Stereoselective synthesis of (R)- and (S)-α-trifluoromethyl aspartic acid via titanium enolate addition to a sulfinimine of trifluoropyruvate

Article abstract of DOI:10.1016/j.tetasy.2004.01.013

The reaction of an enantiomerically pure sulfinimine of trifluoropyruvate with several metal enolates is described. The use of TiCl(O-iPr) ₃/LDA produced the corresponding sulfinamides with high stereocontrol. The latter could be smoothly transformed into each enantiomer of α-trifluoromethyl aspartic acid with high ee, which has been previously synthesized only in racemic form.

Full text of DOI:10.1016/j.tetasy.2004.01.013

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 889–893
Stereoselective synthesis of (R)- and (S)-a-trifluoromethyl
aspartic acid via titanium enolate addition to a sulfinimine of
trifluoropyruvate
Francesco Lazzaro,a Marcello Crucianelli,a,* Francesco De Angelis,a Massimo Frigerio,b
Luciana Malpezzi,b Alessandro Volonteriob and Matteo Zandac,*
aDipartimento di Chimica, Ingegneria Chimica e Materiali, Universitꢀa di LÕAquila, via Vetoio, I-67010 Coppito, Italy
bDipartimento di Chimica, Materiali ed Ingegneria Chimica ÔG. NattaÕ del Politecnico di Milano, via Mancinelli 7, I-20131 Milan, Italy
cCNR––Istituto di Chimica del Riconoscimento Molecolare, sezione ÔA. QuilicoÕ, via Mancinelli 7, I-20131 Milan, Italy
Received 15 December 2003; accepted 13 January 2004
Abstract—The reaction of an enantiomerically pure sulfinimine of trifluoropyruvate with several metal enolates is described. The use
of TiCl(O-iPr)3/LDA produced the corresponding sulfinamides with high stereocontrol. The latter could be smoothly transformed
into each enantiomer of a-trifluoromethyl aspartic acid with high ee, which has been previously synthesized only in racemic form.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
high ee by exploiting a highly diastereoselective Man-
nich-type addition of a titanium enolate to a chiral
sulfinimine of trifluoropyruvate.
a-Trifluoromethyl (Tfm) a-amino acids are extremely
interesting analogues of natural a-amino acids,1 owing
to the unique properties of the Tfm group, such as high
electronegativity, electron density, steric hindrance and
hydrophobic character.2 However, the relatively difficult
availability of most Tfm-amino acids in nonracemic
form, whose asymmetric synthesis often requires com-
plex experimental protocols and hard to handle starting
materials, obstructs a systematic investigation of the
biomedicinal and structural features of a-Tfm a-amino
acids and their peptidic derivatives. Nonracemic a-Tfm-
aspartic acid (Tfm-Asp) is of particular interest, because
Asp is a key component of the RGD sequence (Arg-Gly-
Asp) that mediates the binding of fibrinogen to its
platelet receptor and plays a key role in a variety of
human cerebral and cardiovascular diseases. Recently,
we have been involved in a project aimed at the synthesis
of RGD peptides incorporating Tfm-Asp.3 Although
racemic Tfm-Asp and its derivatives have been
reported,4 to our knowledge Tfm-Asp is hitherto
unknown in nonracemic form. Herein we report a
practical approach to Tfm-Asp and some derivatives in
2. Results and discussion
The enantiomerically pure sulfinimine5 (S)-2 (Scheme 1)
was prepared, according to the literature method,6 by
means of a Staudinger (aza-Wittig) reaction of ethyl
trifluoropyruvate with the iminophosphorane (S)-1. The
Mannich-type reaction of metal enolates of ethyl and
tert-butyl acetate 3a and b with (S)-2 was addressed next
(Table 1).7
The sodium enolates generated in THF by the action of
NaHMDS on 3a and b, afforded the target N-sulfinyl
Tfm-Asp esters 4a and b in low de and modest yields
(entries 1 and 3, respectively), whereas the use of diethyl
ether proved to be detrimental in terms of yield (entry
2). The use of KHMDS (potassium enolate, entry 4) and
LiHMDS (lithium enolate, entry 5) did not produce
beneficial effects. Slightly better results were achieved
with LDA as base (entry 6), which afforded 4a in 24%
de.8 Similar results were observed upon transmetallation
of the lithium enolate with TiCl4 (entry 7). A remarkable
improvement was achieved by performing the trans-
metallation of lithiated 3b with AlCl(Et)2, which gave
* Corresponding authors. Tel.: +39-0862-433780; fax: +39-0862-433-
753 (M.C.), tel.: +39-02-2399-3084; fax: +39-02-2399-3080 (M.Z.);
e-mail addresses: cruciane@univaq.it; matteo.zanda@polimi.it
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.01.013

890
F. Lazzaro et al. / Tetrahedron: Asymmetry 15 (2004) 889–893
O
CO2Et
CF3
N
CO2Et
O
O
R
S
O
S
CF3
O
CO2Et
CF3
Tol
O
CF3COCO2Et
THF, 40 °C
Tol
N
H
RO2C
3
H
PPh3
S
+
S
Tol
N
(S)-1
Tol
N
(S)-2
RO2C
base
additive
(2R,SS)-4
(2S,SS)-4
a R = Et
b R = t-Bu
Scheme 1. Addition of enolates of 3 to the sulfinimine (S)-2.
