A practical method to access enantiopure β-perfluoroalkyl-β-amino acids: diastereoselective reduction of cyclic enamino-esters

Article abstract of DOI:10.1016/j.tetlet.2009.01.159

A highly practical method to access enantiopure β-perfluoroalkyl-β-amino acids was developed, which could be conducted without any expensive reagent, special apparatus/technique, nor tedious chromatographic separation. The condensation of methyl 4,4,4-tri

Full text of DOI:10.1016/j.tetlet.2009.01.159

Tetrahedron Letters 50 (2009) 1889–1892
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Tetrahedron Letters
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A practical method to access enantiopure b-perfluoroalkyl-b-amino acids:
diastereoselective reduction of cyclic enamino-esters
*
*
Yasuhiro Ishida , Nobutaka Iwahashi, Nao Nishizono, Kazuhiko Saigo
Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8658, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly practical method to access enantiopure b-perfluoroalkyl-b-amino acids was developed, which
could be conducted without any expensive reagent, special apparatus/technique, nor tedious chromato-
graphic separation. The condensation of methyl 4,4,4-trifluoro-3-oxobutanoate with (S)-2-amino-2-
Received 18 December 2008
Revised 26 January 2009
Accepted 29 January 2009
Available online 10 February 2009
phenylethanol, followed by an intramoleculer transesterification, gave an enamino-ester with
a
seven-membered ring structure. The hydride reduction of the cyclic enamino-ester proceeded with excel-
lent diastereoselectivity (dr = 95:5–97:3) to give the corresponding cyclic amino-ester. The major isomer
of the cyclic amino-ester was readily separated from the minor one and successfully converted into (S)-3-
amino-4,4,4-trifluorobutanoic acid (five steps, 38% overall yield, >99% ee). Concerning the key step of this
synthesis, the same strategy was applicable to another substrate; the asymmetric hydride reduction of a
cyclic enamino-ester with a pentafluoroethyl group also proceeded in excellent diastereoselectivity
(dr = 96:4).
Ó 2009 Elsevier Ltd. All rights reserved.
Fluorine-containing amino acids have attracted considerable re-
cent attention, owing to their potential application in widespread
of fluorinated enamino-esters bearing an N-benzyl group,4 (iii)
the asymmetric Mannich- or Reformatsky-type reaction of fluori-
nated aldimines with acetic acid equivalents,5 and (iv) the resolu-
tion of racemates through bio-catalyst approach, chromatography,
or crystallization.6 Taking account of practical utility in terms of
accessibility/handling of reagents, synthetic efficiency, and opera-
tional convenience, the first strategy is undoubtedly one of the
most fascinating approaches. Moreover, the same methodology
has been already well investigated for the synthesis of non-fluori-
nated b-amino acids.7 In fact, Fustero and his co-workers have
developed a highly convenient method based on the hydride
reduction of enamino-esters to access various enantio-enriched
b-perfluoroalkyl-b-amino acids. However, the stereoselectivity
achieved in these studies has been limited to an unsatisfactory le-
vel (dr up to 80:20),3b most likely because the perfluoroalkyl group
brought unpredictable effects on the property and reactivity of
neighboring functional groups.
In previous studies, fluorinated enamino-esters with a rela-
tively simple structure were frequently used as substrates, which
possess only one chiral auxiliary on their enamino nitrogen atom
or ester oxygen atom. As a result, the enamino-esters can take
several kinds of conformations, which would give rise to a
number of reaction pathways to make the diastereoselectivity
unsatisfactory.3 To overcome the problem, we designed an enami-
no-ester with a seven-membered ring structure as a key substrate
(6, Scheme 1), in which the enamine and ester functional groups
are ‘‘tethered” by an enantiopure amino alcohol with bifunctional
nature. The characteristic cyclic structure would strictly
define the conformation around the chiral auxiliary and the
scientific fields.1 To date, several kinds of fluorinated
a- and b-ami-
no acids have been studied, of which the characteristics change
dramatically depending on the position of fluorine atom(s). Among
them,
c-fluorinated a-amino acids, d-fluorinated a-amino acids,
and -fluorinated b-amino acids should be regarded as exception-
c
ally important classes; they serve as suitable components for pep-
tide-bond formation, because of their stability, tolerance toward
racemization, and proper reactivity. Particularly, the incorporation
of
nized as a powerful tool to analyze and/or modify the structure and
function of peptides and proteins.1e,g Likewise,
-fluorinated b-
amino acids also should enlarge the scope of peptide engineering.
