; Dettori, G.; Pisano, L.; Siotto, I. Tetrahedron
2005, 60, 3177–3182 and references therein.
12. For a laboratory-scale preparation of lithium dispersion in
´
silicone oil and lithium powder, see: Yus, M.; Martınez, P.;
Gujarro, D. Tetrahedron 2001, 57, 10119–10124.
13. Lithium with high sodium content is 99% purity (0.5–1%
sodium), whilst lithium with low sodium content is 99.9%
purity (0.01% sodium). A high sodium content is reported
to support initiation and to accelerate reductive lithiation
reactions of chloroalkanes. See, for example: Totter, F.;