Indium-mediated diastereoselective allylation of D- and L-glyceraldimines with 4-bromo-1,1,1-trifluoro-2-butene: Highly stereoselective synthesis of 4,4,4-trifluoroisoleucines and 4,4,4-trifluorovaline

Article abstract of DOI:10.1021/jo0601157

A practical and efficient route for the stereoselective synthesis of (2R,3S)- and (2S,3R)-4,4,4-trifluoroisoleucines and (2R,3S)-4,4,4- trifluorovaline was developed. Indium-mediated allylation of (R)-N-benzyl-2,3-O-isopropylideneglyceraldimine 7 with 4-bromo-1,1,1-trifluoro- 2-butene 4 gave the desired homoallylic amine 8 in high diastereoselectivity (>95% de) with moderate yield. The Cbz-protected (2R,35)-4,4,4- trifluoroisoleucine 14 and Boc-protected (2R,3S)-4,4,4-trifluorovaline 21 were then readily prepared from 8. In addition, following the same procedure, Cbz-protected (2S,3R)-4,4,4-trifluoroisoleucine 28, the enantiomer of 14, was prepared starting from (S)-N-benzyl-2,3-O-isopropylideneglyceraldimine 24.

Full text of DOI:10.1021/jo0601157

Indium-Mediated Diastereoselective Allylation of D- and
L-Glyceraldimines with 4-Bromo-1,1,1-trifluoro-2-butene: Highly
Stereoselective Synthesis of 4,4,4-Trifluoroisoleucines and
4,4,4-Trifluorovaline
Qi Chen,† Xiao-Long Qiu,† and Feng-Ling Qing*,†,‡
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy
of Science, 354 Fenglin Lu, Shanghai 200032, China, and Institute of Biological Sciences and
Biotechnology, Donghua UniVersity, 2999 North Renmin Lu, Shanghai 201620, China
flq@mail.sioc.ac.cn
ReceiVed January 19, 2006
A practical and efficient route for the stereoselective synthesis of (2R,3S)- and (2S,3R)-4,4,4-
trifluoroisoleucines and (2R,3S)-4,4,4-trifluorovaline was developed. Indium-mediated allylation of (R)-
N-benzyl-2,3-O-isopropylideneglyceraldimine 7 with 4-bromo-1,1,1-trifluoro-2-butene 4 gave the desired
homoallylic amine 8 in high diastereoselectivity (>95% de) with moderate yield. The Cbz-protected
(2R,3S)-4,4,4-trifluoroisoleucine 14 and Boc-protected (2R,3S)-4,4,4-trifluorovaline 21 were then readily
prepared from 8. In addition, following the same procedure, Cbz-protected (2S,3R)-4,4,4-trifluoroisoleucine
28, the enantiomer of 14, was prepared starting from (S)-N-benzyl-2,3-O-isopropylideneglyceraldimine
24.
Introduction
trifluoromethyl groups is accompanied by a substantial increase
in hydrophobicity, owing to the low polarizability of the fluorine
atoms.5 It must be emphasized that enantiomerically pure
TFAAs are highly desirable for peptide synthesis to avoid
compositional heterogeneity of samples and for exploration of
stereoelectronic and packing effects.6 Therefore, the develop-
ment of an efficient and highly stereoselective route to enan-
tiomerically pure TFAAs promotes both synthetic and biological
research.
Isoleucine and valine are important natural amino acids; their
trifluoromethylated analogues were used in peptide and protein
design. Kumar and co-workers5c reported a peptide system based
on the coiled coil region of the transcriptional activator GCN4
Recently, fluorinated amino acids have attracted increasing
attention because of their extensive utilization as inhibitors of
enzymes,1 antitumor and antibacterial agents,2 probes to follow
biochemical reactions,3 valuable building blocks for the design
of hyperstable protein folds, as well as directing highly specific
protein-protein interactions.4 There has been a special interest
in trifluoromethyl-containing amino acids (TFAAs) in peptide
and protein design, because the replacement of methyl with
* To whom correspondence should be addressed. Fax: 86-21-64166128.
† Shanghai Institute of Organic Chemistry.
‡ Donghua University.
(1) Kollonitsch, J.; Patchett, A. A.; Marburg, S.; Maycock, A. L.; Perkins,
L. M.; Doldouras, G. A.; Duggan, D. E.; Aster, S. D. Nature 1978, 274,
906.
(2) Tsushima, T.; Kawada, K.; Ishihara, S.; Uchida, N.; Shiratori, O.;
Hirata, M. Tetrahedron 1988, 44, 5375.
(3) (a) Dubios, J.; Dugave, C.; Foures, C.; Kaminsky, M.; Tabet, J. C.;
Bory, S.; Gaudry, M.; Marquet, A. Biochemistry 1991, 30, 10506. (b)
Resnati, G. Tetrahedron 1993, 49, 9385.
(5) (a) Wang, P.; Fichera, A.; Kumar, K.; Tirrell, D. A. Angew. Chem.,
Int. Ed. 2004, 43, 3664. (b) Wang, P.; Tang, Y.; Tirrell, D. A. J. Am. Chem.
Soc. 2003, 125, 6900. (c) Bilgic¸er, B.; Fichera, A.; Kumar, K. J. Am. Chem.
Soc. 2001, 123, 4393. (d) Tang, Y.; Ghirlanda, G. W.; Petka, A.; Nakajima,
T.; DeGrado, W. F.; Tirrell, D. A. Angew. Chem., Int. Ed. 2001, 40, 1494.
(e) Xing, X.; Fichera, A.; Kumar, K. Org. Lett. 2001, 3, 1285 and references
therein.
(4) (a) Yoder, N. C.; Kumar, K. Chem. Soc. ReV. 2002, 31, 335. (b)
Neil, E.; Marsh, G. Chem. Biol. 2000, 7, R153.
(6) (a) Xing, X.; Fichera, A.; Kumar, K. J. Org. Chem. 2002, 67, 1722.
(b) Xing, X.; Fichera, A.; Kumar, K. J. Org. Chem. 2002, 67, 8290.
