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Acta Crystallogr Sect E Struct Rep Online. 2009 August 1; 65(Pt 8): o1967.
Published online 2009 July 25. doi:  10.1107/S1600536809028256
PMCID: PMC2977082

(S)-6-{[(S)-2,2-Dimethyl-1,3-dioxolan-4-yl]meth­yl}-5,5-difluoro-5,6-dihydro-2H-pyran-2-one

Abstract

The title compound, C11H14F2O4, is a γ,γ-gem-difluorinated α,β-unsaturated δ-lactone. The dioxolane five-membered ring and the lactone ring adopt half-chair conformations. There are two inter­molecular C—H(...)O inter­actions involving the carbonyl group as an acceptor which stabilize the crystal structure.

Related literature

For related synthetic procedures, see: Borjesson & Welch (1992 [triangle]); Dardonville & Gilbert (2003 [triangle]); Gaunt et al. (2003 [triangle]); Saito et al. (1992 [triangle]); You et al. (2006 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o1967-scheme1.jpg

Experimental

Crystal data

  • C11H14F2O4
  • M r = 248.22
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-65-o1967-efi1.jpg
  • a = 5.8003 (8) Å
  • b = 7.8135 (11) Å
  • c = 25.977 (4) Å
  • V = 1177.3 (3) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.13 mm−1
  • T = 293 K
  • 0.51 × 0.48 × 0.26 mm

Data collection

  • Bruker SMART APEX CCD area-detector diffractometer
  • Absorption correction: multi-scan (SADABS; Bruker, 2001 [triangle]) T min = 0.761, T max = 1.000 (expected range = 0.736–0.968)
  • 6682 measured reflections
  • 1455 independent reflections
  • 1261 reflections with I > 2σ(I)
  • R int = 0.131

Refinement

  • R[F 2 > 2σ(F 2)] = 0.054
  • wR(F 2) = 0.134
  • S = 1.00
  • 1455 reflections
  • 173 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.25 e Å−3
  • Δρmin = −0.32 e Å−3

Data collection: SMART (Bruker, 2001 [triangle]); cell refinement: SAINT (Bruker, 2001 [triangle]); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809028256/gk2220sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809028256/gk2220Isup2.hkl

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

Acknowledgments

Financial support of this project by the Program for Changjiang Scholars and Innovative Research Teams in Universities (No. IRT0526) is acknowledged.

supplementary crystallographic information

Comment

α,β-Unsaturated δ-lactone is a common structural unit of natural products with bioactivity. The structure-activity relationship (SAR) reveals that the unsaturated lactone often plays a key role in the bioactivity. The reason may be that the unsaturated lactone is an excellent potential Michael acceptor for natural nucleophiles such as the amino-acid residues. The title compound is an γ,γ-gem-difluorinated α,β-unsaturated δ-lactone, a better Michael acceptor for the electron-withdrawing of the difluoromethylene group. So it is a useful intermediate for synthesis of the fluorine-containing analogues of natural product with potential bioactivity. The title compound was prepared from L-malic acid according to the method developed by our group (You et al., 2006) and other groups (Borjesson et al., 1992; Dardonville et al., 2003; Gaunt et al., 2003; Saito et al., 1992). Our interest is focused on the changes caused by introducing difluoromethylene group into the lactone ring. Here we report the crystal structure of the title compound.

The absolute configuration of the title compound was determined by the known chirality of the C8 derived from the starting material, L-malic acid. All bond lengths and angles in the lactone ring are within normal ranges. The dioxolane five-membered ring and the lactone ring both adopt a half-chair conformation. Intermolecular interactions C6—H6···O1 and C8—H6···O1 arrange the moleculesd in a head-to-head fashion (see Fig. 2).

Experimental

For the reaction scheme see Figure 3. To a solution of (Z)-6-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)-4,4- difluorohex-2-ene-1,5-diol in CH2Cl2 was added bis-acetoxyiodobenzene (3 eq) and 2,2,6,6-tetramethyl piperidinooxy (0.1 eq) at room temperature. After stirring for 3 h, the reaction was quenched with saturated solution of Na2S2O3 and extracted with CH2Cl2. The combined organic extracts were washed with saturated solution of NaHCO3, NH4Cl, brine, dried over anhydrous MgSO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel (petroleum ether / ethyl acetate = 10:1) to afford the title compound. Crystals suitable for X-ray structural analysis were obtained by slow evaporation of a solution in actone and petroleum ether (1:1, v/v).

