Lewis acid mediated addition of silyl ketene acetals to sulfinimines

Full text of DOI:10.1021/jo990913f

8724
J . Org. Chem. 1999, 64, 8724-8727
N-Benzylidene p-tolylsulfinamide 1, easily available in
Lew is Acid Med ia ted Ad d ition of Silyl
an optically pure form,7 was chosen as a model compound
for this study. Ketene silyl acetals 2 reacted with 1 only
in the presence of Lewis acids, providing N-p-toluene-
sulfinyl-â-amino esters 3 and 4 (Scheme 1).
Keten e Aceta ls to Su lfin im in es
Robert Kawecki
Institute of Organic Chemistry, Polish Academy of Sciences
PL-01-224 Warszawa, ul. Kasprzaka 44, Poland
The yield and diastereoisomeric excess (de) of the
product strongly depends on the Lewis acid used (Table
1). The most effective appeared to be TMSOTf and
BF3‚Et2O. However, the latter gave poorer results at low
temperatures compared to TMSOTf. Mild Lewis acids
such as Yb(OTf)3 or Zn(OTf)2 were ineffective, and usually
the conversion of the substrate was very slow. In the case
of stronger Lewis acids such as TiCl4 or SnCl4 the
substrate was consumed quickly but the yield of expected
product was very low. It was necessary to use at least 1
mol equiv of the Lewis acid, but the excess did not
improve the yield. The preferred solvent was dichlo-
romethane. In one case where acetonitrile was used as
solvent, the stereoselectivity was reversed (entry 12).
Attempts to use enol silyl ethers as nucleophiles were
unsuccessful. When trimethylsilyl ethers of enols derived
from acetophenone or 1-acetylcyclohexene were used,
only traces of expected products were detected.
The presence of strong Lewis acids in the reaction
mixture may lead to racemization at sulfur atom of
sulfinimine. Possibility of such a process in sulfinimine
1 was checked by removal of p-toluenesulfinyl auxiliary
from nonpurified mixture 3c + 4c with TFA in MeOH
and inspection of the ee of the resulting â-amino ester.
In the case of using TMSOTf, the sample of sulfinamide
(de 83%) afforded after acid treatment â-amino ester with
75% ee. A similar result was observed for BF3‚Et2O. The
de of sulfinamide 3c was 77% (Table 1, entry 6), but the
ee of the â-amino ester was only 63%. A possible
explanation is that a small part of the minor diastere-
oisomer of sulfinamide 4c hydrolyzed during aqueous
workup (exact amount of missing â-amino ester was
actually detected in reaction mixture) or partial racem-
ization at the sulfur atom occurred in sulfinimine 1.
The stereoselectivity of this reaction is dependent upon
the ketene substitution. Silyl ketene acetal 2b derived
from phenyl acetate gave with (S)-(+) sulfinimine 1
predominantly diastereoisomer (3S,SS)-4b with 59% de
(entry 2). Ketene 2c under the same reaction conditions
(entry 4) formed sulfinamide (3S,SS)-3c as a main dias-
tereoisomer with 85% de. Although the absolute config-
uration at newly formed stereogenic center is the same
(S), the steric course of these two reactions must be
different. Interestingly, lithium enolate of methyl acetate
reacts with (S)-(+)-1 to give sulfinamide with (3R,SS)
configuration and 80% de.8 Under the same conditions
(THF, -70 °C), the lithium enolate of methyl isobutyrate
gives (3R,SS)-4c as the major diastereoisomer with 51%
de (see Experimental Section). Both methods, i.e., metal
enolate addition and silyl ketene addition, seem to be
complementary.