10.1021/jo0601157 CCC: $33.50 © 2006 American Chemical Society
Published on Web 04/13/2006
3762
J. Org. Chem. 2006, 71, 3762-3767

Indium-Mediated Allylation of Glyceraldimines
SCHEME 1
SCHEME 2
with an unnatural hydrophobic core, prepared by the replacement
of four natural leucine and three natural valine residues with
unnatural 5,5,5-trifluoroleucine (TFL) and 4,4,4-trifluorovaline
(TFV), respectively. The resulting coiled coil structure was more
resistant to thermal- and denaturant-induced unfolding than its
hydrocarbon counterpart. Tirrell and co-workers5b incorporated
D,L-trifluoroisoleucine into proteins in vivo and also found that
some resulting fluorinated proteins could fold into stable and
functional structures. However, Tirrell and co-workers used
racemic trifluoroisoleucine (TFI) prepared only in 3% overall
yield over seven steps,5b and Kumar and co-workers prepared
the enantiomerically pure TFL and TFV by enzymatic resolution.5c
Clearly, the existing approaches for the access of TFI and TFV
are insufficient for the procurement of enough quantities for
further detailed biological evaluation or the synthesis of other
TFI- and TFV-containing compounds. More importantly, to the
best of our knowledge, there is no report on stereoselective
synthesis of TFI and TFV so far. Herein we report a practical
and efficient approach to the highly stereoselective synthesis
of TFI and TFV.
tography (Scheme 2). The absolute configuration of 5a was
confirmed by the X-ray diffraction analysis of its p-nitrobenzoic
ester 6a (see Supporting Information). Treatment of the mixture
of 5a and 5b with p-nitrobenzoic acid in the presence of DCC
and DMAP provided p-nitrobenzoic esters 6a and 6b in 88%
yield. Compounds 6a and 6b could be easily separated by flash
chromatography on silica gel.
In comparison with the indium-mediated allylation of CdO
bonds, the allylation of CdN bonds usually achieves better
enantioselectivity or diastereoselectivity.9 Moreover, the amino
group of the amino acids could be introduced directly in this
way. Accordingly, the reaction between alkene 4 and (R)-N-
benzyl-2,3-O-isopropylideneglyceraldimine 7 derived from 3
and benzylamine in the presence of indium powder in THF or
MeOH was carried out. However, the reaction was complicated,
and the desired product was not obtained. Fortunately, it was
found that the allylation reaction proceeded well in DMF
(Scheme 3). More strikingly, analysis of the crude reaction
mixture by 19F NMR spectroscopy (see Supporting Information)
showed that the reaction occurred highly diastereoselectively
(>95% de). Only a single diastereomer, 8, was isolated in 61%
yield along with 11% of tertiary amine 9, which was formed
by the allylation of benzylamine. Benzylamine probably came
from the hydrolysis of 7. The amine 8 was further hydrogenated
to give primary amine 10 in 89% yield. To confirm the
configuration of compound 8, compound 10 was converted into
amide 11. The configuration of compound 11 was determined
by X-ray diffraction analysis (see Supporting Information).
With the intermediate 10 in hand, optically pure (2R,3S)-
4,4,4-trifluoroisoleucine was synthesized in a straightforward
fashion (Scheme 4). Treatment of amine 10 with CbzCl gave
compound 12 in 93% yield. After the removal of the isopro-
pylidene ketal, the diol 13 was obtained in 94% yield. Finally,
oxidation of the dihydroxyl moiety with RuCl3/NaIO4 success-
fully provided the desired Cbz-protected (2R,3S)-4,4,4-triflu-
oroisoleucine 14 in 76% yield. The 1H, 13C and 19F NMR spectra
of compound 14 showed clearly that no epimerization occurred.
Thus, Cbz-protected (2R,3S)-4,4,4-trifluoroisoleucine was syn-
thesized stereoselectively in 60% overall yield over four steps
starting from amine 8.
Results and Discussion
Several years ago, Loh and Li7 reported the indium-mediated
allylation reaction of aldehydes with 4-bromo-1,1,1-trifluoro-
2-butene in water afforded â-trifluoromethylated homoallylic
alcohols in high yield and excellent diastereoselectivity. Thus,
indium-mediated allylation of chiral pool (R)-2,3-O-isopropyl-
ideneglyceraldehyde 3 with 4-bromo-1,1,1-trifluoro-2-butene 4
was also expected to give â-trifluoromethylated homoallylic
alcohol 5 with good yield and high diastereoselectivity. The
alcohol 5 should be a key intermediate for the preparation of
the two target molecules (Scheme 1). The other key elements
in this synthetic approach included the use of SN2 reaction to
install an amino group, cutting a carbon atom via ozonization
of double bonds, dehydroxylation via Barton’s radical reaction,
deisopropylidenation, and then a final oxidation mediated by
RuCl3/NaIO4.
Alkene 4 was prepared on a large scale in 38% overall yield
over four steps from commercially available ethyl-4,4,4-
trifluoro-3-oxobutanoate.7,8 However, the reaction of aldehyde
3 with alkene 4 in the presence of indium powder in DMF at
room temperature afforded a mixture of homoallylic alcohols
5a and 5b in moderate yield (65%) and low diastereoselectivity
(dr ) 1.5:1), which could not be separated by flash chroma-
In addition, (2R,3S)-4,4,4-trifluorovaline was also readily
synthesized starting from homoallylic amine 8 (Scheme 5).
Exposure of compound 8 to (CF3CO)2O provided amine 15 in
97% yield. Ozonization of 15 followed by reduction with NaBH4
gave the desired alcohol 16 in 86% yield. Removal of the benzyl
(7) (a) Loh, T.-P.; Li, X.-R Angew. Chem., Int. Ed. Engl. 1997, 36, 980.
(b) Loh, T.-P.; Li, X.-R. Eur. J. Org. Chem. 1999, 1893.
(8) (a) Bevilacqua, P. F.; Keith, D. D.; Roberts, J. L. J. Org. Chem.
1984, 49, 1430. (b) Mcbee, E. T.; Pierce, O. R.; Smith, D. D. J. Am. Chem.
Soc. 1954, 76, 3722.
(9) (a) Beuchet, P.; Marrec, N. L.; Mosset, P. Tetrahedron Lett. 1992,
33, 5959. (b) Lu, W.; Chan, T. H. J. Org. Chem. 2000, 65, 8589. (c) For
a review, see: Bloch, R. Chem. ReV. 1998, 98, 1407.
J. Org. Chem, Vol. 71, No. 10, 2006 3763

Chen et al.
