(4S)-3-[(2R,3S)-3-Hydroxy-2-methyl-3-phenylpropionyl]-4-isopropyl- oxazolidin-2-one

Article abstract of DOI:10.1107/S0108270106004884

The molecule of the title compound, C₁₆H₂₁NO ₄, is chiral and has three asymmetric centres. The absolute configuration was not determined via diffraction measurements on the crystal, but was established from the known abso

Full text of DOI:10.1107/S0108270106004884

organic compounds
H1Á Á ÁO2i and C12ÐH12AÁ Á ÁO4ii, with O1Á Á ÁO2i
=
Acta Crystallographica Section C
Crystal Structure
Communications
ii
Ê
Ê
2.871 (3) A and C12Á Á ÁO4 = 3.369 (4) A [symmetry codes: (i)
1
x, 12 + y, z; (ii) 1 x, 12 + y, 1 z]. Atom O1 of the
ISSN 0108-2701
(4S)-3-[(2R,3S)-3-Hydroxy-2-methyl-
3-phenylpropionyl]-4-isopropyl-
oxazolidin-2-one
In-Chul Hwang,a Jung Hee Jang,b Taek Hyeon Kimb* and
Kwang Hab*
aDepartment of Chemistry, Pohang University of Science and Technology, Pohang
790-784, Republic of Korea, and bFaculty of Applied Chemical Engineering,
Chonnam National University, Gwangju 500-757, Republic of Korea
Correspondence e-mail: thkim@chonnam.ac.kr, hakwang@chonnam.ac.kr
Figure 1
The structure of (I), showing the atom-numbering scheme. Displacement
ellipsoids are drawn at the 30% probability level and H atoms are
represented by circles of arbitrary size.
Received 18 January 2006
Accepted 9 February 2006
Online 18 March 2006
The molecule of the title compound, C16H21NO4, is chiral and
has three asymmetric centres. The absolute con®guration was
not determined via diffraction measurements on the crystal,
but was established from the known absolute con®guration of
the starting material. In the crystal structure, the molecules
assemble through intermolecular hydrogen bonds into a
macrostructure with helical channels.
Comment
Chiral auxiliary-based aldol reactions have been the focus of
much interest as the strategy of choice for accessing single
isomers of ꢀ-hydroxy acid derivatives as chiral building blocks
for bioactive compounds (Evans et al., 1981; Ager et al., 1996,
1997; Arya et al., 2000; Evans, Downey et al., 2002; Evans,
Tedrow et al., 2002). We recently reported that the use of a new
N-acyl phenyliminooxazolidine auxiliary resulted in high
diastereoselectivity in alkylation reactions (Lee et al., 2002).
During our ongoing studies of chiral auxiliary-based asym-
metric reactions, the unexpected title compound, (I), was
formed in an aldol reaction and its structure is reported here.
Figure 2
A view of the OÐHÁ Á ÁO hydrogen-bond interactions (dashed lines) in
the crystal structure of (I). [Symmetry code: (i) 1 x, 12 + y, z.]
Compound (I) has three chiral C atoms and is one of eight
possible stereoisomers. Crystallographically, the absolute
con®guration has not been established by anomalous disper-
sion effects, but the R and S con®gurations of the chiral
centres could be assigned by reference to an unchanging
asymmetric centre in the reaction procedure. Atoms C7, C8
and C13 have S, R and S con®gurations, respectively (Fig. 1).
In the crystal structure, molecules of (I) are assembled by
two intermolecular hydrogen-bonding interactions, viz. O1Ð
Figure 3
Aview of the CÐHÁ Á ÁO hydrogen-bond interactions (dashed lines) in the
crystal structure of (I). [Symmetry code: (ii) 1 x, 12 + y, 1 z.]
o196 # 2006 International Union of Crystallography
DOI: 10.1107/S0108270106004884
Acta Cryst. (2006). C62, o196±o198

