Asymmetric addition of titanium and sodium alkoxides to chiral imines

Article abstract of DOI:10.1016/S0957-4166(03)00121-6

A novel method for the alkoxylation of imines was developed using alkoxytitanium(IV) derivatives as the alkoxy nucleophile donors. A rationale of the results obtained using stereochemical models is proposed. The differences in the stereochemical outcome o

Full text of DOI:10.1016/S0957-4166(03)00121-6

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 1161–1166
Asymmetric addition of titanium and sodium alkoxides to chiral
imines
Anna Kulesza,a Adam Mieczkowski,a Jan Roman´skia and Janusz Jurczaka,b,
*
aDepartment of Chemistry, Warsaw University, Pasteura 1, PL-02-093 Warsaw, Poland
bInstitute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, PL-01-224 Warsaw, Poland
Received 6 January 2003; accepted 27 January 2003
Abstract—A novel method for the alkoxylation of imines was developed using alkoxytitanium(IV) derivatives as the alkoxy
nucleophile donors. A rationale of the results obtained using stereochemical models is proposed. The differences in the
stereochemical outcome of the reaction with the titanium species and sodium alkoxides were studied as well as the influence of
chiral auxiliaries such as (2R)-bornano-10,2-sultam, (R)-8-phenylmenthol and 10-N,N-dicyclohexylsulphamoyl-(R)-isoborneol.
© 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
isopropoxy derivative. At this point, we decided to
investigate this type of nucleophilic addition.
In our previous reports on the asymmetric induction
properties of N-glyoxyloyl-(2R)-bornano-10,2-sultam
in nucleophilic addition1 and hetero-Diels–Alder reac-
tions,2,3 we described a stereochemical rationalisation of
the asymmetric induction and the advantages of (2R)-
bornano-10,2-sultam as a chiral auxiliary. The 10-N,N-
dicyclohexylsulphamoyl-(R)-isobornyl glyoxylate was
found to be less beneficial in terms of diastereoselectiv-
ity in the nucleophilic addition of allyltrimethylsilane to
carbonyl compounds.4 Recently, we have reported on
the diastereoselective hetero-Diels–Alder reactions of
N-tosylimines of N-glyoxyloyl-(2R)-bornano-10,2-sul-
tam that have shown a very good diastereofacial differ-
entiation.5 Our initial study on asymmetric nucleophilic
additions to imines bearing different chiral auxiliaries
was focused on the addition of allyl-type reagents such
allyltrimethylsilane6,7 or Barbier reagents8 to N-
tosylimines derived from N-glyoxyloyl-(2R)-bornano-
10,2-sultam and glyoxylates of (R)-8-phenylmenthyl
and 10-N,N-dicyclohexylsulphamoyl-(R)-isobornyl. In
the course of studying the addition of allyltrimethyl-
silane, we examined various Lewis acids in an atempt to
optimise the reaction conditions. Among them, we
tested titanium(IV) isopropoxide, which has been used
successfully as a catalyst for additions to carbonyl
compounds and unexpectedly, we found that instead of
the appropriate allyl addition product we obtained the
2. Results and discussion
The N-tosylimines were obtained from the correspond-
ing derivatives of glyoxylic acid by the method intro-
duced recently by Holmes et al.9 The reaction of
compounds 1a–c with p-toluenesulphonyl isocyanate 2
in refluxing toluene afforded the expected imines 3a–c,
respectively (Scheme 1).
* Corresponding author. Tel.: +48-(22)-823-0944; fax: +48-(22)-822-
5996; e-mail: jjurczak@chem.uw.edu.pl
Scheme 1.
0957-4166/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0957-4166(03)00121-6

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A. Kulesza et al. / Tetrahedron: Asymmetry 14 (2003) 1161–1166
2.1. Addition of titanium alkoxides to chiral imines
Based on that rationale, the opposite absolute configu-
ration (2%R) of the major isomer obtained from the
addition of tetraisopropoxytitanium is a consequence of
chelation of the carbonyl group and the oxygen atom of
the nucleophile by titanium (Fig. 1, B).
