Asymmetric addition of 2-methylfuran and its lithiated derivative to variously N,N-protected L-alaninals

Article abstract of DOI:10.1016/S0957-4166(02)00545-1

The asymmetric reaction of 2-methylfuran 2a and its lithiated derivative 2b with N,N-diprotected L-alaninals 1a-c, carried out under high pressure conditions in the presence of Lewis acid-catalyst, are described. For aldehyde 1a two diastereoisomeric adducts anti-3a and syn-3a were formed, with predominance of the former. In the case of aldehydes 1b and 1c only the anti-diastereoisomers 3b or 3c were formed, but accompanied by two diastereoisomeric oxazolidinones trans-4 and cis-4. The absolute configuration (via X-ray analysis of anti-5 and chemical correlations) and the extent of asymmetric induction were established.

Full text of DOI:10.1016/S0957-4166(02)00545-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 2133–2139
Asymmetric addition of 2-methylfuran and its lithiated derivative
to variously N,N-protected -alaninals
L
Elz; *
bieta Kobrzycka,a Dorota Grykoa and Janusz Jurczaka,b,
aInstitute of Organic Chemistry, Polish Academy of Science, Kasprzaka 44/52, 01-224 Warsaw, Poland
bDeparment of Chemistry, Warsaw University, Pasteura 1, 02-093 Warsaw, Poland
Received 9 August 2002; accepted 5 September 2002
Abstract—The asymmetric reaction of 2-methylfuran 2a and its lithiated derivative 2b with N,N-diprotected L-alaninals 1a–c,
carried out under high pressure conditions in the presence of Lewis acid-catalyst, are described. For aldehyde 1a two
diastereoisomeric adducts anti-3a and syn-3a were formed, with predominance of the former. In the case of aldehydes 1b and 1c
only the anti-diastereoisomers 3b or 3c were formed, but accompanied by two diastereoisomeric oxazolidinones trans-4 and cis-4.
The absolute configuration (via X-ray analysis of anti-5 and chemical correlations) and the extent of asymmetric induction were
established. © 2002 Published by Elsevier Science Ltd.
1. Introduction
2. Results and discussion
It is known that 2,3-O-isopropylidene-D-glyceraldehyde
In the past decade there has been rapidly growing
interest in the synthesis of natural products possessing a
dense array of stereogenic centres with hydroxy and the
amino groups. Among them carbohydrates, including
amino sugars, are of great importance.1–3 During our
studies directed towards the synthesis of polyhydroxyl-
ated compounds, including carbohydrates the highly
reacts with 2-methylfuran 2a in the presence of
ClCH2CO2H to give the desired furylcarbinol.8 We
were intrigued to find out if the same reaction could be
conducted with N,N-diprotected- -alaninals 1 as sub-
L
strates (Scheme 1). Aldehydes 1 used in this study were
obtained from corresponding alcohols using the
TEMPO oxidation method9 and were synthesised
directly prior to use. Though the aldehydes 1 proved to
be unreactive towards 2-methylfuran 2a under normal
pressure, we were delighted to find that they did react if
a high pressure method was applied.
stereoselective reaction of 2,3-O-isopropylidene-D-glyc-
eraldehyde with 2-methylfuryllithium 2b, carried out in
the presence of zinc bromide, proved to be very use-
ful.4,5 High pressure reactions of the same aldehyde
with 2,5-dimethylfuran also exhibited relatively high
anti-diastereoselectivity.6 Similarly, the addition of
furyllithium to N,N-diprotected alaninals led to forma-
tion of the anti-diastereoisomers.7 Therefore, we
decided to extend our stereochemical studies to various
furan derivatives in order to establish the regio- and
stereoselectivity of this reaction. Since N-monopro-
tected a-amino aldehydes are unstable towards lithiated
The reactions of N,N-diprotected- -alaninals 1 with 2a
L
under 20 kbar pressure led to mixtures of products, and
regardless of the N-protecting group, anti-3 was formed
as the major product (Table 1). N-Bn-N-Ts-L-alaninal
1a gave a mixture of anti- and syn-adducts 3a (86:14) in
43% yield (entry 1), and as expected, the addition of 2a
occurs predominantly from the less hindered side of the
Felkin–Anh model, leading to the formation of anti-3a
as the major product. For N-Bn-N-Cbz- 1b and N-Bn-
furan derivatives, we selected N,N-diprotected-
inals 1 as model compounds for these studies.
