product was extracted with CH2Cl2 and dried over Na2SO4.
Evaporation of the solvent offered 0.170 g of the crude product.
Unreacted selenium (29 mg, 39%) was recovered. Silica gel flash
chromatography with first CH2Cl2 and then 10% EtOAc/CH2-
Cl2 gave 100 mg (84% based on recovered Se) of 5 as a colorless
oil: 1H NMR (CDCl3) δ 9.60 (s, br, 1H), 4.73 (td, J ) 9.3,
2.6[J H-C] Hz, 1H), 4.42 (ddd, J ) 9.3, 6.5, 3.4[J H-C] Hz, 1H),
3.93-3.85 (m, J ) 13.4, 9.3, 6.5, 3.2[J H-C] Hz, 1H), 1.92-1.81
(m, J ) 13.4, 6.7 Hz, 1H), 0.98 (d, J ) 6.7 Hz, 3H), 0.94 (d, J )
6.8 Hz, 3H); 13C NMR (CDCl3) δ 187.1 (d, J ) 232 Hz), 74.7,
63.5, 31.9, 16.6 (2C); 77Se NMR (CDCl3) δ 112 (d, J ) 233 Hz);
4-(S)-(-)-(1-Meth yleth yl)-3-[(ph en ylm eth oxy)-[2-13C]-ace-
tyl]-[2-13C]-oxa zolid in e[77Se]-selon e (7). To the previous se-
leno compound 5 (44.7 mg, 0.234 mmol) in 2.5 mL of CH2Cl2, in
an ice bath, was added acetyl chloride 6 (52.2 mg, 0.281 mmol)
in 0.5 mL of CH2Cl2 and triethylamine (0.742 g, 0.304 mmol).
The bright yellow reaction was stirred for 15 min at 0 °C and
then 1 h at rt. When TLC showed disappearance of the starting
material, the reaction was filtered over a pad of silica gel and
rinsed with CH2Cl2. After solvent evaporation in vacuo, the
yellow oil was purified by flash chromatography with 15% ethyl
acetate/hexanes to offer 64 mg (80%) of 7: 1H NMR (CDCl3) δ
7.48-7.32 (m, 5H), 5.26 (d, J ) 147.8 Hz, 2H), 4.82-4.76 (m,
1H), 4.72 (d, J ) 4.1 Hz, 2H), 4.54-4.42 (m, 2H), 2.48-2.38 (m,
1H), 0.99 (d, J ) 7 Hz, 3H), 0.93 (d, J ) 7 Hz, 3H); 13C NMR
(CDCl3) δ 188.5 (d, J ) 241.2 Hz), 72.3 (d, J ) 16.3 Hz)
[unlabeled 7: δ 188.5, 170.9, 137.0, 128.5, 128.2, 128.0, 73.6,
72.2, 70.3, 64.3, 28.8, 18.1, 14.9]; 77Se NMR (CDCl3) δ 447.35
(dd, J ) 16.3, 241.2 Hz); MS + 1 341.1, MS2 + 1 282.1
4-(S)-(-)-(1-Meth yleth yl)-3-(1-oxop r op yl)-[2-13C]-oxa zo-
lid in eselon e (8): 70%; 1H NMR (CDCl3) δ 4.72-4.65 (m, 1H),
4.41-4.29 (m, 2H), 3.53-3.26 (ABX3, J ) 17.9, 7.3 Hz, 2H),
2.33-2.21 (m, 1H), 1.14 (t, J ) 7.2 Hz, 3H), 0.88 (d, J ) 7.0 Hz,
3H), 0.82 (d, J ) 6.9 Hz, 3H); 13C NMR (CDCl3) δ 189.3 (apparent
doublet, J ) 242 Hz, is from 7% 77Se natural abundance), 154.4,
69.4, 64.1, 32.2, 28.8, 18.1, 14.9, 8.6.
MS + 1 192.1, MS2 + 1 86.1, 69.0; HRMS calcd for C513CH11
-
NO77Se 191.0073, obsd 191.0069.