organic compounds
1.0 N HCl (10 ml). After stirring for 1 h, the mixture was diluted with
Et2O (100 ml) and water (100 ml). The organic layer was extracted
with saturated NaHCO3 (50 ml), dried, ®ltered and concentrated.
Flash chromatography (EtOAc±hexane
= 2:8) afforded pure
compound (I) in 58% yield. Single crystals suitable for an X-ray
diffraction study were obtained by slow evaporation of a toluene
solution over a period of one week. 1H NMR (CDCl3): ꢁ 7.42±7.29 (m,
5H), 4.75 (bt, 1H, J = 6.3 Hz), 4.46±4.17 (m, 4H), 3.17 (bd, 1H, J =
6.6 Hz), 2.30±2.23 (m, 1H), 1.10 (d, 1H, J = 6.9 Hz), 0.87 (d, 1H, J =
7.1 Hz), 0.70 (d, 1H, J = 6.9 Hz); 13C NMR (CDCl3): ꢁ 176.7, 154.2,
142.2, 128.5, 128.0, 126.5, 77.4, 63.2, 58.8, 43.9, 28.3, 17.9, 14.8, 14.3;
MS (EI) m/z 291 (M+).
Crystal data
C16H21NO4
Mo Kꢂ radiation
Cell parameters from 634
re¯ections
Mr = 291.34
Monoclinic, P21
a = 11.6191 (10) A
b = 6.1749 (5) A
c = 12.0431 (10) A
ꢀ = 113.394 (2)ꢀ
V = 793.02 (11) A
ꢃ = 1.8±28.2ꢀ
Ê
1
Ê
ꢄ = 0.09 mm
T = 243 (2) K
Ê
Figure 4
Block, colourless
0.1 Â 0.1 Â 0.1 mm
A side view of the hydrogen-bonded left-handed helical chain structure
along the b axis. Dashed lines indicate hydrogen bonds. [Symmetry code:
(i) 1 x, 12 + y, z.]
3
Ê
Z = 2
Dx = 1.220 Mg m
3
Data collection
Bruker SMART 1000 area-detector
CCD diffractometer
' and ! scans
5052 measured re¯ections
1976 independent re¯ections
908 re¯ections with I > 2ꢅ(I)
Rint = 0.041
alcohol group and atom C12 in the oxazolidinone ring act as
hydrogen-bond donors, and atoms O2 and O4 of the ketone
groups act as acceptors (Table 2). The molecules are extended
via these hydrogen bonds into a macrostructure, with a left-
handed helical chain (O1ÐH1Á Á ÁO2i; Fig. 2) and a right-
handed helical chain (C12ÐH12AÁ Á ÁO4ii; Fig. 3) along the b
axis. The cavity of the channel in Fig. 2 has a minimum
ꢃmax = 28.2ꢀ
h = 15 ! 10
k = 7 ! 7
l = 12 ! 15
Re®nement
Re®nement on F2
R[F2 > 2ꢅ(F2)] = 0.040
wR(F2) = 0.061
S = 0.82
1976 re¯ections
194 parameters
H-atom parameters constrained
w = 1/[ꢅ2(Fo2) + (0.0121P)2]
Ê
diameter of 2.816 A. The molecules stack in layers along the b
where P = (Fo + 2Fc2)/3
2
Ê
axis, and the distance between the layers is 6.175 A. The side
(Á/ꢅ)max < 0.001
3
Ê
Áꢆmax = 0.10 e A
view of the hydrogen-bonded left-handed helical chain
structure is shown in Fig. 4. The helices are packed in a
hexagonal-based array.
3
Ê
0.11 e A
Áꢆmin
=
Examination of the structure with PLATON (Spek, 2003)
Ê
reveals a short ring±ring interaction (< 6 A) for oxazolidinone
Table 1
Selected geometric parameters (A, ).
ꢀ
Ê
rings. The centroid±centroid distance between Cg1 (the
centroid of the ®ve-membered ring N1/C11/O3/C12/C13) and
O1ÐC7
1.434 (3)
1.224 (3)
1.357 (3)
1.443 (3)
1.192 (3)
1.384 (4)
N1ÐC11
N1ÐC13
C1ÐC6
C1ÐC2
C1ÐC7
C12ÐC13
1.392 (4)
1.482 (4)
1.379 (4)
1.383 (4)
1.508 (4)
1.512 (4)
