5122
H. C. Aspinall et al. / Tetrahedron Letters 52 (2011) 5120–5123
Table 2
Supplementary data
Conversion of nitriles into oxazolyl compounds
C
D
Supplementary data associated with this article can be found, in
R1 = iPr; R2 = H
R1 = R2 = Me
Isolated yield (%)
Isolated yield (%)
References and notes
O
N
1. Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336.
1
2
3
4
78
58
31
71
60
75
49
77
2. (a) Katkova, M. A.; Balashova, T. V.; Ilichev, V. A.; Konev, A. N.; Isachenkov, N.
A.; Fukin, G. Y.; Ketkov, S. Y.; Bochkarev, M. N. Inorg. Chem. 2010, 49, 5094; (b)
Rai, V. K.; Srivastava, R.; Kamalasanan, M. N. Synth. Met. 2009, 159, 234; (c) Kim,
D.-E.; Kim, W.-S.; Kim, B.-S.; Lee, B.-J.; Kwon, Y.-S. Thin Solid Films 2008, 516,
3637.
R2
R1
OH
N
3. Zhang, Y.; Wang, X. T.; Zhang, X. M.; Liu, T. F.; Xu, W. G.; Gao, S. Inorg. Chem.
2010, 49, 5868.
O
But
4. Zhang, J.; Gao, S.; Che, C.-M. Eur. J. Inorg. Chem. 2004, 956.
5. (a) Allen, L. E. N.; Clarkson, G. J.; Fox, D. J.; Gott, A. L.; Scott, P. J. Am. Chem. Soc.
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2009, 2850; (c) Braun, I.; Rudroff, F.; Mihovilovic, M. D.; Bach, T. Angew. Chem.,
Int. Ed. 2006, 45, 5541.
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10. Schwekendick, K.; Glorius, F. Synthesis 2006, 2996.
11. Ishihara, M.; Togo, H. Tetrahedron 2007, 63, 1474.
12. Sayama, S. Synlett 2006, 1479.
R2
R1
OH
O
MeO
NC
R2
R1
OH
N
O
R2
R1
OH
N
13. Frost, C. G.; Williams, J. M. J. Tetrahedron Lett. 1993, 34, 2015.
14. Fitzpatrick, M. O.; Muller-Bunz, H.; Guiry, P. J. Eur. J. Org. Chem. 2009, 1889.
15. Desmet, M.; Raubenheimer, H. G.; Kruger, G. J. Organometallics 1997, 16, 3324.
16. Casiraghi, G.; Casnati, G.; Puglia, G.; Sartori, G.; Terenghi, G. J. Chem. Soc., Perkin
Trans. 1 1980, 1862.
17. Hansen, T. V.; Skattebøl, L. S. Org. Synth. 2005, 82, 64.
18. Casiraghi, G.; Casnati, G.; Cornia, M.; Pochini, A.; Puglia, G.; Sartori, G.; Ungaro,
R. J. Chem. Soc., Perkin Trans. 1 1978, 318.
O
5
48
37
R2
R1
N
OH
19. Lindoy, L. F.; Meehan, G. V.; Svenstrup, N. Synthesis 1998, 1029.
20. Kalechits, G. V.; Osinovskii, A. G.; Matveenko, Y. V.; Ol’khovik, V. K. Russ. J. Appl.
Chem. 2002, 75, 962.
O
S
21. 2-Hydroxy-3-methylbenzonitrile (1B): Salicylaldehyde (1A) (28.86 g, 1 equiv)
was dissolved in DMSO (200 ml) to give an orange solution. Hydroxylamine
hydrochloride (29.31 g, 2.2 equiv) was charged and the mixturewas stirred at
rt for 20 min to give a yellow solution, this was heated to 100 °C for 6 h before
being allowed to cool. The reaction was quenched into H2O (300 ml) and
extracted with Et2O (5 ꢀ 100 ml). The combined organic layer was washed
with brine (2 ꢀ 50 ml), dried (MgSO4), and evaporated to give a foul smelling
red-brown solid (30.53 g). Semi-pure material suitable for subsequent
reactions was obtained by the extraction of impurities into refluxing heptane
(100 ml) followed by cooling and trituration with cold heptane. Pure material
for characterization was obtained by flash chromatography (product adhered
to silica, eluting with 1:9 EtOAc in hexane, Rf = 0.32) which yielded the title
compound as an orange-red solid (20.58 g, 73%).