Received J une 4, 1999
Recent years showed that homochiral â-amino acids
play an important role in the synthesis of numerous
biologically active compounds,1 and the synthetic meth-
ods leading to derivatives of â-amino acids are of great
significance.1a,b,d One approach to the synthesis of â-ami-
no acids is the addition of silyl ketene acetals to imines
usually catalyzed by Lewis acids.2 Few examples of an
enantioselective version of this reaction are known. 3 The
most versatile methods use imines with a removable
group on the nitrogen atom, such as benzyl or silyl. In
this paper, preparation of optically active â-amino esters
by reaction of homochiral sulfinimines with ketene silyl
acetals in the presence of Lewis acids is described. A new,
camphor-derived chiral auxiliary has been used in these
reactions. Because the behavior of sulfinimines in an
acidic environment has not been studied before, it was
of great interest to recognize their stability and reactivity
in the presence of Lewis acids.
Sulfinimines are known as very good amine precursors.
Reactions studied to date are the addition of organome-
tallic reagents4 including enolates4d,f,g,i and phosphites,4c
reduction,5 and addition of a cyanide group.6 The main
advantage of their use is that after creation of new
stereogenic center, the homochiral sulfinyl auxiliary can
be easily removed by acid treatment and recycled without
loss of optical purity.
(1) (a) J uaristi, E. Enantioselective Synthesis of â-Amino Acids;
Wiley-VCH: New York, 1997. (b) Cardillo, G.; Tomasini, C. Chem. Soc.
Rev. 1996, 25, 117-128. (c) Gellman, S. H. Acc. Chem. Res. 1998, 31,
173-180. (d) Seebach, D.; Overhand, M.; Ku¨hnle, F. N. M.; Martinoni,
B.; Oberer, L.; Hommel, U.; Widmer, H. Helv. Chim. Acta 1996, 79,
913-941.
(2) (a) Cole, D. C. Tetrahedron 1994, 50, 9517-9582. (b) Kleinman,
E. F. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Heathcock, C. H., Eds.; Pergamon Press: New York, 1991; Vol. 2, pp
929-933. (c) Hart, D. J .; Ha, D.-C. Chem. Rev. 1989, 89, 1447-1465.
(3) (a) Higashiyama, K.; Kyo, H.; Takahashi, H. Synlett 1998, 489-
490. (b) Ishitani, H.; Ueno, M.; Kobayashi, S. J . Am. Chem. Soc. 1997,
119, 7153-7154. (c) Shimizu, M.; Kume, K.; Fujisawa, T. Tetrahedron
Lett. 1995, 36, 5227-5230. (d) Ishihara, K.; Miyata, M.; Hattori, K.;
Tada, T.; Yamamoto, H. J . Am. Chem. Soc. 1994, 116, 10520-10524.
(e) Matsumura, Y.; Tomita, T. Tetrahedron Lett. 1994, 35, 3737-3740.
(f) Kunz, H.; Schanzenbach, D. Angew. Chem., Int. Ed. Engl. 1989,
28, 1068-1069. (g) Gennari, C., Venturini, I.; Gislon, G.; Schimperna,
G. Tetrahedron Lett. 1987, 28, 227-230.
(4) (a) Liu, G.; Cogan, D. A.; Ellman, J . A. J . Am. Chem. Soc. 1997,
119, 9913-9914. (b) Moreau, P.; Essiz, M.; Merour, J .-Y.; Bouzard, D.
Tetrahedron: Asymmetry 1997, 8, 591-598. (c) Lefebvre, I. M.; Evans,
S. A. J . Org. Chem. 1997, 62, 7532-7533. (d) Fujisawa, T.; Kooriyama,
Y.; Shimizu, M. Tetrahedron Lett. 1996, 37, 3881-3884. (e) Yang, T.
K.; Chen, R. Y.; Lee, D. S.; Peng, W. S.; J iang, Y. Z.; Mi, A. Q.; J ong,
T. T. J . Org. Chem. 1994, 59, 914-921. (f) Davis, F. A.; Zhou, P.; Reddy,
G. V. J . Org. Chem. 1994, 59, 3243-3245. (g) Davis, F. A.; Reddy, R.
T.; Reddy, R. E. J . Org. Chem. 1992, 57, 6387-6389. (h) Hua, D. H.;
Miao, S. W.; Chen, J . S.; Iguchi, S. J . Org. Chem. 1991, 56, 4-6. (i)
Tang, T. P.; Ellman, J . A. J . Org. Chem. 1999, 64, 12-13.
