Asymmetric synthesis of four isomers of 2-C-trifluoromethylerythritol

Article abstract of DOI:10.1021/jo052282x

Optically active 2-C-trifluoromethylerythritols, analogues of 2-C-methylerythritol, which is a key intermediate in the biosynthesis of isoprenoid with a mevalonate-independent route, were conveniently synthesized from 1,1,1-trifluoro-2,3-epoxypropane.

Full text of DOI:10.1021/jo052282x

SCHEME 1a
Asymmetric Synthesis of Four Isomers of
2-C-Trifluoromethylerythritol
Hua Wang, Xiaoming Zhao, Youhua Li, and Long Lu*
Key Laboratory of Organofluorine Chemistry, Shanghai Institute
of Organic Chemistry, Chinese Academy of Science,
354 Fenglin Road, Shanghai 200032, China
lulong@mail.sioc.ac.cn
ReceiVed NoVember 3, 2005
Optically active 2-C-trifluoromethylerythritols, analogues of
2-C-methylerythritol, which is a key intermediate in the
biosynthesis of isoprenoid with a mevalonate-independent
route, were conveniently synthesized from 1,1,1-trifluoro-
2,3-epoxypropane.
a Reagents and conditions: (a) BF3‚Et2O, BnOH, 45 °C, 65%; (b) Dess-
Martin reagent, rt, 77%; (c) (carbethoxymethyl)triphenylphosphonium
bromide, Et3N, rt, 87% (E/Z 2:1); (d) DIBAL-H, 0 °C, 87%; (e) BzCl,
Et3N, 89%; (f) 1 mol % of OsO4, 5 mol % of (DHQD)2PHAl, 1 equiv
MeSO2NH2, K3Fe(CN)6, K2CO3, t-BuOH/H2O, rt, 78%; (g) K2CO3, MeOH,
94%; (h) Pd/C, H2, MeOH, quant; (i) DIBAL-H, 0 °C, 91%; (j) BzCl, Et3N,
rt, 86%; (k) BCl3, CH2Cl2, MeOH, -78°C, 78%; (l) TBDPSCl, imidazole,
DMF, 76%; (m) trityl chloride, 2,6-lutidine, CH2Cl2, 87%.
Isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophos-
phate (DMAPP) are important intermediates in the terpenoid
biosynthesis. Many studies have accumulated evidence for their
existence in Gram-negative bacteria, algae, and plant chloro-
plasts of a mevalonate-independent pathway (MIP) for the
biosynthesis of terpenoids.1 MIP does not exist in mammals;
therefore, it can be a useful target for screening herbicides,
antibacterial2 and antimalarial drugs.3 The replacement of a
methyl group by trifluoromethyl (CF3) in bioactive compounds
has provided many valuable analogues.4 The introduction of
fluorine atoms to organic compounds often results in a dramatic
change of their physical, chemical, and biological properties.5
Therefore, the development of a synthetic methodology for
fluorinated 2-C-methylerythritol is significant for further studies
on MIP. To our knowledge, there is no report concerning the
synthesis of fluorinated 2-C-methylerythritol analogue. Herein,
we wish to present the preparation of 2-C-trifluoromethyleryth-
ritol.
Our first attempt to synthesize 2-C-trifluoromethylerythritol
is outlined in Scheme 1. The reaction of trifluorooxacylopropane
(1) with benzyl alcohol gave 3-benzyloxy-1,1,1-trifluoropropan-
2-ol (2) in 65% yield.6 Compound 2 was further oxidized by
Dess-Martin reagent to provide the 3-benzyloxy-1,1,1-trifluo-
ropropan-2-one (3) in 77% yield.7 Compound 3 reacted with
(carbethoxymethyl)triphenylphosphonium bromide to form CF3-
substituted olefin as a pair of isomers 4 and 5 in a 1:2 ratio,
which were separable by chromatography. The E-isomer 5 was
reduced with DIBAL-H to provide the allylic alcohol. Followed
by the protection of hydroxyl group with BzCl, intermediate
11 was obtained in 89% yield.