Table 1. Diastereoselectivity of enolate additions to (S)-2a
Entry Ester Base, additive
Solvent Yieldb Ratio
De
(%)
2S:2Rc
1
2
3
4
5
6
7
8
9
3a
3a
3b
3b
3b
3a
3b
3b
3b
NaN(SiMe3)2
NaN(SiMe3)2
NaN(SiMe3)2
KN(SiMe3)2
LiN(SiMe3)2
LDA
THF
Et2O
THF
THF
THF
THF
THF
48
23
52
16
37
42
44
71
78
55:45d
55:45d
62:38
55:45
72:28
62:38d
64:36
83:17
96:4
10
10
24
10
44
24
28
66
92
LDA, TiCl4
LDA, AlCl(Et)2 THF
THF
LDA,
TiCl(O-iPr)3
a The reactions were carried out with a ratio of enolate:imine ¼ 3.0:1.0
at )78 ꢁC (see experimental).
b Isolated yields of the two diastereomers.
c Determined by HPLC analysis.
d The stereochemistry of diastereomers 4a was not assigned.
(2S,SS)-4b in 66% de and 71% overall yield (entry 8).
The optimal result was finally obtained with the Ti(O-
iPr)3-enolate of 3b (entry 9), which produced the
sulfinamide (2S,SS)-4b in very good yield (78%) and
excellent diastereocontrol (92% de).
Figure 2. X-ray structure of the sulfinamide (RS,2R)-4b.
This result, which is in line with the results of Ellman for
unfluorinated N-tert-butylsulfinyl-ketimines7b both in
terms of degree and direction of the stereocontrol, can
be interpreted in terms of a Zimmerman–Traxler-type
transition state TS-1 (Fig. 1), favouring the approach of
the enolate from the re-face of (S)-2.9
racemization of the sulfinimine (S)-2 takes place during
the enolate addition, as already observed in the reaction
with alkyl, benzyl and allyl Grignard reagents.6 How-
ever, the ee of 4b could be raised to 97% by a single
crystallization from diisopropyl ether. This allowed us
to continue the synthesis of Tfm-Asp with nearly
enantiopure material.
Tol
S
N
O
M
The crystallized major sulfinamide (2S,SS)-4b (ee 97%)
was next submitted to cleavage of both the N-sulfinyl
auxiliary and the ester protecting group (Scheme 2).
Treatment with TFA in methanol afforded the free
amino ester (S)-5, along with the co-product p-Tol-
SO2Me. Saponification with KOH followed by purifi-
cation either with the ion-exchange resin IRA or
DOWEX provided in fair yields the target (S)-Tfm-Asp,
respectively, as the hydrochloride salt 6 or in its free
zwitterionic form 7. The same protocol was performed
on (2R,RS)-4b affording the (R)-enantiomers of 6 and 7.
O
EtO2C
OMe
M = Ti(O-i-Pr)3
CF3
TS-1
Figure 1. Proposed transition state.