Refinement

All H atoms could be located in a difference Fourier map. The H atoms from the piran-2-one fragment and the methine H8 atom were fully refined. The remaining H atoms were placed in calculated positions (C-H = 0.97-0.98 Å) and refined using a riding model approximation with Uiso(H) = 1.2Ueq(C) or Uiso(H) = 1.5Ueq(methyl C). Friedel pairs were merged as no significant anomalous scattering effects were observed. The absolute configuration was related to a known chirality (S) of the dioxolane C8 atom. The high Rint value results from a poor quality of the measured crystal.

Figures

Fig. 1.
A view of the molecule of the title compound. Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii.
Fig. 2.
The crystal structure of the title compound, viewed along a axis. Dashed lines indicate the hydrogen bond interactions.
Fig. 3.
The scheme of synthesis of the title compound.

Crystal data

C11H14F2O4Dx = 1.400 Mg m3
Mr = 248.22Melting point: 351 K
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 2723 reflections
a = 5.8003 (8) Åθ = 2.7–27.7°
b = 7.8135 (11) ŵ = 0.13 mm1
c = 25.977 (4) ÅT = 293 K
V = 1177.3 (3) Å3Prismatic, colorless
Z = 40.51 × 0.48 × 0.26 mm
F(000) = 520

Data collection

Bruker SMART APEX CCD area-detector diffractometer1455 independent reflections
Radiation source: fine-focus sealed tube1261 reflections with I > 2σ(I)
graphiteRint = 0.131
Detector resolution: 0 pixels mm-1θmax = 26.5°, θmin = 1.6°
[var phi] and ω scansh = −7→7
Absorption correction: multi-scan (SADABS; Bruker, 2001)k = −9→9
Tmin = 0.761, Tmax = 1.000l = −22→32
6682 measured reflections

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.054H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.134w = 1/[σ2(Fo2) + (0.0757P)2 + 0.0067P] where P = (Fo2 + 2Fc2)/3
S = 1.00(Δ/σ)max = 0.001
1455 reflectionsΔρmax = 0.25 e Å3
173 parametersΔρmin = −0.32 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.024 (5)

Special details

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)