SCHEME 3
SCHEME 4
26 in 88% yield for two steps. Removal of isopropylidene ketal
of 26 in the presence of TsOH in methanol afforded the diol 27
in 93% yield. Finally, oxidation of the dihydroxyl moiety of
27 with RuCl3/NaIO4 provided Cbz-protected (2S,3R)-4,4,4-
trifluoroisoleucine 28 in 71% yield. The optical rotation of 28
([R]20 ) -0.5 (c 0.85, CHCl3)) was opposite to that of its
D
enantiomer Cbz-protected (2R,3S)-4,4,4-trifluoroisoleucine 14
([R]20 ) +0.6 (c 1.10, CHCl3)).
D
The different stereoselectivity in the allylation reaction of
aldehyde 3 and imine 7 could be illustrated by the indium-
chelated six-membered transition state (Figure 1). The CF3 group
group via hydrogenation and protection of the resultant amine
with Boc2O were carried out in a one-pot process to provide
compound 17 in quantitative yield. Treatment of alcohol 17 with
PhOC(S)Cl provided thiocarbonyl derivative 18 in 95% yield.
However, exposure of compound 18 to Bu3SnH (4 equiv)/AIBN
(0.8 equiv) in toluene at 80 °C produced the expected product
19 only in 25% yield. Notably, it was reported that raising the
reaction temperature as well as prolongation of addition time
of Bu3SnH could efficiently increase the yield of the Barton
radical dehydroxylation for the primary hydroxyl substrate.10
Thus, when the reaction temperature was raised to 140 °C (in
xylene) and the addition time of Bu3SnH was prolonged to 12
h, the dehydroxylation of compound 18 proceeded smoothly to
give the desired product 19 in 65% isolated yield. Finally, Boc-
protected (2R,3S)-4,4,4-trifluorovaline 21 was provided in 58%
yield over two steps using the same procedures as described
for the synthesis of amino acid 14 from 12. Although the
absolute configuration of 21 could be determined from the
configuration of homoallylic amine 8, it was not sufficient
because there was the possibility of racemization in the follow-
up steps. To further confirm the configuration of compound 21,
treatment of 21 with trifluoroacetic acid at room temperature
gave free amino acid (2R,3S)-4,4,4-trifluorovaline 22 in quan-
FIGURE 1. Proposed explanation for stereoselectivity.
would be in the equatorial position due to its steric bulki-
ness.7,11,12 The chirality of aldehyde 3 would block the re-face
of itself, thus the indium species would mainly attack the si-
face. In addition, the isopropylidenyl moiety preferentially
favored the equatorial position due to its large steric bulk. All
of these factors led to mainly the formation of transition states
29 and 30, which delivered anti isomer 5a as the main product.
On the other hand, the benzyl group and isopropylidenyl moiety
in E-imine 7 must adopt orthogonal positions so that indium
could efficiently chelate with the nitrogen atom.13 Another
advantage for the orthogonal position of the isopropylidenyl
moiety was that five-membered ring chelation between the
indium and the oxygen atom could occur.7,14 Thus, transition
state 31 or 32 was predominantly formed, leading to the highly
stereoselective generation of syn isomer 8.
titative yield. The optical rotation of 22 ([R]20 ) -12.1 (c
D
0.30, 1 N HCl)) was opposite to that of its reported enantiomer
(2S,3R)-4,4,4-trifluorovaline ([R]20 ) +12.8 (c 0.50, 1 N
D
HCl)),6 therefore, the absolute configuration of 21 was further
confirmed.
We also wanted to extend this methodology to the synthesis
of enantiomer of Cbz-protected (2R,3S)-4,4,4-trifluoroisoleucine
14. The indium-mediated reaction of alkene 4 with (S)-N-benzyl-
2,3-O-isopropylideneglyceraldimine 24 derived from (S)-2,3-
O-isopropylideneglyceraldehyde 23 and benzylamine also pro-
ceeded smoothly to give homoallylic amine 25 in 55% yield
and high diastereoselectivity (>95% de) along with byproduct
tertiary amine 9 in 9% yield (Scheme 6). Hydrogenation of
compound 25 followed by treatment with CbzCl gave compound
In conclusion, we have developed a practical and efficient
route for the stereoselective synthesis of TFI and TFV.
(11) Corey, E. J.; Link, J. O.; Bakshi, R. K. Tetrahedron Lett. 1992, 33,
7107.
(12) Konno, T.; Yamazaki, T.; Kitazume, T. Tetrahedron 1996, 52, 199.
(13) Lu, W.; Chan, T. H. J. Org. Chem. 2000, 65, 8589.
(14) Bernardi, L.; Cere´, V.; Femoni, C.; Pollicino, S.; Ricci, A. J. Org.
Chem. 2003, 68, 3348.
(10) Barton, D. H. R.; Motherwell, W. B.; Stange, A. Synthesis 1981,
743.
3764 J. Org. Chem., Vol. 71, No. 10, 2006

Indium-Mediated Allylation of Glyceraldimines
SCHEME 5
SCHEME 6
p-nitrobenzoic acid (254 mg, 1.52 mmol), DCC (322 mg, 1.56
mmol), and DMAP (5 mg) in methylene chloride (8 mL) was stirred
for 6 h at room temperature. The resulting solid was removed by
filtration, and the solvent was evaporated in vacuo. Ether (20 mL)
was added to the residue, the additional precipitate of DCU was
removed by filtration, and the filtrate was concentrated. The residue
was purified by silica gel column chromatography (petroleum ether/
ethyl acetate ) 30/1) to give 6a (155 mg, 54%) as a white solid
and 6b (97 mg, 34%) as a clear oil. 6a: mp 124-125 °C; [R]20
)
D
1
+61.7 (c 1.25, CHCl3); H NMR (300 MHz, CDCl3) δ 8.26 (d,
J ) 9.0 Hz, 2H), 8.19 (d, J ) 9.0 Hz, 2H), 5.99-5.87 (m, 1H),
5.68-5.55 (m, 3H), 4.22-4.16 (m, 1H), 4.02 (dd, J ) 8.7, 5.7 Hz,
1H), 3.89 (dd, J ) 8.7, 4.8 Hz, 1H), 3.47-3.35 (m, 1H), 1.45 (s,
3H), 1.36 (s, 3H); 19F NMR (282 MHz, CDCl3) δ -69.12 (d, J )
9.3 Hz, 3F); IR (thin film) νmax 2989, 1728, 1529, 1348, 1282,
1186, 1112, 1057, 846, 724 cm-1; MS (ESI) m/z 390 (M + H)+.