O2ÐC10
O3ÐC11
O3ÐC12
O4ÐC11
N1ÐC10
ii
Cg1 is 4.222 A and the dihedral angle between the ring planes
Ê
is 35.9ꢀ. For phenyl rings, the shortest distance between Cg2
(the centroid of the phenyl ring C1±C6) and Cg2iii [symmetry
code: (iii) x, 12 + y, z] is 5.175 A and the dihedral angle is
Ê
42.2ꢀ.
C11ÐO3ÐC12
C11ÐN1ÐC13
O1ÐC7ÐC1
O1ÐC7ÐC8
C1ÐC7ÐC8
O2ÐC10ÐN1
O2ÐC10ÐC8
110.4 (3)
111.3 (3)
112.0 (3)
104.9 (3)
109.7 (3)
117.5 (3)
122.4 (3)
N1ÐC10ÐC8
O4ÐC11ÐO3
O4ÐC11ÐN1
O3ÐC11ÐN1
O3ÐC12ÐC13
N1ÐC13ÐC12
119.9 (3)
121.1 (3)
130.2 (3)
108.7 (3)
106.5 (2)
101.2 (3)
Experimental
The title compound was synthesized following an analogous proce-
dure to that described by Evans, Downey et al. (2002) for related
compounds. To a round-bottomed ¯ask in a glove-box was added
MgBr2ÁOEt2 (36 mg, 0.5 equivalents). The ¯ask was ®tted with a
septum cap and removed to an ambient atmosphere, where it was
charged with N-acylated phenyliminooxazolidine (0.28 mmol, 72 mg,
1 equivalent), EtOAc (3 ml), benzaldehyde (0.30 mmol, 31 ml, 1.1
equivalents), Et3N (0.55 mmol, 77 ml, 2 equivalents) and trimethyl-
silyl chloride (0.41 mmol, 53 ml, 1.5 equivalents). The reaction
mixture was stirred for 26 h and then ®ltered directly through a plug
of silica gel (5.5 cm  4.0 cm) and eluted with Et2O. The eluent was
concentrated, dissolved in tetrahydrofuran (50 ml) and treated with
Table 2
Hydrogen-bond geometry (A, ).
ꢀ
Ê
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
O1ÐH1Á Á ÁO2i
0.83
0.98
2.07
2.48
2.871 (3)
3.369 (4)
161
150
C12ÐH12AÁ Á ÁO4ii
Symmetry codes: (i) x ‡ 1; y ‡ 12; z; (ii) x ‡ 1; y
;
z ‡ 1.
1
2
ꢁ
Acta Cryst. (2006). C62, o196±o198
Hwang et al. C16H21NO4 o197

organic compounds
In the absence of signi®cant anomalous scattering, Friedel oppo-
sites were merged. All H atoms were positioned geometrically and
allowed to ride on their respective carrier atoms, with O1ÐH =
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: AV1281). Services for accessing these data are
described at the back of the journal.
Ê
Ê
0.83 A and Uiso(H) = 1.5Ueq(O1), and CÐH = 0.94±0.99 A and
Uiso(H) = 1.2Ueq(C) or 1.5Ueq(methyl C).
References
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structure: SHELXS97 (Sheldrick, 1997); program(s) used to re®ne
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ORTEP-3 (Farrugia, 1997); software used to prepare material for
publication: SHELXL97.
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This work was supported by the Basic Research Programme
of the Korean Science and Engineering Foundation (grant No.
R05-2004-000-11207-0) (now controlled under the authority of
the Korea Research Foundation). Spectroscopic data were
obtained from the Korea Basic Science Institute, Gwangju
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ꢁ
o198 Hwang et al. C16H21NO4
Acta Cryst. (2006). C62, o196±o198