D. J. Cross et al. / Tetrahedron: Asymmetry 12 (2001) 1801–1806
1805
ethyl acetate in hexane) to afford 1-phenylethanol (27
mg, 26%).
4.12. Phenacyl formate 6
1
H NMR (300 MHz, CDCl ): l 8.2 (1H, s, CHO),
3
8
4.6. Carbonate hydrolysis to prepare diol 5
7
.5–7.2 (5H, m, Ph), 5.35 (2H, s, CH2).
Sodium hydroxide (10 mL, 2 M) was added to the
crude reaction mixture (approx. 4 mmol) dissolved in
diethyl ether (10 mL) at 0°C. The reaction mixture was
allowed to warm to rt and stirred for 2 h. The reaction
mixture was extracted with ethyl acetate (3×25 mL) and
the organic fractions were collected, combined, washed
4
.13. 2-Chloro-l-phenylethanol 11
1
H NMR (300 MHz, CDCl ): l 7.35 (5H, m, Ph), 4.8
3
(
1H, dd, J 3.5, 3.6 Hz, CHOH), 3.7 (1H, dd, J 3.6, 8.7
Hz, CHHCl), 3.6 (1H, dd, J 8.7, 3.6 Hz, CHHCl), 2.8
1H, br s, CHOH). HPLC analysis (Chiracel OD, 250×
4.6 mm, hexane:ethanol:diethylamine 95:5:0.1, 0.5 mL/
(
with brine (10 mL), dried (Na SO ) and concentrated in
2
4
1
2,13
vacuo to give 1-phenylethan-1,2-diol 5.
min), (S) isomer 18.45 min, (R) isomer 22.79 min.
4
.7. Synthesis of phenacyl formate 6 from a-bromoace-
4
.14. 2-Bromo-l-phenylethanol 13
tophenone 12
1
H NMR (300 MHz, CDCl ): l 7.5–7.2 (5H, m, Ph),
3
a-Bromoacetophenone (4 g) and sodium formate (0.77
g) were stirred in DMF (40 mL) at rt for 12 h. Water
4
.9 (1H, m, CHOH), 3.6 (1H, dd, J 3.6 and 10.5 Hz,
CHHBr), 3.5 (1H, dd, J 10.5 and 8.9 Hz, CHHBr), 2.8
(
50 mL) was added and the reaction mixture was
(
1H, d, J=3.2 Hz, CHOH). HPLC analysis (Chiracel
extracted into ether (3×100 mL). The ethereal layers
were collected, combined, dried (MgSO ) and concen-
OD, mm, hexane:ethanol:diethylamine
250×4.6
4
9
2
5:5:0.1, 0.5 ml/mL), (S) isomer 19.24 min, (R) isomer
trated in vacuo to give the crude product which was
purified by Kugelrohr distillation to give phenacyl for-
mate (1.75 g, 54%).
12
3.37 min.
8
Acknowledgements
4.8. 2-Tosyloxy-l-phenylethanol 2
1
H NMR (300 MHz, CDCl ): l 7.7 (2H, d, J 8.3 Hz,
3
We thank the EPSRC and SmithKline Beecham and
Avecia for support of CASE studentships (to J.A.K.
and D.J.C.). Professor D. Games and Dr. B. Stein of
the EPSRC National Mass Spectroscopic service
ArH), 7.32–7.28 (7H, m, Ar/Ph), 4.9 (1H, m, CHOH),
4
.1 (1H, dd, J 10.3, 3.3 Hz, CHHOTs), 4.0 (1H, dd, J
0.3, 8.4 Hz,, CHHOTs), 2.9 (1H, br s, CHOH), 2.4
1
9
D
3 18 3
(
3H, s, CH ), [h] =+48.9 (c 1.15, CHCl ) correspond-
(
Swansea) are thanked for HRMS analysis of certain
ing to 93% e.e. as demonstrated by reduction to 1-
phenylethanol.
compounds. We also acknowledge the generous loan of
ruthenium and rhodium salts by Johnson-Mathey lim-
ited and the use of the EPSRC’s Chemical Database
4.9. 1-Phenylethanol 3
14
Service at Daresbury.