Poulter has reported the synthesis of 4-diphosphocytidyl-2-
C-methyl-D-erythritol.8 Using that process, the enantioselective
target molecule was obtained in 50% ee after the dihydroxylation
of allylic phosphate. Optimizing the reaction conditions indicated
that 1 mol % of OsO4, 5 mol % of ligand, 1 equiv MeSO2NH2,
and room temperature were essential for the asymmetric
(1) (a) Flesch, G.; Rohmer, M. Eur. J. Biochem. 1988, 175, 405-411.
(b) Rohmer, M.; Knani, M.; Simonin, P.; Sutter, B.; Sahm, H. Biochem. J.
1993, 295, 517-524. (c) Lichtenthaler, H. K.; Schwender, J.; Disch, A.;
Rohmer, M. Biochem. J. 1996, 316, 73-80.
(2) Takahashi, S.; Kuzuyama, T.; Watanabe, H.; Seto, H. Proc. Natl.
Acad. Sci. U.S.A. 1998, 95, 9879-9884.
(3) Jomaa, H.; Wiesner, J.; Sanderbrand, S.; Altincicek, B.; Weidemeyer,
C.; Hintz, M.; Turbachova, I.; Eberl, M.; Zeidler, J.; Lichtenthaler, H. K.;
Soldati D.; Beck, E. Science 1999, 285, 1573-1576.
(4) (a) Rivkin, A.; Yoshimura, F.; Gabarda, A. E.; Chou, T. C.; Dong,
H.; Tong, W. P.; Danishefsky, S. J. J. Am. Chem. Soc. 2003, 125, 2899-
2901. (b) Rivkin, A.; Biswas, K.; Chou, T. C.; Danishefsky, S. J. Org.
Lett. 2003, 4, 4081-4084.
(5) (a) Organofluorine Chemistry: Principles and Commercial Applica-
tions; Banks, R. E., Smart, B. E., Tatlow, J. C., Eds.; Plenum: New York,
1994. (b) Welch, J. T.; Eswaraksrishnan, S. Fluorine in Bioorganic
Chemistry; Wiley: New York, 1991. (c) Biomedical Frontiers of Fluorine
Chemistry; Ojima, I., McCarthy, J. R., Welch, J. T., Eds.; ACS Symposium
Series 639; American Chemical Society: Washington, DC, 1996.
(6) Sznaidman, M. L.; Beauchamp, L. M. Nucleosides Nucleotides 1996,
15, 1315-1321.
10.1021/jo052282x CCC: $33.50 © 2006 American Chemical Society
Published on Web 03/21/2006
3278
J. Org. Chem. 2006, 71, 3278-3281

TABLE 1. Substituent Influence on the Asymmetric
Dihydroxylationa
entry
substrate
ligand
product
yield (%)
eec (%)
1
2
3
4
5
6
7
8
9
6
8
9
10
7
4
4
5
5
(DHQD)2PHAl
(DHQD)2PHAl
(DHQD)2PHAl
(DHQD)2PHAl
(DHQD)2PHAl
(DHQD)2PHAl
(DHQ)2PHAl
12c
12e
12f
12g
12d
12ab
12b
12h
12i
81
76
81
83
81
81
77
87
79
<5
<5
<5
<5
27
86
55
83
50
(DHQD)2PHAl
(DHQ)2PHAl
FIGURE 1. Model used to determine the absolute configuration of
12a and ∆δ values (δS - δR) obtained for the MTPA ester (300 MHz).
a Reaction are performed with 1 mol % of OsO4 and 5 mol % of
(DHQD)2PHAl catalyst at room temperature. b ee value of 12a was
measured as 99% after one-step recrystallization from hexane. c Determined
by HPLC analysis.