L-alan-
N-Boc- -alaninal 1c two compounds were isolated in
L
each case, one of which proved to be the anti-adduct 3
(entries 2 and 3). Surprisingly, we did not isolate syn-
adducts 3 but instead we observed the formation of
oxazolidinone 4. Presumably compounds trans-4 and
cis-4 were formed after addition of 2-methylfuran 2a to
a-amino aldehydes 1.
* Corresponding author. Tel.: +48 22 632 05 78; e-mail: jurczak@
icho.edu.pl
0957-4166/02/$ - see front matter © 2002 Published by Elsevier Science Ltd.
PII: S0957-4166(02)00545-1

2134
E. Kobrzycka et al. / Tetrahedron: Asymmetry 13 (2002) 2133–2139
Scheme 1.
Table 1. Addition of 2-methylfuran 2a to aldehyde 1 in the presence of ClCH2CO2H under 20 kbar pressure at 55°C
Entry
Aldehyde
anti-3:syn-3:trans-4:cis-4
Yield of 3 (%)
Yield of 4 (%)
1
2
3
1a
1b
1c
86:14:0:0
75:0:25:0
90:0:9:1
43
34
24
–
12
3
yield (Table 4, entry 2). The use of SnCl4 caused a
sudden drop in the yield but the diastereoselectivity
remained at the same very high level (entry 3). A
similar result was obtained when the reaction was car-
ried out in the presence of AlCl3 (entry 5). The applica-
tion of ZnBr2 as a catalyst in this reaction resulted in
exclusive formation of oxazolidinones trans-4:cis-4 in
the ratio 85:15 (entry 4). Adduct 3 did not form under
these conditions, in contrast to the similar reactions of
1a and 1b with 2b.
Disappointed by the results of the high pressure reac-
tions, we turned our attention to a Lewis acid-catalysed
addition of 2-methylfuryllithium 2b. The uncatalysed
addition of 2b to aldehydes
1 proceeded with
diastereoselectivities ranging from high (for 1a, Table 2,
entry 1) to very high (for 1b, Table 3, entry 1 and 1c,
Table 4, entry 1) but with rather moderate yields.
N-Bn,N-Ts-protected 1a led to exclusive formation of 3
irrespective of the conditions used (Table 2, entries
2–6). In these cases the subsequent oxazolidinone for-
mation reaction did not occur.
The extent of the asymmetric induction was determined
on the basis of H NMR spectra. For adducts 3 the
1
The best diastereoselectivity for the reaction of alde-
hyde 1a with 2b was observed when the reaction was
carried out in the presence of triethylaluminium. How-
ever, a rather low yield (33%) was obtained (entry 6). In
the presence of other Lewis acids (BF3·OEt2, SnCl4,
ZnBr2 and AlCl3), a mixture of anti-3a and syn-3a
formed in ratios of around 85:5, again with the anti-iso-
mer predominating (Table 2).
integration of separate signals from the methyl group
present in the amino acid fragment was used, whereas
for oxazolidinone 4 the integration of signals derived
from the methyl group present on the oxazolidinone
ring was applied, and this measurement was further
confirmed by integration of the signals for the methyl
group of the furan moiety. Having determined the
extent of the asymmetric induction, we studied its direc-
tion by establishing the configuration of the newly
The addition of Lewis acids BF3·OEt2, SnCl4, ZnBr2,
AlCl3 to the reaction of N-Bn,N-Cbz- -alaninal 1b with
L
furan derivative 2b, carried out at −78°C, led to only a
slight improvement in the yield but a decrease in the
diastereoselectivity of the reaction when compared to
the uncatalysed reaction. In these cases trans-4 was also
formed, in addition to anti-3b (Table 3). Increasing the
temperature of the reaction catalysed by ZnBr2 to
−63°C led to higher yield but the formation of cis-4 was
observed (Table 3, entry 5).
