supplementary materials


bt5753 scheme

Acta Cryst. (2012). E68, o232    [ doi:10.1107/S1600536811053852 ]

(3S*,4S*,E)-tert-Butyl 3,4-dibromo-5-oxocyclooct-1-enecarboxylate

M. Blanco, N. M. Garrido, F. Sanz and D. Diez

Abstract top

The title compound, C13H18Br2O3, was prepared by a bromination reaction of (1E,3Z)-methyl 5-oxocycloocta-1,3-dienecarboxylate, which was obtained by an epoxydation reaction of tert-butyl cyclooct-1,3-dienecarboxylate. The crystal structure confirms unequivocally the absolute configuration of both chiral centres to be S. In the crystal, C-H...O interactions link the molecules into chains running along the c axis.

Comment top

In our research group there has been an enormous interest in the synthesis of conjugated unsaturated esters used as starting material in the Michael addition of enantiomerically pure lithium amides (Davies et al., 2005) as a base tool in the asymmetric synthesis of β-amino acids and alkaloids because of their interest and value in the development of biologically active compounds for the pharmacology industry (Fülöp et al., 2001). Considering that the reactivity of the cycloocta-1,5-diene is very peculiar, highlighting its trend in basic medium to conjugate its double bonds (Huber et al., 1969) because of the greater thermodynamic stability (Huber et al., 1970), is necessary and important to establish the exact structure in this class of unsaturated rings. This conjugation was determined previously for an isomer of compound 1 (tert-butyl cyclooct-1,7-dienecarboxylate) (Garrido et al., 2008) and herein for compound 1 (tert-butylcyclooct-1,3-dienecarboxylate) by R—X spectroscopy of compound 6 which confirms unequivocally its configuration and structure. The crystal was afforded by epoxydation reaction of compound 1 with MCPBA and bromination reaction of compound 4 (Fig. 1).

The crystal contains an unique molecule in the asymmetric unit. The title molecule consists of a ring cyclooctene with two bromine atoms, a carbonyl group and a tert-butoxycarbonyl group as susbtituents. All the bond lengths and angles are within the normal ranges. The Br1—C3 and Br2—C4 bond lengths are 1.956 (4) Å and 1.946 (4) Å, respectively. The bromine atoms at C3 and C4 are nearly coplanar with the cycloctene ring being the Br1—C3—C4—C5 and Br2—C4—C3—C2 torsion angles of 173.6 (3)° and -173.0 (1)°, respectively. In the case of the tert-butoxycarbonyl group at C1 is also coplanar with the cycloctene ring being the O2—C9—O1—C1 torsion angle of 178.2 (7)°. The carbonyl group at atom C5 is twisted with the cycloctene ring being the O3—C5—C4—C3 torsion angle of 123.3 (8)°.

In the crystal structure, molecules are connected by intermolecular C—H···O interactions to form infinite chains running along [001] direction, which seems to be effective in the stabilization of the structure (Table 1).

Related literature top

For the Michael addition of enantiomerically pure lithium amides, see: Davies et al. (2005). For their importance in pharmacology, see: Fülöp et al. (2001). For the reactivity of the cycloocta-1,5-diene in basic medium, see: Huber et al. (1969, 1970). For the preparation of analogous unsaturated cyclooctane esters, see: Garrido et al. (2008).

