A catalytic enantioselective access to optically active 2-imidazoline from N-sulfonylimines and isocyanoacetates

Full text of DOI:10.1021/jo980949s

J . Org. Chem. 1999, 64, 1331-1334
1331
asymmetric synthesis of oxazoline by using a gold(I)
complex catalyzed aldol reaction in the presence of chiral
ferrocenylphosphine ligands. The reaction of methyl
isocyanoacetate (5b) with aldehydes catalyzed by bis-
(cyclohexyl isocyanide)gold(I) tetrafluoroborate (3) and
chiral ferrocenylphosphine (2) showed high enantiose-
lectivity with enantiomeric excesses as high as 97-99%.
To probe the ability of the gold(I) catalyst (3) with chiral
ferrocene ligand (2) to induce the enantioselectivity in a
similar reaction, we examined the reaction of imine under
identical conditions. On treatment of methyl isocyanoac-
etate (5b) with N-tosyl-p-chlorobenzaldimine (4a ) in the
presence of 3 and 2, the ee values of cis- and trans-2-
imidazoline (67:33) obtained were only 14% and 25%,
respectively. Interestingly, when the neutral gold(I)
complex Me2SAuCl (1) with chiral ferrocenylphosphine
(2) was used as catalyst, the asymmetric induction of this
reaction of 5b with 4a could be brought to good levels.
A typical procedure is illustrated by the synthesis of
6b (Scheme 1). The catalytic system was prepared in situ
by mixing Me2SAuCl (1) and chiral ferrocenylphosphine
(2) together. A mixture of 4b and 5a (1:1) was allowed to
react in the presence of 0.5 mol % catalyst in CH2Cl2 at
25 °C for 20 h to afford 2-imidazoline in quantitative yield
after simple treatment. A 96:4 ratio of cis/trans isomers
A Ca ta lytic En a n tioselective Access to
Op tica lly Active 2-Im id a zolin e fr om
N-Su lfon ylim in es a n d Isocya n oa ceta tes
Xiao-Ti Zhou, Ying-Rui Lin,* Li-Xin Dai, J ie Sun,
Li-J un Xia, and Ming-Hua Tang
Laboratory of Organometallic Chemistry, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences, 354
Fenglin Lu, Shanghai 200032, China
Received May 19, 1998
Optically active 2-imidazolines are not only widespread
in natural products but are also useful intermediates for
the synthesis of biologically active molecules.1 Chiral
2-imidazolines as versatile chiral building blocks, chiral
auxiliaries, and chiral ligands have attracted consider-
able recent interest.2 Especially, chiral 2,3-diamino acids,
which could be easily obtained from chiral 2-imidazolines,
are a constituent of several antibiotics as well as other
biologically active compounds.3 The general approaches
to optically active 2-imidazoline usually started from
chiral amino acids or optically active 1,2-diamines. These
methods included the use of a stoichiometric amount of
chiral reagents or chiral starting materals.4 Recently, a
catalytic stereoselective synthesis of 2-imidazoline has
been reported. The Ru(II)-catalyzed aldol reaction of
isocyanoacetate with N-sulfonylimines gave trans-2-
imidazolines stereoselectively,5 whereas an Au(I) complex
catalyzed analogous reaction afforded cis-2-imidazoline
as the major product.6 However, to the best of our
knowledge, a catalytic enantioselective access to optically
active 2-imidazoline by a similar approach has not been
reported. Here, we wish to describe an efficient asym-
metric synthesis from N-sulfonylimines with isocyanoac-
etate to give optically active 2-imidazolines in high yields
and moderate to high ee values (Scheme 1).
1
was obtained on the basis of the H NMR spectrum of
the crude product (6b), and the enantiomeric excess of
the cis- and trans-2-imidazolines was determined to be
74% and 26%, respectively, by HPLC analysis. The initial
ee value of 74% for cis-6b could be easily raised to 99%
by a single recrystallization from THF/n-hexane. The
optically pure cis-2-imidazoline (6b) was converted to 7b
by hydrolysis. The absolute configuration of 7b was
determined to be 2R,3R by X-ray crystallography as
shown in ref 9. Thus, the absolute configuration of cis-
6b was assigned as (4R,5R)-4-(ethoxycarbonyl)-5-p-bro-
mophenyl)-1-N-tosyl-2-imidazoline.
