Synthesis of enantiomerically pure ethylenediamines from chiral sulfinimines: A new twist to the Strecker reaction

Article abstract of DOI:10.1016/S0040-4020(01)00886-9

Addition of various cyanide nucleophiles on chiral t-butylsulfinimine and p-tolylsulfinimine derivatives are described and demonstrated that aliphatic t-butylsulfinimines are excellent substrates for a new variant of the Strecker reaction where cyanide ions are delivered through ethylisopropoxyaluminum cyanide or trimethylsilylcyanide combined with a Lewis acid catalyst. The reaction proceeds with high yield and high diastereoselectivity, which can be further improved by additional crystallizations.

Full text of DOI:10.1016/S0040-4020(01)00886-9

TETRAHEDRON
Pergamon
Tetrahedron 57 02001) 8861±8866
Synthesis of enantiomerically pure ethylenediamines
from chiral sul®nimines: a new twist to the Strecker reaction
p
Â
Stephane Mabic and Alex A. Cordi
Institut de Recherches Servier, 11 rue des Moulineaux, 92150 Suresnes, France
Received 20 February 2001; revised 30 August 2001; accepted 4 September 2001
AbstractÐAddition of various cyanide nucleophiles on chiral t-butylsul®nimine and p-tolylsul®nimine derivatives are described and
demonstrated that aliphatic t-butylsul®nimines are excellent substrates for a new variant of the Strecker reaction where cyanide ions are
delivered through ethylisopropoxyaluminum cyanide or trimethylsilylcyanide combined with a Lewis acid catalyst. The reaction proceeds
with high yield and high diastereoselectivity, which can be further improved by additional crystallizations. q 2001 Elsevier Science Ltd. All
rights reserved.
1. Introduction
the addition of cyanide nucleophiles on chiral imines
obtained by condensation of the aldehyde with a chiral
amine. In contrast to previous work,4 preliminary
experiments usingenantiopure a-methylbenzylamine or
The Strecker reaction1 has been used for many years to
synthesize aminonitriles and the correspondingaminoacids.
In recent years, various enantioselective or diastereoselec-
tive versions of this reaction have been described in the
literature,2a±k allowingthe isolation of enantiopure
compounds. In our search for new imidazoline derivatives
of general formula 1 as antidepressants,3 stereoselective
synthesis 0Fig. 1) of substituted ethylene diamine inter-
mediates of type 2 was of interest. Ethylene diamines
were usually obtained via the reduction of the corresponding
aminonitriles 3, conveniently prepared by the Strecker
reaction on the aldehydes 4.
Figure 2.
Our strategy for chirality induction on the a carbon relied on
Figure 1.
Keywords: amino nitriles; asymmetric induction; diamines; Strecker reac-
tion.
Correspondingauthor. Tel.: 133-1-5572-2235; fax: 133-1-5572-2430;
e-mail: alex.cordi@fr.netgrs.com
Scheme 1. Reagents and conditions: 0a) Py´TsOH, MgSO4, CH2Cl2, 258C,
89%; 0b) Et2AlCN, i-PrOH, THF, 95% or TMSCN, CH2Cl2, 258C, Lewis
acid catalyst 0see Table 2).
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020001)00886-9

8862
S.Mabic, A.A.Cordi / Tetrahedron 57 '2001) 8861±8866
Table 1.
Solvent
magnesium sulfate and a catalytic amount of pyridinium
tosylate 0Scheme 1).14 This sul®nimine is remarkably stable
and can be easily puri®ed by silica gel chromatography. As
could be expected, the 0E) isomer only was formed, as indi-
cated by the J15N±1H couplingconstant value 03±4 Hz)
measured in the NMR spectra.16,17 In accordance with this
spectroscopic result, the relative energy values of the two
isomers calculated at the semiempirical level 0PM3) indi-
cated a higher stability for the 0E) isomer. Two cyanide
delivery agents were evaluated to prepare the cyanosul-
®namide 8 with contrastingresults: the ethylisopropoxy-
aluminumcyanide formed from diethylaluminumcyanide
and i-propylalcohol,18 and the trimethylsilylcyanide in
combination with a Lewis acid catalyst.
T 08C)
Yield 0%)a
Ratio 8a/8bb
THF
THF
CH2Cl2
n-Heptane
Toluene
25
0
25
25
25
95
86
92
93
88
97/3
97/3
93/7
96/4
98/2
a
Isolated yields.