The addition of isopropoxytitanium to imines was car-
ried out using 1 molar equivalent of the nucleophile
and afforded easily separable, crystalline diastereoiso-
mers. The reaction proved the advantage of (2R)-bor-
nano-10,2-sultam over other auxiliaries, resulting in
excellent diastereoselectivity (d.e. >97%). The less struc-
Another stereodifferentiating effect has its origin in the
p–p stacking of the (R)-8-phenylmenthyl moiety of 1b.
It provides excellent asymmetric induction in the reac-
tions of its various derivatives such as acrylates,
acetamidoacrylates, glyoxylates and many others.10 In
addition, the stereoselectivity is believed to benefit from
face-to-face p–p interactions between the aryl moiety
and the unsaturated reacting site in the s–trans confor-
mation due to chelation by the titanium species as
shown in Fig. 2.
turally
rigid
10-N,N-dicyclohexylsulphamoyl-(R)-
isoborneol system gave lower levels of asymmetric
induction. In contrast with the previous results, the
N-tosylimine of (R)-8-phenylmenthylglyoxylate dis-
played moderate stereoselectivity in this reaction. With
all of these chiral auxiliaries we obtained the (2%R)
diastereoisomer in excess (Table 1).
Table 1. Results of addition of tetraisopropoxytitanium to
N-tosylimines
Imine
Yield (%)
Diastereomeric ratio R:S
2a
2b
2c
50
55
56
100:0
77:23
84:16
In order to provide a thorough rationalisation for
alkoxylation with tetraisopropoxytitanium we have to
mention the results of addition of allyltrimethylsilane to
the corresponding N-tosylimines of N-glyoxyloyl-(2R)-
Figure 2.
bornano-10,2-sultam
that
afforded
the
(2%S)
diastereoisomer as the major product. In the case of the
allyl nucleophile, we proposed that the SO2/CO syn-
periplanar, CO/CHNTs s–cis planar conformer A was
most likely to take part in the transition state due to its
high reactivity reinforced by the cooperative stereoelec-
tronic effect, as recently formulated by Chapuis et al.2,3
for N-glyoxyloyl-(2R)-bornano-10,2-sultam 1a (Fig. 1).
62.2. Addition of sodium alkoxides to chiral imines
The above stereochemical model is supported by the
results from the addition of simple sodium alkoxides to
N-tosylimines. These reactions provide the opposite
diastereoisomer (2%S) as the predominant one for all
chiral auxiliaries (Table 2). Introduction of a non-
chelating nucleophile releases the s–trans conformation
of CO/CNTs imposed by titanium (Fig. 1, conformer
B, and Fig. 2) and leads to the preferred s–cis confor-
mation being the one (Fig. 3).
Figure 1.
Figure 3.
Table 2. Results of addition of sodium alkoxides to N-tosylimines
Imine
Nucleophile
Yield (%)
Diastereomeric ratio R:S
2b
2b
2c
2c
2c
PriO−Na+/10% Ti(O-iPr)4
PriO−Na+
65
70
38
54
46
23:77
25:75
18:82
35:65
27:73
PriO−Na+
MeO−Na+
EtO−Na+

A. Kulesza et al. / Tetrahedron: Asymmetry 14 (2003) 1161–1166
1163
As Oppolzer has proposed,11 the most favourable con-
formation is reached when the alkoxy CꢀH bond is
syn-periplanar to the CꢁO moiety of the ester (as
supported by recent X-ray analysis).12 As a conse-
quence, these prosthetic groups possess an identical
sterically-induced Ca-si topicity, where the (E)CꢁN
bond is s–cis to the CꢁO bond (Fig. 3). PM3 calcula-
tions confirmed the thermodynamic stability and higher
reactivity of s–cis conformers over the s–trans forms.13
The influence of the steric bulk of the nucleophilic
species was also investigated. The diastereoselectivity
rises for more sterically demanding alkoxides such as
isopropoxide and it drops to the lowest value for the
methoxy derivative. Due to the high basicity of the
nucleophiles, during the reactions with (2R)-bornano-
10,2-sultam as the chiral auxiliary, hydrolysis of the
imide bond was observed and no product was recov-
ered from the reaction mixture.