Table 2. Addition of 2b to aldehyde 1a in the presence of
Lewis acids
Entry
Lewis acid
anti-3a:syn-3a:
trans-4:cis-4
Yield of 3 (%)
1
2
3
4
5
6
–
83:17:0:0
85:15:0:0
83:17:0:0
84:16:0:0
82:18:0:0
\95:0:0:0
59
89
75
61
95
33
BF3·OEt2
SnCl4
ZnBr2
AlCl3
AlEt3
We were delighted to find that the reaction of N-Bn,N-
Boc-
L
-alaninal 1c with furan derivative 2b, catalysed by
BF3·OEt2, afforded anti-adduct 3c exclusively in 95%

E. Kobrzycka et al. / Tetrahedron: Asymmetry 13 (2002) 2133–2139
2135
Table 3. Addition of 2-methylfuryllithium 2b to aldehyde 1b in the presence of Lewis acids
Entry
Lewis acid
anti-3b:syn-3b:trans-4:cis-4
Yield of anti-3b (%)
Yield of 4 (%)
1
2
3
4
5
6
7
–
\95:0:0:0
81:0:19:0
83:0:17:0
83:0:17:0
64:0:29:17
82:0:18:0
83:0:17:0
56
56
56
51
51
71
49
–
BF3·OEt2
SnCl4
ZnBr2
ZnBr2
AlCl3
13
11
10
29
16
27
a
a
AlCl3
a Reactions were carried out at −63°C
Table 4. Addition of 2-methylfuryllithium 2b to aldehyde 1c in the presence of Lewis acids
Entry
Lewis acid
anti-3c:syn-3c:trans-4c:cis-4c
Yield of anti-3c (%)
Yield of 4 (%)
1
2
3
4
5
–
\95:0:0:0
\95:0:0:0
\95:0:0:0
0:0:85:15
95:0:5:0
33
95
64
–
–
–
–
61
4
BF3·OEt2
SnCl4
ZnBr2
AlCl3
60
formed stereogenic centre has (S)-absolute configura-
tion. The other diastereoisomer of 3a possesses the
opposite (R)-configuration. For the remaining two
adducts 3b and 3c chemical correlations with 3a were
used as shown in Scheme 2. In order to assign the
stereochemical course of the addition of 2-methylfuran
formed stereogenic centre. Furylcarbinol 3a was trans-
formed into the O-protected derivative
5 using
triphenylsilyl chloride,10 which afforded suitable single
crystals for X-ray analysis (Fig. 1).
The X-ray crystal structure provided final proof of the
structure and stereochemistry of products. Compound
3a bears the amino and the hydroxy groups unequivo-
cally in an anti-orientation, this means that the newly
2a to N-Bn,N-Cbz- -alaninal 1b, the Cbz- group in the
L
major product 3b was replaced with a Tosyl group11
1
giving adduct anti-3a. The H and 13C NMR spectra
Figure 1. ORTEP diagram of the molecule 5, showing thermal ellipsoids at 30% probability level and C1(S), C2(S) configuration
of the chirality centres.

2136
E. Kobrzycka et al. / Tetrahedron: Asymmetry 13 (2002) 2133–2139
Scheme 2.
for 3a obtained from 3b were identical to those taken
for anti-3a obtained from the reaction of 1a with 2a.
Therefore the anti-configuration was assigned for com-
pound 3b. Hydrogenation12 of anti-3b gave the
monoprotected derivative 6, which was further sub-
jected to the reaction with Boc2O13 affording adduct 3c.
The analytical data for compound 3c were identical
with those obtained for the compound 3c being the
Furthermore, the oxazolidinones trans-4 and cis-4 were
distinguished on the strength of NOE difference mea-
surements (Fig. 2). The illustrated NOE measurements
(11%) on the oxazolidinone ring 4 (4 being the result of
the treatment of 3b with BuLi), established the cis-rela-
tionship between the newly formed hydroxyl- and adja-
cent methyl-bearing stereocentre, thereby securing the
stereochemical assignments of compounds 4. Hence the
second diastereoisomer of 4 unequivocally has the
methyl and furyl substituents in a trans-relationship
and the formation of this compound was observed
during the reactions described in this paper.
result of the addition of 2a to N-Bn,N-Boc-L-alaninal
1c. We concluded that the major product of the reac-
tion of 2a with 1c possesses the amino and the hydroxy
groups also in the anti-orientation.