xyzUiso*/Ueq
O10.3246 (5)0.3829 (4)1.04388 (8)0.0741 (7)
O20.3476 (3)0.4190 (2)0.96034 (7)0.0476 (5)
O30.3431 (4)0.1554 (3)0.85332 (9)0.0639 (7)
O40.1373 (4)0.1699 (3)0.78051 (8)0.0644 (6)
F10.5404 (4)0.7375 (2)0.92182 (8)0.0666 (6)
F20.8095 (3)0.5889 (3)0.88536 (7)0.0720 (6)
C10.4418 (5)0.4245 (4)1.00830 (11)0.0517 (7)
C20.6747 (6)0.4915 (4)1.01335 (13)0.0570 (8)
C30.7764 (5)0.5731 (4)0.97527 (13)0.0559 (8)
C50.6553 (4)0.5857 (4)0.92469 (11)0.0473 (6)
C60.4949 (4)0.4373 (3)0.91582 (10)0.0393 (6)
C70.3425 (5)0.4559 (3)0.86946 (11)0.0436 (6)
H7A0.43760.47610.83940.052*
H7B0.24330.55460.87410.052*
C80.1945 (5)0.2985 (4)0.86032 (11)0.0468 (6)
C90.0516 (6)0.3041 (4)0.81085 (13)0.0612 (8)
H9A−0.11070.28720.81830.073*
H9B0.07060.41310.79350.073*
C100.2494 (5)0.0526 (4)0.81349 (11)0.0529 (7)
C110.0790 (8)−0.0735 (4)0.83574 (15)0.0712 (9)
H11A0.0221−0.14640.80880.107*
H11B−0.0473−0.01240.85100.107*
H11C0.1539−0.14180.86150.107*
C120.4412 (7)−0.0334 (6)0.7860 (2)0.0917 (14)
H12A0.54560.05120.77280.137*
H12B0.3803−0.09980.75810.137*
H12C0.5218−0.10730.80940.137*
H20.758 (6)0.483 (5)1.0503 (15)0.070 (10)*
H30.936 (7)0.614 (5)0.9775 (14)0.070 (10)*
H60.588 (4)0.335 (3)0.9143 (11)0.038 (7)*
H80.084 (5)0.278 (3)0.8868 (12)0.039 (7)*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0934 (15)0.0921 (17)0.0369 (11)−0.0240 (15)0.0040 (11)0.0066 (13)
O20.0503 (9)0.0605 (11)0.0319 (9)−0.0088 (9)−0.0024 (7)0.0022 (9)
O30.0785 (13)0.0511 (11)0.0622 (14)0.0125 (11)−0.0381 (12)−0.0168 (12)
O40.0925 (15)0.0675 (13)0.0331 (10)0.0026 (13)−0.0193 (11)0.0025 (11)
F10.0884 (12)0.0420 (8)0.0694 (13)0.0005 (8)−0.0035 (10)−0.0024 (10)
F20.0613 (10)0.0915 (13)0.0633 (12)−0.0178 (10)0.0215 (9)−0.0051 (11)
C10.0662 (15)0.0513 (15)0.0377 (14)−0.0059 (14)−0.0075 (13)0.0004 (14)
C20.0676 (17)0.0553 (15)0.0481 (16)−0.0037 (15)−0.0169 (15)−0.0088 (15)
C30.0468 (14)0.0617 (17)0.0591 (18)−0.0077 (13)−0.0064 (13)−0.0158 (16)
C50.0487 (12)0.0468 (14)0.0465 (15)−0.0032 (12)0.0073 (12)−0.0055 (13)
C60.0424 (12)0.0418 (13)0.0336 (13)0.0014 (10)0.0024 (10)−0.0028 (12)
C70.0532 (13)0.0448 (13)0.0328 (12)0.0013 (11)−0.0011 (11)0.0044 (11)
C80.0569 (14)0.0484 (14)0.0352 (13)0.0006 (12)−0.0093 (13)0.0018 (13)
C90.0747 (17)0.0619 (18)0.0470 (17)0.0064 (15)−0.0250 (16)−0.0014 (16)
C100.0641 (15)0.0534 (16)0.0414 (15)0.0008 (13)−0.0142 (13)−0.0082 (14)
C110.096 (2)0.0593 (19)0.058 (2)−0.0092 (18)−0.0136 (18)−0.0016 (18)
C120.084 (2)0.094 (3)0.098 (3)0.008 (2)0.006 (2)−0.031 (3)

Geometric parameters (Å, °)