The 2%R absolute configurations were determined for
4a–c by X-ray analysis (Figs. 4–6, respectively).
2.3. Addition of tetra-1,2:3,4-di-O-isopropylidene-a-D-
galactopyranosyltitanium to 3a
In the course of our studies, we decided to investigate
the outcome of addition of chiral titanium nucleophiles
to imines. Transition metals have already been used to
assemble sugars in novel architectures14 and the tita-
nium–carbohydrate complexes were applied as the chi-
ral catalysts eg. in enantioselective allylation of
carbonyl compounds15 and aldol reaction.16 The
molecules so formed take advantage of the inherent
properties of both sugar and metal. The formation of
chiral complex 8 involved reaction of tetra-1,2:3,4-di-O-
Figure 4. Crystal structure of N-((2%R)-N%-p-toluenesulpho-
nylisopropoxyglycinoyl)-(2R)-bornano-10,2-sultam imide (R)-
4a.
isopropylidene-a-D
-galactopyranose with Ti(O-Pri)4 in
Et2O to afford titanium complex 8 (Scheme 2), which
was used in situ in the alkoxylation reaction with
N-tosylimine of N-glyoxyloyl-(2R)-bornano-10,2-sul-
tam. Such double stereocontrol resulted in >95% asym-
metric induction. More detailed analysis was
unmanageable due to the instability of the product.
Figure 5. Crystal structure of N-((2%R)-N%-p-toluenesulpho-
nylisopropoxyglycine)-8-(R)-phenylmenthyl ester (R)-4b.
Figure 6. Crystal structure of N-((2%R)-N%-p-toluenesulpho-
nylisopropoxyglycine)-10-N,N-dicyclohexylsulphamoyl-(2R)-
isoborneyl ester (R)-4c.
Scheme 2.

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A. Kulesza et al. / Tetrahedron: Asymmetry 14 (2003) 1161–1166
3. Conclusions
4.2.1.
N-((2%R)-N%-p-Toluenesulphonylisopropoxygly-
cinoyl)-(2R)-bornano-10,2-sultam imide, (R)-4a. Mp=
155–158°C; [h]2D0=−68.3 (c 1, CHCl3); IR 3276, 2970,
1942, 1697, 1345, 1169 cm−1; 1H NMR (200 MHz,
CDCl3): l 7.74 (d1/2AB, J=8.4, 2H), 7.25 (d1/2AB,
J=8.4, 2H), 5.94 (d, J=9.8, 2H), 4.13 (septet, J=6.0,
1H), 3.71 (t, J=6.3, 1H), 3.42 (qAB, 2H), 2.40 (s, 3H),
2.00–1.80 (m, 4H), 1.53–1.22 (m, 3H), 1.19 (d, J=6.2,
3H), 1.17 (d, J=6.4, 3H), 1.08 (s, 3H), 0.95 (s, 3H); 13C
NMR (200 MHz, CDCl3): l 165.7, 143.6, 137.8, 129.7,
127.1, 79.0, 71.0, 65.0, 52.8, 49.0, 47.8, 44.3, 37.6, 32.7,
26.4, 23.1, 21.6, 21.0, 20.4, 19.9; ESIMS m/e (%) 991
(2M+Na)+ (15), 507 (M+Na) (100); HRMS (EI) calcd
for C22H32N2NaO6S2 (M+Na): 507.1617. Found:
507.1594. Anal. calcd for C22H30N2O6S2: C, 54.5; H,
6.7; N, 5.8; S, 13.7. Found: C, 54.4; H, 7.0; N, 5.7; S,
13.2%.