In order to establish the relative configuration of oxa-
zolidinones formed upon the addition of 2-methylfuran
2a or its derivative 2b to N-Bn,N-Cbz- 1b or N-Bn,N-
3. Conclusions
Boc- -alaninal or 1c corresponding anti-adducts were
L
The diastereoselective additions of 2-methylfuran 2a
transformed into oxazolidinones 4 (Scheme 3). Treat-
ment of anti-3b or anti-3c with trifluoroacetic acid led
to a diastereoisomeric mixture of oxazolidinones 4 with
trans-predominance in both cases whereas treatment of
anti-3b with BuLi afforded exclusively cis-4. If we
assume that inversion of the configuration at the car-
bon atom substituted with the hydroxy group is, as
reported,14 highly unlikely to proceed under basic con-
ditions, it must occur under acidic conditions. The
results presented suggest that the main oxazolidinone 4,
formed during the addition reaction in the presence of
a Lewis acid, has the methyl and the furyl groups in a
trans-relationship.
and its lithiated derivative 2b to N,N-diprotected-L-
alaninals 1 proceed via the Felkin–Anh transition
state15,16 and attack by a furyl reagent occurs from the
less hindered side of the model, predominantly afford-
ing anti-furylcarbinol 3. Regardless of the N-protecting
group we were able to obtain the anti-adducts 3 with
very high diastereoselectivities by choosing appropriate
reaction conditions. Although it was not possible to
directly reverse the stereochemical course of the addi-
tion, the trifluoroacetic acid-catalysed oxazolidinone
formation reaction offers a means to access the syn-
diastereoisomer 3.
Scheme 3.
Figure 2.

E. Kobrzycka et al. / Tetrahedron: Asymmetry 13 (2002) 2133–2139
2137
4. Experimental
4.1. General remarks
mixture was allowed to reach rt. Then, it was diluted
with water (25 mL) and extracted with Et2O (2×10 mL).
The combined organic extracts were washed with brine
(10 mL), HCl (1 M, 10 mL), satd NaHCO2aq (10 mL),
and again with brine (10 mL), dried over MgSO2. Flash
chromatography (hexanes/AcOEt, gradually from 9:1
to 7:3) afforded a mixture of anti- and syn-diastereoiso-
mers type 3 and/or oxazolidinones 4.
All chemicals were used as received unless otherwise
noted. Reagent grade solvents (CHCl3, CH2Cl2, hex-
anes, AcOEt) were distilled prior to use. All reported
NMR spectra were recorded with a Bruker spectrome-
ter at 500 (1H NMR) and 125 (13C NMR) MHz or
Varian Gemini spectrometer at 200 (1H NMR) and 50
(13C NMR) MHz. Chemical shifts are reported as d
values relative to TMS peak defined at d=0.00 (1H
NMR) or d=0.0 (13C NMR). IR spectra were obtained
on a Perkin–Elmer 1640 FTIR. Mass spectra were
obtained on an AMD-604 Intectra instrument using the
EI or LSIMS technique. Chromatography was per-
formed on silica (Kieselgel 60, 200–400 mesh). Optical
rotations were recorded using a JASCO DIP-360 polar-
imeter with a thermally jacketed 10 cm cell. Melting
points were determined using Kofler hot-stage appara-
tus and are uncorrected.
4.3.3. Addition of 2-methylfuryllithium, 2b to N,N-dipro-
tected L-alaninals 1 in the presence of Lewis acid: general
procedure. To a cold solution (−78°C) of an a-amino
aldehyde 1 (0.2 mmol) in dry THF (15 mL) was slowly
added a Lewis acid [BF3·OEt2, AlCl3 or ZnBr2 (0.2
mmol) or SnCl4 (0.1 mmol)] and, after stirring for 1 h
at rt, the solution was cooled to −78 or −63°C. The
precooled solution of 2-methylfuryllithium 2b (3 mmol)
in dry THF (10 mL) was added dropwise. After stirring
for 1 h, satd NH4Claq (10 mL) was added and the
reaction mixture was allowed to reach rt. Standard
work-up followed by flash chromatography (hexanes/
AcOEt, gradually from 9:1 to 7: 3) afforded a mixture
of anti- and syn-diastereoisomers type 3 and/or oxazo-
lidinones 4.
High pressure reactions were carried out in a piston–
cylinder type apparatus with working volume of about
90 mL. Construction details have been reported previ-
ously.17 Pressure was measured with a manganine coil
calibrate to 0.1 kbar. Temperatures were measured with
a thermocouple calibrated to 1°C.