In recent years, chemists have shown great interest
in using chiral ferrocenes as ligands of transition metal
complexes in asymmetric catalysis, and successful results
have been obtained in several asymmetric reactions.7 In
1986, Hayashi and Ito8a et al. reported an elegant
(7) (a) Marquarding, D.; Klusacek, H.; gokel, G.; Hoffmann, P.; Ugi,
I. J . Am. Chem. Soc. 1970, 92, 5389. (b) Hayashi, T.; Kumada, M. Acc.
Chem. Res. 1982, 15, 395. (c) Sawamura, M.; Ito, Y. Chem. Rev. 1992,
92, 857. (d) Riant, O.; Samael, O.; Kagan, H. B. J . Am. Chem. Soc.
1993, 115, 5835. (e) Togni, A. Angew. Chem., Int. Ed. Engl. 1996, 35,
1475. (f) Riant, O.; Samuel, O.; Flessner, T.; Taudien, S.; Kagan, H. J .
Org. Chem. 1997, 62, 6733. (g) Advances in Asymmetric Synthesis;
Hassner, A., Ed.; J AI press.: London, 1997; Vol. 2, p 190 and references
therein.
(1) (a) Betschart, C.; Hegedus, L. S. J . Am. Chem. Soc. 1992, 114,
5010. (b) Chern, J .-W.; Liaw, Y.-C.; Chen, C.-S.; Rong, J .-G.; Huang,
C.-L.; Chan, C.-H.; Wang, A. H. J . Heterocycles 1993, 36, 1091. (c)
Rondu, F.; Bihan, G. L.; Godfroid, J . J . J . Med. Chem. 1997, 40, 3793.
(d) Haiao, Y.; Hegedus, L. S. J . Org. Chem. 1997, 62, 3586.
(2) (a) J ones, R. C. F.; Howard, K. J .; Snaith, J . S. Tetrahedron Lett.
1996, 37, 1711. (b) J ones, R. C. F.; Howard, K. J .; Snaith, J . S.
Tetrahedron Lett. 1996, 37, 1707. (c) Morimoto, T.; Tachikana, K.;
Achiwa, K. Synlett 1997, 783. (d) Dalko, P. I.; Langlois, Y. Chem.
Commun. 1998, 331.
(8) (a) Ito, Y.; Sawamura, M.; Hayashi, T. J . Am. Chem. Soc. 1986,
108, 6405. (b) Hayashi, T.; Sawamura, M.; Ito, Y. Tetrahedron 1992,
48, 1999.
(9) Single-crystal X-ray structure of 7b:
(3) (a) Dunn, P. J .; Haner, R.; Rapoport, H. J . Org. Chem. 1990, 55,
5017 and references therein. (b) Pfammatter, E.; Seebach, D. Liebigs.
Ann. Chem. 1991, 1323. (c) Nakamura, Y.; Hirai, M.; Tamotsu, K.;
Yonezawa, Y.; Shin, C. Bull. Chem. Soc. J pn. 1995, 68, 1369. (d)
Fernandez-megia, E.; Sardina, F. J . Tetrahedron Lett. 1997, 38, 673.
(e) Soloshonok, V. A.; Avilov, D. V.; Kukhar, V. P.; Meervelt, L. V.;
Mischenko, N. Tetrahedron Lett. 1997, 38, 4671. (f) Han, H.; Yoon, J .;
J anda, K. D. J . Org. Chem. 1998, 63, 2045. (g) Merino, P.; Lanaspa,
A.; Merchan, F. L.; Tejero, T. Tetrahedron: Asymmetry 1998, 9, 629.
(4) (a) Dalko, P. I.; Langlois, Y. Tetrahedron Lett. 1992, 33, 5213.
(b) Dauwe, C.; Buddras, J . Synthesis 1995, 171. (c) Ojima, I. Acc. Chem.
Res. 1995, 28, 383.
(5) Lin, Y.-R.; Zhou, X.-T.; Dai, L.-X.; Sun, J . J . Org. Chem. 1997,
62, 1799.