One of the most promising applications of -fluorinated b-amino
c- or d-fluorinated a-amino acids into peptides has been recog-
c
c
acids is to incorporate them into the oligomers of b-amino acids
(b-peptides); b-peptides have been found to show various intrigu-
ing structures and functions, and their partial fluorination would
allow us for their further facile manipulation.2 At present, however,
chemistry of
c-fluorinated b-amino acids has not been explored
adequately, where even their stereoselective synthesis still re-
mains as a challenging target.3–6
Several groups have reported the asymmetric synthesis of b-
perfluoroalkyl-b-amino acids, which might be classified into the
following four categories: (i) the asymmetric reduction of fluori-
nated enamino-esters,3 (ii) the asymmetric proton shift reaction
* Corresponding authors. Tel.: +81 3 5841 7268; fax: +81 3 5802 3348 (Y.I.).
E-mail address: ishida@chiral.t.u-tokyo.ac.jp (Y. Ishida).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.01.159

1890
Y. Ishida et al. / Tetrahedron Letters 50 (2009) 1889–1892
F3C
N
F3C
O
Ph
Ph
(iii)
(i)
OMe
OMe
OMe
75%a
74%c
F3C
HN
F3C
HN
F3C
F3C
H2N
60%a
H O
O
OH
2
(iv)
(v)
quant
(vi)
84%c
O
O
(S)-4
H2N
•HCl
O
O
74%a
O
O
OMe
OH
H2N
Ph
OH
CF3
O
Ph
Ph
(3S,5S)-7
63%c
(ii)
81%b
(iii)
(S)-6
(S)-8
(S)-1
NH
3
75%a
(S)-
O
Yield based on the isolation by
a: column chromatography, b :distillation, and c: crystallization/precipitation.
74%c
5
(S)-
Scheme 1. Synthesis of (S)-3-amino-4,4,4-trifluorobutanoic acid ((S)-1). Reagents and conditions: (i) CH3CO2H (1 equiv), CH2Cl2, reflux, 12 h; (ii) CH3CO2H (3 equiv), CHCl3,
reflux, 12 h; (iii) SnBr4 (0.3 equiv), o-xylene, 130 °C, 4 h; (iv) NaBH3CN (1.2 equiv), HCl (10 equiv), CH2Cl2/dioxane (2:1, v/v), À78 °C to rt, 96 h; (v) H2 (1 atm), Pd/C (cat), HCl
(10 equiv), MeOH/dioxane (9:1, v/v), 16 h; (vi) HCl aq (3 M), reflux, 12 h, then propylene oxide (excess), MeOH, rt.
E/Z-isomerism of the enamino part, which would be favorable to
achieve the face-selective transformation of the prochiral enami-
no part. Herein, we report a highly efficient and practical method
for the synthesis of enantiopure b-trifluoromethyl-b-amino acid
via the diastereoselective hydride reduction of an enamino-ester
with a cyclic structure (Scheme 1).
Taking account of the time course of product ratios, the ring
cleavage of the oxazolidine (S)-5 was considered to be the rate-
determining step in the present seven-membered ring formation.
Therefore, we tested several Lewis acid catalysts, which are gener-
ally known to catalyze the cleavage of similar oxazolidine rings
(Table 1, entries 4–9).4a To our delight, some Lewis acids were
found to promote the transformation more efficiently, and excep-
tionally excellent yield was achieved when SnBr4 was used (entries
8 and 9), most likely because of its proper Lewis acidity and oxo-
philicity. As we expected, essentially the same result was achieved
for the seven-membered ring formation from the oxazolidine (S)-5
(Scheme 1, (iii), bottom). The reaction catalyzed by SnBr4 pro-
ceeded so cleanly that the target compound ((S)-6) was able to
be isolated from a crude mixture only by simple crystallization.