4.3.4.
(1S,2S)-N-Benzyl-N-[2-(5-methylfuran)-2-yl-2-
hydroxy-1-methylethyl]-4-methylbenzenesulfonamide,
1
anti-3a. Yield 37%; H NMR (200 MHz, CDCl3): l
1.12 (d, J=6.8 Hz, 3H), 1.97 (brs, 1H), 2.23 (d, J=1.0
Hz, 3H), 2.44 (s, 3H), 4.21 (dq, J=3.4 Hz, J=6.8 Hz,
1H), 4.27 (AB/2, J=15.9 Hz, 1H), 4.57 (AB/2, J=15.9
Hz, 1H), 4.70 (d, J=4.4 Hz, 1H), 5.87 (dq, J=3.1 Hz,
J=1.0 Hz, 1H), 6.03 (d, J=3.1 Hz, 1H), 7.21–7.26 (m,
7H), 7.6 (m, 2); 13C NMR (50 MHz, CDCl3): l 12.9,
13.2, 21.0, 49.7, 58.7, 71.9, 106.7, 108.8, 127–129 (Ar),
138.4, 138.5, 143.8, 152.0, 152.6; IR (film): 1496, 2943,
3435 cm−1; LSIMS (+) NBA 821 (2M+Na)+, 422 (M+
Na)+. Anal. calcd for C22H25NO4S: C, 66.14; H, 6.31;
N, 3.51. Found: C, 66.12; H, 6.28; N, 3.49%. [h]2D0=
+19.6 (c 0.9, CH2Cl2).
4.2. High pressure reactions of 2-methylfuran, 2a with
N,N-diprotected L-alaninals, 1
A Teflon ampoule containing a solution of 1 (0.2
mmol), 2-methylfuran 2a (0.76 mmol) and chloroacetic
acid (0.04 mmol) in dry CH2Cl2 (2 mL) was placed in a
high-pressure vessel filled with pentane. The pressure
was slowly (10 min) evaded to 20 kbar at 55°C. After
24 h the reaction mixture was cooled and decom-
pressed. Further it was diluted with CH2Cl2 (4 mL) and
water (5 mL) then extracted with Et2O (2×10 mL). The
combined organic extracts were washed with satd
NaHCO2aq (10 mL), water (10 mL) and brine (10 mL),
dried over MgSO2. Flash chromatography (hexanes/
AcOEt, gradually from 9:1 to 7:3) afforded a mixture of
anti- and syn-diastereoisomers type 3 and/or oxazolidi-
nones 4.
4.3.5.
(1S,2R)-N-Benzyl-N-[2-(5-methylfuran)-2-yl-2-
hydroxy-1-methylethyl]-4-methylbenzenesulfonamide,
syn-3a. Yield 6%; 1H NMR (500 MHz, toluene-d8,
90°C): l 0.85 (d, J=6.6 Hz, 3H), 1.98 (s, 3H), 2.40 (s,
3H), 2.4–2.5 (brs, 1H), 4.33 (m, 1H), 4.22 (AB/2, J=
15.9 Hz, 1H), 4.47 (AB/2, J=15.6 Hz, 1H), 4.7 (m,
1H), 5.63 (dq, J=3.0 Hz, J=1.0 Hz, 1H), 5.97 (d,
4.3. Addition of 2-methylfurylllithium, 2b to
inals, 1
L-alan-
J=3.0 Hz, 1H), 7.2–7.4 (m, 7H), 7.61–7.66 (m, 2H); 13
C
NMR (125 MHz, toluene-d8): l 13.2, 15.9, 21.1, 49.0,
59.4, 70.1, 106.7, 108.8, 127–129 (Ar), 138.3, 138.6,
143.3, 150.9, 153.1; IR (film): 1499, 2943, 3440 cm−1;
LSIMS (+) NBA C22H25NO4S 821 (2M+Na)+, 422 (M+
Na)+.
4.3.1. Preparation of 2-methylfuryllithium, 2b. To a cold
solution of 2-methylfuran (0.6 mmol) in dry THF (10
mL) was slowly added a solution of n-BuLi in hexane
(1.6 M, 0.6 mmol) and the resulting mixture was stirred
at rt for 4 h.