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Lett. 1996, 37, 4969.
10.1021/jo980949s CCC: $18.00 © 1999 American Chemical Society
Published on Web 02/02/1999

1332 J . Org. Chem., Vol. 64, No. 4, 1999
Notes
Sch em e 1
Ta ble 1. Rea ction of N-Su lfon ylim in es 4 w ith Eth yl
Isocya n oa ceta te 5a Ca ta lyzed by Ch ir a l
value of trans-2-oxazoline decreased to 83% with the
longer reaction time (entry 4). On the contrary, for the
reactions with imines, 1 and 2 are a better combination
than that of 3 and 2. The ee values of cis-2-imidazoline
were obviously increased from 14% and 37% (entries 2
and 3) to 49% and 74% (entries 5 and 6), respectively.
F er r ocen ylp h osp h in e (2)-Me2SAu Cl Com p lexa
time ratiob of cis-6 cis-6 (% ee)d trans-6
no.
R
(h) cis/trans (%)c
(confign)
(% ee)d
1
2
3
4
5
6
7
8
9
p-ClPh
p-BrPh
0-BrPh
p-IPh
p-NO2Ph
p-CF3Ph
Ph
24
20
20
20
24
20
24
34
48
48
>96:4
>96:4
85:15
96:4
94:6
90:10
92:8
96:4
96:4
92:8
91
90
76
86
84
82
85
88
89
79
60 (4R,5R)
74 (4R,5R)
72 (4R,5R)
88 (4R,5R)
62 (4R,5R)
46 (4R,5R)
61 (4R,5R)
47 (4R,5R)
58 (4R,5R)
58 (4R,5R)
26
25
In general, the isocyanide is a stronger coordinating
ligand with gold(I) than thioether. Thioether is supposed
to be displaced by phosphine ligands more easily in the
present reactions. However, we also found that the
neutral gold(I) complex AuCl(c-HexNC) with ligand 2
shows an enantioselectivity as good as the 1 + 2 system
for the reaction of 4a and 5a (cis-6a : [R]20D -175°). Togni
and Pastor10 reported a crystal structure of neutral gold-
(I)-chiral aminoferrocenylphosphine and suggested that
there were a similar transition state structure in the
stereoselective step in the presence of neutral and
cationic gold(I) complexes for the aldol reaction of alde-
hydes. However, the changes in the enantioselectivity
listed in Table 2 cannot be explained using the same
transition state. We also noticed that a different chemical
shift in 31P NMR spectrum were observed in the two
catalytic systems. Up to now, we cannot rationalize the
above result in a reasonable explanation.
27
32
15
p-CH3Ph
p-CH3OPh
10 R-naphthyl
28
a
The reaction was carried out in CH2Cl2 at 25 °C for 20-48 h.
4/5/catalyst ) 1/1/0.005. Determined by 1H NMR analysis before
b
isolations. c Isolated yields. Determined by HPLC analysis using
d
a chiral OD or AD column.
We found that the enantioselectivity was not affected
by the electronic property of the substituents on phenyl
ring of imine. For example, although p-CF3 group is a
stronger withdrawing group than p-CH3 group (Table 1,
entries 6 and 8), the ee values of 6f and 6g are almost
the same. However, as we can see from Table 1, the same
reaction of N-tosyl p-Cl-, p-Br-, and p-I-benzaldimine
gave ee values of 60, 74, and 88%, respectively. It appears
that the larger substituent in the phenyl group gives a
higher enantioselectivity. On the other hand, the alkyl
group R in the ester group (-COOR, R ) Me (5b), Et (5a ),
i-Pr (5c)) on the isocyanoacetate could also affect both
trans/cis selectivity and enantioselectivity of the products.
In the case of the reaction of 4a with 5b, 5a , and 5c, cis/
trans ratios of 91:9, >96:4, and 93:7 were given respec-
tively with the corresponding ee values of 49%, 60%, and
66%. The better results were obtained in the use of 5a
or 5c with imine (4) in the present conditions.