An X-ray crystallographic study on the cyclic enamino-ester (S)-
6 revealed its intriguing structural characteristics (Fig. 1a).14
Owing to the ring system of (S)-6, the phenyl group at the C(3)
was arranged at the axial position of the seven-membered ring.
As a result, the phenyl group efficiently covered the re-face of
the enamino moiety, which was expected to enhance the si-face
selective transformation of the enamino moiety.
We next performed the key step of the present synthetic route,
the diastereoselective reduction of the cyclic enamino-ester (S)-6
(Table 2). Unexpectedly, however, (S)-6 showed low reactivity un-
der usual reduction conditions, which have been applied for the
reduction of a wide range of enamines (entries 1–3).3,7 We then
examined several reductants and additives, and finally found that
the combination of NaBH3CN/HCl was effective for the conversion
of (S)-6 into the corresponding amino-ester with a cyclic structure
(7, entry 5). For efficient activation of the enamino part of (S)-6, the
basicity of which is considered to be lower than that of usual en-
amines because of the electron-withdrawing nature of the trifluo-
romethyl group, an excess amount of a strong Brønsted acid was
essential. As a result, special reductants tolerant to acidic condi-
tions should be employed. The absolute configuration of the major
isomer of the cyclic amino-ester 7 was unambiguously determined
to be (3S,5S) by an X-ray crystallographic analysis (Fig. 1b), which
is in good agreement with that we anticipated from the structure
of its precursor (S)-6 (Fig. 1a).14 Worth noting is the excellent dia-
stereoselectivity achieved here ((3S,5S)-7:(3S,5R)-7 = 95:5, entry
5), which is the highest value for the diastereoselective reduction
of enamines bearing a fluoroalkyl group, as far as we are aware
of. The diastereoselectivity was further improved when the reac-
tion was conducted at À78 °C, as might be expected ((3S,5S)-
7:(3S,5R)-7 = 97:3, entry 6). Comparing with the results of previous
studies,3 we can clearly deduce that conformational constraint ow-
ing to the cyclic structure of (S)-6 was a crucial factor for the effi-
cient stereocontrol of the present reduction.
Taking account of the easiness in preparation, chirality-induc-
tion ability, and easiness in removal, we chose (S)-2-amino-2-
phenylethanol ((S)-phenylglycinol, (S)-3) as an auxiliary unit.
According to the method established by Soloshonok and his co-
workers,8 the enamino-ester (S)-4 was prepared by the condensa-
tion of methyl 4,4,4-trifluoro-3-oxobutanoate (2) with (S)-3 in
acceptable yield (Scheme 1, (i), 60% yield). Owing to the nucleophi-
licity of the amino unit properly controlled by the coexistence of
acetic acid, the aminolysis of the ester group did not take place
at all. In addition, among the possible tautomers/stereoisomers
(enamine/imine tautomerism with E/Z isomerism), the (Z)-enami-
no-ester (S)-4 was exclusively generated, most likely owing to the
stabilization by intramolecular hydrogen-bonding interaction.
Only a problem was the gradual conversion of (S)-4 into the oxa-
zolidine (S)-5 via the nucleophilic attack of the hydroxy group to
the carbon at the b-position of the ester group, which reduced
the yield of (S)-4 to some extent.9 Although this side reaction is
unfavorable for the synthesis of (S)-4, the resultant oxazolidine
(S)-5 might be regarded as a useful synthetic equivalent of the ena-
mino-ester (S)-4, because the oxazolidine unit can be potentially
cleaved by the action of acids, etc.5a,10 and because (S)-5 has a
relatively low boiling point (150 °C/3 mmHg) suitable for the
isolation from a reaction mixture by distillation. Therefore, we
re-optimized reaction conditions for the formation of the oxazoli-
dine (S)-5, and found that the oxazolidine was selectively obtained
by conducting the condensation in the presence of three equiva-
lents of acetic acid (Scheme 1, (ii), 81%).