The optimized procedure (Table 1, entry 9) was per-
formed also on the enantiomeric sulfinimine (R)-2,
affording (RS,2R)-4b as the major product. The stereo-
chemistry of the latter compound, and therefore of all
the compounds derived from 4b, was unambiguously
determined by X-ray diffraction of suitable single crys-
tals (Fig. 2).10
3. Conclusion
Chiral HPLC analysis showed that the major diastereo-
mers 4b were obtained in 80–84% ee. Apparently, partial
In conclusion, we have developed an efficient and stereo-
selective synthesis of both enantiomers of a-Tfm-

F. Lazzaro et al. / Tetrahedron: Asymmetry 15 (2004) 889–893
891
0.795 mmol) was added dropwise via a syringe while
stirring. The mixture was allowed to warm to 0 ꢁC and,
after 5 min, cooled to )78 ꢁC. Then, 107 lL
(0.795 mmol) of t-butyl acetate 3b was added dropwise
and the resulting solution stirred for 30 min. Next,
ClTi(Oi-Pr)3 (88 lL, 0.795 mmol) was added dropwise to
form the yellow-coloured Ti-enolate, and the solution
stirred for 30 min. A solution of sulfinimine (S)-2
(0.265 mmol), prepared in situ as previously described,6
dissolved in 0.8 mL of THF, was added dropwise and
the mixture stirred for 30 min. Upon reaction comple-
tion, 1 mL of NH4Cl (satd) was added at )78 ꢁC and
allowed to warm to rt. The mixture was then diluted
with ethyl acetate, the aqueous layer separated and
extracted with ethyl acetate. The collected organic
fractions were washed with brine, dried and concen-
trated in vacuo. Purification of the crude by FC (n-hex/
EtOAc 80:20) afforded 3.5 mg of the minor diastereomer
(2R,SS)-4b (Rf >) and 84 mg of the major (2S,SS)-4b
(Rf <) with a 78% overall yield. Sulfinamides 4b were
found to be rather unstable in CHCl3 solution at rt.
After one week, almost complete cleavage of the
N-sulfinyl group was observed.
CO2H
1. KOH,
CO2Et
CF3
CO2Et
CF3
N
O
TFA, MeOH
(83%)
MeOH/H2O
+H3N
CF3
S
H2N
Tol
Cl-
2. IRA
(72%)
H
HO2C
HO2C
t-Bu-O2C
(S)-6
(S)-5
(2S,SS)-4b
CO2H
CF3
1. KOH,
MeOH/H2O
+H3N
-O2C
(S)-7
2. DOWEX
(54%)
Scheme 2. Elaboration of the major sulfinamide 4b into a-Tfm-
aspartic acid (S)-7 and its hydrochloride (S)-6.
aspartic acid in high ee exploiting a stereocontrolled
Mannich-type reaction of tert-butyl acetate titanium
enolate with a chiral sulfinimine of trifluoropyruvate.
4. Experimental
4.1. General
Chemical shifts (d) are reported in parts per million
(ppm) of the applied field. Coupling constants (J) are
reported in hertz. Me4Si was used as the internal stan-
(2R,SS)-4b (Rf ¼ 0:68, n-hex/EtOAc 70:30): Oil.
20
D
½aꢁ ¼ þ75:6 (c ¼ 0:39, CHCl3). 1H NMR (CDCl3):
7.60 (d, J ¼ 8 Hz, 2H), 7.29 (d, J ¼ 8 Hz, 2H), 5.58 (s,
1H), 4.45–4.25 (m, 2H), 3.44 (s, 2H), 2.40 (s, 3H), 1.49
(s, 9H), 1.29 (t, J ¼ 7:2 Hz, 3H). 13C NMR (CDCl3):
166.6, 166.0, 142.1, 141.8, 129.7, 125.5, 123.7 (q,
J ¼ 286:7 Hz), 82.8, 64.7 (q, J ¼ 28:2 Hz), 63.8, 37.0,
28.0, 21.4, 13.8. 19F NMR (CDCl3): )76.83 (s). HRMS
calcd for C18H24F3NO5S (MHþ) 424.1405, found
424.1409. HPLC analysis: tR ¼ 23:04 min. Chiral HPLC
analysis: tR ¼ 7:62 min, ee 91%.
1
dard (dH and dC ¼ 0:00) for H and 13C nuclei, while
C6F6 was used as the external standard (dF ¼ ꢀ162:90)
for 19F nuclei. Peak multiplicities are abbreviated: sin-
glet, s; doublet, d; triplet, t; quartet, q; multiplet, m; etc.
1H NMR spectra were recorded at 200 MHz, 13C NMR
at 50.3 MHz, 19F NMR at 235.2 MHz. Anhydrous THF
was obtained by distillation from sodium. In all other
cases commercially available reagent-grade solvents
were employed without purification. Reactions per-
formed in dry solvents were carried out under a nitrogen
atmosphere. Melting points are uncorrected and were
obtained on a capillary apparatus. HRMS analyses have
been performed by electron spray ionization (ESI) (po-
sitive ion mode). Analytical thin-layer chromatography
(TLC) was routinely used to monitor reactions. Plates
precoated with E. Merck silica gel 60 F254 of 0.25 mm
thickness were used. Merck silica gel 60 (230–400 ASTM
mesh) was employed for flash chromatography (FC).