TABLE 2. Results of Deprotection
dihydroxylation of 11 to 12j. Otherwise, the reaction proceeded
rather slowly. Under these conditions, 12j was obtained in 81%
yield, though disappointingly with less than 5% ee. Finally, the
deprotection of 12j gave the racemic 13b in 94% yield. To
increase the selectivity of the asymmetric dihydroxylation, a
new strategy was discussed for the preparation of 2-C-
trifluoromethylerythritol. First, we studied the influence of
different protecting groups on the dihydroxylation of the olefins.
A series of CF3-substituted olefins were synthesized according
to Scheme 1, and a modified procedure was used for the
preparation of 12. The preliminary results of the asymmetric
dihydroxylation are summarized in Table 1.9
The dihydroxylation of 4-10 gave 12a-i in 76-87% yields
(Table 1). The hydroxy protecting groups have no significant
influence on the enantioselectivity when the hydroxy group is
at the position R to the CF3 (entries 2-4). However, the
protecting group for the â-OH the affects ee value considerably
(entries 5 and 6). For instance, the ee value of 12c where the
hydroxyl is unprotected is less than 5% (entries 1 and 5), and
it was increased to 27% upon protection with BzCl. Replacing
-CH2OBz moiety with an ester group further improved the
enantioselectivity from 27% ee to 86% ee (entries 5 and 6).
Wipf and co-workers have described an asymmetric dihy-
droxylation of (E)-benzyl-2-(trifluoromethyl)but-2-enoate with
73% ee.10 Presently, this is the only example for the asymmetric
dihydroxylation of olefin where both CF3 and ester groups
attached to the same sp2 carbon atom. In general, the dihy-
droxylation is difficult due to the electron-withdrawing nature
of both the CF3 and ester groups.
The absolute configuration of 12a was determined by a single-
crystal X-ray diffraction study11 and the Mosher ester method.12
The (R)- and (S)-MTPA derivatives of 12a were prepared by
the treatment of 12a with (R)- and (S)-2-methoxy-2-phenyl-2-
trifluoromethylacetic acid in the presence of N,N′-dicyclohexyl-
carbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP)
in CH2Cl2. The ∆δ values (δS - δR) are summarized and labeled
in Figure 1. According to the ∆δ, the absolute configuration of
12a was deduced as (2S, 3R). These results are in agreement
with Sharpless’ rule.9c
Reduction of 12a with LiAlH413 and then palladium-catalyzed
hydrogenation14 provided the desired product 13a as an oil. The
other three isomers (13b, 13c, and 13d) were prepared using
the same procedure (Table 2).
In conclusion, we have developed an efficient synthesis of
2-C-trifluoromethylerythritols from 1,1,1-trifluoro-2,3-epoxypro-
pane. The four stereoisomers were obtained in good yields by
an improved asymmetric dihydroxylation with moderate to high
ee.
To synthesize the other two isomers of 12a,b, both 4 and 5
were chosen as the substrates and (DHQ)2PHAl was used instead
of (DHQD)2PHAl. As a result, both 12h and 12i were obtained
in ca. 87% and 79% yields, with 83% ee and 50% ee,
respectively (Table 1).
Experimental Section
3-Benzyloxy-1,1,1-trifluoropropan-2-one (3). To a well-stirred
solution of 3-benzyloxy-1,1,1-trifluoropropan-2-ol (2.18 g, 10
mmol) in CH2Cl2 (20 mL) was added Dess-Martin (DM) reagent
(7) (a) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155-4156.
(b) Yoshichika, K.; Yuko, S.; Katsuhiko, I. Org. Lett. 2001, 3, 457-460.
(c) Linderman, R. J.; Graves, D. M. J. Org. Chem. 1989, 54, 661-668. (d)
Kimura M.; Yamazaki T.; Kitazume T.; Kubota T. Org. Lett. 2004, 6, 4651-
4654
(8) (a) Koppisch, A. T.; Poulter, C. D. J. Org. Chem. 2002, 67, 5416-
5418. (b) Koppisch, A. T.; Blagg, B. S. J.; Poulter, C. D. Org. Lett. 2000,
2, 215-217.