Anal. Calcd for C17H18F3 NO6: C, 52.45; H, 4.66; N, 3.60. Found:
Compared with those reported methods on the synthesis or
procurement of racemic or chiral TFI and TFV, the following
advantages of our synthetic route are noteworthy: (1) The
starting materials could be prepared in large scale. (2) The key
indium-mediated allylation reaction was operationally simple
and highly stereoselective. (3) The synthesis of â-trifluorometh-
yl-R-amino acids starting from the trifluoromethylated homoal-
lylic amine was efficient, producing a high yield in a straight-
forward fashion.
C, 52.68; H, 4.71; N, 3.32. 6b: [R]20 ) -42.8 (c 0.75, CHCl3);
D
1H NMR (300 MHz, CDCl3) δ 8.32 (d, J ) 9.0 Hz, 2H), 8.22 (d,
J ) 9.0 Hz, 2H), 5.98-5.86 (m, 1H), 5.67-5.64 (m, 1H), 5.52-
5.40 (m, 2H), 4.42-4.36 (m, 1H), 4.10 (dd, J ) 8.7, 6.6 Hz, 1H),
3.83 (dd, J ) 8.7, 5.7 Hz, 1H), 3.19-3.06 (m, 1H), 1.45 (s, 3H),
1.34 (s, 3H); 19F NMR (282 MHz, CDCl3) δ -68.46 (d, J ) 9.0
Hz, 3F); IR (thin film) νmax 2989, 1728, 1529, 1282, 1186, 1092,
846, 724 cm-1; MS (ESI) m/z 390 (M + H)+. Anal. Calcd for
C17H18 F3NO6: C, 52.45; H, 4.66; N, 3.60. Found: C, 52.19; H,
4.51; N, 3.27.
Experimental Section
1-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2-(trifluoromethyl)but-
3-en-1-ol (5). To a stirred solution of (R)-2,3-O-isopropylidene-
glyceraldehyde 3 (2.7 g, 20.7 mmol) in DMF (35 mL) at room
temperature was added 1,1,1-trifluoro-4-bromo-2-butene 4 (6.7 g,
35.5 mmol), followed by indium powder (4.1 g, 35.5 mmol). The
resulting mixture was stirred for 48 h at room temperature, treated
with 1 N HCl (10 mL), and extracted with ethyl acetate (3 × 15
mL). The combined organic layers were washed sequentially with
water and brine, dried over anhydrous Na2SO4, and concentrated
in vacuo. The residue was purified by silica gel column chroma-
tography (petroleum ether/ethyl acetate ) 20/1) to afford 5 (3.24
g, 65%). 1H NMR (300 MHz, CDCl3) δ 6.00-5.81 (m, 1H), 5.52-
5.29 (m, 2H), 4.17-3.71 (m, 4H), 3.22-2.62 (m, 1H), 2.21 (br,
1H), 1.45-1.33 (m, 6H); 19F NMR (282 MHz, CDCl3) δ -67.97
(d, J ) 9.0 Hz, 1.2F), δ -68.12 (d, J ) 11.5 Hz, 1.8F); IR (thin
film) νmax 3468, 2992, 1375, 1261, 1071, 846 cm-1; MS (ESI) m/z
241 (M + H)+, 263 (M + Na)+. Anal. Calcd for C10H15F3O3: C,
50.00; H, 6.29. Found: C, 49.67; H, 6.58.
(1R,2S)-N-Benzyl-1-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)-2-(tri-
fluoromethyl)but-3-en-1-amine (8) and (E)-N-Benzyl-4,4,4-tri-
fluoro-N-((E)-4,4,4-trifluorobut-2-enyl)but-2-en-1-amine (9). A
mixture of 2,3-O-isopropylidene-D-glyceraldehyde (1.05 g, 8.12
mmol), benzylamine (869 mg, 8.12 mmol), and anhydrous MgSO4
(1.47 g, 12.24 mmol) in CH2Cl2 (24 mL) was stirred overnight.
The white solid was removed by filtration, and the solvent was
evaporated in vacuo to afford (R)-N-benzyl-2,3-O-isopropylidene-
glyceraldimine 7 (1.75 g, 98%), which was used directly in the
next step without further purification. To a stirred solution of 7
(1.0 g, 4.6 mmol) in anhydrous DMF (15 mL) at room temperature
was added 1,1,1-trifluoro-4-bromo-2-butene 4 (1.72 g, 9.1 mmol),
followed by indium powder (780 mg, 6.8 mmol). The resulting
mixture was stirred for 15 h at room temperature and then treated
with 1 N HCl (10 mL) and extracted with ethyl acetate (3 × 15
mL). The combined organic layers were washed sequentially with
water and brine, dried over anhydrous Na2SO4, and concentrated
in vacuo. The residue was purified by silica gel column chroma-
tography (petroleum ether/ethyl acetate ) 20/1) to afford 8 (916
mg, 61%) and 9 (160 mg, 11%). 8: [R]20D ) -16.1 (c 0.95, CHCl3);
1H NMR (300 MHz, CDCl3) δ 7.37-7.22 (m, 5H), 5.97-5.84 (m,
(1S,2S)-1-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2-(trifluoro-
methyl)but-3-enyl 4-Nitrobenzoate (6a) and (1R,2R)-1-((R)-2,2-
Dimethyl-1,3-dioxolan-4-yl)-2-(trifluoromethyl)but-3-enyl 4-Ni-
trobenzoate (6b). A mixture of 5 (177 mg, 0.74 mmol),
J. Org. Chem, Vol. 71, No. 10, 2006 3765

Chen et al.