Determined by H NMR and LC.
b
1
1-0naphthyl)ethylamine led to low diastereoselectivities
0data not shown). We decided then to investigate the use
of sul®nimines in a similar reaction. Chiral sul®namides
such as the t-butyl and the p-tolyl derivatives, 5 and 6,
respectively 0Fig. 2), have been described as very potent
chiral auxiliaries. The addition of hydrides5±7 or alkyl
residues8,9 on the a carbon of sul®nimes generated from
both 5 and 6 has been well documented, and the addition
of diethylaluminumcyanide on p-tolylsul®nimine deriva-
tives has been reported as well.6,10±12 On the other hand,
reports on the addition of various cyanide nucleophiles on
chiral t-butylsul®nimine derivatives have been scarce. We
report here the results of our investigations of this reaction.
In the former conditions, the reaction took place in high
yield and high diastereoselectivity at room temperature in
solvents of diverse polarity and chelatingability, such as
THF, CH2Cl2, n-heptane and toluene 0Table 1). A decrease
of the temperature affected slightly the yield but increased
signi®cantly the reaction time 04±30 h) without improving
the diastereoselectivity ratio 0entry 2). The diastereo-
isomeric purity of the product 8a could be further increased
to 99/1 by crystallization from n-hexanes. The absolute
con®guration of the newly created chiral center was deter-
mined as 0R), by single crystal X-ray diffraction.
2. Chemistry
In the second procedure, usingTMSCN, the reaction did not
proceed in the absence of a Lewis acid catalyst or below
108C. The reaction was then performed usinga large variety
of Lewis acid catalysts, leadingto the results summarized in
Synthesis of t-butylsul®nimine 7 from aldehyde 413 and
t-butylsul®namide 514,15 took place in high yields, at room
temperature in dichloromethane, in the presence of dry
Table 2.
Entry
R±CN
Catalyst
Reaction time 0h)
Yield 0%)a
Ratio 8a/8bb
c
1
2
3
4
5
6
7
8
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TBS
ZnI2
ZnI2
24
48
48
48
48
24
48
48
48
48
48
24
48
20
48
18
24
48
48
6
74
80
86
89
61
20
3
24/76
30/70
27/73
83/17
52/48
57/43
85/15
32/68
82/18
72/28
35/65
81/19
81/19
58/42
20/80
97/3
98/2
98/2
87/13
52/48
92/8
16/84
±
±
ZnBr2
c
Ti0O-i-Pr)4
TiCl4
AlCl3
CeCl3
BF3´OEt2
MgCl2
MgBr2´OEt2
SnCl4
ZrBr4
Zr0O-t-Bu)4
ZrI4
Yb0OTf)3
d
e
72
57
66
74
89
74
94
38
98
90
48
13
91
27
68
,5
,5
,5
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
c
Sc0OTf)3
Y0OTf)3
La0OTf)3
Sm0OTf)3
Sm0O-i-Pr)3
SmCl3
ZnI2
Sc0OTf)3
Yb0OTf)3
Ti0O-i-Pr)4
c
48
24
48
48
48
TBS
TBS
TBS
±
Conditions: The reaction was run with ca. 0.2 equiv. of catalyst at 258C in CH2Cl2.
Yields were measured by LC after ®ltration on silica gel to eliminate the catalyst and were in complete accordance with isolated yields. Unless otherwise
a
noted, remainingresidual startingmaterial 7 and products 8a/8b accounted for .90% of the startingsul®nimine 7. The major side-product was identi®ed as
the cyanohydrine.
Diastereoisomeric ratio was measured by LC.
Performed twice to check the reproducibility.
Degradation of the sul®nimine.
b
c
d
e
The formation of a hydrated form of the catalyst might have precluded the reaction to work.

S.Mabic, A.A.Cordi / Tetrahedron 57 '2001) 8861±8866
8863
Scheme 2. Reagents and conditions: 0a) LiHMDS, THF, 2788C; 0b) NH4Cl, 83%; 0c) Py´TsOH, MgSO4, CH2Cl2, 258C; 0d) Ti0OEt)4, CH2Cl2, D; 0e) Et2AlCN,
i-PrOH, THF, 94% or TMSCN, CH2Cl2, 258C, Lewis acid catalyst 0see Table 3).