Experimental top

Epoxydation reaction, synthesis of (1E,3Z)-tert-butyl 5-oxocycloocta-1,3-dienecarboxylate 4. Compound 1 (623.8 mg, 3.0 mmol, 1 equiv) was dissolved in DCM (30 ml), and stirred at 0°C, MCPBA (568.5 mg, 3.3 mmol, 1.1 equiv) was added slowly and the solution was stirred for 5 h at room temperature. The reaction mixture was quenched with saturated Na2S2O3 (10 ml), extracted with DCM (3 x 80 ml), washed with H2O, saturated NaHCO3 and Na2S2O3. The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. Purification by silica gel for flash column chromatography (Hex/EtOAc (99:1 v/v) gave recovery of starting material (16%), (1Z,3R*,4S*) tert-butyl cycloocta-1,3-diene carboxylate 3,4 oxide 2 (450 mg, 67%), (1R*,2S*,3E) tert-butyl cycloocta-3,4-diene carboxylate 1,2 oxide 3 (47 mg, 7%), (1E,3Z)-tert-butyl 5-hydroxycycloocta-1,3-dienecarboxylate 5 (47 mg, 7%) and (1E,3Z)-tert-butyl 5-oxocycloocta-1,3-dienecarboxylate 4 as a pale yellow oil (27 mg, 4%), IR νmax (neat): 2976 and 2868 (C—H), 1707 (C=OOtBu), 1663 (C=O), 1456, 1370, 1292 (C—O), 1252, 1157 cm-1. 1H NMR (400 MHz; CDCl3): δ 1.52 (9H, s, COOC(CH3)3); 2.10 (2H, quint, J 6.6, H-7); 2.50 (2H, t, J 6.6, H-8); 2.57 (2H, t, J 6.6, H-6); 6.03 (1H, d, J 12.6, H-4); 6.57 (1H, dd, J 5.5 and 12.6, H-3); 7.26 (1H, d, J 5.5, H-2). 13C RMN (50 MHz; CDCl3): δ 26.3 (CH2, C-7); 28.0 (CH3 x 3, COOC(CH3)3); 31.8 (CH2, C-8); 38.5 (CH2, C-6); 81.4 (C, COOC(CH3)3); 133.6 (CH, C-4); 134.7 (CH, C-2); 135.8 (CH, C-3); 140.1 (C, C-1); 165.5 (C, COOC(CH3)3); 205.2 (C, C-5). m/z (Cl+) (rel. intensity): 222 (M+, 5) 205 (3), 186 (5), 166 (19), 149 (19), 121 (22), 94 (13), 77 (26), 57 (100).

Synthesis of (3R*,4R*,E)-tert-butyl 3,4-dibromo-5-oxocycloocta-1-enecarboxylate 6. Compound 4 (27.00 mg, 0.12 mmol) was dissolved in CCl4 (10 ml) and the reaction system was stirred and cooled down at 0°C. After, Br2 (0.01 ml, 31 mmol) was added and stirred for 30 min, the ice bath was removed and stirred for 4 h at r.t. The reaction mixture was dissolved in DCM (20 ml), washed with HCl 2 N., NaHCO3(sat.), H2O and NaCl (sat.); dried over Na2SO4, filtered and concentrated in vacuo. It afforded tert-butyl 3,4-dibromo-5-oxocyclooct-1-enecarboxylate 6 (43.00 mg, 91%) which crystallizes in Hex/EtOAc (1:1 v/v), mp 161–162 °C, IR νmax (neat): 2976 and 2930 (C—H), 1712 (C=O), 1449 (C=C), 1369, 1292 (C—O), 1253, 1159, 1127, 1110 (C—Br) cm-1. 1H NMR (400 MHz; CDCl3): δ 1.47 (9H, s, COOC(CH3)3); 2.00–3.02 (6H, m, H-6, H-7, H-8); 4.23 (1H, d, J 11.2, H-4); 5.01 (1H, dd, J 11.2 and 9.6, H-3); 6.80 (1H, d, J 9.6, H-2). 13C RMN (50 MHz; CDCl3): δ 27.1 (CH2, C-7); 27.8 (CH2, C-8); 28.2 (CH3 x 3, COOC(CH3)3); 37.8 (CH2, C-6); 46.8 (CH); 60.4 (CH); 82.2 (C,COOC(CH3)3); 137.5 (CH, C-2); 138.1 (C, C-1); 164.7 (C, COOC(CH3)3); 202.0 (C, C-5). HRMS (ESI) m/z calcd.for C13H18Br2O3 [M+Na]:402.9515; found 402.9543; R—X.

Refinement top

The hydrogen atoms were positioned geometrically, with C—H distances constrained to 0.93 Å (aromatic CH), 0.96 Å (methyl CH3), 0.97 Å methylene CH2), 098 Å (methine CH) and refined in riding mode with Uiso(H) = xUeq(C), where x = 1.5 for methyl H atoms and x = 1.2 for all other atoms.