1H), 5.41-5.32 (m, 2H), 4.36-4.30 (m, 1H), 3.98-3.87 (m, 3H),
3.72-3.68 (m, 1H), 3.28-3.18 (m, 1H), 2.91 (dd, J ) 3.9, 2.4 Hz,
1H), 1.70 (br, 1H), 1.38 (s, 3H), 1.33 (s, 3H); 19F NMR (282 MHz,
CDCl3) δ -66.10 (d, J ) 9.6 Hz, 3F); 13C NMR (75.5 MHz, CDCl3)
δ 139.9, 129.2, 128.3, 128.1, 127.1, 126.5 (q, J ) 168.3 Hz), 122.5,
109.3, 75.4, 66.9, 54.9, 50.9, 50.1 (q, J ) 14.7 Hz), 26.3, 25.3; IR
(thin film) νmax 3356, 3088, 3031, 2989, 2937, 1456, 1381, 1261,
1125, 850, 742 cm-1; MS (ESI) m/z 330 (M + H)+. Anal. Calcd
for C17H22F3NO2: C, 61.99; H, 6.73; N, 4.25. Found: C, 61.91;
H, 6.43; N, 4.15. 9: 1H NMR (300 MHz, CDCl3) δ 5.37-5.27 (m,
5H), 6.44-6.37 (m, 2H), 5.91-5.79 (m, 2H), 3.61 (s, 2H), 3.20-
3.19 (m, 4H); 19F NMR (282 MHz, CDCl3) δ -64.54 (s, 3F); IR
(thin film) νmax 3034, 2928, 1685, 1328, 1122, 981, 741 cm-1; MS
(ESI) m/z 324 (M + H)+. Anal. Calcd for C15H15F6N: C, 55.73;
H, 4.68; N, 4.33. Found: C, 56.03; H, 4.94; N, 4.08.
as a clear oil. 12: [R]20D ) +28.6 (c 0.95, CHCl3); 1H NMR (300
MHz, CDCl3) δ 7.39-7.25 (m, 5H), 5.18-5.08 (m, 3H), 4.33-
4.27 (m, 1H), 4.11-4.02 (m, 2H), 3.63 (dd, J ) 8.4, 7.2 Hz, 1H),
2.40-2.28 (m, 1H), 1.77-1.67 (m, 2H), 1.41 (s, 3H), 1.34 (s, 3H),
1.04 (t, J ) 7.5 Hz, 3H); 19F NMR (282 MHz, CDCl3) δ -65.67
(d, J ) 9.9 Hz, 3F); IR (thin film) νmax 3452, 3345, 3056, 2988,
2889, 1726, 1512, 1251, 1066, 847, 742 cm-1; MS (ESI) m/z 376
(M + H)+. Anal. Calcd for C18H24F3NO4: C, 57.59; H, 6.44; N,
3.73. Found: C, 57.99; H, 6.31; N, 3.57.
Benzyl (2S,3R,4S)-1,2-Dihydroxy-4-(trifluoromethyl)hexan-
3-ylcarbamate (13). A mixture of 12 (460 mg, 1.23 mmol) and
p-toluenesulfonic acid monohydrate (233 mg, 1.23 mmol) in
methanol (14 mL) was stirred overnight. The reaction was quenched
with water and extracted with ethyl acetate (3 × 10 mL). The
combined organic layers were washed with water and brine, dried
over anhydrous Na2SO4, and concentrated in vacuo. The residue
was purified by silica gel column chromatography (petroleum ether/
ethyl acetate ) 2/1) to give 13 (385 mg, 94%) as a white solid.
13: mp 79-80 °C; [R]20D ) +16.5 (c 0.40, CHCl3); 1H NMR (300
MHz, CDCl3) δ 7.38-7.27 (m, 5H), 5.21-5.12 (m, 3H), 4.10-
4.04 (m, 1H), 3.94-3.89 (m, 1H), 3.60-3.57 (m, 2H), 2.50-2.45
(m, 1H), 2.19 (br, 2H), 1.76-1.69 (m, 2H), 1.04 (t, J ) 6.9 Hz,
3H); 19F NMR (282 MHz, CDCl3) δ -65.02 (d, J ) 7.9 Hz, 3F);
IR (thin film) νmax 3388, 3329, 2974, 2893, 1695, 1504, 1263, 1049,
752, 696 cm-1; MS (ESI) m/z 336 (M + 1). Anal. Calcd for
C15H20F3NO4: C, 53.73; H, 6.01; N, 4.18. Found: C, 53.58; H,
5.88; N, 3.95.
(2R,3S)-2-(Benzyloxycarbonyl)-3-(trifluoromethyl)pentano-
ic acid (14). To a stirred mixture of 13 (80 mg, 0.24 mmol) in
CCl4 (1 mL), CH3CN (1 mL), and H2O (1.5 mL) at room
temperature were added NaIO4 (210 mg, 0.98 mmol) and RuCl3‚
H2O (2 mg). Stirring was allowed to continue for 6 h. Then ethyl
acetate (20 mL) was added, and the mixture was dried over
anhydrous Na2SO4 directly and concentrated in vacuo. The residue
was purified by silica gel column chromatography (petroleum ether/
ethyl acetate ) 2/1) to give 14 (58 mg, 76%) as a white solid. 14:
mp 90-92 °C; [R]20D ) +0.6 (c 1.10, CHCl3); 1H NMR (300 MHz,
CD3COCD3) δ 7.27-7.16 (m, 5H), 6.28 (d, J ) 9.6 Hz, 1H), 5.04-
4.95 (m, 2H), 4.63 (dd, J ) 9.3, 3.0 Hz, 1H), 2.88-2.74 (m, 1H),
1.69-1.46 (m, 2H), 0.97 (t, J ) 7.8 Hz, 3H); 19F NMR (282 MHz,
CD3COCD3) δ -61.47 (d, J ) 10.7 Hz, 3F); 13C NMR (75.5 MHz,
CD3COCD3) δ 172.2, 158.0, 138.1, 129.6, 129.1, 129.0, 128.6 (q,
J ) 168.7 Hz), 67.6, 52.6, 48.0 (q, J ) 15.6 Hz), 19.7, 12.0; IR
(thin film) νmax 3342, 3070 (br), 1725, 1550, 1274, 1145, 1095,
735, 696 cm-1; MS (ESI) m/z 320 (M + H)+; HRMS calcd for
C14H16F3NO4Na, 342.0924; found, 342.0923. Anal. Calcd for
C14H16F3NO4: C, 52.67; H, 5.05; N, 4.39. Found: C, 52.69; H,
5.07; N, 4.16.
(1R,2S)-1-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2-(trifluoro-
methyl)butan-1-amine (10). A mixture of 10% palladium on
charcoal (181 mg) and 8 (570 mg, 1.73 mmol) in ethyl acetate (14
mL) was stirred under hydrogen for 4 h at room temperature.