1
H NMR (300 MHz, CDCl ): l 7.31–7.24 (5H, m,
3
ArH), 4.87 (1H, dq, J 6.4, 3.1 Hz, CHOH), 2.2 (1H,
References
. (a) Palmer, M. J.; Wills, M. Tetrahedron: Asymmetry
1999, 10, 2045–2061; (b) Palmer, M.; Walsgrove, T.;
Wills, M. J. Org. Chem. 1997, 62, 5226; (c) Wills, M;
Gamble, M.; Palmer, M.; Smith, A. R. C.; Studley, J. R.;
Kenny, J. A. J. Mol. Catal. A: Chem. 1999, 146, 139–148;
brs, OH), 1.50 (3H, d, J 6.4 Hz, CH ). HPLC analysis
3
(
Chiracel OD, 250×4.6 mm), hexane:ethanol:
1
diethylamine=95:5:0.1 (0.5 mL/min), (R) isomer 14.55
min, (S) isomer 17.16 min.
1
d
4.10. Cyclic carbonate 4
1
(
d) Kenny, J. A.; Palmer, M. J.; Smith, A. R. C.; Wals-
H NMR (300 MHz, CDCl ): l 7.46 –7.35 (5H, m,
3
grove, T.; Wills, M. Synlett 1999, 1615; (e) Smith, A. R.
C.; Kenny, J. A.; Heck, A. J. R.; Kettenes-van der Bosch,
J. J.; Wills, M. Tetrahedron: Asymmetry 1999, 10, 3267–
ArH), 5.68 (1H, dd, J 8.5, 8.3 Hz, CHH), 4.81 (1H, dd,
J 8.5, 8.3 Hz, CHH), 4.24 (1H, dd, J 8.1 and 8.5 Hz,
1
0
D
CH). [h] =+51.2 (c 1.0, CHCl ) corresponding to
2
2
3
3270; (f) Wills, M.; Palmer, M. J.; Smith, A. R. C.;
9
4% e.e. as demonstrated by hydrolysis to the 1-
Kenny, J. A.; Walsgrove, T. Molecules 2000, 5, 1–15; (g)
Kenny, J. A.; Versluis, K.; Heck, A. J. R.; Walsgrove, T.;
Wills, M. Chem. Commun. 2000, 99–100; (h) Kawamoto,
A.; Wills, M. Tetrahedron: Asymmetry 2000, 11, 3257–
3261.
phenylethan-1,2-diol.
4.11. 1-Phenylethan-1,2-diol 5
1
H NMR (300 MHz, CDCl ): l 7.2–7.1 (5H, m, ArH),
3
4
.6 (1H, dd, J 3.4, 8.3 Hz, CHOH), 4.4 (1H, brs, OH),
2. For monotosylated diamines with Ru(II) in iso-PrOH or
4
3
.1 (1H, brs, OH), 3.51 (1H, dd J 3.4, 11.7 Hz, CHH),
.43 (1H, dd, J 8.4, 11.7, CHH). [h] =+65.5 (c 1.25,
HCO H/TEA, see: (a) Hashiguchi, S.; Fujii, A.; Take-
2
D
hara, J.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1995,
117, 7562; (b) Fujii, A.; Hashiguchi, S.; Uematsu, N.;
Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1996, 118,
2521; (c) P u¨ ntener, K.; Schwink, L.; Knochel, P. Tetra-
hedron Lett. 1996, 37, 8165. For monotosylated diamines
1
8
CHCl ) corresponding to 94% (S) e.e. HPLC analysis
3
(
Chiracel OD, 250×4.6 mm, hexane:iso-propanol:
diethylamine=90:10:0.1, 0.5 mL/min), (R) isomer 21.73
1
1
min, (S) isomer 23.65 min.