(5) (a) Hose, D. R. J .; Raynham, T.; Wills, M. Tetrahedron: Asym-
metry 1993, 4, 2159-2162. (b) Hose, D. R. J .; Mahon, M. F.; Molloy,
K. C.; Raynham, T.; Wills, M. J . Chem. Soc., Perkin Trans. 1 1996,
691-703.
In the course of our work on new homochiral organo-
sulfur auxiliaries it was found that reaction of sulfinate
(7) Davis, F. A.; Reddy, R. E.; Szewczyk, J . M.; Reddy, G. V.;
Portonovo, P. S.; Zhang, H.; Fanelli, D.; Reddy, R. T.; Zhou, P.; Carroll,
P. J . Org. Chem. 1997, 62, 2555-2563.
(8) Davis, F. A.; Reddy, R. E.; Szewczyk, J . M. J . Org. Chem. 1995,
60, 7037-7039.
(6) Davis, F. A.; Reddy, R. E.; Portonovo, P. S. Tetrahedron Lett.
1994, 35, 9351-9354.
10.1021/jo990913f CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/12/1999

Notes
J . Org. Chem., Vol. 64, No. 23, 1999 8725
Ta ble 2. TMSOTf-Med ia ted Ad d ition of Silyl Keten e
Aceta ls to 10-Isobor n ylsu lfin im in es
Sch em e 1
entry
substrate
product
yield, %
ee, % (config)
1
2
3
2a + 7a
2c + 7a
2c + 7b
9a
9b
9c
63
74
79
81 (S)
81 (S)
40
Sch em e 3
Ta ble 1. Effect of Lew is Acid on Ad d ition of Silyl
Keten e Aceta ls to Su lfin im in e 1a
ketene temp,
yield
entry acetal
°C
Lewis acid 3 + 4, % de,%b(config)c
1
2
3
4
5
6
7
8
9
2a
2b
2c
2c
2c
2c
2c
2c
2c
2c
2c
2c
-70
-70
20
-70
-70
20
-70
20
20
20
TMSOTfd
TMSOTfd
TMSOTf
TMSOTf
TMSOTfd
BF3‚Et2O
BF3‚Et2O
BF3‚Et2O
Et2AlCle
68
80
40
79
75
56
9
35
28
39
19
17
50
59 (3S,SS)
71 (3SR,SSRS)
85 (3S,SS)
91 (3SR,SSRS)
77 (3S,SS)
34 (3SR,SSRS)
42 (3SR,SSRS)
47 (3SR,SSRS)
60 (3SR,SSRS)
61 (3SR,SSRS)
26 (3RS,SSRS)
of sulfinate 5 with Grignard reagents9b and on this basis
was made the assignment at sulfur atom. 2-Hydroxy
derivative of sulfinamide 6 can be isolated by quenching
the reaction mixture with aq NH4Cl (see Supporting
Information). However, the use of TMS derivative 6 was
more convenient due to its better solubility. It also turned
out that 6 is stable enough toward hydrolysis and can
be stored for a long time without decomposition. Con-
densation of sulfinamide 6 with aromatic aldehydes was
performed in boiling toluene or by reaction of its anion
generated by n-butyllithium in THF at -40 °C. In both
cases optically pure sulfinimines were obtained as con-
firmed by NMR. The yield of product 7a was higher using
n-butyllithium (70%) than carrying out the reaction in
boiling toluene (41%). Aliphatic aldehydes can be conve-
niently condensed with 6 in dichloromethane in the
presence of MgSO4. The reactions of ketene silyl acetals
2 with sulfinimines 7 (Table 2) were successful only when
TMSOTf was used as the Lewis acid. Aromatic sulfin-
imines 7a and 7b gave expected â-amino esters 9 in good
yields as opposed to aliphatic sulfinimine 7c which gave
only traces of the product. Sulfinamide 8 was not isolated,
as most of the product, even after basic workup, was
already hydrolyzed to â-amino ester 9 and sulfinate 5
(Scheme 3). The enantiomeric excess of 9b was 81% as
e
10
11
12
EtAlCl2
Yb(OTf)3
f
20
20
f
Yb(OTf)3
a
Reaction solvent was CH2Cl2 except for entries 8 and 12 which
was CH3CN. Reaction time was 16 h except for entries 1, 2 which
was 6 h and entries 4, 5 which was 2 h. Calculated from 1H NMR
b
spectra of crude reaction mixture. cConfiguration of the major
diastereoisomer was determined by conversion of enantiomerically
enriched sulfinamide (TFA, MeOH) to known â-amino esters 9b3f
and 9d 8 (R1 ) Ph, R2 ) H, R3 ) Me). TMSOTf was added 30
d
min prior to addition of 2. e 1 M solution in hexane. f 0.5 equiv.