Filtration and the removal of the solvent gave the crude product,
which was purified by column chromatography on silica gel
(petroleum ether/ethyl acetate ) 3/1) to give 10 (372 mg, 89%) as
1
a yellow oil. 10: [R]20 ) +2.5 (c 1.05, CHCl3); H NMR (300
D
MHz, CDCl3) δ 4.26-4.18 (m, 1H), 4.05 (dd, J ) 8.1, 6.6 Hz,
1H), 3.73-3.68 (m, 1H), 2.94-2.91 (m, 1H), 2.07-1.94 (m, 1H),
1.75 (dq, J ) 14.7, 7.2 Hz, 2H), 1.71 (br, 2H), 1.43 (s, 3H), 1.37
(s, 3H), 1.03 (t, J ) 7.2 Hz, 3H); 19F NMR (282 MHz, CDCl3) δ
-64.01 (d, J ) 9.6 Hz, 3F); 13C NMR (75.5 MHz, CDCl3) δ 128.0
(q, J ) 281.9 Hz), 109.3, 77.6, 66.8, 52.6, 47.9 (q, J ) 23.0 Hz),
26.6, 25.2, 18.8 (q, J ) 2.9 Hz), 11.9; IR (thin film) νmax 2988,
2940, 2887, 1373, 1253, 1163, 1064, 861 cm-1; MS (ESI) m/z 242
(M + H)+; HRMS calcd for C10H19F3NO2, 242.1372; found,
242.1362.
N-((1R,2S)-1-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2-(trifluo-
romethyl)butyl)-4-nitrobenzamide (11). To a suspension of
4-nitrobenzoic acid (100 mg, 0.6 mmol) in methylene chloride (5
mL) was added oxalyl chloride (57 µL) and DMF (10 µL). The
resulting suspension was stirred for 2 h at room temperature. The
mixture was concentrated. The residue was dissolved in methylene
chloride (5 mL) and treated with 10 (144 mg, 0.6 mmol in 2.5 mL
methylene chloride) and triethylamine (98 µL). The resulting
mixture was stirred overnight at room temperature. The reaction
was quenched with water and extracted with methylene chloride.
The combined organic layers were washed with water and brine,
dried over anhydrous Na2SO4, and concentrated in vacuo. The
residue was purified by silica gel column chromatography (petro-
leum ether/ethyl acetate ) 15/1) to give 11 (30 mg, 13%) as a
white solid. 11: mp 122-124 °C; [R]20D ) +34.6 (c 0.85, CHCl3);
1H NMR (300 MHz, CDCl3) δ 8.32 (d, J ) 9.0 Hz, 2H), 7.93 (d,
J ) 9.0 Hz, 2H), 6.51 (d, J ) 9.0 Hz, 1H), 4.60-4.55 (m, 1H),
4.48-4.44 (m, 1H), 4.16-4.10 (m, 1H), 3.72-3.66 (m, 1H), 2.57-
2.45 (m, 1H), 1.86-1.74 (m, 2H), 1.45 (s, 3H), 1.37 (s, 3H), 1.10
(t, J ) 6.9 Hz, 3H); 19F NMR (282 MHz, CDCl3) δ -65.07 (d,
J ) 9.9 Hz, 3F); 13C NMR (75.5 MHz, CDCl3) δ 165.3, 149.8,
139.7, 128.0, 127.5 (q, J ) 284.6 Hz), 124.0, 109.8, 74.4, 66.8,
48.6, 46.8 (q, J ) 23.8 Hz), 26.4, 24.5, 19.0, 11.8; IR (thin film)
N-Benzyl-N-((1R,2S)-1-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)-2-
(trifluoromethyl)but-3-enyl)-2,2,2-trifluoroacetamide (15). To a
stirred solution of 8 (200 mg, 0.60 mmol) in methylene chloride
(8 mL) was added trifluoroacetic anhydride (277 mg, 1.32 mmol)
dropwise. The reaction mixture was stirred for 1 h at room
temperature. The mixture was washed with water and brine, dried
over anhydrous Na2SO4, and concentrated in vacuo. The residue
was purified by silica gel column chromatography (petroleum ether/
ν
max 3270, 2925, 1644, 1558, 1351, 1174, 870, 707 cm-1; MS (ESI)
ethyl acetate ) 20/1) to give 15 (249 mg, 97%) as a rotamer. 15:
m/z 391 (M + H)+; HRMS calcd for C17H21F3N2O5Na, 413.1313;
found, 413.1295.
1
[R]20 ) -1.1 (c 1.05, CHCl3); H NMR (300 MHz, CDCl3) δ
D
7.36-7.26 (m, 5H), 5.51-5.29 (m, 3H), 4.97-4.80 (m, 2H), 4.57-
4.31 (m, 2H), 4.06-4.01 (m, 2H), 3.44-3.31 (m, 2H), 1.34-1.19
(m, 6H); 19F NMR (282 MHz, CDCl3) δ -66.81 (m, 0.37F), -67.41
(s, 2.63F), -68.71 (m, 0.37F), -69.04 (s, 2.63F); IR (thin film)
νmax 3034, 2991, 1695, 1453, 1250, 1151, 1074 cm-1; MS (ESI)
m/z 426 (M + H)+. Anal. Calcd for C19H21F6NO3: C, 53.65; H,
4.98; N, 3.29. Found: C, 53.82; H, 5.13; N, 3.27.
Benzyl (1R,2S)-1-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2-(tri-
fluoromethyl)butylcarbamate (12). To a stirred solution of 10 (320
mg, 1.33 mmol) in THF (16 mL) was added CbzCl (341 mg, 2.0
mmol), followed by saturated aqueous NaHCO3 (5 mL). The
reaction mixture was stirred for 2 h at room temperature. The
reaction was quenched with water and extracted with ethyl acetate
(3 × 10 mL). The combined organic layers were washed with water
and brine, dried over anhydrous Na2SO4, and concentrated in vacuo.
