M. D’Auria et al. / Tetrahedron xxx (2016) 1e7
5
stirring. A solution of bromobenzene (0.63 g; 4 mmol) in dry Et2O
(10 ml) was added dropwise to the mixture and gently heated by
the means of a flux of hot air. When the reaction started (exo-
thermic) the heat flux was managed checking the temperature at
60e75 ꢁC. After 1 h the conversion was checked by TLC (8:2 hex-
anes/ethyl acetate) and the reaction was quenched by adding
dropwise a saturated NH4Cl solution. The aqueous solution was
extracted with Et2O and the organic phase washed with water. The
collected organic fractions were dried over anhyd sodium sulfate
and the solvent evaporated at low pressure, to give 370 mg of crude
oil. The crude product was purified by silica gel chromatography
(85:15 hexanes/ethyl acetate) and the 2-triisopropylsilyl-1,3-
oxazole-5-phenyl-methanol recovered (610 mg, 92 %). Oil; MS, m/
z: 331 (Mþ), 289, 247, 224, 200, 157, 133, 115, 96, 77, 59, 41; 1H NMR
(500 MHz; CDCl3) d: 7.44e7.40 (m, 2H), 7.39e7.30 (m, 3H), 6.86 (s,
1H), 5.89 (s, 1H), 3.14 (br s, 1H), 1.39 (h, J¼8.0 Hz, 3H), and 1.09 ppm
(d, J¼8.0 Hz, 18H); 13C NMR (100 MHz; CDCl3)
d: 168.9, 155.1, 140.4,
128.5, 126.6, 123.9, 68.7, 18.3, and 10.9 ppm; Elemental Analysis: C,
68.90; H, 8.72; N, 4.31. Calcd for C19H29NO2Si: C, 68.83; H, 8.82; N,
4.22%.
4.2. (5-Triisopropyl-2-oxazolyl)-1-ethanol (4c)
Fig. 8. HSOMO and LSOMO of the biradical intermediate C.
Yield: 85%. Oil; MS, m/z: 269 (Mþ); 1H NMR (500 MHz; CDCl3)
d:
6.94 (s, 1H), 5.00e4.92 (m, 1H), 3.26 (d, J¼2.0 Hz, 1H), 1.53 (d,
3. Conclusions
J¼6.5 Hz, 3H), 1.36 (h, J¼8.0 Hz, 3H), and 1.10 ppm (d, J¼8.0 Hz,
18H); 13C NMR (100 MHz; CDCl3)
d: 157.1, 145.1, 113.9, 59.5, 21.6,
18.3, and 10.8 ppm; Elemental Analysis: C, 62.31; H, 10.25; N, 5.10.
Calcd for C14H27NO2Si: C, 62.40; H, 10.10; N, 5.20%.
We have shown that the photochemical reaction between 5-
oxazolylmethanol derivatives and some aromatic carbonyl com-
pounds (benzaldehyde and benzophenone) gives the correspond-
ing oxetanes with good diastereoselectivity. The results show that
4.3. (5-Triisopropyl-2-oxazolyl)-1-propanol (4d)
ꢀ
€
the hydroxyl directing effect in the PaternoeBuchi reaction de-
scribed in the case of allylic alcohols and furylmethanol derivatives
can be present also in the case of 5-oxazolyl methanol derivatives.
The attack of the excited carbonyl compound occurs only on the
same side where the hydroxyl group is present. On the basis of the
obtained results we can exclude the possible competing role of the
lone pair of nitrogen in the formation of a complex between the
excited triplet state of the carbonyl compound and the substrate.
The results are in agreement with the formation of a hydrogen
bond between the reagents. Furthermore, we have shown that, in
this case, the reaction with benzaldehyde showed an unusual endo
stereoselectivity. The observed stereoselectivity can be predicted
on the basis of an interaction between HSOMO and LSOMO in the
biradical intermediate.
Yield: 87%. Oil; MS, m/z: 283 (Mþ), 266, 241, 224, 199, 180, 157,
131,103, 75, 43; 1H NMR (500 MHz; CDCl3)
d: 6.94 (s,1H), 4.76e4.68
(m, 1H), 2.70 (d, J¼8.0 Hz, 1H), 1.95e1.82 (m, 2H), 1.42e1.35 (m, 3H),
1.11 (d, J¼7.0 Hz, 18H), and 0.93 ppm (t, J¼7.0 Hz, 3H); 13C NMR
(100 MHz; CDCl3) d: 157.6, 144.2, 114.3, 64.8, 27.5, 21.7, 12.3, and
10.5 ppm; Elemental analysis: C, 64.00; H 10.25; N, 5.02. Calcd for
15H29NO2Si: C, 63.55; H, 10.31; N, 4.94%.
C
4.4. (5-Triisopropyl-2-oxazolyl)-1-butanol (4e)
Yield: 85%. Oil; MS, m/z: 297 (Mþ); 1H NMR (500 MHz; CDCl3)
d:
6.93 (s, 1H), 4.70e4.65 (m, 1H), 2.93 (d, J¼6.0 Hz, 1H), 1.80e1.76 (m,
2H), 1.75e1.72 (m, 2H), 1.36 (h, J¼8.0 Hz, 3H), 1.13 (d, J¼8.0 Hz, 18H),
and 0.95 ppm (t, J¼7.0 Hz, 3H); 13C NMR (100 MHz; CDCl3)
d: 157.6,
4. Experimental
145.0, 100.4, 64.4, 35.6, 21.6, 18.4, 15.6, and 10.7 ppm; Elemental
analysis: C, 64.50; H, 11.02; N, 4.58. Calcd for C16H31NO2Si: C, 64.59;
H, 10.50; N, 4.71%.
4.1. General procedure for synthesis of 2,5 disubstituted ox-
azolyl methanol derivatives. Preparation of (5-triisopropyl-2-
oxazolyl)-phenylmethanol (4b)
4.5. Deprotection of (2-triisopropylsilyl-2-oxazolyl)-phenyl-
methanol (4a)
A
mixture of 2-triisopropylsilyl-1,3-oxazole-5-carbaldehyde
(500 mg; 2 mmol); magnesium (0.1 g; 4 mmol) and a single crys-
tal of iodine were placed in a three neck 250 ml flask and dry Et2O
(15 ml) was added under an inert atmosphere and with magnetic
To a solution of 4b (0.1 g, 0.3 mmol) in THF (10 ml) in a 100 ml
flask under vigorous stirring 1 M HCl(aq) (1 ml) was added. An
TIPS
TIPS
H
TIPS
H
H
Me
Me
Me
rotation
O
O
N
N
*
O
N
*
OH
OH
Ph
OH
Ph
O
O
O
Ph
*
H
*
H
H
Fig. 9. Coupling of radical carbon atoms in the biradical intermediate C.