Sch em e 2
1
determined by H NMR using tert-butylphenylphosphi-
nothioic acid10 as a chiral solvating agent. This value is
comparable with those obtained using p-tolylsulfinyl
derivative 1 and ketene silyl acetal 2c (Table 1, entry
4). With ketene 2a , ee is even higher using sulfinimine
7a . The main advantage of using 10-isobornylsulfinate
5 is that removal of sulfinyl auxiliary is easy (no
necessary to use TFA) and quantitative. Epimerization
at the sulfur atom and side reactions were not detected
as opposed to p-toluenesulfinyl derivative.8 The optical
purity of sulfinate 5 and sulfinimines 7 can be easily
checked by 1H NMR due to the presence of several
stereogenic centers.
o
59 with lithium hexamethyldisilazide in THF at -30 C
followed by TMSCl quenching afforded primary sulfina-
mide 6 in 80% yield (Scheme 2). The stereochemistry of
this reaction was assumed to be the same as the reaction
(9) (a) Wolinsky, J .; Marhenke, R. L. J . Org. Chem. 1975, 40, 1766-
1770. (b) Kawecki, R.; Urban˜czyk-Lipkowska, Z. Synthesis 1996, 603-
605.
(10) Drabowicz, J .; Dudzin˜ski, B.; Mikołajczyk, M.; Colonna, S.;
Gaggero, N. Tetrahedron: Asymmetry 1997, 8, 2267-2270; Omelan˜c-
zuk, J .; Mikołajczyk, M. Tetrahedron: Asymmetry 1996, 7, 2687-2694.

8726 J . Org. Chem., Vol. 64, No. 23, 1999
Notes
mmol). The reaction mixture was stirred for 1 h at -20 °C. The
solution was cooled to -70 °C, and sulfinimine (S)-(+)-1 (324
mg, 1.3 mmol) in THF (1.5 mL) was added slowly. Stirring was
continued for 4 h, and a saturated solution of NH4Cl was added
at -70 °C. The reaction mixture was extracted three times with
dichloromethane (2 mL), and the organic extracts were dried
(MgSO4). Filtration and evaporation gave pure sulfinamides 3c
and 4c (410 mg, 89%). The de of the (3R,SS) diastereoisomer
was 51%, as determined by 1H NMR.