We have shown that gold complexes 1 and 3 gave
different enantioselectivity in the reaction with imines
by using the same chiral ferrocenyl ligand (2). The results
listed in Table 2 indicated that 1 and 3 behave differently
in reactions with aldehyde and imine. For the reaction
with aldehyde, the combination of 3 and 2 gave better
results than that of 1 and 2, showing higher stereose-
lectivity and higher ee values with shorter reaction time.
For instance, the reaction of 5b with p-chlorobenzalde-
hyde provided trans-2-oxazoline with an ee value of 94%
([R] ) +274°, lit.8b +273°) in 24 h (entry 1). When Me2-
SAuCl (1) was used instead of 3, we found that the ee
In summary, a catalytic enantioselective reaction of
N-sulfonylimines with isocyanoacetates has been achieved
by using chiral Me2SAuCl-ferrocenylphophine catalyst.
The mildness of the reaction conditions, the simplicity
of the procedure, and rather high ee values, from which
a optically pure cis-2-imidazoline could be easily obtained
by a single recrystallization, will offer a convenient and
efficient method for the synthesis of the optically pure
2, 3-diamino acids and other useful optically active
derivatives. Further investigation is now in progress.
Exp er im en ta l Section
Ma ter ia ls a n d Gen er a l Meth od s. 1H NMR spectra were
recorded in CDCl3 at 300 MHz. All N-sulfonylimines 4,11
isocyanoacetates 5,12 and Au(I) complexes13 were prepared
according to literature methods. Ferrocenylphosphine 2 was
prepared according to the reported procedure.8b,14 THF and
n-hexane were refluxed with sodium and then freshly distilled.
(10) Togni, A.; Pastor, S. D. J . Organomet. Chem. 1990, 381, C21.
(11) (a) Love, B. E.; Raje, P. S.; Williams, T. C., II. Synlett 1994,
493. (b) J ennings, W. B.; Lovely, C. T. Tetrahedron Lett. 1988, 29, 3725.
(12) Hartman, G. D.; Weinstock, L. M. Org. Synth. 1988, 6, 620.
(13) Bonati, F.; Minghetti, G. Gazz. Chim. Ital. 1973, 103, 373.

Notes
J . Org. Chem., Vol. 64, No. 4, 1999 1333
Ta ble 2. Rea ction of p-Cl-ben za ld eh yd e a n d N-Su lfon ylim in e w ith Isocya n oa ceta te 5 Ca ta lyzed by Au (I) Com p lexes 1
a n d 3a
Au(I)
complex
ratiob of
cis/trans
no.
substrate
time (h)
product (ee %)c
1
2
p-ClPhCHO/CNCH2CO2Me (5b)
p-ClPhCHdNTs (4a )/5b
3
3
24
55
5/95
67/33
trans-2-oxazoline (94)
cis-2-imidazoline (14)
trans-2-imidazoline (25)
cis-2-imidazoline (37)
trans-2-oxazoline (83)
cis-2-imidazoline (49)
cis-2-imidazoline (74)
3
4
5
6
p-BrPhCHdNTs (4b)/CNCH2CO2Et (5a )
p-ClPhCHO/5b
p-ClPhCHdNTs (4a )/5b
p-BrPhCHdNTs (4b)/5a
3
1
1
1
55
50
24
20
90/10
17/83
88/12
96/4
a
b
The reaction was carried out in CH2Cl2 at 25 °C. Determined by 1H NMR analysis before isolations. c Determined by HPLC analysis
using a chiral OD column.
Dichloromethane was distilled immediately prior to use from
CaH2 under nitrogen. All melting points are uncorrected.
Gen er a l P r oced u r e for th e Me2SAu Cl-F er r ocen ylp h os-
p h in e Ca ta lyzed Rea ction of N-Su lfon ylim in es (4) w ith
Eth yl Isocya n oa ceta te (5a ). A mixture of Me2SAuCl (1, 1.2
mg, 0.004 mmol) and chiral ligand (2, 2.4 mg, 0.0033 mmol) in
4 mL of CH2Cl2 was stirred for 15 min, and then to the resultant
solution were added sequentially 195 mg of 4a (0.66 mmol) and
75-80 mg of 5a (0.66-0.70 mmol). The reaction mixture was
stirred under nitrogen at 25 °C for 20-24 h until 4a was not
detected by silica TLC. After removal of the catalyst by filtration,
the solvent was removed under vacuum to give a crude trans/
cis mixture of 2-imidazoline, which was isolated by preparative
TLC (petroleum ether (60-90 °C):ethyl acetate:dichloromethame
) 4:2:1) to give cis-(4R,5R)-2-imidazoline (6a ). The enantiomeric
excess of cis-6a was determined by HPLC analysis, and the cis/
trans ratio was determined by using 1H NMR spectra of the
crude product. The chemical yield of cis/trans-2-imidazoline was
nearly quantitative. The yields of cis-2-imidazolines are listed
in Table 1.