(9) (a) Bennani, Y. L.; Sharpless, K. B. Tetrahedron Lett. 1993, 34,
2079-2082. (b) Kolb, H. C.; Andersson, P. G.; Sharpless, K. B. J. Am.
Chem. Soc. 1994, 116, 1278-1291. (c) Kolb, H. C.; VamNieuwenhze, M.
S.; Sharpless, K. B. Chem. ReV. 1994, 94, 2483-2547.
(10) Wipf, P.; Henninger, T. C.; Geib, S. J. J. Org. Chem. 1998, 63,
6088-6089.
(11) See the Supporting Information. Crystallographic data of 12a has
been deposited with the Cambridge Crystallographic Centre as CCDC
253465. Copies of the data can be obtained, free of charge, via the
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, U.K., e-mail: deposit@ccdc.cam.ac.uk.
(12) (a) Sullivan, G. R.; Dale, J. A.; Mosher, H. S. J. Org. Chem. 1973,
38, 2143-2147. (b) Xiao, L.; Yamazaki, T.; Kitazume, T.; Yonezawa, T.;
Sakamoto, Y.; Nogawa, K. J. Fluorine Chem. 1997, 84, 19-23.
(13) Seebach, D.; Eberle, M. Synthesis 1986, 37-40.
(14) Heathcock, C. H.; Ratcliffe, R. J. Am. Chem. Soc. 1971, 93, 1746-
1757.
J. Org. Chem, Vol. 71, No. 8, 2006 3279

(5.58 g, 13 mmol). The reaction mixture was stirred at room
temperature for 5 h and then diluted with CH2Cl2 (30 mL) and
poured into a solution of Na2S2O3 (0.26 M) in a saturated solution
of NaHCO3 (50 mL). The organic layer was separated and washed
with saturated aqueous NaHCO3 (2 × 30 mL) and water (2 × 30
mL). The combined aqueous phase was extracted with CH2Cl2 (2
× 30 mL). The organic phase was combined, dried over MgSO4,
and filtered. The solvent was removed under reduced pressure,,
and the residue was purified by a distillation under reduced pressure
to afford 3 as a colorless liquid in 77% yield along with a small
liquid: 1H NMR (CDCl3) δ 4.16 (s, 2H), 4.59 (s, 2H), 5.16 (q,
2H, J ) 2.4 Hz), 6.32 (t, 1H, J ) 6.0 Hz), 7.30-7.37 (m, 5H),
7.48 (t, 2H, J ) 7.8 Hz), 7.63 (t, 1H, J ) 6.9 Hz), 8.09 (d, 2H, J
) 8.1 Hz); 19F NMR (CDCl3) δ 61.5 (s); 13C NMR (CDCl3) δ
60.9 (s), 67.9 (q, J ) 3.2 Hz), 72.7 (s), 123.3 (q, J ) 274.8 Hz),
127.9 (s), 128.0 (s), 128.3 (s), 128.6 (s), 129.8 (s), 133.1 (s), 133.4
(s), 133.8 (q, J ) 7.1 Hz), 137.3 (s), 166.2 (s); IR (thin film) νmax
3067, 2868, 1725, 1453, 1276 cm-1; MS (EI): m/z 244 (M+
-
106). Anal. Calcd for C19H17O3F3: C, 65.14; H, 4.86. Found: C,
65.31; H, 5.04.
1
amount of hydrate (8.8%): bp 45-47 °C (0.1 mmHg); H NMR
(Z)-Benzoic Acid 1,1,1-Trifluoro-2-hydroxymethylbut-3-enyl
Ester (8). A solution of BCl3 in n-hexane (1 M) was added to
mixture of 7 (350 mg, 1 mmol) in CH2Cl2 at -78 °C. The reaction
mixture was stirred at -78 °C for 1 h and quenched with methanol.