The results presented here show a rather low reactivity
of sulfinimines with derivatives of enol silyl ethers. This
may be due to weak activation of the CdN bond by the
sulfinyl group (compared to N-sulfonylimines11) or a
different interaction with Lewis acids than observed in
simple imines. The latter hypothesis seems to be reason-
able in light of the high dependence of the above-
mentioned reaction on the Lewis acid used. Unfortu-
nately, very little is known about the site of protonation
(1S, 2R, 4R, SS)-7,7-Dim eth yl-2-(tr im eth ylsilyloxy)bicyclo-
[2.2.1]h ep ta n e-1-m eth a n esu lfin a m id e (6). To a solution of
lithium hexamethyldisilazide, prepared from HMDS (34 mmol,
5.40 g) and n-butyllithium (1.6 M in hexane, 34 mmol, 21 mL)
in THF (80 mL) at -30 °C, was added a solution of sulfinate 5
(17 mmol, 3.37 g) in THF (18 mL). The mixture was stirred at
-30 °C for 3 h. Trimethylsilyl chloride (50 mmol, 5.46 g) was
added dropwise, and the solution was stirred for next 2 h at -30
°C. The cooling bath was removed, and the mixture was left
overnight at room temperature. A saturated solution of NH4Cl
was added, and the reaction mixture was extracted three times
with CH2Cl2. The organic extract was dried and evaporated to
give 3.9 g (80%) of waxy solid which was pure enough for next
steps. Analytically pure sample was obtained by crystallization
from hexane. Yield 1.46 g (first crop) and 0.48 g from second
1
of sulfinimines. H NMR spectra of sulfinimine 1 with
BF3‚Et2O or TMSOTf recorded at room temperature do
not exhibit any changes in chemical shifts. This aspect
of the chemistry of sulfinimines is now under investiga-
tion.
Exp er im en ta l Section
All reactions were performed under an argon atmosphere.
Anhydrous solvents were obtained as follows: THF was distilled
from sodium benzophenone ketyl, dichloromethane was distilled
from CaH2, acetonitrile was distilled from P2O5. Boron trifluoride
etherate and diisopropylamine were distilled from CaH2. Ketene
silyl acetals were prepared by known procedures.12 Melting
points were uncorrected. NMR spectra were recorded at 200 and
500 MHz (1H NMR).
Gen er a l P r oced u r e for P r ep a r a tion of N-p-Tolu en e-
su lfin yl-â-a m in o Acid Ester s. N-benzylidene-p-tolyl-sulfina-
mide 1 (160 mg, 0.66 mmol) and ketene silyl acetal 2 (1 mmol)
were dissolved in dry CH2Cl2 (4 cm3) under argon and cooled to
-70 °C. Lewis acid (0.8 mmol) was added slowly, and the
reaction mixture was kept for the time and temperatures
indicated in Table 1. The reaction mixture was quenched with
saturated solution of NaHCO3 and extracted with dichlo-
romethane. Organic extracts were dried and evaporated. Chro-
matography on silica gel (CH2Cl2 and MeOH, 50:1) gave mixture
of diastereoisomers.
Meth yl N-(p-tolylsu lfin yl)-3-a m in o-2,2-d im eth yl-3-p h e-
n ylp r op a n oa te (3c a n d 4c). IR (KBr): 3177 (NH), 1729 (Cd
O), 1089, 1057 (SO) cm-1 (3S,SS)-(3c). 1H NMR (CDCl3, ref
TMS): δ 1.07 (s, 3H), 1.28 (s, 3H), 2.29 (s, 3H), 3.69 (s, 3H),
4.36 (d, J ) 7.6 Hz, 1H), 5.56 (d, J ) 7.6 Hz, 1H), 6.85-7.15 (m,
9H). 13C NMR (CDCl3, ref 77 ppm): δ 21.1, 21.4, 24.7, 47.0, 51.9,
62.6, 125.7, 127.0, 127.5, 127.8, 128.8, 139.5, 140.7, 140.8, 176.7.
(3R,SS)-(4c): 1H NMR (CDCl3, ref TMS): δ 1.13 (s, 3H), 1.17
(s, 3H), 2.41 (s, 3H), 3.66 (s, 3H), 4.54 (d, J ) 5.6 Hz, 1H), 5.12
(d, J ) 5.6 Hz, 1H), 7.3 (m, 7H), 7.52 (m, 2H). 13C NMR (CDCl3,
ref 77 ppm): δ 21.0, 21.3, 24.1, 47.0, 52.1, 64.5, 125.3, 127.8,
127.9, 128.7, 129.4, 138.5, 141.2, 142.3, 176.5. HR LSIMS calcd
for C19H24NO3S (M + H)+: 346.1477, found: 346.1460. Anal.