The residue was purified by silica gel column chromatography
(petroleum ether/ethyl acetate ) 10/1) to give 12 (462 mg, 93%)
(R)-2-((R)-(Benzylamino)-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)-
methyl)-3,3,3-trifluoropropan-1-ol (16). Ozone was bubbled
through a solution of 15 (240 mg, 0.56 mmol) in methylene chloride
(30 mL) at -78 °C. The reaction was monitored by TLC, and
3766 J. Org. Chem., Vol. 71, No. 10, 2006

Indium-Mediated Allylation of Glyceraldimines
NaBH4 (372 mg, 9.8 mmol) in ethanol (15 mL, 95%) was then
added. The resulting mixture was stirred for 3 h at room temper-
ature. The reaction was quenched with water and extracted with
methylene chloride (3 × 10 mL). The combined organic layers were
washed with water and brine, dried over anhydrous Na2SO4, and
concentrated in vacuo. The residue was purified by silica gel column
chromatography (petroleum ether/ethyl acetate ) 5/1) to give 16
(160 mg, 86%) as a clear oil. 16: [R]20D ) -12.0 (c 0.80, CHCl3);
1H NMR (300 MHz, CDCl3) δ 7.34-7.26 (m, 5H), 4.55-4.40 (m,
1H), 4.12-3.92 (m, 4H), 3.79-3.69 (m, 2H), 3.05-3.03 (m, 1H),
2.81-2.67 (m, 1H), 1.44 (s, 3H), 1.36 (s, 3H); 19F NMR (282 MHz,
CDCl3) δ -65.79 (d, J ) 9.3 Hz, 3F); IR (thin film) νmax 3363,
2989, 1456, 1382, 1054, 857, 741 cm-1; MS (ESI) m/z 334 (M +
H)+. Anal. Calcd for C16H22F3NO3: C, 57.65; H, 6.65; N, 4.20.
Found: C, 57.49; H, 6.80; N, 3.92.
tert-Butyl (1R,2R)-1-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)-3,3,3-
trifluoro-2-(hydroxymethyl)propylcarbamate (17). A mixture of
10% palladium on charcoal (116 mg), di-tert-butyl dicarbonate (131
mg, 0.60 mmol) and 16 (135 mg, 0.41 mmol) in ethyl acetate (10
mL) was stirred under hydrogen for 4 h at room temperature.
Filtration and the removal of the solvent gave the crude product,
which was purified by column chromatography on silica gel
(petroleum ether/ethyl acetate ) 5/1) to give 17 (140 mg, 100%)
as a white solid. 17: mp 81-82 °C; [R]20D ) +17.8 (c 0.65, CHCl3);
1H NMR (300 MHz, CDCl3) δ 5.06 (d, J ) 9.9 Hz, 1H), 4.41-
4.36 (m, 1H), 4.21-4.15 (m, 1H), 4.11 (dd, J ) 12.3, 6.6 Hz, 1H),
3.96-3.80 (m, 2H), 3.73-3.67 (m, 1H), 2.62-2.49 (m, 1H), 1.45
(s, 12H), 1.38 (s, 3H); 19F NMR (282 MHz, CDCl3) δ -65.42 (d,
J ) 10.4 Hz, 3F); 13C NMR (75.5 MHz, CDCl3) δ 156.5, 126.2
(d, J ) 169.0 Hz), 110.0, 80.6, 74.9, 67.0, 57.4, 48.6 (q, J ) 14.0
Hz), 47.8, 28.2, 26.2, 25.2; IR (thin film) νmax 3297, 2986, 1678,
1559, 1124, 1059 cm-1; MS (ESI) m/z 366 (M + Na)+; HRMS
calcd for C14H24F3NO5Na, 366.1497; found, 366.1498.
NMR (75.5 MHz, CDCl3) δ 155.5, 127.4 (q, J ) 280.7 Hz), 109.5,
79.9, 74.1, 66.5, 49.4, 41.2 (q, J ) 24.8 Hz), 28.3, 26.2, 24.9, 10.1;
IR (thin film) νmax 3383, 2988, 1687, 1533, 1175, 1069, 867 cm-1
;
MS (ESI) m/z 350 (M + Na)+; HRMS calcd for C14H25F3NO4,
328.1733; found, 328.1730.
tert-Butyl (2S,3R,4S)-1,1,1-Trifluoro-4,5-dihydroxy-2-meth-
ylpentan-3-ylcarbamate (20). A mixture of 19 (86 mg, 0.26 mmol)
and p-toluenesulfonic acid monohydrate (24 mg, 0.13 mmol) in
methanol (5 mL) was stirred overnight. The reaction was quenched
with water and extracted with ethyl acetate (3 × 10 mL). The
combined organic layers were washed with water and brine, dried
over anhydrous Na2SO4, and concentrated in vacuo. The residue
was purified by silica gel column chromatography (petroleum ether/
ethyl acetate ) 2/1) to give 20 (62 mg, 83%) as a white solid. 20:
mp 102-103 °C; [R]20D ) +18.3 (c 0.30, CHCl3); 1H NMR (300
MHz, CD3COCD3) δ 5.89 (d, J ) 9.9 Hz, 1H), 4.20-4.18 (m,
1H), 3.95-3.84 (m, 3H), 3.46 (br, 2H), 2.79-2.64 (m, 1H), 1.42
(s, 9H), 1.24 (d, J ) 6.9 Hz, 3H); 19F NMR (282 MHz, CD3COCD3)
δ -65.11 (d, J ) 9.0 Hz, 3F); 13C NMR (75.5 MHz, CD3COCD3)
δ 156.2, 128.4 (q, J ) 280.2 Hz), 78.6, 70.2, 63.2, 50.3, 39.6 (q,
J ) 24.4 Hz), 27.6, 10.1 (q, J ) 3.2 Hz); IR (thin film) νmax 3338,
2926, 1723, 1679, 1270, 1168 cm-1; MS (ESI) m/z 310 (M + Na)+;
HRMS calcd for C11H20F3NO4Na, 310.1237; found, 310.1236.