The 1,2-nucleophilic addition of different titanium and
sodium alkoxides to three N-tosylimines bearing differ-
ent chiral auxiliaries has been described. Excellent
stereoselectivities were obtained with (2R)-bornano-
10,2-sultam. The application of the titanium-complexed
nucleophile leads to an excess of the opposite
diastereoisomer to that obtained in predominance with
sodium alkoxides, which suggests the chelation of both
substrates by the metal. Finally, we have introduced the
chiral complex tetra-1,2:3,4-di-O-isopropylidene-a-D-
galactopyranosyl titanium(IV) as a nucleophile for such
addition reactions.
4. Experimental
4.2.2.
N-((2%R)-N%-p-Toluenesulphonylisopropoxy-
Reagent grade solvents (CH2Cl2, hexanes, EtOAc,
THF) were distilled prior use. All reported NMR spec-
tra were recorded on a Varian Gemini spectrometer
operating at 200 MHz (1H NMR) or 50 MHz (13C
NMR). Chemical shifts are reported as l values relative
to TMS pas internal standard (l=0). IR spectra were
recorded on a Perkin–Elmer 1640 FTIR. Mass spectra
were obtained on an AMD-604 Intectra instrument
using the electron impact (EI) mode. Column chro-
matography was performed on silica (Kieselgel 60, 200–
400 mesh). Optical rotations were recorded using a
JASCO DIP-360 polarimeter with a thermally jacketed
10 cm cell. All air- or moisture-sensitive reactions were
carried out in a flame-dried glassware under argon.
glycine)-8-(R)-phenylmenthyl ester, (R)-4b. Mp=85–
1
88°C; [h]2D0=+5.0 (c 1, CHCl3); H NMR (200 MHz,
CDCl3): l 7.79 (d1/2AB, J=8.4, 2H), 7.34–7.12 (m,
5H), 5.49 (d, J=10, 1H), 4.74 (d, J=10, 1H), 4.60 (td,
J1=4.4, J2=10.6, 1H), 3.99 (septet, J=6.2, 1H), 2.40
(s, 3H), 1.87–1.70 (m, 1H), 1.56–1.34 (m, 3H), 1.28 (s,
3H), 1.21 (s, 3H), 1.17–1.12 (m, 6H), 1.06–0.84 (m, 3H),
0.77 (d, J=6.4, 3H), 0.59–0.42 (m, 1H); 13C NMR (200
MHz, CDCl3): l 166.7, 150.1, 143.5, 129.7, 128.7,
128.1, 127.0, 125.7, 125.5, 79.7, 77.1, 69.9, 50.2, 40.8,
40.1, 34.3, 31.1, 28.6, 26.9, 25.5, 22.8, 21.7, 21.6, 21.0.
4.2.3.
N-((2%S)-N%-p-Toluenesulphonylisopropoxy-
glycine)-8-(R)-phenylmenthyl ester, (S)-4b. Oil; [h]2D0=
+31.7 (c 1, CHCl3); IR (KBr): 3285, 2968, 2926, 1735,
1344, 1167 cm−1; H NMR (200 MHz, CDCl3): l 7.70
1
4.1. General procedure of preparation of N-toluene-
sulphonylimines 3a–c
(d1/2AB, J=8.4, 2H), 7.37–7.14 (m, 7H), 5.00 (d, J=
9.2, 1H), 4.68 (td, J1=4.2, J2=10.8, 1H), 4.42 (J=9.4,
1H), 3.71 (septet, J=6.2, 1H), 2.41 (s, 3H), 2.04–1.20
(m, 7H), 1.14 (d, J=7.4, 6H), 1.02–0.97 (m, 6H), 0.82
(d, J=6.6, 3H), 0.67–0.49 (m, 1H); 13C NMR (200
MHz, CDCl3): l 166.5, 151.8, 143.4, 138.6, 129.7,
129.5, 128.3, 126.9, 125.8, 79.5, 70.8, 50.2, 40.7, 39.3,
34.4, 31.1, 29.2, 28.8, 26.3, 23.1, 22.4, 21.7, 21.5, 21.3;
MS (EI) m/e (%) 442 (M+H)+(23), 242 (12), 215 (31),
119 (70), 105 (100); HRMS (EI) calcd for
C28H39NNaO5S (M+Na): 524.2447. Found: 524.2451.