Computing details top

Data collection: APEX2 (Bruker 2006); cell refinement: SAINT (Bruker 2006); data reduction: SAINT (Bruker 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: Mercury (Macrae et al., 2006); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. Reaction scheme for the synthesis of the title compound.
[Figure 2] Fig. 2. Molecular structure of C13H18Br2O3. Displacement ellipsoids are drawn at the 50% probability level. Hydrogen atoms are shown as spheres of arbitrary radius.
[Figure 3] Fig. 3. Crystal packing of C13H18Br2O3 view along a axis, showing intermolecular C—H···O interactions.
(3S*,4S*,E)-tert-Butyl 3,4-dibromo-5-oxocyclooct-1-enecarboxylate top
Crystal data top
C13H18Br2O3F(000) = 760
Mr = 382.09Dx = 1.669 Mg m3
Orthorhombic, Pca21Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2c -2acCell parameters from 9578 reflections
a = 14.0658 (4) Åθ = 4.6–66.5°
b = 9.5990 (3) ŵ = 6.76 mm1
c = 11.2657 (3) ÅT = 298 K
V = 1521.07 (8) Å3Prismatic, colourless
Z = 40.24 × 0.14 × 0.10 mm
Data collection top
Bruker APEXII CCD area-detector
diffractometer
2170 independent reflections
Radiation source: fine-focus sealed tube2153 reflections with I > 2σ(I)
graphiteRint = 0.048
phi and ω scansθmax = 66.5°, θmin = 4.6°
Absorption correction: multi-scan
(SADABS; Bruker, 2006)
h = 1616
Tmin = 0.370, Tmax = 0.509k = 1111
10215 measured reflectionsl = 1013
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.029H-atom parameters constrained
wR(F2) = 0.075 w = 1/[σ2(Fo2) + (0.0448P)2 + 0.2923P]
where P = (Fo2 + 2Fc2)/3
S = 1.09(Δ/σ)max = 0.001
2170 reflectionsΔρmax = 0.32 e Å3
166 parametersΔρmin = 0.46 e Å3
1 restraintAbsolute structure: Flack (1983), 803 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: 0.06 (3)
Crystal data top
C13H18Br2O3V = 1521.07 (8) Å3
Mr = 382.09Z = 4
Orthorhombic, Pca21Cu Kα radiation
a = 14.0658 (4) ŵ = 6.76 mm1
b = 9.5990 (3) ÅT = 298 K
c = 11.2657 (3) Å0.24 × 0.14 × 0.10 mm
Data collection top
Bruker APEXII CCD area-detector
diffractometer
2170 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2006)
2153 reflections with I > 2σ(I)
Tmin = 0.370, Tmax = 0.509Rint = 0.048
10215 measured reflectionsθmax = 66.5°
Refinement top
R[F2 > 2σ(F2)] = 0.029H-atom parameters constrained
wR(F2) = 0.075Δρmax = 0.32 e Å3
S = 1.09Δρmin = 0.46 e Å3
2170 reflectionsAbsolute structure: Flack (1983), 803 Friedel pairs
166 parametersFlack parameter: 0.06 (3)
1 restraint
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Br10.76354 (2)0.96781 (4)0.67951 (5)0.04630 (14)
Br20.94176 (3)0.72748 (4)0.77399 (5)0.05922 (16)
O10.9457 (2)1.4186 (4)1.0183 (4)0.0671 (10)