Calcd for C19H23NO3S: C, 66.06; H, 6.71; N, 4.05; S, 9.28.
Found: C, 65.95; H, 6.89; N, 4.09; S, 9.12.
crop (40%). Mp 146-148 °C; [R]22 ) -116.6 (c ) 0.98, CHCl3);
D
IR (KBr): 3269 (NH), 1047 (SO) cm-1. 1H NMR (CDCl3, ref 7.26
ppm): δ 0.01 (s, 9H), 0.77 (s, 3H), 0.95 (s, 3H), 1.0 (m, 1H), 1.3
(m, 1H), 1.4 (m, 5H), 2.50, 3.18 (AB, J ) 12.7 Hz, 2H), 3.87 (dd,
J ) 3.6, 7.1 Hz, 1H), 4.40 (br, 2H), 13C NMR (CDCl3 ref 77
ppm): δ 0.2, 19.9, 20.4, 27.2, 30.1, 41.8, 44.6, 48.5, 50.0, 57.5,
76.7. MS: 289 (M+), 225 (M+ - SONH2). Anal. Calcd for C13H27
-
NO2SSi: C, 53.93; H, 9.40; N, 4.84. Found: C, 53.98; H, 9.59;
N, 4.66.
Typ ica l P r oced u r e for th e Syn th esis of 10-Isobor n yl
Su lfin im in es. (1S,2R,4R,SS)-7,7-Dim eth yl-N-(p h en ylm eth -
ylen e)-2-(tr im eth ylsilyloxy)bicyclo[2.2.1]h ep ta n e-1-m eth -
a n esu lfin a m id e (7a ). To a stirred solution of sulfinamide 6
(1.264 g, 4.4 mmol) in THF (18 mL) was added a solution of
n-butyllithium (1.6 M in hexane, 3.0 mL, 4.8 mmol) at -40 °C,
and the resulting white slurry was stirred for 1 h. The solution
of benzaldehyde (0.56 g, 5.3 mmol) in THF (1.5 mL) was added
at -20 °C, and the reaction mixture was stirred for 4 h, warmed
to room temperature, and left to stand overnight. Saturated
solution of NH4Cl was added, and the reaction mixture was
extracted three times with dichloromethane (15 mL). Combined
organic layers were dried, filtered, and evaporated. Purification
by chromatography on silica gel (CH2Cl2 and hexane 1:1 and
then CH2Cl2) afforded 1.16 g (70%) of a colorless oil. [R]22
)
D
-59.1 (c ) 1.82, CH2Cl2), IR (CH2Cl2) 1575, 1608 (CdN), 1089
1
(SO) cm-1. H NMR (CDCl3, ref 7.26 ppm): δ 0.12 (s, 9H), 0.82
(s, 3H), 1.07 (s, 3H), 1.1 (m, 1H), 1.5-1.9 (m, 6H), 2.26; 3.61
(AB, J ) 12.9 Hz, 2H), 4.10 (dd, J ) 3.9, 6.6 Hz, 1H), 7.5 (m,
3H), 7.85 (m, 2H), 8.62 (s, 1H). 13C NMR (CDCl3, ref 77 ppm):
δ ) 0.3, 20.1, 20.5, 27.4, 30.7, 42.1, 44.8, 48.8, 50.3, 57.3, 77.0,
128.8, 129.3, 132.2, 134.0, 160.9. HRMS: calcd for C20H31NO2-
SSi (M)+: 377.1845; found: 377.1846. Calcd for C19H28NO2SSi
(M - CH3)+: 362.1610; found: 362.1608.