The reaction mixture was allowed to warm to ambient temperature,
and 5 mL of 5% aq NaHCO3 was carefully added. After being
washed with water (3 × 10 mL), the organic phase was dried over
Na2SO4 and concentrated in a vacuum. The residue was purified
on silica gel (PE/EtOAc ) 4:1, Rf ) 0.4) to afford 8 (202 mg,
78% yield) as a colorless liquid: 1H NMR (CDCl3) δ 1.98 (s, 1H),
4.33 (s, 2H), 5.14 (q, 2H, J ) 2.4 Hz), 6.31 (t, 1H, J ) 6.0 Hz),
7.47 (t, 2H, J ) 7.5 Hz), 7.60 (t, 1H, J ) 6.9 Hz), 8.07 (d, 2H, J
) 7.2 Hz); 19F NMR (CDCl3) δ -61.4 (s); 13C NMR (CDCl3) δ
60.9 (q, J ) 2.9 Hz), 61.2 (t, J ) 2.4 Hz), 123.8 (q, J ) 280.3
Hz), 128.5 (s), 129.7 (s), 130.4 (s), 132.5 (q, J ) 1.7 Hz), 133.4
(CDCl3) δ 4.53 (s, 2H), 4.70 (s, 2H), 7.28-7.39 (m, 5H); 19F NMR
(CDCl3) δ -78.1 (s); 13C NMR (CDCl3) δ 69.9 (s), 73.6 (s), 115.3
(q, J ) 292.3 Hz), 128.1 (s), 128.5 (s), 128.7 (s), 136.1 (s) 188.4
(q, J ) 34.9 Hz); MS (EI) m/z 218 (M+, 3.8), 91 (C7H7+, 100.0).
2-Benzyloxymethyl-1,1,1-trifluorobut-3-enoic Acid Ethyl Es-
ter (Z/E) (4/5). To a solution of 3 (2.20 g, 10 mmol) in benzene
(20 mL) were added (carbethoxymethyl)triphenylphosphonium
bromide (4.29 g, 10 mmol) and Et3N (2.02 g, 20 mmol). The
reaction mixture was stirred at room temperature for 6 h, diluted
with 50 mL of petroleum ether, and stirred for a further 30 min.
The triphenylphosphine oxide was filtered off, and the filtrate was
concentrated in a vacuum. The residue was purified on silica gel
(PE/EtOAc ) 100/1) to give 5 (Rf ) 0.5, 1.393 g) and 4 (Rf )
0.45, 0.712 g) in 87% total yield as a colorless liquid.
(s), 166.3 (s); IR (thin film) νmax 3434, 1724, 1603, 1278 cm-1
;
1
4: H NMR (CDCl3) δ 1.32 (t, 3H, J ) 7.2 Hz), 4.19 (t, 2H, J
MS (EI) m/z 260 (M+, 3.9). Anal. Calcd for C12H11O3F3: C, 55.39;
) 0.5 Hz), 4.25 (q, 2H, J ) 7.2 Hz), 4.62 (s, 2H), 6.50 (t, 1H, J
) 2.0 Hz), 7.33∼7.39 (m, 5H); 19F NMR (CDCl3) δ 63.4 (s); 13C
NMR (CDCl3) δ 13.9 (s), 61.5 (s), 66.4 (q, J ) 3.5 Hz), 73.1 (s),
122.0 (q, J ) 273.8 Hz), 125.2 (q, J ) 3.7 Hz), 127.7 (s), 128.1
(s), 128.6 (s), 135.3 (q, J ) 30.9 Hz), 137.0 (s), 164.6 (s); IR (thin
film) νmax 3066, 2987, 1740, 1455, 1268 cm-1; MS (EI) m/z 289
(M+ + 1, 6.7), 259 (M+ - C2H5, 0.6), 91 (C7H7+, 100.0). Anal.