Diastereoselectivities were determined by HPLC analy-
ses of the corresponding addition products 4 using a
Merck LiChroCARTꢂ 125-4 LiChrospherꢂ 100 RP-18
(5 lm) column, H2O/CH3CN 50:50, 0.8 mL/min. Chiral
HPLC analyses were carried out using a Chiralcel OD
column, n-hex/iso-propanol 95:5, 0.8 mL/min. The imi-
nophosphorane (S)-1 was prepared according to the
literature.6
20
Enantiomeric (2S,RS)-4b showed ½aꢁ ¼ ꢀ69:45 (c ¼
D
0:44, CHCl3). Chiral HPLC analysis: tR ¼ 6:78 min, ee
84%.
(2S,SS)-4b (Rf ¼ 0:62, n-hex/EtOAc 70/30): Mp (i-
20
Pr2O) ¼ 115 ꢁC. ½aꢁ ¼ þ4:3 (c ¼ 0:7, CHCl3). 1H NMR
(CDCl3): 7.65 (d, JD¼ 8 Hz, 2H), 7.31 (d, J ¼ 8 Hz, 2H),
5.44 (s, 1H), 4.35 (q, J ¼ 7 Hz, 2H), 3.45–3.41 (m, 2H),
2.41 (s, 3H), 1.44 (s, 9H), 1.31 (t, J ¼ 7 Hz, 3H). 13C
NMR (CDCl3): 167.2, 166.0, 142.4, 141.8, 129.8, 125.9,
123.2 (q, J ¼ 288:2 Hz), 82.6, 65.2 (q, J ¼ 28:7 Hz), 63.6,
34.8, 27.9, 21.4, 13.8. 19F NMR (CDCl3): )77.12 (s).
HPLC analysis: tR ¼ 16:82 min. Chiral HPLC analysis:
tR ¼ 8:15 min, ee 80%. Anal. Calcd for C18H24F3NO5S:
C, 51.06; H, 5.71; N, 3.31. Found: C, 50.99; H, 5.72; N,
3.73.
20
Enantiomeric (2R,RS)-4b showed ½aꢁ ¼ ꢀ5:3 (c ¼ 0:43,
D
CHCl3). Chiral HPLC analysis: tR ¼ 6:52 min, ee 97%.
4.2. Synthesis of 4-tert-butyl 1-ethyl N-[(4-methylphen-
yl)sulfinyl]-2-(trifluoromethyl)aspartates (2S,SS)- and
(2R,SS)-4
4.3. Synthesis of a-trifluoromethyl aspartic acid
a-carboxy ethyl ester (S)-5
The procedure with ClTi(O-i-Pr)3 is described as an
example.
(0.795 mmol) in 2 mL of dry THF was cooled to )78 ꢁC.
A 2.5 M n-hexane solution of n-butyllithium (320 lL,
A
solution of 113 lL of (i-Pr)2NH
To a stirred and cooled (0 ꢁC) solution containing
(2S,SS)-4b (200 mg, 0.473 mmol, 97% ee) dissolved in
8 mL of methanol, trifluoroacetic acid (73 lL,

892
F. Lazzaro et al. / Tetrahedron: Asymmetry 15 (2004) 889–893
0.945 mmol) was added dropwise. The mixture was
allowed to warm to 0 ꢁC and stirred for 2 h. After
evaporation of the solvent, the crude was diluted
with water and diethyl ether and, after separation, the
organic layer extracted with a (15%) aqueous solution of
HCl. After evaporation of the collected aqueous layers,
the residue was loaded onto a Dowex 50 W-X8 column,
affording 90 mg of (S)-5 (83%).
4.6. X-ray diffraction of (2R,RS)-4b
A suitable crystal (block, colourless, 0.6 · 0.5 · 0.2 mm
in dimension) was obtained from i-Pr2O. Intensity data
were collected on a Siemens P4 diffractometer with
graphite monochromated Cu-Ka radiation (k ¼
1:54179 Aꢁ), using h=2h scan technique. Unit cell para-
meters were determined using 60 reflections in the range
10 6 2h 6 54ꢁ; a total of 2688 reflections were collected
up to 136ꢁ in 2h and index range: ꢀ1 6 h P 23,
ꢀ10 6 k P 1, ꢀ13 6 l P 1. No crystal decay was
observed. Crystal data: C18H24O5NF3S, Mr ¼ 423:4,
20
(S)-5: Mp ¼ 155 ꢁC (dec). ½aꢁ ¼ þ22:4 (c ¼ 0:52, H2O).