P h en yl N-(p-Tolylsu lfin yl)-3-a m in o-3-p h en ylp r op a n oa te
(3b a n d 4b). IR (KBr): 3291 (NH), 1754 (CdO), 1090, 1023 (SO)
1
cm-1, (3S,SS)-(4b). H NMR (CDCl3, ref TMS): δ 2.26 (s, 3H),
3.14 and 3.20 (ABX, J ) 17.5, 6.5 Hz, 2H), 4.81 (ddd, J ) 6.5,
6.5, 7.0 Hz, 1H), 5.09 (d, J ) 7.0 Hz, 1H), 6.82 (m, 2H), 7.1-7.5
(m, 12H). 13C NMR (CDCl3, ref 77 ppm): δ 21.1, 42.5, 53.3, 121.2,
125.7, 125.7, 126.5, 127.5, 128.4, 129.1, 129.2, 140.5, 140.7, 141,0,
150.0, 169.1. (3R,SS)-(3b). 1H NMR (CDCl3, ref TMS): δ 2.30
(s, 3H), 3.0 (d, J ) 6.0 Hz, 2H), 4.95 (m, 2H), 6.79 (m, 2H), 7.0-
7.5 (m, 12H). 13C NMR (CDCl3, ref 77 ppm): δ 21.1, 42.2, 54.6,
121.1, 125.2, 125.7, 127.1, 127.9, 128.6, 129.1, 129.3, 140.1, 141.2,
141.8, 150.0, 169.0. Anal. Calcd for C22H21NO3S: C, 69.63; H,
5.58; N, 3.69; S, 8.45. Found: C, 69.45; H, 5.58; N, 3.64; S, 8.30.
Ad d ition of Lith iu m En ola te of Meth yl Isobu tyr a te to
Su lfin im in e 1. To the solution of LDA prepared by addition of
n-butyllithium (1.6 M in hexane, 1.05 mL, 1.7 mmol) to the
solution of diisopropylamine (172 mg, 1.7 mmol) in THF (5 mL)
was added dropwise at -20 °C methyl isobutyrate (174 mg, 1.7
(1S,2R, 4R,SS)-7,7-Dim eth yl-N-(4-m eth oxyp h en ylm eth -
ylen e)-2-(tr im eth ylsilyloxy)bicyclo[2.2.1]h ep ta n e-1-m eth -
a n esu lfin a m id e (7b). Crude product was purified by crystal-
lization from hexane. Yield 1.764 g (86%). Mp 112-113 °C; [R]22
D
) -59.5 (c ) 1.12, CHCl3). IR (KBr): 1599 (CdN), 1093 (SO)
cm-1 1H NMR (CDCl3, ref 7.26 ppm): δ 0.12 (s, 9H), 0.81 (s,
.
3H), 1.07 (s, 3H), 1.1 (m, 1H), 1.5-1.9 (m, 6H), 2.24 and 3.57
(AB, J ) 12.8 Hz, 2H), 3.87 (s, 3H), 4.09 (dd, J ) 4.0, 6.8 Hz,
1H), 7.0 (m, 2H), 7.8 (m, 2H), 8.54 (s, 1H). 13C NMR (CDCl3, ref
77 ppm): δ 0.3, 20.2, 20.5, 27.4, 30.7, 42.1, 44.9, 48.8, 50.3, 55.4,
57.5, 77.1, 114.2, 127.2, 131.2, 160.0, 162.9. Anal. Calcd for
C21H33NO3SSi: C, 61.88; H, 8.16; N, 3.44. Found: C, 61.95; H,
8.24; N, 3.29.
(1S,2R, 4R,SS)-7,7-Dim eth yl-N-(2-m eth ylp r op ylid en e)-2-
(tr im eth ylsilyloxy)bicyclo[2.2.1]h ep ta n e-1-m eth a n esu lfi-
n a m id e (7c). To a solution of sulfinamide 6 (0.482 mg, 1.7 mmol)
in dichloromethane (7.5 mL) were added anhydrous magnesium
sulfate (ca. 200 mg) and a few crystals of pyridinium p-
toluenesulfonate. Freshly distilled isobutyraldehyde (0.6 g, 8.3
(11) Shimada, S.; Saigo, K.; Abe, M.; Sudo, A.; Hasegawa, M. Chem.