Tosyl isocyanate (1.5 mmol, 0.23 ml) was added under
Ar to a solution of the corresponding glyoxylic acid
derivative (1.5 mmol) in toluene (10 ml) and the reac-
tion mixture was heated under reflux for 24 h. The
obtained imines were used without purification for the
alkoxylation reactions.
4.2. General procedure for addition of tetraisopropoxy-
titanium to N-toluenesulphonylimines 3a–c
4.2.4.
N-((2%R)-N%-p-Toluenesulphonylisopropoxy-
glycine)-10-N,N-dicyclohexylsulphamoyl-(2R)-isoborneyl
ester, (R)-4c. Mp=135–137°C; [h]2D0=−10.9 (c 1,
CHCl3); IR: 3270, 2932, 2856, 1746, 1598 cm−1; 1H
NMR (200 MHz, CDCl3): l 7.80–7.66 (m, 2H), 7.33–
7.22 (m, 2H), 5.86 (d, J=9.4, 1H), 5.22 (d, J=9.0, 1H),
4.90–4.80 (m, 1H), 4.00 (m, 1H), 3.39–3.18 (m, 3H),
2.75 (d, 1H), 2.40 (s, 3H), 1.98–1.08 (m, 33H), 0.99 (s,
3H), 0.86 (s, 3H); 13C NMR (200 MHz, CDCl3): l
166.0, 143.3, 138.0, 129.5, 127.0, 80.4, 80.0, 69.2, 57.8,
54.7, 49.9, 49.3, 44.4, 39.2, 32.9, 32.6, 30.9, 27.0, 26.4,
25.1, 22.5, 21.6, 21.4, 20.3, 19.8; MS (EI) m/e (%): 666
M+ (10), 606 (12), 451 (100), 387 (20), 244 (35), 228
(40), 200 (35); HRMS (EI) calcd for C34H54N2NaO7S2
(M+Na): 689.3265. Found: 689.3322. Anal. calcd for
C34H54N2O7S2: C, 61.2; H, 8.2; N, 4.2; S, 9.6. Found:
C, 61.4; H, 8.3; N, 4.3; S, 9.5%.
Tetraisopropoxytitanium (0.048 ml, 0.32 mmol) was
added to a solution of the N-tosylimine of 10-N,N-
dicyclohexylsulphamoyl-(R)-isobornyl glyoxylate 2c
obtained from 10-N,N-dicyclohexylsulphamoyl-(2R)-
isobornyl glyoxylate (1c; 146 mg, 0.32 mmol) in toluene
(5 ml). The reaction mixture was stirred at room tem-
perature overnight, then worked up with NaHCO3, and
extracted several times with EtOAc. The organic
extracts were combined, dried over MgSO4, and evapo-
rated under reduced pressure. The product was purified
by flash chromatography using 10% Et2O–toluene as an
eluent to afford the separated diastereoisomers. In the
case of the product derived from (2R)-bornano-10,2-
sultam and (R)-8-phenylmenthol, 20% EtOAc–toluene
was used as an eluent.

A. Kulesza et al. / Tetrahedron: Asymmetry 14 (2003) 1161–1166
1165
4.2.5.