Calcd for C14H15O3F3: C, 58.33; H, 5.21. Found: C, 58.21; H, 5.25.
H, 4.26. Found: C, 55.55; H, 4.30.
(Z)-Benzoic Acid 2-(tert-Butyldiphenyl-ilanyloxymethyl)-1,1,1-
trifluorobut-3-enyl Ester (9). To a well-stirred solution of 8 (160
mg, 0.62 mmol) and imidazole (64 mg, 0.94 mmol) in 2 mL of
DMF was added TBDPSCl (205 mg, 0.74 mmol) at 0 °C. The
reaction mixture was stirred overnight at room temperature. After
completion of the reaction (monitored by TLC), the reaction was
quenched with 5 mL of water. The mixture was stirred for 30 min,
and the aqueous phase was extracted with CH2Cl2 (3 × 10 mL).
The organic phase was dried over Na2SO4 and concentrated. The
residue was purified on silica gel (PE/EtOAc ) 100:1 Rf ) 0.4) to
afford 9 (233 mg, 76% yield) as a colorless oil: 1H NMR (CDCl3)
δ 4.31 (s, 2H), 5.10-5.13 (m, 2H), 6.34 (t, 1H, J ) 6.0 Hz),
7.7.237.46 (m, 8H), 7.567.64 (m, 1H), 7.647.68 (m, 4H), 8.058.08
(m, 2H); 13C NMR (CDCl3) δ 61.9 (s), 60.8 (q, J ) 2.4 Hz), 61.7
(q, J ) 2.3 Hz), 123.3 (q, J ) 274.4 Hz), 128.4 (s) 128.8 (s), 129.7
(s), 129.9 (s), 130.0 (s), 130.4 (s), 130.8 (s), 131.1 (q, J ) 6.4 Hz),
131.6 (s), 132.8 (s), 133.2 (s), 135.5 (s), 166.1 (s); 19F NMR
(CDCl3) δ -61.5 (s); IR (thin film) νmax 3074, 2934, 1727, 1429,
1274, 1115 cm-1; MS (EI) m/z 441 (M+ - 57, 3.7). Anal. Calcd
for C28H29O3F3: C, 67.47; H, 5.82. Found: C, 67.44; H, 5.83.
(Z)-Benzoic Acid 1,1,1-Trifluoro-2-trityloxymethylbut-3-enyl
Ester (10). To a well-stirred solution of 8 (160 mg, 0.62 mmol)
and trityl chloride (259 mg, 0.94 mmol) in 2 mL of CH2Cl2 was
added 1 mL of 2,6-lutidine at 0 °C in 30 min. The reaction mixture
was stirred overnight at room temperature. After completion of the
reaction (monitored by TLC), the reaction mixture was quenched
with 5 mL of water. The mixture was stirred for 30 min and
extracted with CH2Cl2 (3 × 10 mL). The organic phase was dried
with Na2SO4 and concentrated. The residue was subjected to silica
gel (PE/EtOAc ) 100:1, Rf ) 0.3) to afford 10 (251 mg, 86.7%
yield) as a white solid: 1H NMR (CDCl3) δ 3.72 (s, 2H), 5.04 (s,
2H), 6.29 (t, 1H, J ) 6.3 Hz), 7.13-7.24 (m, 9H), 7.35-7.40 (m,
8H), 7.50 (t, 1H, J ) 6.0 Hz), 8.01 (t, 2H, J ) 6.6 Hz). 13C NMR
(CDCl3) δ 60.9 (q, J ) 3.2 Hz), 62.0 (q, J ) 1.6 Hz), 87.7 (s),
123.3 (q, J ) 273.9 Hz), 127.5 (s), 127.8 (s), 128.0 (s), 128.2 (s),
128.5 (s), 128.6 (s), 128.8 (s), 129.0 (s), 129.4 (s), 129.8 (s), 129.9
(s), 132.4 (q, J ) 2.4 Hz), 133.2 (s), 143.5 (s), 166.1 (s); 19F NMR
(CDCl3) δ -75.5 (s); IR (thin film) νmax 3066, 2875, 1721, 1450,
1273 cm-1; MS (EI) m/z 502 (M+, 0.1). Anal. Calcd for
C31H25O3F3: C, 74.10; H, 4.98. Found: C, 74.15; H, 5.11.