2.43 (s, 3 H), 3.47-3.55 (m, 1 H), 3.65-3.71 (m, 1H), 5.18 (dd, J
) 11.35, 1.82 Hz, 1 H), 5.47 (d, J ) 11.35 Hz, 1 H), 7.09-7.21
(m, 3 H), 7.28 (d, J ) 8.30 Hz, 2 H), 7.48-7.51 (m, 1H), 7.60 (d,
) 8.06 Hz, 2 H), 7.79 (d, J ) 1.77 Hz, 1H); IR 1751 cm-1, 1610
cm-1; MS m/z 451 (M+, 8), 378 (5), 155 (28), 91 (63). Anal. Calcd
for C19H19 BrN2O4S: C, 50.56; H, 4.24; N, 6.20. Found: C, 50.29;
H, 4.16; N, 6.02.
(4R,5R)-cis-4-(E t h oxyca r b on yl)-5-(4-iod op h en yl)-1-N-
tosyl-2-im id a zolin e (cis-6d ): 86% yield; mp 130-131.5 °C;
[R]20 -207° (c 1.00, THF); 88% ee (determined by HPLC
D
analysis using a CHIRALCEL OD column: 25 cm × 0.46 cm
i.d.; eluent, 20% i-PrOH in hexane; flow rate, 0.7 mL/min, (+)-
6d tR ) 20.513 min, (-)-6d tR ) 27.100); 1H NMR (CDCl3/TMS)
δ 0.81 (t, 3 H), 2.43 (s, 3 H), 3.63-3.74 (m, 2 H), 5.10 (d, J )
11.12 Hz, 1 H),5.20 (d, J ) 11.12 Hz, 1 H), 6.73 (d, J ) 8.10 Hz,
2 H), 7.15 (d, J ) 8.10 Hz, 2 H), 7.37-7.42 (m, 4 H), 7.77 (s,
1H); IR 1751 cm-1, 1610 cm-1; MS m/z 498 (M+ + 1, 8), 425 (7),
342 (100), 270 (2), 155 (18). Anal. Calcd for C19H19 IN2O4S: C,
45.79; H, 3.84; N, 5.62. Found: C, 45.77; H, 3.59; N, 5.36.
(4R,5R)-cis-4-(E t h oxyca r b on yl)-5-(4-n it r op h en yl)-1-N-
(4R,5R)-cis-4-(Eth oxyca r bon yl)-5-(4-ch lor op h en yl)-1-N-
tosyl-2-im id a zolin e (cis-6e): 84% yield; mp 118-120 °C; [R]20
D
tosyl-2-im id a zolin e (cis-6a ): 91% yield; [R]20 -182° (c 1.00,
D
-233° (c 1.00, THF); 62% ee (determined by HPLC analysis
using a CHIRALPKA AD column: 25 cm × 0.46 cm i.d.; eluent,
40% i-PrOH in hexane; flow rate, 0.7 mL/min, (-)-6e tR ) 38.963
min, (+)-6e tR ) 53.017); 1H NMR (CDCl3/TMS) δ 0.82 (t, 3 H),
2.41 (s, 3 H), 3.52-3.60 (m, 1 H), 3.70-3.78 (m, 1H), 5.17 (d, J
) 11.59 Hz, 1 H), 5.25 (d, J ) 11.59 Hz, 1 H), 7.17-7.27 (m, 4
H), 7.47 (d, J ) 8.12 Hz, 2 H), 7.79 (s, 1 H), 8.01 (d, J ) 8.51 Hz,
2 H); IR 1738 cm-1, 1628 cm-1; MS m/z 417 (M+ + 1, 26), 344
(18), 262 (88), 155 (65), 91 (100). Anal. Calcd for C19H19N3O6S:
C, 54.67; H, 4.58; N, 10.07. Found: C, 54.53; H, 4.61; N, 10.04.