O20.79492 (19)1.3427 (3)0.9957 (3)0.0429 (6)
O30.9590 (2)0.9175 (4)1.0552 (3)0.0605 (8)
C10.9148 (3)1.2311 (3)0.8856 (4)0.0368 (7)
C20.8510 (2)1.1346 (3)0.8551 (3)0.0359 (7)
H20.78901.14500.88240.043*
C30.8733 (2)1.0108 (3)0.7796 (4)0.0350 (7)
H30.92851.03130.72940.042*
C40.8964 (3)0.8890 (4)0.8617 (3)0.0403 (7)
H40.83910.86320.90600.048*
C50.9749 (3)0.9286 (4)0.9494 (4)0.0403 (8)
C61.0669 (3)0.9841 (5)0.9021 (4)0.0481 (10)
H6B1.07000.96520.81760.058*
H6A1.11890.93470.93980.058*
C71.0806 (3)1.1419 (5)0.9221 (5)0.0503 (10)
H7B1.06851.16271.00500.060*
H7A1.14631.16550.90570.060*
C81.0164 (3)1.2335 (4)0.8455 (4)0.0455 (9)
H8B1.03961.32860.84790.055*
H8A1.01971.20180.76380.055*
C90.8876 (3)1.3426 (3)0.9735 (3)0.0407 (8)
C100.7509 (3)1.4418 (4)1.0807 (5)0.0488 (10)
C110.7934 (4)1.4216 (6)1.2022 (4)0.0701 (13)
H11A0.79171.32461.22270.105*
H11B0.75761.47401.25940.105*
H11C0.85811.45341.20200.105*
C120.7647 (6)1.5884 (5)1.0332 (7)0.086 (2)
H12A0.83141.60921.02950.130*
H12B0.73381.65371.08490.130*
H12C0.73771.59500.95520.130*
C130.6482 (4)1.3957 (6)1.0791 (6)0.0723 (14)
H13A0.62231.40911.00110.108*
H13B0.61251.44971.13530.108*
H13C0.64441.29881.10000.108*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Br10.0408 (2)0.0566 (2)0.0415 (2)0.00053 (14)0.0054 (2)0.01174 (18)
Br20.0757 (3)0.0393 (2)0.0626 (3)0.01023 (16)0.0059 (2)0.0133 (2)
O10.0599 (18)0.0619 (19)0.079 (3)0.0142 (15)0.0064 (16)0.0333 (17)
O20.0436 (13)0.0401 (12)0.0451 (15)0.0075 (11)0.0017 (12)0.0121 (11)
O30.0719 (19)0.0752 (19)0.0343 (17)0.0037 (15)0.0071 (14)0.0051 (16)
C10.0403 (17)0.0328 (15)0.0374 (19)0.0002 (13)0.0039 (17)0.0032 (14)
C20.0355 (16)0.0375 (15)0.0347 (18)0.0076 (13)0.0050 (14)0.0044 (14)
C30.0347 (17)0.0374 (14)0.0330 (17)0.0026 (13)0.0021 (16)0.0025 (15)
C40.0439 (18)0.0394 (15)0.038 (2)0.0016 (14)0.0021 (17)0.0007 (14)
C50.0402 (19)0.0435 (16)0.037 (2)0.0070 (16)0.0026 (16)0.0026 (16)
C60.0339 (19)0.057 (2)0.054 (3)0.0070 (16)0.0030 (17)0.0068 (19)
C70.0347 (17)0.060 (2)0.056 (3)0.0034 (17)0.0025 (17)0.0164 (19)
C80.044 (2)0.0453 (17)0.047 (2)0.0076 (15)0.0098 (17)0.0082 (15)
C90.050 (2)0.0352 (15)0.037 (2)0.0011 (15)0.0018 (16)0.0017 (14)
C100.066 (2)0.0397 (17)0.040 (2)0.0135 (17)0.009 (2)0.0088 (18)
C110.088 (3)0.082 (3)0.041 (3)0.001 (3)0.006 (2)0.006 (2)
C120.138 (5)0.038 (2)0.083 (4)0.026 (3)0.038 (4)0.002 (2)
C130.063 (3)0.076 (3)0.078 (4)0.019 (2)0.005 (3)0.023 (3)
Geometric parameters (Å, °) top
Br1—C31.956 (4)C6—H6A0.9700
Br2—C41.946 (4)C7—C81.528 (7)
O1—C91.206 (5)C7—H7B0.9700
O2—C91.328 (5)C7—H7A0.9700
O2—C101.486 (5)C8—H8B0.9700
O3—C51.217 (5)C8—H8A0.9700
C1—C21.334 (5)C10—C111.507 (7)
C1—C81.499 (5)C10—C131.511 (7)