Lett. 1992, 1445-1448.
(12) Colvin, E. Silicon Reagents in Organic Synthesis; Academic
Press: London, 1988; p 101.

Notes
J . Org. Chem., Vol. 64, No. 23, 1999 8727
mmol) was added, and the resulting slurry was gently shaken
for 3 days at room temperature. Filtration and evaporation of
volatiles gave pure sulfinimine 7c as a colorless oil. Chroma-
tography on silica gel (dichloromethane) afforded 0.531 g (93%)
of analytically pure product. [R]22D ) +8.4 (c ) 1.03, CHCl3). IR
a short pad of silica gel eluting CH2Cl2 until removal of all
quantity of sulfinate 5 and then eluting with CH2Cl2 and MeOH,
5:1. Yield 70 mg (79%).
Meth yl 3-Am in o-2,2-d im eth yl-3-(4-m eth oxyp h en yl)p r o-
p a n oa te (9c). Oil. IR (neat): 1728 (CdO). 1H NMR (CDCl3, ref
CHCl3, 7.26 ppm): δ 1.07 (s, 3H), 1.14 (s, 3H), 1.61 (br 2H), 3.69
(neat) 1621 (CdN), 1090 (SO) cm-1 1H NMR (CDCl3, ref 7.26
,
(s, 3H), 3.80 (s, 3H), 4.20 (s, 1H), 6.84 (m, 2H), 7.20 (m, 2H), 13
C
ppm): δ 0.09 (s, 9H), 0.80 (s, 3H), 1.05 (s, 3H), 1.16 (d, J ) 6.8
Hz, 6H), 1.47 (m, 1H), 1.74 (m, 6H), 2.08 (d, J ) 12.9 Hz, 1H),
2.69 (m, 1H), 3.45 (d, J ) 12.9 Hz, 1H), 4.04 (dd, J ) 3.9, 6.7
Hz, 1H), 7.96 (d, J ) 4.4 Hz, 1H). 13C NMR (CDCl3, ref 77 ppm):
δ 0.2, 18.9, 20.1, 20.5, 27.4, 30.8, 34.6, 42.1, 44.9, 48.8, 50.3, 57.2,
77.0, 171.6. HRMS: calcd for C17H33NO2SSi (M)+: 343.2001;
found: 343.2024.
Gen er a l P r oced u r e for P r ep a r a tion of â-Am in o Ester s
9. To the solution of sulfinimine 7b (152 mg, 0.37 mmol) in
dichloromethane (3.5 mL) cooled to -70 °C, was added dropwise
TMSOTf (118 mg, 0.53 mmol). The mixture was stirred for 15
min at -70 °C and ketene silyl acetal 2 (105 mg, 0.60 mmol)
was added, dropwise. The solution was kept for 6 h at -70 °C.
Water (1 mL) was added and the cooling bath was removed.
After the reaction mixture was stirred 30 min at room temper-
ature, saturated NaHCO3 solution (3 mL) was added and stirring
was continued for next 30 min. The mixture was extracted three
times with CH2Cl2, and the combined organic layers were dried,
filtered, and evaporated. The residue was chromatographed on
NMR (CDCl3, ref 77 ppm): δ 19.4, 23.5, 47.8, 51.7, 55.1, 61.2,
113.1, 129.0, 133.9, 158.7, 177.8. Anal. Calcd for C13H19NO3: C,
65.80; H, 8.07; N, 5.90. Found: C, 65.47; H, 8.01; N, 5.93.
Ack n ow led gm en t. This work is part of the Institute
of Organic Chemistry research program sponsored by
State Committee for Scientific Research. The generous
gift of (R)-tert-butylphenylphosphinothioic acid by Prof.
M. Mikołajczyk and Dr. B. Dudzin´ski is greatly acknowl-
edged.
Su p p or tin g In for m a tion Ava ila ble: Determination of
configuration for compounds 3b, 4b, 3c, 4c and 13C NMR
spectra of sulfinimines 7a and 7c. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O990913F