With two kinds of the precursors (S)-4 and (S)-5 in hand, we at-
tempted intramolecular ester formations, which apparently
seemed to proceed smoothly under general transesterification con-
ditions. In fact, Abarbri and his co-workers reported the synthesis
of similar cyclic enamino-esters by using a base catalyst, which
had a structure almost identical to that of (S)-4 except for their side
chain residue originated from the amino alcohol component.11
However, under the same conditions, the enamino-ester (S)-4
was quantitatively converted into the oxazolidine (S)-5 at the ini-
tial stage of the reaction (Table 1, entry 1). In general, perfluoroal-
kyl groups are known to stabilize neighboring acetals/aminals
because of their electron-withdrawing effect.12 Harsher conditions
gave rise to an unexpected rearrangement reaction to afford 9 (en-
try 2), which was most likely started by the abstraction of the ben-
zylic proton.13 When a Brønsted acid catalyst was used, the
starting material was again converted into the oxazolidine (S)-5,
and the seven-membered ring formation did not proceed effi-
ciently (entry 3).
In the context of diastereoisomer separation, additional
benefits were brought by the cyclic structure. Owing to the
fixation of the direction of dipoles in the cyclic structure, the two

Y. Ishida et al. / Tetrahedron Letters 50 (2009) 1889–1892
1891
Table 1
Synthesis of the cyclic enamino-ester (S)-6
F3C
N
F3C
HN
Ph
F3C
Ph
Conditions
O
OMe
HN
Ph
O
H O
O
O
OH
Me
(S)-4
(S)-6
9
Entry
Reagent (equiv)
Temp (°C)
Time (h)
Ratioa (%)
Isolated yield of (S)-6 (%)
4
5
6
9
1b
2c
3c
4d
5b
6b
7c
8c
9c
NaH (2)
NaH (2)
100
130
144
83
111
111
144
144
144
17
2
3
8
6
6
4
8
18
0
0
0
0
0
72
0
0
88
23
97
>95
<1
20
22
6
5
20
2
<1
>95
3
78
94
>99
0
57
0
0
0
0
0
0
0
—
—
—
—
36
—
37
73
75
TsOHÁH2O (0.1)
BF3ÁOEt2 (2)
TiCl4 (2)
Ti(OiPr)4 (2)
SnCl4 (2)
SnBr4 (2)
SnBr4 (0.3)
0
0
a
Determined by 19F NMR.
Toluene was used as a solvent.
o-Xylene was used as a solvent.
Dichloroethane was used as a solvent.
b
c
d
allowed us for the base-line separation of the diastereoisomers
by general column chromatography. As a more practical method,
the major isomer (3S,5S)-7 was isolated by single-batch crystalliza-
tion, taking advantage of its high crystallinity (Scheme 1, (iv)).
Finally, the diastereopure amino-ester (3S,5S)-7 thus obtained
was successfully converted into the target b-trifluoromethyl-b-
amino acid 1, via the hydrogenolysis of the N-benzyl group, fol-
lowed by acid-promoted transesterification/hydrolysis (Scheme 1,
(v) and (vi)). During the deprotection processes, essentially no
racemization took place, which was confirmed by the chiral HPLC
analysis of the N,O-protected derivative of 1, as established in a lit-
erature.4e The absolute configuration of the amino acid was unam-
biguously deduced to be S from that of the cyclic amino-ester
determined by an X-ray analysis ((3S,5S)-7). To our surprise, this
is the first unambiguous determination of the absolute configura-
tion of the amino acid 1, based on an X-ray crystallographic
analysis.14,15
a
Top View
Side View
Side View
F3C
O
O
HN
Ph
O
6
(S)-
b
Top View
F3C
HN
O
Ph
(3S,5S)-7
Figure 1. X-ray crystal structure of (a) (S)-6 and (b) (3S,5S)-7. Hydrogen atoms are
omitted for clarity.