1
5: H NMR (CDCl3) δ 1.31 (t, 3H, J ) 7.2 Hz), 4.25 (q, 2H, J
) 7.2 Hz), 4.80 (s, 2H), 4.86 (s, 2H), 6.53 (t, 1H, J ) 0.6 Hz),
7.28∼7.39 (m, 5H); 19F NMR (CDCl3) δ 67.5 (s); 13C NMR
(CDCl3) δ 14.0 (s), 61.4 (s), 62.6 (s), 73.1 (s), 122.8 (q, J ) 273.9
Hz), 125.9 (q, J ) 6.9 Hz), 127.8 (s), 127.83 (s), 128.4 (s), 137.5
(s), 140.3 (q, J ) 29.1 Hz), 164.2 (s); IR (thin film) νmax 2987,
1731, 1307, 1207, 1180 cm-1; MS (EI) m/z 289 (M+ + 1, 8.2),
259 (M+ - C2H5, 0.6), 91 (C7H7+, 100.0). Anal. Calcd for
C14H15O3F3: C, 58.33; H, 5.21. Found: C, 58.04; H, 5.30.
(Z)-2-Benzyloxymethyl-1,1,1-trifluorobut-3-en-4-ol (6). A so-
lution of DIBAL-H (1 M in toluene, 4.4 mL) was slowly added to
a well-stirred solution of 4 (576 mg, 2 mmol) in THF (5 mL) at 0
°C. The reaction mixture was stirred at 0 °C for 2 h and quenched
with HCl (1 M, 5 mL). The mixture was stirred for 30 min, and
the aqueous phase was extracted with CH2Cl2 (3×10 mL). The
organic phase was dried over Na2SO4, concentrated, and purified
on silica gel (PE/EtOAc ) 7:1, Rf ) 0.3) to afford 6 (422 mg,
87% yield) as a colorless liquid: 1H NMR (CDCl3) δ 1.83-2.02
(m, 1H), 4.11 (s, 2H), 4.46 (s, 2H), 4.54 (s, 2H), 6.25 (t, 1H, J )
5.8 Hz), 7.29-7.40 (m, 5H); 19F NMR (CDCl3) δ 61.1 (s); 13C
NMR (CDCl3) δ 58.9 (q, J ) 2.7 Hz), 68.3 (q, J ) 2.7 Hz), 72.6
(s), 123.2 (q, J ) 274.1 Hz), 126.7 (q, J ) 27.9 Hz), 127.7 (s),
127.9 (s), 128.9 (s), 137.5 (s), 139.5 (q, J ) 3.5 Hz); IR (thin film)