THF 60% ee (determined by HPLC analysis using a CHIRAL-
CEL OD column: 25 cm × 0.46 cm i.d.; eluent, 15% i-PrOH in
hexane; flow rate, 0.7 mL/min, (+)-6a tR ) 19.667 min, (-)-6a
tR ) 26.320 min). The optically pure cis-2-imidazoline was
obtained from the filtrate by recrystallization in THF/n-hexane
in 40% yield and 99% ee: mp 139.5-140 °C; [R]20D -298° (c 1.00,
THF); 1H NMR (CDCl3/TMS) δ 0.80 (t, 3 H), 2.39 (s, 3 H), 3.54-
3.77 (m, 2 H), 5.11 (d, J ) 11.28 Hz, 1 H), 5.18 (d, J ) 11.28 Hz,
1 H), 6.92 (d, J ) 8.32 Hz, 2 H), 7.05 (d, J ) 8.32 Hz, 2 H), 7.12
(d, J ) 8.06 Hz, 2 H), 7.38 (d, J ) 8.06 Hz, 2 H), 7.75 (s, 1H); IR
1750 cm-1, 1610 cm-1; MS m/z 406 (M+ + 1, 4), 333 (13), 251
(100), 178 (3), 155 (30), 91 (74). Anal. Calcd for C19H19
ClN2O4S: C, 56.08; H, 4.70; N, 6.88. Found: C, 56.24; H, 4.74;
N, 6.69.
(4R ,5R )-cis-4-(E t h oxyca r b on yl)-5-(4-t r iflu or om e t h yl-
p h en yl)-1-N-tosyl-2-im id a zolin e (cis-6f): 82% yield; mp 130-
132 °C; [R]20D -149° (c 1.00, THF); 46% ee (determined by HPLC
analysis using a CHIRALCEL OD column: 25 cm × 0.46 cm
i.d.; eluent, 20% i-PrOH in hexane; flow rate, 0.7 mL/min, (+)-
(4R,5R)-cis-4-(Eth oxyca r bon yl)-5-(4-br om op h en yl)-1-N-
1
6f tR ) 16.080 min, (-)-6f tR ) 21.720); H NMR (CDCl3/TMS)
tosyl-2-im id a zolin e (cis-6b): 90% yield; [R]20 -192° (c 1.01,
D
δ 0.76 (t, 3 H), 2.37 (s, 3 H), 3.54-3.60 (m, 1 H), 3.67-3.73 (m,
1H), 5.24 (s, 2 H), 7.09-7.16 (m, 4 H), 7.32-7.41 (m, 4H), 7.79
(s, 1H); IR 1752 cm-1, 1610 cm-1; MS m/z 440 (M+ + 1, 42), 367
(18), 285 (100), 212 (2), 155 (53), 91 (97). Anal. Calcd for C20H19
F3N2O4S: C, 54.54; H, 4.34; N, 6.36. Found: C, 54.26; H, 4.12;
N, 6.57.
THF); 74% ee (determined by HPLC analysis using a CHIRAL-
CEL OD column: 25 cm × 0.46 cm i.d.; eluent, 20% i-PrOH in
hexane; flow rate, 0.7 mL/min, (+)-6b tR ) 24.390 min, (-)-6b
tR ) 30.177 min). The optically pure cis-2-imidazoline was
obtained from the filtrate by the recrystallization in THF/n-
hexane in 37% yield and 99% ee: mp 143.5-144 °C; [R]20D -259°
(4R ,5R )-cis-4-(E t h oxyca r b on yl)-5-p h e n yl-1-N -t osyl-2-
1
(c 1.00, THF); H NMR (CDCl3/TMS) δ 0.82 (t, 3 H), 2.41 (s, 3
im id a zolin e (cis-6g): 85% yield; mp 152-154 °C; [R]20 -175°
D
H), 3.59-3.77 (m, 2 H), 5.11 (d, J ) 11.35 Hz, 1 H), 5.18 (d, J )
11.35 Hz, 1 H), 6.87 (d, J ) 8.39 Hz, 2 H), 7.16 (d, J ) 8.21 Hz,
2 H), 7.21 (d, J ) 8.39 Hz, 2 H), 7.39 (d, J ) 8.21 Hz, 2 H), 7.75
(s, 1H); IR 1751 cm-1, 1610 cm-1; MS m/z 451 (M+, 20), 378 (5),
155 (24), 91 (64). Anal. Calcd for C19H19 BrN2O4S: C, 50.56; H,
4.24; N, 6.20. Found: C, 50.38; H, 4.18; N, 6.04.