1H NMR (D2O): 4.16 (q, JD¼ 7:1 Hz, 2H), 2.78 (ABq,
J ¼ 16:7 Hz and Dm ¼ 96 Hz, 2H), 1.14 (t, J ¼ 7:1 Hz,
3H). 13C NMR (D2O): 178.0, 172.8, 126.6 (q,
J ¼ 284:2 Hz), 66.7, 65.7 (q, J ¼ 27:2 Hz), 41.8, 15.8. 19F
NMR (D2O): )75.02 (s). HRMS calcd for C7H10F3NO4
(MHþ) 230.0640, found 230.0635.
orthorhombic, space group P212121, a ¼ 19:319ð2Þ,
3
ꢁ
ꢁ
b ¼ 9:965ð1Þ, c ¼ 10:919ð1Þ A, V ¼ 2102:1ð1Þ A , Z ¼ 4,
Dc ¼ 1:338 g cmꢀ3, l ¼ 1:863 mmꢀ1, F ð000Þ ¼ 888; k ¼
ꢁ
1:54179 A, room temperature. The structure was solved
by direct methods using an SIR9711 program, which
revealed the position of all nonH atoms; H atoms were
located at calculated positions and refined in a riding
model. The refinement was carried out on F2 by full-
matrix least-squares procedure with SHELXL9712 for 257
parameters, with anisotropic temperature factors for
nonH atoms. The final stage converged to R ¼ 0:053
(Rw ¼ 0:124) for 2023 observed reflections, with
I P 2rðIÞ, and R ¼ 0:068 (Rw ¼ 0:137) for all unique
reflections after merging. The mean shift/error was 0.003
and the goodness of fit, S, was 1.097. The final difference
map showed a maximum and minimum residual peaks
20
Enantiomeric (R)-5 showed ½aꢁ ¼ ꢀ21:1 (c ¼ 0:53,
D
H2O).
4.4. Synthesis of a-trifluoromethyl aspartic acid hydro-
chloride (S)-6
To a solution containing (S)-5 (60 mg, 0.24 mmol) dis-
solved in 5 mL of a 70:30 methanol/water mixture, 3 mL
of a 0.5 M aqueous solution of KOH was added drop-
wise and the resulting mixture stirred overnight at rt.
The reaction solution was acidified to pH ¼ 1 by slowly
adding an aqueous solution of HCl (1 M), and the sol-
vent then evaporated. The residue was dissolved in
water, and loaded onto an IRA-410 column. Elution with
1 M HCl afforded 41mg (72%) of hydrochloride (S)-6.
of 0.26 and )0.24 e Aꢀ3, respectively. The absolute
ꢁ
configuration was assigned by the Flack13 parameter
x ¼ ꢀ0:05ð4Þ for the (R) absolute configuration and
x ¼ 0:96ð4Þ for the inverse one, and by an R-factor test
R ¼ 0:053 and R ¼ 0:059 for the (R) and (S) configura-
tions, respectively.
20
(S)-6: Mp ¼ 185 ꢁC (dec). ½aꢁ ¼ þ23:5 (c ¼ 0:25, H2O).
D
1H NMR (D2O): 3.10 (ABq, J ¼ 18 Hz and Dm ¼ 68 Hz,
2H). 13C NMR (D2O): 174.5, 168.8, 125.5 (q,
J ¼ 284:2 Hz), 65.6 (q, J ¼ 28:4 Hz), 37.0. 19F NMR
(D2O): )73.76 (s). HRMS calcd for C7H10F3NO4
(MHþ) 230.0640, found 230.0638.
Acknowledgements
We thank MIUR (Cofin 2002, Project ÔPeptidi Sintetici
BioattiviÕ), Politecnico di Milano and CNR for
economic support.
20
Enantiomeric (R)-6 showed ½aꢁ ¼ ꢀ24:3 (c ¼ 0:25,
D
H2O).
References and notes
4.5. Synthesis of a-trifluoromethyl aspartic acid (S)-7
1. (a) Fluorine-containing Amino Acids: Synthesis and Prop-
erties; Kukhar, V. P., Soloshonok, V. A., Eds.; Wiley:
Chichester, 1995; (b) Sutherland, A.; Willis, C. L. Nat.