N-((2%S)-N%-p-Toluenesulphonylisopropoxy-
1.46–1.10 (m, 30H), 0.99 (s, 3H), 0.88 (s, 3H); 13C
NMR (200 MHz, CDCl3): l 166.2, 165.8, 143.4, 138.4,
138.0, 129.6, 129.5, 129.0, 128.2, 127.0, 126.7, 126.4,
82.0, 81.2, 80.5, 80.2, 63.0, 57.7, 54.4, 48.8, 49.3, 49.4,
39.2, 33.0, 3.27, 32.5, 30.8, 30.6, 27.0, 26.0, 26.5, 26.4,
25.2, 25.1, 21.6, 20.3, 19.8; MS (EI) m/e (%): 606 (52),
562 (12), 525 (15), 451 (100), 387 (11), 298 (75), 254
(22), 180 (38); HRMS (EI) calcd for C33H52N2NaO7S2
(M+Na): 675.3108. Found: 675.3149.
glycine)-10-N,N-dicyclohexylsulphamoyl-(2R)-isoborneyl
ester, (S)-4c. Mp=171–173°C; [h]2D0=−3.5 (c 1,
CHCl3); H NMR (200 MHz, CDCl3): l 7.81–7.65 (m,
1
2H), 7.33–7.22 (m, 2H), 6.49 (d, J=9.2, 1H), 4.96 (d,
J=9.4, 1H), 4.70–4.59 (m, 1H), 4.00 (m, 1H), 3.40–3.17
(m, 3H), 2.65 (d, J=13.4, 1H), 2.40 (s, 3H), 1.98–1.08
(m, 33H), 0.99 (s, 3H), 0.86 (s, 3H); 13C NMR (200
MHz, CDCl3): l 166.4, 143.7, 138.1, 129.4, 127.0, 80.4,
80.1, 69.5, 57.8, 54.4, 49.8, 49.2, 44.4, 39.3, 32.8, 32.6,
30.9, 27.1, 26.5, 25.1, 22.5, 21.3, 21.4, 20.4, 19.8.
4.4. Preparation of complex 8
Ti(O-iPr)4 (0.5 mmol, 0.15 ml) was added dropwise to a
stirred solution of 1,2:3,4-di-O-isopropylidene-a-D-
4.3. General procedure for addition of sodium alkoxides
to N-toluenesulphonylimine, 3c
galactose (1.9 mmol, 500 mg) in dry diethyl ether (10
ml) at 0°C. The reaction mixture was allowed to warm
to room temperature and stirred for 12 h. The volatiles
were evaporated under reduced pressure at 50°C and
the complex was used without purification for the addi-
tion to imine 3a.
Sodium ethoxide (1.6 ml, 0.4 mmol) was added to a
solution of the N-tosylimine of 10-N,N-dicyclohexylsul-
phamoyl-(R)-isobornyl glyoxylate 2c obtained from 10-
N,N-dicyclohexylsulphamoyl-(2R)-isobornyl glyoxylate
(1c; 167 mg, 0.4 mmol) in toluene (5 ml). The reaction
mixture was stirred at room temperature for 1 hour and
then neutralised with NH4Cl, extracted with EtOAc,
dried over MgSO4 and evaporated under reduced pres-
sure. The product was purified by flash chromatogra-
phy using 30% Et2O–hexane as eluent. The separation
of isomers was unfeasible due to instability of products
except for compound (S)-5c.
4.5. Addition of tetra-1,2:3,4-di-O-isopropylidene-a-D-
galactopyranosyltitanium to 3a
To a stirred solution of imine 3a (1 mmol) in dry
toluene (5 ml) the solution of 8 in toluene (5 ml) was
added. The reaction mixture was quenched with
NH4Cl, extracted with CH2Cl2, dried over MgSO4, and
evaporated. The product was purified by flash chro-
matography using as eluent 10% EtO2 in toluene to give
the product in 30% yield (200 mg).