4.3.6.
(1S,2S)-N-Benzyl,N-[2-(5-methylfuran)-2-yl-2-
4.3.2. Addition of 2-methylfuryllithium, 2b to N,N-dipro-
hydroxy-1-methylethyl]carbamic acid benzyl ester anti-
1
tected
L
-alaninals, 1 with no catalyst added: general
3b. Yield 35%; H NMR (500 MHz, toluene-d8, 90°C):
procedure. A precooled solution of 2-methylfuryllithium
2b (0.6 mmol) in dry THF (10 mL) was added dropwise
to a cold solution (−78°C) of an a-amino aldehyde 1
(0.2 mmol) in dry THF (15 mL). After stirring for 0.5
h, satd NH4Claq (10 mL) was added and the reaction
l 1.25 (d, J=7.0 Hz, 3H), 1.78 (brs, 1H), 1.95 (d,
J=0.9 Hz, 3H), 3.95 (dq, J=5.5 Hz, J=7.0 Hz, 1H),
4.21 (AB/2, J=15.8 Hz, 1H), 4.33 (AB/2, J=15.8 Hz,
1H), 4.89 (brs, 1H), 5.02 (m, 2H), 5.69 (dq, J=2.0 Hz,
J=0.9 Hz, 1H), 6.1–6.6 (m, 1H), 7.0–7.1 (m, 10H); 13C

2138
E. Kobrzycka et al. / Tetrahedron: Asymmetry 13 (2002) 2133–2139
NMR (125 MHz, toluene-d8, 90°C): l 13.3, 15.4, 28.6,
51.7, 51.9, 59.0, 59.5, 71.5, 71.9, 106.6, 107.9, 125–129
(Ar), 137.0, 151.1, 154.4, 157.0; IR (film): 1696, 2941,
3429 cm−1; LSIMS (+) NBA 402 (M+Na)+; HR EI
C23H25NO4 (M)+ calcd 379.1784, found 379.1779;
[h]2D0=−25.0 (c 1.1, CH2Cl2).
4.4.4.
(4S,5S)-3-Benzyl-4-methyl-5-(5-methylfuran-2-
yl)oxazolidinon-2-one, cis-4. 1H NMR (500 MHz,
CDCl3): l 0.95 (d, J=7.3 Hz, 3H), 2.25 (d, J=0.8 Hz,
3H), 4.17 (AB/2, J=15.3 Hz, 1H), 4.83 (AB/2, J=15.3
Hz, 1H), 5.36 (d, J=8.4 Hz, 2H), 5.91 (dq, J=3.2 Hz,
J=1.0 Hz, 1H), 6.25 (d, J=3.2 Hz, 1H), 7.4–7.3 (m,
5H); 13C NMR (125 MHz, CDCl3): l 13.0, 14.0, 44.9,
53.8, 73.0, 106.2, 110.9, 127–128 (Ar), 136.0, 146.8,
153.2, 157.7; IR (film): 1564, 1753, 2923 cm−1; EI m/z
271 (M)+, 136, 122, 111, 91; HR EI C16H17NO3 (M)+
calcd 271.1208, found 271.1205; [h]2D0=+40.5 (c 0.5,
CH2Cl2).
4.3.7.
(1S,2S)-N-Benzyl,N-[2-(5-methylfuran)-2-yl-2-
hydroxy-1-methylethyl]carbamic acid tert-butyl ester,
anti-3c. Yield 24%; 1H NMR (500 MHz, toluene-d8,
90°C): l 1.09 (d, J=7.1 Hz, 3H), 1.34 (s, 9H), 1.87 (s,
1H), 2.02 (brs, 3H), 4.13 (AB/2, J=15.7 Hz, 1H), 4.47
(AB/2, J=15.7 Hz, 1H), 4.65 (dq, J=5.9 Hz, J=7.1
Hz, 1H), 4.91 (brs, 1H), 5.72 (dq, J=2.3 Hz, J=1.1 Hz,
1H), 6.11 (d, J=2.3 Hz, 1H), 6.9–7.1 (m, 5H); 13C
NMR (125 MHz, toluene-d8, 90°C): l 13.3, 15.4, 28.6,
51.7, 51.9, 59.0, 59.4, 71.5, 71.9, 106.6, 107.9, 125–129
(Ar), 137.7, 151.1, 151.3, 154.0; IR (film): 1564, 1753,
2923 cm−1; EI m/z 335 (M)+, 271, 124, 178, 134; HR EI
C20H27NO4 (M)+ calcd 345.1940, found 345.1936. Anal.
calcd for C20H27NO4: C, 69.54; H, 7.88; N, 4.06. Found
C, 69.51; H, 7.92; N, 4.04%. [h]2D0=+25.3 (c 0.9,
CH2Cl2).