Worth noting is the fact that chromatographic separation was
not required throughout the present synthetic route (Scheme 1),
which allowed us several-decagram scale preparation of 1. In fact,
we confirmed that the present synthesis can be conducted in a
0.2 mol scale with essentially no decrease in yield nor in enantio-
purity. The present synthesis would offer an alternative practical
diastereoisomers exhibited large difference in their polarity (Rf val-
ues on a silica gel TLC plate developed with CHCl3: 0.37 and 0.20
for (3S,5S)-7 (major) and (3S,5R)-7 (minor), respectively), which
Table 2
Asymmetric reduction of the cyclic enamino-ester (S)-6
F3C
F3C
HN
Ph
F3C
O
Conditions
O
O
HN
Ph
HN
Ph
O
O
O
(S)-6
(3S,5S)-7
(3S,5R)-7
Conv.a (%)
Entry
Reductant (equiv)
Additive (equiv)
Solv.
dra
Yieldb (%)
1c
2c
3c
4c
5c
6d
H2ÁPd/C (–)
none (–)
Znl2 (3)
AcOH (35)
HCl (1)
HCl (10)
HCl (10)
MeOH
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
n.r.
n.r.
n.r.
30
>99
97
—
—
—
90:10
95:5
97:3
—
—
—
—
73
74
NaBH4 (5)
NaBH3CN (6)
NaBH3CN (6)
NaBH3CN (1.2)
NaBH3CN (1.2)
e
e
e
a
Determined by 19F NMR.
Isolated yield of the major isomer ((3S,5S)-7).
Reaction was conducted at rt for 48 h.
b
c
d
e
Reaction was conducted at À78 °C to rt for 96 h.
Containing 33% (v/v) of dioxane.

1892
Y. Ishida et al. / Tetrahedron Letters 50 (2009) 1889–1892
15; (d) Sutherland, A.; Willis, C. L. Nat. Prod. Rep. 2000, 17, 621; (e) Yoder, N. C.;
F5C2
F5C2
F5C2
NaBH3CN (1.2 eq)
HCl (10 eq)
Kumar, K. Chem. Soc. Rev. 2002, 31, 335; (f) Qiu, X.-L.; Meng, W.-D.; Qing, F.-L.
Tetrahedron 2004, 60, 6711; (g) Jäckel, C.; Koksch, B. Eur. J. Org. Chem. 2005,
4483.
O
O
O
HN
Ph
HN
Ph
(3S,5S)-11
d.r. = 96:4
Isolated yield of (3S,5S)-11: 64%
HN
Ph
(3S,5R)-11
CH2Cl2/dioxane
(2:1, v/v)
rt, 48 h
O
O
O
2. (a) Seebach, D.; Matthews, J. L. Chem. Commun. 1997, 2015; (b) Cheng, R. P.;
Gellman, S. H.; DeGrado, W. F. Chem. Rev. 2001, 101, 3219.
(S)-10
3. (a) Fustero, S.; Salavert, E.; Pina, B.; Ramírez de Arellano, C.; Asensio, A.
Tetrahedron 2001, 57, 6475; (b) Fustero, S.; Pina, B.; Salavert, E.; Navarro, A.;
Ramírez de Arellano, M. C.; Fuentes, A. S. J. Org. Chem. 2002, 67, 4667; (c)
Fustero, S.; Sánchez-Roselló, M.; Sanz-Cervera, J. F.; Aceña, J. L.; del Pozo, C.;
Fernández, B.; Bartolomé, A.; Asensio, A. Org. Lett. 2006, 8, 4633.
4. (a) Soloshonok, V. A.; Kirilenko, A. G.; Kukhar, V. P.; Resnati, G. Tetrahedron Lett.
1993, 34, 3621; (b) Soloshonok, V. A.; Kirilenko, A. G.; Galushko, S. V.; Kukhar, S.