4.3.1. N-((2%S)-N%-p-Toluenesulphonylmethoxyglycine)-
10-N,N-dicyclohexylsulphamoyl-(2R)-isoborneyl ester,
1
(S)-5c. Oil; [h]2D0=−16.1 (c 1, CHCl3); H NMR (200
MHz, CDCl3): l 7.75–7.69 (m, 2H), 7.34–7.26 (m, 2H),
6.39 (d, J=9.2, 1H), 4.97 (d, J=9.4, 1H), 4.82–4.73 (m,
3H), 3.35–3.15 (m, 4H), 2.61–2.11 (m, 6H), 2.46–1.0 (m,
25H), 0.98 (s, 3H), 0.86 (s, 3H); 13C NMR (200 MHz,
CDCl3): l 165.6, 143.5, 129.6, 127.3, 82.9, 80.5, 57.6,
54.1, 54.0, 49.7, 49.3, 44.4, 39.2, 33.1, 32.4, 31.6, 30.7,
29.7, 27.0, 26.4, 25.1, 22.7, 21.6, 20.3, 20.0.
4.5.1. N-((2%R)-N%-p-Toluenesulphonyl-1,2:3,4-di-O-iso-
propylidene-a- -galactopyranosylglycinoyl)-(2R)-bornano-
D
10,2-sultam imide, 9a. Oil; [h]2D0=−37.1 (c 1.0, CHCl3);
1
IR: 3267, 2989, 2961, 2941, 1700, 1346, 1167 cm−1; H
NMR (500 MHz, CDCl3): l 7.74 (d1/2AB, J=8.3, 2H),
7.36–7.30 (m, 2H), 6.06 (d, J=9.8, 1H), 5.49 (d, J=
4.99, 1H), 5.38 (d, 9.8, 1H), 4.55 (dd, J1=2.3, J2=7.9,
1H), 4.36 (m, 1H), 4.20 (dd, J1=1.8, J2=7.9, 1H),
4.08–4.00 (m, 1H), 3.87 (m, 1H), 3.74 (m, 1H), 3.68 (m,
1H), 3.11 (qAB, 2H), 2.43 (s, 3H), 2.021.80 (m, 5H),
1.52 (s, 3H), 1.43 (s, 3H), 1.32 (s, 6H), 1.23–1.40 (m,
2H), 1.05 (s, 3H), 0.95 (s, 3H); ESI m/e (%) 1391
(2M+Na)+(100), 706 (M+Na) (15); HRMS (EI) calcd
for C31H44N2NaO11S2 (M+Na): 707.2242. Found:
707.2279.
4.3.2.
N-((2%S/R)-N%-p-Toluenesulphonylmethoxy-
glycine)-10-N,N-dicyclohexylsulphamoyl-(2R)-isoborneyl
ester (S/R)-5c. IR: 3276, 2933, 2856, 1745, 1598 cm−1;
1H NMR (200 MHz, CDCl3): l 7.76–7.69 (m, 2H),
7.33–7.25 (m, 2H), 6.43 (d, J=9.2, 0.65H), 6.24 (d,
J=8.4, 0.35H), 5.24 (d, J=8.2, 0.35H), 4.97 (d, J=9.2,
0.65H), 4.83–4.74 (m), 2.18–2.25 (m), 2.02–0.98 (m); 13
C
NMR (200 MHz, CDCl3): l 165.9, 165.5, 143.5, 138.4,
138.1, 129.6, 129.5, 128.3, 127.0, 126.7, 125.3, 82.8,
82.3, 80.5, 57.7, 57.5, 54.5, 54.3, 54.1, 54.0, 49.9, 49.7,
49.3, 49.2, 44.4, 39.2, 33.1, 33.0, 32.6, 32.4, 30.7, 30.6,
27.0, 26.4, 25.1, 21.6, 21.5, 20.3, 19.9, 19.8; MS (EI)
m/e (%): 638 M+(2), 606 (30), 451 (100), 387 (12), 298
(30), 254 (10), 244 (40), 180 (12); HRMS (EI) calcd for
C32H50N2NaO7S2 (M+Na): 661.2652. Found: 661.2932.