Table 3.
the diethylaluminumcyanide procedure, the catalysts cited
above led to the second diastereoisomer 8b. The effect of the
salt form was best exempli®ed with Sm0III) salts where
tri¯ate and chloride 0entries 19 and 21) gave low chemical
yields and high diastereoselectivity, while the i-propoxide
salt 0entry 20) afforded high yield and low diastereo-
selectivity. Increasingthe size of the cyanide agent using
the tert-butyldimethylsilylcyanide instead of the trimethyl-
silylcyanide led to an increased diastereoisomeric ratio in
the case of ZnI2 0entry 22), but appeared detrimental with
other catalysts 0entries 23±25).
Entry
Catalyst
ZnI2
Sc0OTf)3
Ti0O-i-Pr)4
Sm0O-i-Pr)3
Yb0OTf)3
Reaction time 0h) Yield 0%)a Ratio 12a/12bb
1
2
3
4
5
24
36
20
4
,10
75
77
70
±
17/83
29/71
14/86
32/68
40
71
Conditions: the reaction was run with 2 equiv. of TMSCN, and ca.
0.2 equiv. of catalyst at 258C in CH2Cl2.
a
Yields were measured by LC on the reaction mixture after silica gel
®ltration to eliminate the catalyst.
Diastereoisomeric ratio was measured by LC.
b
To access the enantiomeric form of the newly created chiral
center, one can run the same reactions startingfrom the
enantiomeric form of the sul®namide 5. In an attempt to
investigate further these reactions, we have chosen the
0SS) p-tolylsul®namide 6, easily obtained by substitution
of the menthyl sul®nate ester 9 with lithium bis0trimethyl-
silyl)amide and hydrolysis with NH4Cl, accordingto a
literature procedure 0Scheme 2).19 The condensation of 6
with our prototypical aldehyde 4 followingthe experimental
procedure used with the t-butyl analog 5, afforded the sul-
®nimine 11 0Scheme 2) with much lower yield 022%). Use
of Ti0OEt)4 resulted in a poor 27% yield also. Improved
yields 051%) were obtained when 6 was not isolated, and
the silylated intermediate anion 10 condensed directly with
the aldehyde 4.19,20 Addition of ethyl-i-propoxyaluminum-
cyanide to the sul®nimine 11 led to the cyanosul®namide in
high diastereoselectivity 0ratio 12a/12b: 3/97) and high
yield 095%). Crystallizations afforded the pure diastereo-
isomer 12b. The TMSCN procedure was then investigated,
and ®ve Lewis acids catalysts were selected 0Table 3), based
on the results obtained with the tert-butylsul®nimine 7.
Yields were lower 0,77%) and the diastereoselectivity
never exceeded 14/86. Use of ZnI2 never allowed an
ef®cient catalysis of the reaction and resulted instead in
degradation of the sul®nimine 11.
Table 2. The nature of the metal, as well as the salt form of
the metal, have a profound in¯uence on the yield and the
diastereoselectivity of the reaction. Tri¯ate salts Sc0OTf)3,
Y0OTf)3, and La0OTf)3 0entries 16±18) provided particu-
larly ef®cient diastereoselectivity 0.97/3), with the highest
yield observed with Sc0OTf)3. The most strikingobser-
vation was the inversion of the diastereoselectivity obtained
with ZnI2, BF3, SnCl4 and Yb0OTf)3 0entries 1, 8, 11 and
15). Indeed, while 8a was the major product obtained with
Scheme 3. Reagents and conditions: 0a) 0i) BH3 DMS, THF, D; 0ii) HCl,
MeOH, D, 67%; 0b) 0i) HC0vNH)NH2´AcOH, EtOH, 258C; 0ii) HO2C±
CHvCH±CO2H, i-PrOH/Ether, 67%.
To complete the evaluation of this synthetic route, two more
steps were carried out: a reduction/deprotection sequence

8864
S.Mabic, A.A.Cordi / Tetrahedron 57 '2001) 8861±8866
Figure 3.
and the cyclization of the resultingethylene diamine 2 to the
imidazoline 1 0Scheme 3). The ®rst step proceeded
smoothly by reactingthe cyanosul®namide 8a with borane
dimethylsul®de complex in THF under re¯ux.21,22
Hydrolysis of the boride intermediate with a methanolic
solution of hydrogen chloride led to the cleavage of the
nitrogen±sulfur bond and afforded the ethylene diamine as
its bis-hydrochloride salt. No racemization occurred during
these steps. The freshly prepared free diamine was
combined with formamidine acetate in ethanol, and the
®nal imidazoline 1a was isolated as the hemi-fumarate by
crystallization from isopropanol/ether. A similar sequence
afforded the pure enantiomer 1b 0ee.99/1) from the cyano-
sul®namide 12b.