(2R,3S)-2-(tert-Butoxycarbonyl)-4,4,4-trifluoro-3-methylbu-
tanoic Acid (21). To a stirred mixture of 20 (87 mg, 0.30 mmol)
in CCl4 (2 mL), CH3CN (2 mL), and H2O (3 mL) at room
temperature were added NaIO4 (321 mg, 1.50 mmol) and RuCl3‚
H2O (2 mg). Stirring was allowed to continue for 12 h. Then ethyl
acetate (20 mL) was added, and the mixture was dried over
anhydrous Na2SO4 directly and concentrated in vacuo. The residue
was dissolved in saturated NaHCO3, and the aqueous phase was
washed with ethyl acetate, acidified with saturated NaHSO4, and
extracted again with ethyl acetate. The organic phase was then dried
and evaporated. The residue was recrystallized from petroleum ether
to give 21 (58 mg, 71%) as a white solid. 21: mp 85-86 °C;
[R]20D ) -13.2 (c 0.80, CHCl3); 1H NMR (300 MHz, CD3COCD3)
δ 6.28 (d, J ) 9.0 Hz, 1H), 4.75 (dd, J ) 9.3, 5.4 Hz, 1H), 3.34-
3.22 (m, 1H), 1.65 (s, 9H), 1.47 (d, J ) 6.9 Hz, 3H); 19F NMR
(282 MHz, CD3COCD3) δ -69.11 (d, J ) 9.3 Hz, 3F); 13C NMR
(75.5 MHz, CD3COCD3) δ 170.6, 155.5, 127.4 (q, J ) 279.1 Hz),
79.1, 53.2, 40.0 (q, J ) 25.4 Hz), 27.5, 10.3 (q, J ) 2.5 Hz); IR
(thin film) νmax 3370, 2983 (br), 1737, 1643, 1263, 1177, 1026
cm-1; MS (ESI) m/z 270 (M - H)-; HRMS calcd for C10H16F3-
NO4Na, 294.0918; found, 294.0923.
O-Benzyl O-(R)-2-((R)-(tert-Butoxycarbonyl)-((S)-2,2-dimeth-
yl-1,3-dioxolan-4-yl)methyl)-3,3,3-trifluoropropyl Carbonothio-
ate (18). To a stirred mixture of 17 (225 mg, 0.66 mmol), pyridine
(0.14 mL), and DMAP (18 mg) in methylene chloride (18 mL) at
room temperature was added dropwise phenyl chlorothionoformate
(227 mg, 1.32 mmol). The resulting mixture was stirred for 6 h at
room temperature. The reaction was quenched with water and
washed with water and brine. The organic layers was dried over
anhydrous Na2SO4 and concentrated in vacuo. The residue was
purified by silica gel column chromatography (petroleum ether/
ethyl acetate ) 20/1) to give 18 (298 mg, 95%) as a clear oil. 18:
1
[R]20 ) -9.6 (c 0.60, CHCl3); H NMR (300 MHz, CDCl3) δ
D
(2R,3S)-4,4,4-Trifluorovaline (22). To a stirred mixture of 21
(78 mg, 0.29 mmol) in CH2Cl2 (5 mL) at room temperature was
added CF3COOH (0.4 mL) dropwise. The mixture was stirred
7.45-7.40 (m, 2H), 7.33-7.26 (m, 1H), 7.12-7.09 (m, 2H), 5.03
(d, J ) 9.6 Hz, 1H), 4.91 (dd, J ) 12.0, 4.5 Hz, 1H), 4.79 (dd,
J ) 12.3, 6.6 Hz, 1H), 4.42-4.37 (m, 1H), 4.23 (dd, J ) 8.7, 4.8
Hz, 1H), 4.08 (dd, J ) 8.4, 7.2 Hz, 1H), 3.74-3.68 (m, 1H), 3.16-
3.05 (m, 1H), 1.48 (s, 3H), 1.45 (s, 9H), 1.36 (s, 3H); 19F NMR
(282 MHz, CDCl3) δ -65.52 (d, J ) 8.7 Hz, 3F); 13C NMR (75.5
MHz, CDCl3) δ 194.4, 155.4, 153.3, 129.6, 126.7, 125.8 (q, J )
281.8 Hz), 121.8, 109.9, 80.4, 73.9, 68.2, 66.5, 47.9, 45.8 (q, J )
24.9 Hz), 28.3, 26.2, 24.7; IR (thin film) νmax 3453, 2984, 2936,
1718, 1492, 1161, 771 cm-1; MS (ESI) m/z 502 (M + Na)+; HRMS
calcd for C21H28F3NO6SNa, 502.1487; found, 502.1481.
overnight and then concentrated in vacuo to give 22 (49 mg, 100%)
1
as a white solid. 22: [R]20 ) -12.1 (c 0.30, 1 N HCl); H NMR
D
(300 MHz, D2O) δ 3.78 (d, J ) 4.5 Hz, 1H), 3.04-2.92 (m, 1H),
1.12 (d, J ) 7.2 Hz, 3H); 19F NMR (282 MHz, D2O) δ -69.17 (d,
J ) 9.0 Hz, 3F).
Acknowledgment. We thank the National Natural Science
Foundation of China (No. 20325210, 20472105), Ministry of
Education of China, and Shanghai Municipal Scientific Com-
mittee for funding this work.
tert-Butyl (1R,2S)-1-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)-3,3,3-
trifluoro-2-methylpropylcarbamate (19). Tributylstannane (0.64
mL, 2.10 mmol) in xylene (12 mL) is added during 12 h to 18
(210 mg, 0.44 mmol) in xylene (6 mL) at 140 °C under nitrogen.
After heating for an additional 12 h, the reaction mixture was
concentrated in vacuo. The residue was purified by silica gel column
chromatography (petroleum ether/ethyl acetate ) 20/1) to give 19
Supporting Information Available: Experimental procedures
1
and characterization data for compound 25-28, H NMR spectra
for all compounds, 13C NMR spectra for compounds 8, 10, 11, 14,
17-21, 25, and 28, 19F NMR spectra for compounds 8, 14, 21, 25,
and 28, and 19F NMR spectrum of analysis for the reaction of
compounds 4 and 7. ORTEP drawing of the X-ray structure of
compounds 6a and 11 and X-ray crystallographic details for
compounds 6a and 11 (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
(93 mg, 65% yield) as a white solid. 19: mp 60-61 °C; [R]20
)
D
1
+27.5 (c 0.50, CHCl3); H NMR (300 MHz, CDCl3) δ 4.90 (d,
J ) 9.9 Hz, 1H), 4.36-4.31 (m, 1H), 4.03 (dd, J ) 8.1, 6.6 Hz,
1H), 3.96-3.91 (m, 1H), 3.67-3.62 (m, 1H), 3.58-3.45 (m, 1H),
1.45 (s, 9H), 1.44 (s, 3H), 1.34 (s, 3H), 1.21 (d, J ) 7.2 Hz, 3H);
19F NMR (282 MHz, CDCl3) δ -69.19 (d, J ) 9.3 Hz, 3F); 13C
JO0601157
J. Org. Chem, Vol. 71, No. 10, 2006 3767