(c 1.02, THF); 61% ee (determined by HPLC analysis using a
CHIRALPAK AD column: 25 cm × 0.46 cm i.d.; eluent, 20%
i-PrOH in hexane; flow rate, 0.7 mL/min, (-)-6g tR ) 22.513
min, (+)-6g tR ) 35.180); 1H NMR (CDCl3/TMS) δ 0.75 (t, 3 H),
2.37 (s, 3 H), 3.49-3.55 (m, 1 H), 3.65-3.68 (m, 1 H), 5.17 (s, 2
H), 7.00 (d, J ) 7.10 Hz, 2 H), 7.07-7.18 (m, 5 H), 7.40 (d, J )
8.19 Hz, 2 H), 7.76 (s, 1 H); IR 1749 cm-1, 1614 cm-1; MS m/z
372 (M+ + 1, 21), 299 (18), 217 (100), 155 (28), 91 (78). Anal.
Calcd for C19H20N2O4S: C, 61.27; H, 5.41; N, 7.52. Found: C,
61.09; H, 5.59; N, 7.32.
(4R,5R)-cis-4-(Eth oxyca r bon yl)-5-(2-br om op h en yl)-1-N-
tosyl-2-im id a zolin e (cis-6c): 76% yield; mp 128-130 °C; [R]20
D
-298° (c 1.05, THF); 72% ee (determined by HPLC analysis
using a CHIRALCEL OD column: 25 cm × 0.46 cm i.d.; eluent,
20% i-PrOH in hexane; flow rate, 0.7 mL/min, (-)-6c tR ) 16.860
min, (+)-6c tR ) 21.387); 1H NMR (CDCl3/TMS) δ 0.82 (t, 3 H),
(4R,5R)-cis-4-(Eth oxyca r bon yl)-5-(4-m eth ylp h en yl)-1-N-
tosyl-2-im id a zolin e (cis-6h ): 88% yield; mp 130-132 °C; [R]20
D
-160° (c 1.00, THF); 47% ee (determined by HPLC analysis
using a CHIRALCEL OD column: 25 cm × 0.46 cm i.d.; eluent,
20% i-PrOH in hexane; flow rate, 0.7 mL/min, (+)-6h tR ) 15.610
min, (-)-6h tR ) 21.730); 1H NMR (CDCl3/TMS) δ 0.78 (t, 3 H),
(14) (a) Hayashi, T.; Mise, T.; Fukushima, M.; Kagotani, M.;
Nagashima, N.; Hamada, Y.; Matsumoto, A.; Kawakami, S.; Konishi,
M.; Yamamoto, K.; Kumada, M. Bull. Chem. Soc. J pn. 1980, 53, 1138.
(b) Hayashi, T.; Yamazaki, A. J . Organomet. Chem. 1991, 413, 295.

1334 J . Org. Chem., Vol. 64, No. 4, 1999
Notes
2.25 (s, 3 H), 2.38 (s, 3 H), 3.58-3.69 (m, 2 H), 5.14 (s, 2 H),
6.89 (s, 4 H), 7.12 (d, J ) 8.07 Hz, 2 H), 7.05 (d, J ) 8.07 Hz, 2
H), 7.75 (s, 1 H); IR 1753 cm-1, 1609 cm-1; MS m/z 386 (M+ + 1,
42), 313 (11), 231 (100), 155 (20), 91 (63). Anal. Calcd for C20H22
N2O4S: C, 62.15; H, 5.73; N, 7.25. Found: C, 62.06; H, 5.62; N,
7.15.