4.5. (1S,2S)-N-Benzyl-N-[2-(5-methylfuran-2-yl)-2-
triphenylsilanyloxy-1-methylethyl]-4-methylbenzenesul-
fonamide, 5
1H NMR (500 MHz, CDCl3): l 1.37 (d, J=6.9 Hz,
3H), 1.90 (s, 3H), 2.00 (s, 3H), 3.92 (AB/2, J=15.7 Hz,
1H), 4.43 (AB/2, J=15.7 Hz, 1H), 4.63 (dq, J=8.4 Hz,
J=6.9 Hz, 1H), 4.91 (d, J=8.4 Hz, 1H), 5.53 (dq,
J=3.1 Hz, J=1.0 Hz, 1H), 5.75 (d, J=3.1 Hz, 1H),
6.9–7.2 (m, 20H), 7.55 (m, 4H); 13C NMR (125 MHz,
CDCl3): l 13.2, 16.2, 20.1, 49.4, 58.7, 72.3, 106.5, 110.7,
140–127 (Ar), 151.2, 152.1; IR (KBr): 1114, 1150, 1338,
3068 cm−1; LSIMS (+) NBA 680 (M+Na)+; mp=135–
136°C [h]2D0=−39.3 (c 1.1, CH2Cl2).
4.4. Chemical correlations
4.4.1. Oxazolidinone formation under acidic conditions.
To a solution of anti-3b or anti-3c (0.3 mmol) in
CH2Cl2 (10 mL) was slowly added CF3CO2H (1.5
mmol). After 1 h stirring at rt, the reaction mixture was
diluted with water (5 mL) and extracted with Et2O
(2×10 mL). The combined organic phases were washed
with brine (10 mL), dried over MgSO4. Flash chro-
matography (hexanes/AcOEt, gradually from 9:1 to
7:3) afforded a mixture of oxazolidinones 4.
4.5.1. X-Ray crystallography of compound 5. X-Ray
diffraction measurement of the suitable crystal com-
pound 5 was carried out with a Nonius MACH3 dif-
fractometer using graphite monochromated Cu Ka
radiation (see Table 5). Intensities were collected at
room temperature using ꢀ–2q scan technique. Intensity
of the three control reflections measured every 200
reflections showed no loss of intensity. The data were
corrected for Lorentz and polarisation factors. The
structure was solved by direct methods18 [xray 1] and
refined by a full-matrix least-squares procedure with the
use of the SHELXL program19 [xray 2]. The non-
hydrogen atoms were refined anisotropically, whereas
H-atoms were placed at their calculated positions and
4.4.2. Oxazolidinone formation using BuLi. To a pre-
cooled (−20°C) solution of 3b (0.05 mmol) in dry THF
(10 mL) was slowly added a solution of BuLi in hexane
(1.6 M, 0.06 mmol). The reaction mixture was allowed
to reach rt and was stirred at that temperature for 1 h.
The mixture was diluted with water (25 mL) and
extracted with Et2O (2×10 mL). The combined organic
phases were washed with brine (10 mL), HCl (1 M, 10
mL), satd NaHCO3aq (10 mL) and again with brine (10
mL) and dried over MgSO4. Flash chromatography
(hexanes/AcOEt, gradually from 9:1 to 7:3) afforded a
mixture of oxazolidinones cis-4 in the yield of 96%.
Table 5. Crystallographic data and refinement details for 5
Empirical formula
Formula weight
Wavelength (A)
Crystal system
Space group
Unit cell dimensions
C40H39NO4SSi
657.87
,
1.54178
Orthorhombic
P212121
4.4.3.