V. Tetrahedron Lett. 1994, 35, 5063; (c) Soloshonok, V. A.; Ono, T.; Soloshonok, I.
V. J. Org. Chem. 1997, 62, 7538; (d) Soloshonok, V. A.; Ohkura, H.; Yasumoto, M.
J. Fluorine Chem. 2006, 127, 924; (e) Soloshonok, V. A.; Ohkura, H.; Yasumoto, M.
J. Fluorine Chem. 2006, 127, 930.
5. (a) Lebouvier, N.; Laroche, C.; Huguenot, F.; Brigaud, T. Tetrahedron Lett. 2002,
43, 2827; (b) Funabiki, K. Nagamori; Matsui, M. J. Fluorine Chem. 2004, 125,
1347; (c) Fustero, S.; Jiménez, D.; Sanz-Cervera, J. F.; Sánchez-Roselló, M.;
Esteban, E.; Simón-Fuentes, A. Org. Lett. 2005, 7, 3433; (d) Santos, M. D.;
Crousse, B.; Bonnet-Delpon, D. Synlett 2008, 399.
6. (a) Galushko, S. V.; Shishkina, I. P.; Soloshonok, V. A. J. Chromatogr. 1992, 592,
345; (b) Soloshonok, V. A.; Kirilenko, A. G.; Fokina, N. A.; Shishkina, I. P.;
Galushko, S. V.; Kukhar, V. P.; Švedas, V. K.; Kozlova, E. V. Tetrahedron:
Asymmetry 1994, 5, 1119; (c) Soloshonok, V. A.; Kirilenko, A. G.; Fokina, N. A.;
Kukhar, V. P.; Galushko, S. V.; Švedas, V. K.; Resnati, G. Tetrahedron: Assymmetry
1994, 5, 1225; (d) Michaut, V.; Metz, F.; Paris, J.-M.; Plaquevent, J.-C. J. Fluorine
Chem. 2007, 128, 889.
7. (a) Cimarelli, C.; Palmieri, G. J. Org. Chem. 1996, 61, 5557; (b) Ikemoto, N.;
Tellers, D. M.; Dreher, S. D.; Liu, J.; Huang, A.; Rivera, N. R.; Njolito, E.; Hsiao, Y.;
McWilliams, J. C.; Williams, J. M.; Armstrong, J. D., III; Sun, Y.; Mathre, D. J.;
Grabowski, E. J. J.; Tillyer, R. D. J. Am. Chem. Soc. 2004, 126, 3048.
8. (a) Ohkura, H.; Berbasov, D. O.; Soloshonok, V. A. Tetrahedron 2003, 59, 1647;
(b) Berbasov, D. O.; Ojemaye, I. D.; Soloshonok, V. A. J. Fluorine Chem. 2004, 125,
603.
Scheme 2. Asymmetric reduction of an analogous cyclic enamino-ester having a
pentafluoroethyl group ((S)-10).
synthetic route to enantiopure 1, which had been limited to the
synthesis based on the asymmetric proton shift reaction4d,e or
the resolution of its racemate.6b–d
Considering the fact that 4-fluorinated 3-oxoalkanoates and
their equivalents are one of the most easily accessible classes of
fluorinated building blocks, the present method would be highly
general for the preparation of a wide range of b-fluoroalkyl-b-ami-
no acids. As a preliminary study to prove the generality, an analo-
gous cyclic enamino-ester bearing a pentafluoroethyl group in the
place of a trifluoromethyl group ((S)-10) was prepared and em-
ployed for the same hydride reduction (Scheme 2).16 As was ex-
pected, the cyclic enamino-ester (S)-10 was converted into the
corresponding cyclic amino-ester (3S,5S)-11 with excellent diaste-
reoselectivity (dr = 96:4) without any optimization of the reaction
conditions. The major isomer could be easily separated from the
minor isomer by simple column chromatography, taking advan-
tage of large difference in their polarity. Moreover, the absolute
configuration of the major isomer, deduced from 1H and 19F NMR
studies, was consistent with the case of (S)-6 ((3S,5S)-isomer),
which implies that the face selectivity of the hydride addition
was controlled by a common mechanism. In other words, the abso-
lute configuration of the major isomer might be rationally pre-
dicted in the present hydride reduction.