Typ ica l P r oced u r e for th e Gr a m Sca le: 5.8 mg (0.019
mmol) of 1 and 12.1 mg (0.016 mmol) of 2 in 15 mL of CH2Cl2
were stirred for 15 min, and then to the mixture were added
980 mg of 4a (3.34 mmol) and 388 mg of 5a (3.43 mmol). The
mixture was stirred under nitrogen at 25 °C for 24 h until 4a
was not detected by silica TLC. Removal of the catalyst by
filtration through silica and evaporation of the solvent under
vacuum gave a cis/trans mixture (90:10) of 2-imidazoline quan-
titatively. The cis isomer was isolated by column chromatogra-
phy over silica gel eluting with petroleum ether (60-90 °C)-
ethyl acetate-dichloromethame (4:2:1) to give 60% ee of cis-
(4R,5R)-cis-4-(Eth oxyca r bon yl)-5-(4-m eth oxylp h en yl)-1-
N-tosyl-2-im id a zolin e (cis-6i): 89% yield; mp 119-120 °C;
[R]20 -170° (c 1.00, THF); 58% ee (determined by HPLC
D
analysis using a CHIRALCEL OD column: 25 cm × 0.46 cm
i.d.; eluent, 20% i-PrOH in hexane; flow rate, 0.7 mL/min, (+)-
1
6i tR ) 21.567 min, (-)-6i tR ) 28.007); H NMR (CDCl3/TMS)
(4R,5R)-2-imidazoline 6a (1.12 g) in 82% yield, [R]20 -185° (c
D
δ 0.75 (t, 3 H), 2.33 (s, 3 H), 3.49-3.57 (m, 1 H), 3.62-3.73 (m,
1 H), 3.68 (s, 3 H), 5.10 (s, 2 H), 6.55 (d, J ) 8.57 Hz, 2 H), 6.86
(d, J ) 8.57 Hz, 2 H), 7.08 (d, J ) 8.20 Hz, 2 H), 7.34 (d, J )
8.20 Hz, 2 H), 7.70 (s, 1H); IR 1730 cm-1, 1611 cm-1; MS m/z
402 (M+ + 1, 4), 329 (8), 247 (95), 174 (6), 155 (9), 91 (49). Anal.
Calcd for C20H22 N2O5S: C, 59.68; H, 5.51; N, 6.96. Found: C,
59.60; H, 5.54; N, 6.63.
1.005, THF). The optically pure cis-6a (99% ee) was obtained in
39% yield from the filtrate by the recrystallization in THF/
hexane (12 mL/24 mL): mp 139-139.5 °C; [R]20 -311° (c 1.05,
D
THF).
Ack n ow led gm en t. Financial support from National
Natural Science Foundation of China (project no.
29772046) and Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, is gratefully
acknowledged.
(4R,5R)-cis-4-(Eth oxyca r bon yl)-5-(r-n a p h th yl)-1-N-tosyl-
2-im id a zolin e (cis-6j): 79% yield; mp 151-153 °C; [R]20D -227°
(c 1.00, THF); 58% ee (determined by HPLC analysis using a
CHIRALCEL OD column: 25 cm × 0.46 cm i.d.; eluent, 10%
i-PrOH in hexane; flow rate, 0.7 mL/min, (-)-6j tR ) 41.050 min,
1
(+)-6j tR ) 47.157); H NMR (CDCl3/TMS) δ 0.21 (t, 3 H), 2.39
(s, 3 H), 3.02-3.10 (m, 1 H), 3.34-3.49 (m, 1H), 5.39 (d, J )
11.43 Hz, 1 H), 5.96 (d, J ) 11.43 Hz, 1 H), 7.18-7.93 (m, 12H);
IR 1738 cm-1, 1630 cm-1; MS m/z 422 (M+ + 1, 10), 349 (7), 267
(100), 194 (15), 155 (16), 91 (34). Anal. Calcd for C23H22 N2O4S:
C, 65.38; H, 5.25; N, 6.63. Found: C, 65.06; H, 5.41; N, 6.63.
Su p p or tin g In for m a tion Ava ila ble: X-ray structural
analysis of 7b. This material is available free of charge via
the Internet at http://acs.org.
J O980949S