4.6. X-Ray data
X-Ray single-crystal diffraction experiments were car-
ried out on a Kuma KM4CCD k-axis diffractometer
,
using Mo Ka radiation (0.7107 A). The program used
to solve and refine was SHELX-97.17
4.3.3. N-((2%S/R)-N%-p-Toluenesulphonylethoxyglycine)-
10-N,N-dicyclohexylsulphamoyl-(2R)-isoborneyl
ester
C22H32N2O6S2 (R-4a), M=484.61, monoclinic, a=
11.550(2), b=12.211(2), c=17.882(4), h=90, i=
103.31(3), k=90°, space group P21, Z=4, Dcalcd=1.311
Mg/m3, v(Mo Ka)=0.256 mm−1, 23243 reflections
measured, 23243 [Rint=0.0568] unique reflections,
which were used in all calculations. Data/restraints/
parameters 23243/1/587. The final R1=0.0954 (all
(S/R)-6c. Oil; IR: 3274, 2933, 2856, 1745, 1598 cm−1;
1H NMR (200 MHz, CDCl3): l 7.79–67 (m, 2H),
7.36–7.22 (m 2H), 6.43 (d, J=9.2, 0.37H); 6.12 (d,
J=7.8, 0.63H), 5.29 (d, J=7.8, 0.63H), 4.90 (m, 2H),
4.80–4.70 (m, 1H), 3.82–3.62 (m, 2H), 3.61–3.40 (m,
2H), 3.38–3.17 (m, 3H), 2.63 (m, 1H), 2.40 (s, 3H),

1166
A. Kulesza et al. / Tetrahedron: Asymmetry 14 (2003) 1161–1166
data), 0.04(10). Residual electron density 0.304 and
−0.200 e A .
References
−3
,
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5663.
C56H78N2O10S2 (R-4b), M=501.66, Monoclinic, a=
24.643(5), b=11.741(2), c=19.761(4), h=90, i=
102.24(3), k=90°, space group C2, Z=4, Dcalcd=1.193
Mg/m3, v(Mo Ka)=0.152 mm−1, 9879 reflections mea-
sured, 4897 (Rint=0.0448) unique reflections, which
were used in all calculations. Data/restraints/parame-
ters 4897/1/819. The final R1=0.0718 (all data), s=
−3
,
0.2(2). Residual electron density 0.314 and −0.217 A .
C34H54N2O7S2 (R-4c), M=666.91, orthorhombic, a=
10.089 (2), b=14.267(3), c=25.303(5), space group
P212121, Z=4, Dcalcd=1.216 Mg/m3, 47355 reflections
measured, 4752 (Rint=0.0688) unique reflections, which
were used in all calculations. Data/restraints/parame-
ters 4752/0/534. The final R1=0.0622 (all data), s=
−3
,
0.0(1). Residual electron density 0.168 and −0.163 A .
The crystallographic data for the structure reported in
this paper have been deposited with the Cambridge
Crystallographic Data Center as supplementary publi-
cation no. CCDC 199881–199883 for compounds R-4a,
R-4b and R-4c, repectively. Copies of the data can be
obtained free of charge on application to CCDC, 12
Union Road, Cambridge CB21EZ, UK (fax (+44)
1223336033; e-mail: deposit@ccdc.cam.ac.uk).
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ment of Crystal Structures; University of Go¨ttingen: Ger-
many, 1993.
Acknowledgements
This work was supported by Polish State Commitee for
Scientific Research, Grant PBZ 6.05/T09/1999. The X-
ray measurements were undertaken in the Crystallo-
graphic Unit of the Physical Chemistry Laboratory at
the Chemistry Department of the University of
Warsaw.