Figure 5.
still remnant on the structure of the crystallized cyano-
sul®namide product 8a.
In the case of the trimethylsilylcyanide addition catalysed
by Lewis acids, no straightforward explanation is at hand
and different mechanisms must compete in order to account
for the contrastingresults obtained. Amongseveral possi-
bilities, two major hypotheses seem relevant. In the ®rst
hypothesis, the metal is complexed by the imine nitrogen
atom, activatingthe double bond and facilitatingthe
delivery of the cyanide on the face away from the t-butyl
group, as in the case of the Zn0II) catalysis 0Fig. 5A). The
diastereoisomeric excess and the result observed with the
tert-butyldimethylsilylcyanide relative to the trimethylsilyl-
cyanide 0Table 2, entries 1 and 22) are compatible with a
sterically induced diastereoselectivity. The transition state is
indeed ¯exible, because of the possible rotation around the
N±S bond. The second hypothesis relies on the chelation of
the metal by both the nitrogen atom and the oxygen atom,
resultingin a four membered transition state 0Fi.g 5B).
Addition of the nucleophile occurs then on the less hindered
face of the sul®nimine, away from the tert-butyl group.
The rigid geometry of the transition state is compatible
with the very high diastereoselectivity observed with some
of the metals. The p-tolyl group of the sul®nimine 11 is not
as bulky as the tert-butyl group, which might explain the
poorer diastereoselectivity observed for 12 relative to 8.
3. Discussion
Diastereoselective addition of nucleophiles to tert-butyl
sul®nimines has been exempli®ed in the literature, but the
addition of the cyanide nucleophiles to sul®nimines issued
from aliphatic aldehydes has seldom been reported. In these
studies, we have shown that deliveringcyanide with ethyl-
isopropoxyaluminumcyanide to chiral sul®nimes 7 and 11
afforded the cyanosul®namide derivatives 8 and 12 with
high yield and high diastereoselectivity. The high diastereo-
selectivity is presumably linked to the existence of a very
rigid transition state where the aluminum, the oxygen, the
sulfur, the nitrogen and the two carbon atoms form a six
membered ring0Fig. 3). Both the tert-butyl group and the
aliphatic part of the sul®nimine 7 adopt an equatorial
position, which increases the stability of the transition
state. Because of the Al±O chelation, the cyano group is
transferred on the same side than the oxygen atom, away
from the sterically demanding tert-butyl group. The validity
of the transition state hypothesis and the resultingabsolute
0R) stereochemistry at the a carbon of 8a were con®rmed by
the X-ray diffraction data 0Fig. 4). Although the aluminum
atom has disappeared, the six membered transition state is
The relationship between the alternate mechanisms and the
intrinsic nature of the metal is reinforced when the dia-
stereoselectivity ratios are positionned in the place of the
elements in the periodic table 0Fig. 6). There is indeed a
strongcorrelation between the position in the periodic table
and the diastereoisomeric ratio. All three tri¯ate salts of
group IIIB metals 0Sc, Y, La) yielded very high diastereo-
selectivity 0.97/3). From left to right, the ratio is inversed
in a monotonous manner suggesting that the acidity or the
basicity of the element induce the direction of the stereo-
selectivity measured.
In conclusion, we have demonstrated that aliphatic t-butyl-
sul®nimines are excellent substrates for a new variant of the
Strecker reaction when cyanide ions are delivered through
ethylisopropoxyaluminum cyanide or trimethylsilylcyanide
Figure 4.