In summary, a new synthetic method to access enantiopure
b-perfluoroalkyl-b-amino acids was established, which could be
conducted without any expensive reagent, special apparatus/
technique, nor tedious chromatographic separation. Concerning
the key asymmetric hydride reduction, prominent reliability of
the present method was demonstrated in terms of stereoselectivi-
ty, predictability of the stereochemical preference, and easiness in
isomer separation. Such a practical and reliable synthetic method
would contribute to the further exploration of b-perfluoroalkyl-
b-amino acids, including their application to de-novo peptide
chemistry.
9. (a) Slusarczuk, G. M. J.; Joullié, M. M. J. Org. Chem. 1971, 36, 37; (b) Yamanaka,
H.; Tamura, K.; Funabiki, K.; Fukunishi, K.; Ishihara, T. J. Fluorine Chem. 1992, 57,
177.
10. Ishii, A.; Miyamoto, F.; Higashiyama, K.; Mikami, K. Tetrahedron Lett. 1998, 39,
1199.
11. Richard, S.; Prié, G.; Guignard, A.; Thibonnet, J.; Parrain, J.-L.; Duchêne, A.;
Abarbri, M. Helv. Chim. Acta. 2003, 86, 726.
12. Simmons, H. E.; Wiley, D. W. J. Am. Chem. Soc. 1960, 82, 2288.
13. A plausible mechanism for the formation of 9 is as follows: For examples of a
related rearrangement reaction, see: (a) Soloshonok, V. A.; Ohkura, H.;
Yasumoto, M. Mendeleev Commun. 2006, 16, 165; (b) Soloshonok, V. A.;
Ohkura, H.; Yasumoto, M. J. Fluorine Chem. 2006, 127, 708.
F3C
N
F3C
N−
F3C
F3C
H+
Base
O
O
O
H
H
N
N
O
9
Ph
O−
O−
O
O
Ph
H
Ph
Ph
Me
(S)-6
14. Crystallographic data for the determination of the absolute configuration of
1 has been limited to one report (Kukhar, V. P.; Soloshonok, V. A.; Švedas, V.
K.; Kotik, N. V.; Galaev, I. Y.; Kirilenko, A. G.; Kozlove, E. V. Bioorgan. Khim.
1993, 19, 474). However, the assignment was based on an X-ray crystal
structure of (–)-1 having neither chiral internal reference nor heavy atom
indispensable for the observation of anomalous X-ray scattering. In
comparison with the present result, the assignment made by Kukhar et al.
was confirmed to be correct.
15. As far as we know (S)-6 and (3S,5S)-7 have been deposited with the Cambridge
Crystallographic Data Center as Supplementary Publication Numbers CCDC
709483 and CCDC 709484, respectively. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif, by emailing data_request@
ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre,
12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
Supplementary data
Supplementary data (determination of the enantiomeric purity
of 3-amino-4,4,4-trifluorobutanoic acid (1)) associated with this
article can be found, in the online version, at doi:10.1016/
j.tetlet.2009.01.159.
References and notes
1. (a) For reviews, see: Fluorine in Bioorganic Chemistry; Welch, J. T.,
Eswarakrishnan, S., Eds.; John Wiley & Sons: New York, 1991; (b) Fluorine
Containing Amino Acids: Synthesis and Properties; Kukhar, V. P., Soloshonok, V. A.,
Eds.; John Wiley & Sons: New York, 1995; (c) Tolman, V. Amino Acids 1996, 11,
16. The cyclic enamino-ester (S)-10 was prepared from an easily available
fluorinated building block (ethyl 4,4,5,5,5-pentafluoroethylpent-1-ynoate).
See Ref. 11.