P h en ylm eth oxy-[2-13C]-a cetyl Ch lor id e (6). Phenylmeth-
oxy-[2-13C]-acetic acid was first synthesized using a procedure
modified from Gravestock et al.11a A typical example is as follows.
To a suspension of NaH (1 g, 60% dispersion in mineral oil, 25.0
mmol) in dry THF (35 mL) under Ar at 0 °C was added a solution
of benzyl alcohol (1.17 mL, 11.3 mmol) in THF (5 mL). After the
mixture was stirred for 1 h, a solution of bromo-[2-13C]-acetic
acid (1.0 g, 7.1 mmol) in THF (20 mL) was added and the mixture
was refluxed overnight. The mixture was quenched with metha-
nol (20 mL), diluted with water, and washed with ether. The
aqueous layer was then acidified with concd HCl to pH 4 and
extracted with ethyl acetate. The combined ethyl acetate extracts
were dried (Na2SO4) and filtered, and the solvent was evaporated
to give 1.14 g (96% yield) of crude product as a slightly yellow
oil. NMR spectra were analogous to unlabeled commercial
samples and showed sufficient purity for subsequent reactions:
1H NMR (CDCl3) δ 7.44-7.37 (m, 5H), 4.70 (d, J ) 4.3 Hz, 2H),
4.20 (d, J ) 144.2 Hz, 2H); 13C NMR (CDCl3) δ 175.5 (d, J ) 61
Hz), 136.6, 128.6, 128.2, 128.1, 127.7, 127.1, 73.4, 66.5; MS + 1
166.5, 148.3.
4-(S)-(-)-(1-m eth yleth yl)-3-[(ph en ylm eth oxy)-[2-13C]-ace-
tyl]-[2-13C]-oxa zolid in eselon e (9): 72%; 1H NMR (CDCl3) δ
7.48-7.32 (m, 5H), 5.26 (d, J ) 147.8 Hz, 2H), 4.82-4.76 (m,
1H), 4.72 (d, J ) 4.1 Hz, 2H), 4.54-4.42 (m, 2H), 2.48-2.38 (m,
1H), 0.99 (d, J ) 7 Hz, 3H), 0.93 (d, J ) 7 Hz, 3H); 13C NMR
(CDCl3) δ 188.6, 72.2.
Ack n ow led gm en t. We gratefully acknowledge par-
tial financial support from the National Stable Isotopes
Program, NIH NIBIB Institute (RR 02231), and the Los
Alamos National Laboratory Laboratory Directed Re-
search and Development (LDRD) fund X1CG and XAB2.
Work done at Los Alamos National Laboratory was
performed under the auspices of the U.S. Department
of Energy.
The acid chloride was obtained using the procedure of Miller
et al.11b The acid (8.0 g, 48.0 mmol) was dissolved in dry CH2Cl2
(150 mL) and chilled to 0 °C under Ar. A solution of (COCl)2
(50.0 mL, 2 M in CH2Cl2, 100.0 mmol) was added, and the
solution was stirred 4 h and then allowed to gradually warm to
ambient overnight. The solvent was coevaporated with toluene,
and the product was distilled under reduced pressure (0.65
mmHg, bp14 88-90 °C) to give 5.65 g (63%) of acid chloride 6 as
a clear oil: 1H NMR (CDCl3) δ 7.48-7.38 (m, 5H), 4.72 (d, J )
4.0 Hz, 2H), 4.50 (d, J ) 148.5 Hz, 2H); 13C NMR (CDCl3) δ 171.9
(d, J ) 57 Hz), 136.1, 134.0, 130.1, 128.7, 128.5, 128.2, 74.8, 73.6;
MS 184.5.
Su p p or tin g In for m a tion Ava ila ble: Spectral data for
compounds 5-9, R-13C benzyloxyacetic acid, and R-13C ben-
zyloxyacetyl chloride. This material is available free of charge
(14) For the unlabeled compound, lit. bp 81-83 °C, 0.6 mm:
Bennington, F.; Morin, R. D. J . Org. Chem. 1961, 26, 194.
J O049747O
5152 J . Org. Chem., Vol. 69, No. 15, 2004