(5S)-3-Chloro-4-(2,5-dihydro-1H-pyrrol-1-yl)-5-[(1R,2S,5R)-2-isopropyl-5-methyl­cyclo­hex­yloxy]furan-2(5H)-one

Jian-Hua Fu; Zhao-Yang Wang; Fu-Ling Xue; Jing-Pei Huo

doi:10.1107/S1600536810051226

. 2010 Dec 11;67(Pt 1):o73. doi: 10.1107/S1600536810051226

(5S)-3-Chloro-4-(2,5-dihydro-1H-pyrrol-1-yl)-5-[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy]furan-2(5H)-one

Jian-Hua Fu ^a, Zhao-Yang Wang ^a,^*, Fu-Ling Xue ^a, Jing-Pei Huo ^a

PMCID: PMC3050327 PMID: 21522785

Abstract

The title compound, C₁₈H₂₆ClNO₃, was obtained via a tandem asymmetric Michael addition–elimination reaction of 3,4-dichloro-5-(S)-(l-menthyloxy)furan-2(5H)-one and 2,5-dihydro-1H-pyrrole in the presence of potassium fluoride. In the molecule, the nearly planar dihydropyrrole ring [maximum atomic deviation = 0.019 (3) Å] is oriented at a dihedral angle of 10.73 (8)° to the the nearly planar furanone ring [maximum atomic deviation = 0.011 (2) Å]; the cyclohexane ring adopts a chair conformation. In the crystal, molecules are linked via weak intermolecular C—H⋯O hydrogen bonds, forming supramolecular chains running along the b axis.

Related literature

The title compound is a derivative of 4-amino-2(5H)-furanone. For the biological activity of 4-amino-2(5H)-furanones, see: Lattmann et al. (1999 ▶, 2005 ▶, 2006 ▶); Rowland et al. (2007 ▶); Kim et al. (2002 ▶). For asymmetric Michael addition reactions of 2(5H)-furanone, see: He et al. (2006 ▶). For the synthesis of the title compound, see: Song et al. (2009 ▶).

Experimental

Crystal data

C₁₈H₂₆ClNO₃
M _r = 339.85
Orthorhombic,
a = 7.192 (2) Å
b = 9.622 (3) Å
c = 27.534 (9) Å
V = 1905.4 (10) Å³
Z = 4
Mo Kα radiation
μ = 0.21 mm⁻¹
T = 298 K
0.23 × 0.20 × 0.16 mm

Data collection

Bruker APEXII area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.952, T _max = 0.966
9627 measured reflections
3363 independent reflections
1708 reflections with I > 2σ(I)
R _int = 0.053

Refinement

R[F ² > 2σ(F ²)] = 0.052
wR(F ²) = 0.129
S = 1.02
3363 reflections
211 parameters
H-atom parameters constrained
Δρ_max = 0.11 e Å⁻³
Δρ_min = −0.14 e Å⁻³
Absolute structure: Flack (1983 ▶), 1398 Friedel pairs
Flack parameter: 0.14 (12)

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT (Bruker, 2008 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810051226/xu5106sup1.cif

e-67-00o73-sup1.cif^{(19.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810051226/xu5106Isup2.hkl

e-67-00o73-Isup2.hkl^{(165KB, hkl)}

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
C16—H16⋯O2ⁱ	0.93	2.42	3.320 (6)	164

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Symmetry code: (i) Inline graphic .

Acknowledgments

The work was supported by the National Natural Science Foundation of China (grant No. 20772035) and the Natural Science Foundation of Guangdong Province, China (grant No. 5300082).

supplementary crystallographic information

Comment

Molecules possessing 2(5H)-furanone moiety, are extremely useful heterocyclic compounds, due to their significant biological activities, such as antibacterial, anti-inflammatory and antitumor. (Lattmann et al., 2005; Rowland et al., 2007; Kim et al., 2002). 5-Alkoxy-3,4-dihalo-2(5H)-furanones, being a kind of synthons, are widely used in asymmetric and pharmaceutical synthesis reactions. (Lattmann et al., 2006). At the same time, 4-amino-2(5H)-furanones are showing an antibiotic activity against MRSA (Lattmann et al., 1999; Lattmann et al., 2006). Therefore, we are interested in the tandem Michael addition-elimination reaction of the chiral synthon 3,4-dichloro-5-(S)-(l-menthyloxy)-2(5H)-furanone and 2,5-dihydro-1H-pyrrole in the present of potassium fluoride.

The structure of the title compound (I) is illustrated in Fig. 1. The crystal structure of the title compound, which has four chiral centers (C4(S), C5(R), C6(S), C9(R)), contains a five-membered furanone ring and a six-membered ring connected each other via C4—O3—C5 ether bond. The furanone ring of C4—O1—C1—C2—C3 is approximately planar, whereas the six-membered ring displays a chair conformation.

Experimental

The precursor 3,4-dichloro-5-(S)-(l-menthyloxy)-2(5H)-furanone was prepared according to the literature procedure (Song et al., 2009). After the mixture of 3,4-dichloro-5-(S)-(l-menthyloxy)-2(5H)-furanone (2.0 mmol) and potassium fluoride (6.0 mmol) was dissolved in absolute tetrahydrofuran (2.0 mL) under nitrogen atmosphere, tetrahydrofuran solution of 2,5-dihydro-1H-pyrrole (2.0 mmol) was added. The reaction was carried out under the stirring at room temperature for 6 h. Once the reaction was complete, the solvents were removed under reduced pressure. The residual solid was dissolved in dichloromethane. Then the combined organic layers from extraction were concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography with the gradient mixture of petroleum ether and ethyl acetate to give the product yielding (I) 0.561 g (82.4%).