(4S,5R)-3-Benzyl-4-methyl-5-(5-methylfuran-2-
yl)oxazolidinon-2-one, trans-4. 1H NMR (500 MHz,
CDCl3): l 1.21 (d, J=7.3 Hz, 3H), 2.23 (d, J=0.8 Hz,
3H), 4.17 (AB/2, J=15.3 Hz, 1H), 4.82 (AB/2, J=15.3
Hz, 1H), 4.85 (d, J=7.3 Hz, 2H), 5.91 (dq, J=3.2 Hz,
J=0.8 Hz, 1H), 6.22 (d, J=3.2 Hz, 1H), 7.32 (m, 5H);
13C NMR (125 MHz, CDCl3): l 13.5, 17.6, 46.0, 54.4,
76.5, 106.5, 111.3, 127–128 (Ar), 135.9, 147.2, 153.9,
157.3; IR (film): 1565, 1755, 2923 cm−1; EI m/z 271
(M)+, 136, 122, 111, 91; HR EI C16H17NO3 (M)+ calcd
271.1208, found 271.1209; [h]2D0=−144.5 (c 1.3,
CH2Cl2).
,
a (A)
10.819(2)
12.065(2)
54.622(5)
7130(2)
,
b (A)
,
c (A)
Volume (A )
3
,
Z
8
Absorption coefficient (mm−1
Reflections collected
Independent reflections
Data/restrains/parameters
Final R indices [I\2|(I)]
Absolute structure parameter
)
1.453
7896
7130 [R(int)=0.0278]
7130/0/848
R1=0.0448, wR2=0.1173
0.01(2)

E. Kobrzycka et al. / Tetrahedron: Asymmetry 13 (2002) 2133–2139
2139
their thermal parameters were set at the level 20%
higher that for the parent atoms. Crystallographic data
for 5 have been deposited with the Cambridge Crystal-
lographic Data Centre as supplementary publication
numbered CCDC 191344. Copies of the data can be
obtained free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK [fax: +44(0)-
1233-336033 or e-mail: deposit@ccdc.cam.ac.uk].
2. Atta-ur-Rachman Studies in Natural Products Chemistry;
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4148.
5. Jurczak, J.; Kobrzycka, E.; Raczko, J. Polish J. Chem.
1999, 73, 29–41.
6. Jurczak, J.; Pikul, S. Tetrahedron 1988, 44, 4569–4573.
7. Raczko, J.; Gołe˛biowski, A.; Krajewski, J. W.; Gluzinski,
P.; Jurczak, J. Tetrahedron Lett. 1990, 31, 3797–3800.
8. Zamojski, A.; Grzeszczyk, B.; Dziewiszek, K.; Jarosz, S.
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2000, 65, 1743–1749.
4.6. (2S)-(N-Benzylamino)-(1S)-(5-methylfuran-2-
yl)propan-1-ol, 6
1H NMR (200 MHz, CDCl3): l 1.03 (d, J=6.4 Hz,
3H), 2.25 (d, J=0.9 Hz, 3H), 2.52 (brs, 1H), 3.05 (m,
1H), 3.75 (AB/2, J=13.2 Hz, 1H), 3.93 (AB/2, J=13.2
Hz, 1H), 4.58 (d, J=1.6 Hz, 1H), 4.69 (brs, 1H), 5.89
(dq, J=3.0 Hz, J=0.9 Hz, 1H), 6.31 (d, J=3.0 Hz,
1H), 7.2–7.5 (m, 5H); 13C NMR (50 MHz, CDCl3): l
13.9, 17.8, 45.9, 54.4, 106.6, 111.3, 127–129 (Ar), 135.8,
147.1, 153.7, 157.3; IR (film): 1496, 2943, 3435 cm−1;
LSIMS (+) NBA 268 (M+Na)+ 246 (M+H)+, 271, 124,
178, 134; HR LSIMS C15H19NO2 (M+H)+ calcd
246.1494, found 246.1494.
13. Gołe˛biowski, A.; Gorins, G.; Johnson, C. R.; Kiciak, K.
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Acknowledgements
This work was supported by the Polish State Commit-
tee for Scientific Research, Grant PBZ 6.05/T09/1999.
18. Sheldrick, G. M. Acta Crystallogr. 1990, A46, 467.
19. Sheldrick G. M. SHELX-93: Program for Refinement of
Crystal Structures, University of Go¨ttingen, Germany,
1993.
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