C1—C91.508 (5)C10—C121.518 (7)
C2—C31.495 (5)C11—H11A0.9600
C2—H20.9300C11—H11B0.9600
C3—C41.526 (5)C11—H11C0.9600
C3—H30.9800C12—H12A0.9600
C4—C51.529 (6)C12—H12B0.9600
C4—H40.9800C12—H12C0.9600
C5—C61.498 (6)C13—H13A0.9600
C6—C71.543 (6)C13—H13B0.9600
C6—H6B0.9700C13—H13C0.9600
C9—O2—C10122.1 (3)C1—C8—C7112.6 (4)
C2—C1—C8125.0 (3)C1—C8—H8B109.1
C2—C1—C9119.5 (3)C7—C8—H8B109.1
C8—C1—C9115.4 (3)C1—C8—H8A109.1
C1—C2—C3123.9 (3)C7—C8—H8A109.1
C1—C2—H2118.1H8B—C8—H8A107.8
C3—C2—H2118.1O1—C9—O2125.9 (3)
C2—C3—C4108.0 (3)O1—C9—C1122.2 (3)
C2—C3—Br1109.3 (2)O2—C9—C1111.9 (3)
C4—C3—Br1110.8 (2)O2—C10—C11109.7 (4)
C2—C3—H3109.6O2—C10—C13101.7 (4)
C4—C3—H3109.6C11—C10—C13110.7 (5)
Br1—C3—H3109.6O2—C10—C12108.3 (4)
C3—C4—C5110.8 (3)C11—C10—C12112.9 (5)
C3—C4—Br2111.9 (3)C13—C10—C12113.0 (5)
C5—C4—Br2106.8 (2)C10—C11—H11A109.5
C3—C4—H4109.1C10—C11—H11B109.5
C5—C4—H4109.1H11A—C11—H11B109.5
Br2—C4—H4109.1C10—C11—H11C109.5
O3—C5—C6122.5 (4)H11A—C11—H11C109.5
O3—C5—C4118.6 (4)H11B—C11—H11C109.5
C6—C5—C4118.9 (3)C10—C12—H12A109.5
C5—C6—C7113.9 (3)C10—C12—H12B109.5
C5—C6—H6B108.8H12A—C12—H12B109.5
C7—C6—H6B108.8C10—C12—H12C109.5
C5—C6—H6A108.8H12A—C12—H12C109.5
C7—C6—H6A108.8H12B—C12—H12C109.5
H6B—C6—H6A107.7C10—C13—H13A109.5
C8—C7—C6114.1 (4)C10—C13—H13B109.5
C8—C7—H7B108.7H13A—C13—H13B109.5
C6—C7—H7B108.7C10—C13—H13C109.5
C8—C7—H7A108.7H13A—C13—H13C109.5
C6—C7—H7A108.7H13B—C13—H13C109.5
H7B—C7—H7A107.6
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C3—H3···O3i0.982.573.525 (5)165.
C8—H8A···O3i0.972.633.590 (6)172.
Symmetry codes: (i) −x+2, −y+2, z−1/2.
Table 1
Hydrogen-bond geometry (Å, °)
top
D—H···AD—HH···AD···AD—H···A
C3—H3···O3i0.982.573.525 (5)165.
C8—H8A···O3i0.972.633.590 (6)172.
Symmetry codes: (i) −x+2, −y+2, z−1/2.
Acknowledgements top

The authors are grateful to the FSE, the Spanish MICINN (EUI 2008–00173) and (CTQ 2009–11172/BQU) and the Junta de Castilla y Leon (Spain) for financial support (GR-178 and SA001A09). The authors also thank Grupo Santander for the doctoral fellowship awarded to MB.

references
References top

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Davies, S. G., Smith, A. D. & Price, P. D. (2005). Tetrahedron Asymmetry, 16, 2833–2891.

Flack, H. D. (1983). Acta Cryst. A39, 876–881.

Fülöp, F. (2001). Chem. Rev. 101, 2181–2204.

Garrido, N. M., Blanco, M., Cascón, I. F., Díez, D. & Vicente, V. M. (2008). Tetrahedron Asymmetry, 19, 2895–2900.

Huber, A. J. & Reimlinger, H. (1969). Synthesis, pp. 97–112.

Huber, A. J. & Reimlinger, H. (1970). Synthesis, pp. 405–430.

Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453–457.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.