O1—C11.193 (4)C6—H60.96 (3)
O2—C11.361 (3)C7—C81.518 (4)
O2—C61.445 (3)C7—H7A0.9700
O3—C101.418 (3)C7—H7B0.9700
O3—C81.424 (4)C8—C91.530 (4)
O4—C91.402 (4)C8—H80.95 (3)
O4—C101.414 (4)C9—H9A0.9700
F1—C51.362 (3)C9—H9B0.9700
F2—C51.358 (3)C10—C121.482 (5)
C1—C21.455 (5)C10—C111.511 (5)
C2—C31.316 (5)C11—H11A0.9600
C2—H21.08 (4)C11—H11B0.9600
C3—C51.493 (4)C11—H11C0.9600
C3—H30.98 (4)C12—H12A0.9600
C5—C61.505 (3)C12—H12B0.9600
C6—C71.501 (4)C12—H12C0.9600
C1—O2—C6119.5 (2)O3—C8—C7108.3 (2)
C10—O3—C8107.82 (19)O3—C8—C9104.1 (2)
C9—O4—C10107.9 (2)C7—C8—C9114.5 (2)
O1—C1—O2118.2 (3)O3—C8—H8111.6 (17)
O1—C1—C2123.9 (3)C7—C8—H8113.8 (17)
O2—C1—C2117.8 (3)C9—C8—H8104.2 (17)
C3—C2—C1121.5 (3)O4—C9—C8105.0 (2)
C3—C2—H2120 (2)O4—C9—H9A110.7
C1—C2—H2118 (2)C8—C9—H9A110.7
C2—C3—C5118.9 (3)O4—C9—H9B110.7
C2—C3—H3122 (2)C8—C9—H9B110.7
C5—C3—H3118 (2)H9A—C9—H9B108.8
F2—C5—F1105.4 (2)O4—C10—O3104.5 (2)
F2—C5—C3110.7 (2)O4—C10—C12110.3 (3)
F1—C5—C3109.6 (3)O3—C10—C12108.7 (3)
F2—C5—C6107.8 (2)O4—C10—C11110.7 (3)
F1—C5—C6111.1 (2)O3—C10—C11109.9 (3)
C3—C5—C6112.0 (3)C12—C10—C11112.3 (3)
O2—C6—C7107.65 (18)C10—C11—H11A109.5
O2—C6—C5108.6 (2)C10—C11—H11B109.5
C7—C6—C5114.4 (2)H11A—C11—H11B109.5
O2—C6—H6106.4 (16)C10—C11—H11C109.5
C7—C6—H6112.1 (17)H11A—C11—H11C109.5
C5—C6—H6107.4 (16)H11B—C11—H11C109.5
C6—C7—C8112.3 (2)C10—C12—H12A109.5
C6—C7—H7A109.1C10—C12—H12B109.5
C8—C7—H7A109.1H12A—C12—H12B109.5
C6—C7—H7B109.1C10—C12—H12C109.5
C8—C7—H7B109.1H12A—C12—H12C109.5
H7A—C7—H7B107.9H12B—C12—H12C109.5
C6—O2—C1—O1−168.5 (3)O2—C6—C7—C8−62.7 (3)
C6—O2—C1—C215.5 (4)C5—C6—C7—C8176.5 (2)
O1—C1—C2—C3−163.5 (3)C10—O3—C8—C7−140.1 (2)
O2—C1—C2—C312.3 (5)C10—O3—C8—C9−17.9 (3)
C1—C2—C3—C5−4.4 (5)C6—C7—C8—O3−59.2 (3)
C2—C3—C5—F2−148.5 (3)C6—C7—C8—C9−174.8 (2)
C2—C3—C5—F195.6 (3)C10—O4—C9—C821.3 (3)
C2—C3—C5—C6−28.1 (4)O3—C8—C9—O4−2.0 (3)
C1—O2—C6—C7−170.7 (2)C7—C8—C9—O4116.0 (3)
C1—O2—C6—C5−46.3 (3)C9—O4—C10—O3−32.7 (3)
F2—C5—C6—O2173.1 (2)C9—O4—C10—C12−149.4 (3)
F1—C5—C6—O2−71.9 (3)C9—O4—C10—C1185.6 (3)
C3—C5—C6—O251.1 (3)C8—O3—C10—O431.3 (3)
F2—C5—C6—C7−66.6 (3)C8—O3—C10—C12149.1 (3)
F1—C5—C6—C748.3 (3)C8—O3—C10—C11−87.6 (3)
C3—C5—C6—C7171.3 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C8—H8···O1i0.95 (3)2.66 (3)3.578 (4)161 (2)
C6—H6···O1ii0.96 (3)2.44 (3)3.318 (4)151 (2)

Symmetry codes: (i) x−1/2, −y+1/2, −z+2; (ii) x+1/2, −y+1/2, −z+2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: GK2220).

References

  • Borjesson, L. & Welch, C. H. (1992). Tetrahedron, 48, 6325–6334.
  • Bruker (2001). SMART, SAINT and SADABS Bruker AXS Inc., Madison, Wisconsin, USA.
  • Dardonville, C. & Gilbert, I. H. (2003). Org. Biomol. Chem.1, 552–559. [PubMed]
  • Gaunt, M. J., Jessiman, A. S., Orsini, P., Tanner, H. R., Hook, D. F. & Ley, S. V. (2003). Org. