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

Magda Blanco; Narciso M Garrido; Francisca Sanz; David Diez

doi:10.1107/S1600536811053852

. 2011 Dec 23;68(Pt 1):o232. doi: 10.1107/S1600536811053852

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

Magda Blanco ^a, Narciso M Garrido ^a,^*, Francisca Sanz ^b, David Diez ^a

PMCID: PMC3254564 PMID: 22259514

Abstract

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.

Related literature

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

Crystal data

C₁₃H₁₈Br₂O₃
M _r = 382.09
Orthorhombic,
a = 14.0658 (4) Å
b = 9.5990 (3) Å
c = 11.2657 (3) Å
V = 1521.07 (8) Å³
Z = 4
Cu Kα radiation
μ = 6.76 mm⁻¹
T = 298 K
0.24 × 0.14 × 0.10 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2006 ▶) T _min = 0.370, T _max = 0.509
10215 measured reflections
2170 independent reflections
2153 reflections with I > 2σ(I)
R _int = 0.048

Refinement

R[F ² > 2σ(F ²)] = 0.029
wR(F ²) = 0.075
S = 1.09
2170 reflections
166 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.46 e Å⁻³
Absolute structure: Flack (1983 ▶), 803 Friedel pairs
Flack parameter: 0.06 (3)

Data collection: APEX2 (Bruker 2006 ▶); cell refinement: SAINT (Bruker 2006 ▶); data reduction: SAINT; 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 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811053852/bt5753sup1.cif

e-68-0o232-sup1.cif^{(16.4KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811053852/bt5753Isup2.hkl

e-68-0o232-Isup2.hkl^{(106.7KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811053852/bt5753Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C3—H3⋯O3ⁱ	0.98	2.57	3.525 (5)	165
C8—H8A⋯O3ⁱ	0.97	2.63	3.590 (6)	172

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Symmetry code: (i) Inline graphic .

Acknowledgments

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.

supplementary crystallographic information

Comment

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).

Experimental

Epoxydation reaction, synthesis of (1E,3Z)-tert-butyl 5-oxocycloocta-1,3-dienecarboxylate4. 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. 1}H 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 (CH₃x 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-enecarboxylate6. 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. 1}H 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 (CH₃x 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.