S.Mabic, A.A.Cordi / Tetrahedron 57 '2001) 8861±8866
8865
4.1.2. Procedure usingdiethylaluminumcyanide. To a
solution of Et2AlCN 017.1 mmol, 1 M solution in toluene,
17.1 mL) in anhydrous THF 030 mL), i-PrOH 02.7 mL) was
added under a nitrogen atmosphere. The mixture was stirred
for 15 min at 258C before transferringvia a cannula to a dry
ice cooled solution of sul®nimine 7 011.4 mmol, 3.0 g) in
anhydrous THF 070 mL). The reaction mixture was stirred
at 258C under an inert atmosphere and the reaction was
monitored by TLC. After 2 h, the reaction mixture was
cooled down to 2788C and a 10% aqueous NaHCO3 solu-
tion 015 mL) was added. The suspension was ®ltered and
the ®ltrate was extracted with EtOAc 03£100 mL). The
combined organic phase was washed with brine, dried
over MgSO4, ®ltered and evaporated under reduced pres-
sure. Silica gel column chromatography 0cyclohexane/
EtOAc 60:40) on the crude extract yielded the cyanosul-
®namide 8a/8b 02.98 g, 10.8 mmol) as a white powder in
a 95% yield and a 95/5 diastereoisomeric ratio. Recrystalli-
zation twice from n-hexanes 050 mL)/toluene 024 mL) at
2208C afforded the cyanosul®namide 8a as a single dia-
Figure 6.
combined with a Lewis acid catalyst. The reaction proceeds
with high yield and high diastereoselectivity, which can be
further improved by additional crystallizations. Ensuing
function transformations can be carried out to afford ethyl-
ene diamines with high enantiopurity. The tert-butyl sul-
®namide has revealed more appropriate than its p-tolyl
analogon aliphatic aldehydes. The scope of these reactions
on aromatic aldehydes and ketones is under investigation.
stereoisomer 0ee$99%) mpˆ109±1108C. [a]23 ˆ2188
D
1
0CHCl3, cˆ11 mgmL 21). H NMR 0CDCl3, 300 MHz) d
7.20 0m, 4H), 4.25 0q, 1H), 3.6 0d, 1H), 3.15 0m, 2H), 2.70
0m, 3H), 2.15 0m, 2H), 1.25 0s, 9H). IR 0Nujol, cm21) 3260,
2240, 1370, 1080. Anal. Calcd for C16H22N2OS: C, 66.17;
H, 7.63; N, 9.65; S, 11.04. Found C, 66.45; H, 7.56; N, 9.42;
S, 11.08. X-Ray crystallography was performed on this
material.
4. Experimental
4.1. General
4.1.3. Procedure usingTMSCN. To a solution of sul®ni-
mine 7 0263 mg, 1 mmol) in anhydrous CH2Cl2 010 mL),
ZnI2 060 mg, 0.2 mmol) and then TMSCN 0270 mL,
2 mmol) were added at 258C. The reaction mixture was
stirred under a nitrogen atmosphere at this temperature
and the reaction was monitored by TLC. After 48 h, the
solvent was evaporated under reduced pressure and the
crude reaction mixture was separated by silica gel column
chromatography to give 404 mg 073% yield) of a mixture of
diastereoisomers 8a/8b 0ratio 25/75) as a yellowish oil.
Reagents were commercially available and of synthetic
grade. H NMR spectra relative to TMS, were recorded on
1
Bruker 200 or 400 MHz spectrometers. Infrared spectra
were obtained as nujol emulsion, on a Bruker Fourier trans-
form spectrometer. All new substances were homogeneous
in TLC and exhibited spectroscopic data consistent with the
assigned structures. Elemental analyses 0C, H, N) were
performed on a Carlo Erba 1108 instrument and are in
agreement with the calculated values within the 1/20.4%
range unless otherwise stated. Melting points were obtained
on a Reichert hot stage microscope and are uncorrected.
Optical rotations were measured on a Perkin±Elmer 241
Polarimeter. Silica gel 60, Merck 230±400 mesh, was
used for both ¯ash and medium pressure chromatography.
TLC were performed on pre-coated 5£10 cm, Merck silica
gel 60 F254 plates 0layer thickness 0.25 mm). Liquid
Chromatography analysis 0LC) of the diastereoisomers
were performed on a C18, 3.5 mm, Kromasil column eluted
with a gradient of CH3CN/H2O/CH3SO3H from 25/1000/1
to 1000/25/1 at a ¯ow rate of 0.2 mL min21, at 408C and
detection at 210 nm. The purity of the enantiomers 01a and
1b) was determined by capillary electrophoresis on a HP
3DCE instrument equipped with a polyvinyl alcohol capil-
lary eluted with tri-O-methyl-b-cyclodextrine in Tris buffer
pHˆ2.5 and detection at 200 nm.
4.1.4. Reduction with BH3´Me2S. To a solution of sul®na-
mide 8a 0800 mg, 2.9 mmol) in THF 05 mL) at re¯ux,
BH3´Me2S 0304 mL, 3.2 mmol) was added dropwise over
a 10 min period. The reaction mixture was heated at re¯ux
for 25 min. After coolingdown to 25 8C, a saturated metha-
nolic HCl solution 015 mL) was added dropwise. The
mixture was heated at re¯ux for 3 h to evaporate the solvent.
This procedure was repeated twice, and the crude was then
dissolved in MeOH 015 mL). The solvent was evaporated
under reduced pressure and this was repeated twice. The
product 2a was ®nally obtained as a yellowish solid
0870 mg, 92% purity). Washing with warm CH3CN and
recrystallization from MeOH afforded the bis hydrochloride
1
salt of the diamine as a white solid, mpˆ219±2208C. H
NMR 0DMSO-d6, 300 MHz) d 8.55 0m, 6H), 7.15 0m, 4H),
3.50 0m, 1H), 3.13 0m, 4H), 2.55 0m, 3H), 1.8 0m, 2H). IR
0Nujol, cm21) 3200±2400. Enantiomeric ratio .95/5
0Chiral LC did not afford a more accurate measure of the
ee).
4.1.1. 5-Indan-2-ylmethyl-tert-butylsul®namide .7). Pre-
pared accordingto the literature procedure. 23 Colorless oil.
1H NMR 0CDCl3, 300 MHz) d 8.15 0t, 1H), 7.21 0m, 4H),
3.15 0m, 2H), 2.90 0m, 1H), 2.73 0m, 4H), 1.21 0s, 9H). IR
0cm21
) 1621, 1363, 1182, 1088. Anal. Calcd for
4.1.5. 5-Indan-2-ylmethyl-4,5-dihydro-1H-imidazole;
hemi-fumarate. The freshly prepared free base diamine
C15H21NOS: C, 68.40; H, 8.04; N, 5.32; S, 12.17. Found:
C, 68.67; H, 7.85; N, 5.13; S, 12.01.
was treated as previously reported.24 White crystals,

8866
S.Mabic, A.A.Cordi / Tetrahedron 57 '2001) 8861±8866
mpˆ202±2048C. 1H NMR 0DMSO-d6, 300 MHz) d 7.55 0s,
1H), 7.1 0m, 4H), 6.35 0s, 1H), 3.95 0m, 1H), 3.65 0m, 1H),
3.25 0m, 1H), 3.0 0m, 2H), 2.57 0m, 3H), 1.65 0m, 2H). IR
0Nujol, cm21) 3400±1800, 1600, 1550. Anal. Calcd for
C13H16N2, 1/2C4H4O4: C, 69.75; H, 7.02; N, 10.84. Found
C, 69.76; H, 6.92; N, 10.74. 0ee$99%).
Â
4. Cordi, A. A.; Lacoste, J.-M.; Le Borgne, F.; Herve, Y.;
Vaysse-Ludot, L.; Descombes, J.-J.; Courchay, C.; Laubie,
M.; Verbeuren, T. J. J.Med.Chem. 1997, 40, 2931±2935.
5. Borg, D.; Cogan, D. A.; Ellman, J. A. Tetrahedron Lett. 1999,
40, 6709±6712.
6. Hua, D. H.; Lagneau, N.; Wang, H.; Chen, J. Tetrahedron:
Asymmetry 1995, 6, 349±352.
7. Hose, D. R. J.; Mahon, M. F.; Molloy, K. C.; Raynham, T.;
Crystallographic data 0excluding structure factors) for the
structure in this paper have been deposited with the
Cambridge Crystallographic Data Center as supplementary
publication numbers CCDC 158084.
Wills, M. J.Chem.Soc,. Perkin Trans.1
1996, 691±703.
8. Tang, T. P.; Ellman, J. A. J.Org.Chem. 1999, 64, 12±13.
9. Chan, W. H.; Lee, A. W. M.; Xia, P. F.; Wong, W. Y.
Tetrahedron Lett. 2000, 41, 5725±5728.
10. Davis, F. A.; Srirajan, V. J.Org.Chem. 2000, 65, 3248±3251.
Acknowledgements
Â
11. Portonovo, P. S.; Liang, B.; Jouille, M. M. Tetrahedron:
Asymmetry 1999, 10, 1451±1455.
Single crystal X-ray diffraction was performed by
L. Tchertanov at the CNRS unit of Gif sur Yvette. We
thank Professor H. Kagan for interesting discussions.