υmax 3387, 2929, 1456, 1387, 1170 cm-1; MS (EI) m/z 246 (M+,
0.9), 91 (C7H7+, 100.0). Anal. Calcd for C12H13O2F3: C, 58.54; H,
5.28. Found: C, 58.47; H, 5.34.
(Z)-Benzoic Acid 2-Benzyloxymethyl-1,1,1-trifluorobut-3-enyl
Ester (7). To a solution of 6 (492 mg, 2 mmol) and BzCl (214
mg, 2 mmol) in CH2Cl2 (4 mL) was slowly added Et3N (404 mg,
2 mmol) at 0 °C in 30 min. The reaction mixture was stirred for 4
h, diluted with 10 mL of CH2Cl2, and washed with water (3 × 10
mL). The organic phase was dried over Na2SO4 and concentrated
in a vacuum. The residue was purified on silica gel (PE/EtOAc )
4/1, Rf ) 0.4) to afford 7 (624 mg, 89% yield) as a colorless
3280 J. Org. Chem., Vol. 71, No. 8, 2006

(2R,3S)-2-Benzyloxymethyl-1,1,1-trifluoro-2,3-dihydroxybu-
tyric Acid Ethyl Ester (12a). Compound 4 (140 mg, 0.5 mmol)
was added in one portion to a mixture consisting of K3Fe(CN)6
(493 mg, 1.5 mmol) and K2CO3 (207 mg, 1.5 mmol), OsO4 (0.1 M
in H2O, 0.05 mL, 0.005 mmol), (DHQD)2PHAL (20 mg, 0.02
mmol), and MeSO2NH2 (46 mg, 0.5 mmol) in 1:1 tert-butyl alcohol/
water (5 mL) at 0 °C. The mixture was stirred for 12 h at room
temperature. After completion of the reaction (monitored by TLC),
the reaction mixture was quenched with 5 mL of saturated NaHSO3.
The mixture was stirred for 30 min and extracted with EtOAc (3
× 10 mL). The organic phase was dried over Na2SO4 and
concentrated. The residue was purified on silica gel (PE/EtOAc )
3:1, Rf ) 0.3) to afford 12a (130 mg) as a white solid in 81%
yield: mp 63.5-64.5 °C; 1H NMR (CDCl3) δ 1.20 (t, 3H, J ) 7.2
Hz), 3.37 (d, 1H, J ) 6.0 Hz), 3.71 (d, 1H, J ) 9.3 Hz), 3.88 (d,
1H, J ) 9.9 Hz), 4.05-4.19 (m, 3H), 4.47 (s, 1H), 4.49-4.62 (m,
2H), 7.33-7.37 (m, 5H); 13C NMR (CDCl3) δ 13.8 (s), 62.9 (s),
67.1 (s), 69.2 (s), 74.2 (s), 76.5 (q, J ) 29.7 Hz), 124.3 (q, J )
284.9 Hz), 128.1 (s), 128.2 (s), 128.5 (s), 136.9 (s), 171.7 (s); 19F
NMR (CDCl3) δ -77.4 (s); IR (thin film) νmax 3497, 3430, 1738,
1250, 1099 cm-1; MS (EI) m/z 322 (M+, 0.6). Anal. Calcd for
+20.0 (c 0.81, CHCl3); tR (2R,3S) ) 23.97min, tR (2S,3R) )
25.87min (Chiralpak AS, column no. AS00CE-JG019, λ ) 220
nm, Hex/i-PrOH ) 95:5, 0.7 mL/min).
(2R,3R)-2-C-Trifluoromethylerythritol (13a): oil, in 91%
1
yield; H NMR (MeOH-d4) δ 3.70-3.84 (m, 4H), 3.92-3.95 (m,
1H); 13C NMR (MeOH-d4) δ 60.0 (s), 62.1 (s), 71.0 (s), 76.0 (q, J
) 24.0 Hz), 126.1 (q, J ) 285.6 Hz); 19F NMR (MeOH-d4) δ -77.7
(s); IR (thin film) νmax 3391, 2908, 1641, 1180, 1147, 1045 cm-1
;
MS (ESI) m/z 191.1 (M + H+); HRMS (M + Na+) calcd for
C5H9O4F3Na 213.0353, found 213.0345; [R]20 +7.9 (c 0.6,
D
MeOH).
Acknowledgment. We thank the National Natural Science
Foundation of China (Grant No. 29825104 and 29632003) and
the Chinese Academy of Science for financial support.
Supporting Information Available: Experimental procedures
and characterization data for all new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
C14H17O5F3: C, 52.17; H, 5.28. Found: C, 52.21; H, 5.33; [R]20
JO052282X
D
J. Org. Chem, Vol. 71, No. 8, 2006 3281