Prod. Rep. 2000, 621–631.
2. Banks, R. E.; Tatlow, J. C.; Smart, B. E. Organofluorine
Chemistry: Principles and Commercial Applications; Ple-
num Press: New York, 1994.
3. (a) Dal Pozzo, A.; Muzi, L.; Moroni, M.; Rondanin, R.;
de Castiglione, R.; Bravo, P.; Zanda, M. Tetrahedron
1998, 54, 6019–6028; (b) Dal Pozzo, A.; Dikovskaya, K.;
Moroni, M.; Fagnoni, M.; Vanini, L.; Bergonzi, R.; de
Castiglione, R.; Bravo, P.; Zanda, M. J. Chem. Res. 1999,
468–469.
4. (a) Soloshonok, V. A.; Gerus, I. I.; YagupolÕskii, Yu. L.;
KukharÕ, V. P. J. Org. Chem. USSR (Engl. Transl.) 1987,
23, 2034–2038; (b) Kobzev, S. P.; Soloshonok, V. A.;
Galushko, S. V.; YagupolÕskii, Yu. L.; KukharÕ, V. P.
J. Gen. Chem. USSR (Engl. Transl.) 1989, 59, 801–803;
Working under the same experimental conditions as
described above and after the end of reaction, the crude
solution was acidified to pH ¼ 1 by adding an aqueous
solution of HCl (1 M) and then evaporated. The residue
was dissolved in water and loaded onto a Dowex 50 W-
X8 column, affording 26 mg of free aminoacid (S)-7
(54% yield) upon elution with a 7.5% aqueous ammonia
solution.
20
(S)-7: Oil. ½aꢁ ¼ þ23:5 (c ¼ 0:17, H2O). 1H NMR
D
(D2O): 2.70 (ABq, J ¼ 16:7 Hz and Dm ¼ 65 Hz, 2H).
13C NMR (D2O): 178.5, 172.9, 126.8 (q, J ¼ 283:7 Hz),
20
66.0 (q, J ¼ 26:6 Hz), 40.1. 19F NMR (D2O): )74.00 (s).
Enantiomeric (R)-7 showed ½aꢁ ¼ ꢀ18:4 (c ¼ 0:19,
D
H2O). HRMS calcd for C5H6F3NO4 (MHþ) 202.0327,
found: 202.0319.

F. Lazzaro et al. / Tetrahedron: Asymmetry 15 (2004) 889–893
893
(c) Osipov, S. N.; Kolomiets, A. F.; Fokin, A. Bull. Acad.
Sci. USSR Div. Chem. Sci. (Engl. Transl.) 1989, 38, 673;
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(f) Laurent, P.; Henning, L.; Burger, K.; Hiller, W.;
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9. (a) It is known that (S)-2 exists in its geometrically
homogeneous E-form (see Ref. 6). (b) Attempts to prepare
N-tert-butylsulfinylimines of trifluoropyruvate were
unsuccessful (see Ref. 6).
10. Full data (excluding structure factors) of the crystal
structure have been deposited with Cambridge Crystallo-
graphic Data Centre as supplementary publication no.
226689. Copies of the data can be obtained, free of charge,
on application to CCDC, 12 Union Road, Cambridge,
CB2 1EZ, UK [fax: +44(0)-1223-336033 or e-mail:
deposit@ccdc.cam.ac.uk].
5. For a review of sulfinimine chemistry see: Davis, F. A.;
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ꢂ
Fustero, S.; Garcıa Soler, J.; Meille, S. V.; Panzeri, W.;
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M.; Zanda, M. Tetrahedron Lett. 1998, 39, 7771–7774.
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N-sulfinyl-ketimines, see: (a) Davis, F. A.; Reddy, R. T.;
Reddy, R. E. J. Org. Chem. 1992, 57, 6387–6389; (b) Tang,
T. P.; Ellman, J. A. J. Org. Chem. 1999, 64, 12–13.
11. Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G.
L.; Giacovazzo, C.; Guagliardi, A. A.; Moliteni, G. G.;
Polidori, G. P.; Spagna, R. J. Appl. Cryst. 1999, 32, 115–
119.
12. Sheldrick, G. M. SHELXL97, Release 97-2, Program for
the Refinement of Crystal Structures, 1997, University of
€
Gottingen, Germany.
13. Flack, H. D. Acta Cryst. 1983, A39, 876–881.
8. The stereochemistry of diastereomers 4a was not assigned.