12. Davis, F. A.; Fanelli, D. L. J.Org.Chem. 1998, 63, 1981±
1985.
13. Bedos, P.; Amblard, M.; Subra, G.; Dodey, P.; Luccarini,
J.-M.; Paquet, J.-L.; Pruneau, D.; Aumelas, A.; Martinez, J.
J.Med.Chem. 2000, 43, 2387±2394.
References
14. Cogan, D. A.; Liu, G.; Kim, K.; Backes, B. J.; Ellman, J. A.
J.Am.Chem.Soc. 1998, 120, 8011±8019.
1. Strecker, A. Ann.Chem.Pharm. 1850, 75, 27±45.
2. 0a) Ishitani, H.; Komiyama, S.; Kobayashi, S. Angew.Chem,.
15. Liu, G.; Cogan, D. A.; Owens, T. D.; Tang, T. P.; Ellman, J. A.
J.Org.Chem. 1999, 64, 1278±1284.
Int.Ed.Engl.
1998, 37, 3186±3188. 0b) Ishitani, H.;
16. Yeh, H. J. C.; Ziffer, H.; Jerina, D. M. J.Am.Chem.Soc. 1973,
95, 2741±2743.
Komiyama, S.; Hasegawa, Y.; Kobayashi, S. J.Am.Chem.
Soc. 2000, 122, 762±766. 0c) Krueger, C. A.; Kuntz, K. W.;
Dzierba, C. D.; Wirschun, W. G.; Gleason, J. D.; Snapper,
M. L.; Hoveyda, A. H. J.Am.Chem.Soc. 1999, 121, 4284±
4285. 0d) Sigman, M. S.; Vachal, P.; Jacobsen, E. N. Angew.
Chem., Int. Ed. Engl. 2000, 39, 1279±1281. 0e) Postel, D.;
Nguyen van Nhien, A.; Pillon, M.; Villa, P.; Ronco, G.
Tetrahedron Lett. 2000, 41, 6403±6406. 0f) Holmes, I. P.;
Kagan, H. B. Tetrahedron Lett. 2000, 41, 7457±7460.
0g) Dave, R. H.; Hosangadi, B. D. Tetrahedron 1999, 55,
11295±11308. 0h) Iyer, M. S.; Gigstad, K. M.; Namdev,
N. D.; Lipton, M. J.Am.Chem.Soc. 1996, 118, 4910±4911.
0i) Kobayashi, S.; Ishitani, H. Chem.Rev. 1999, 99, 1069±
1094. 0j) Rebiere, F.; Samuel, O.; Ricard, L.; Kagan, H. B.
J.Org.Chem. 1991, 56, 5991±5999. 0k) Davis, F. A.; Zhou,
P.; Chen, B.-C. Chem.Soc.Rev. 1998, 27, 13±18.
17. Buchanan, G. W.; Dawson, B. A. Org.Magn.Reson. 1980, 13,
293±297.
18. Davis, F. A.; Portonovo, P. S.; Reddy, R. E.; Chiu, Y.-H.
J.Org.Chem. 1996, 61, 440±441.
19. Davis, F. A.; Zhang, Y.; Andemichael, Y.; Fang, T.; Fanelli,
D. L.; Zhang, H. J.Org.Chem. 1999, 64, 1403±1406.
20. Davis, F. A.; Reddy, R. E.; Szewczyk, J. M.; Portonovo, P. S.
Tetrahedron Lett. 1993, 34, 6229±6232.
21. Brown, H. C.; Choi, Y. M.; Narasimhan, S. J.Org.Chem.
1982, 47, 3153±3163.
22. Brown, H. C.; Choi, Y. M.; Narasimhan, S. Synthesis 1981,
605±606.
23. Liu, G.; Cogan, D. A.; Ellman, J. A. J.Am.Chem.Soc. 1997,
119, 9913±9914.
24. Cordi, A. A.; Lacoste, J.-M.; Descombes, J.-J.; Courchay, C.;
Laubie, M.; Vanhoutte, P. M.; Verbeuren, T. J. J.Med.Chem.
1995, 38, 4056±4069.
3. Cordi, A. A.; Berque-Bestel, I.; Persigand, T.; Lacoste, J.-M.;
Newman-Tancredi, A.; Audinot, V.; Millan, M. J. J.Med.
Chem. 2001, 44, 787±805.