6
7
93
82
93
85
N
R2
R1
O
O
N
R2
R1
structure as shown below. Delocalization of the negative charge on
the phenol would render the second nitrile much less susceptible
to nucleophilic attack.
IR (NaCl, Nujol mull): ArOH 3301.5, C„N 2233.8; MS (CI+, NH3): m/z = 151.1
(M+NH4+, 100%); 1H NMR (400 MHz, CDCl3) d ppm 7.35 (1H, t, J = 1.0 Hz, H4),
7.33 (1H, t, J = 1.0 Hz, H6), 6.90 (1H, t, J = 7.7 Hz, H5), 5.93 (1H, s, OH), 2.29 (3H,
s, CH3) 13C NMR (100 MHz, CDCl3) d ppm 157.4 (COH), 136.4 (C4), 130.5 (C6),
126.6 (C3), 121.4 (C5), 117.2 (CN), 99.2 (C1), 16.3 (CH3); CHN (C12H16O2) found:
C 72.35, H 5.28N 10.39; required: C 72.16, H 5.30, N 10.52.
O
O
22. Chill, S. T.; Mebane, R. C. Synth. Commun. 2009, 39, 3601.
NC
NC
23. (S)-2-(4-Isopropyl-4,5-dihydrooxazol-2-yl)-6-methylphenol (1C): ZnCl2 (2.18 g,
0.1 equiv) was charged into a 250 ml Schlenk flask and heated under vacuum
until molten (heatgun) before being allowed to cool under an argon
atmosphere. S-valinol (23.92 g, 1.5 equiv) and nitrile 1B (20.58 g, 1.0 equiv)
were dissolved in chlorobenzene (100 ml) and charged into the flask in one go.
The resulting dark red solution was heated to 131 °C for 72 h, before being
cooled and the solvent was evaporated. The resulting dark oil was quenched
into 2 M HCl (200 ml) and extracted with CH2Cl2 (5 ꢀ 100 ml). The combined
organic phase was washed with H2O (100 ml) which was back-extracted with
CH2Cl2 (2 ꢀ 50 ml). The combined organic phase was dried (MgSO4) and the
solvent evaporated to give a dark red oil (31.48 g). This was purified by flash
chromatography (product adhered to silica, eluting with 1:9 EtOAc in hexane,
Rf = 0.73) to yield the title compound as a pale orange oil which slowly
crystallized on standing (26.50 g, 78%). IR (ATR): Ar-H 2958.3, C@N 1635.3; MS
(CI+, NH3): m/z = 220 (M+H+, 100%); 1H NMR (400 MHz, CDCl3) d ppm 12.59
(1H, br s, OH), 7.49 (1H, dd, J = 7.8, 1.6 Hz, H5), 7.23 (1H, dd, J = 7.3, 0.8 Hz, H3),
6.77 (1H, pent, J = 7.6 Hz, H4), 4.37–4.46 (1H, m, H40), 4.06–4.17 (2H, m, H50),
2.29 (3H, s, CH3), 1.79 (1H, dq, J = 13.3, 6.7 Hz, CH(CH3)2), 0.98 (6H, dd, J = 28.6,
6.5 Hz, CH(CH3)2); 13C NMR (100 MHz, CDCl3) d 165.8 (C20), 158.7 (COH), 134.6
(C5), 126.1 (C6), 125.9 (C3), 118.4 (C4), 110.3 (C2), 71.9 (C50), 70.3 (C40), 33.5
(CH(CH3)2), 19.1 (CH(CH3)2), 16.3 (CH3); CHN (C13H17NO2) found: C 71.21, H
7.81, N 6.42; required: C 71.21, H 7.81, N 6.39.
O
N
O
N
H
H
In conclusion, we have developed a convenient synthesis of a di-
verse range of oxazolyl ligands, both chiral and achiral. Our method
uses cheap and readily available starting materials and we have
shown that it can be applied equally successfully to ligands with
electron-donating/-withdrawing and sterically demanding/unde-
manding substituents. All of the reactions are homogeneous and
can be scaled-up without difficulty: we have routinely prepared
oxazolyl compounds in quantities of >25 g. We believe that our
method will be particularly useful for oxazolylphenols for which
there has previously been no general applicable route.
Acknowledgment
24. Gomez, M.; Jansat, S.; Muller, G.; Aullon, G.; Maestro, M. A. Eur. J. Inorg. Chem.
2005, 4341.
We thank EPSRC for support (studentship to O.B.).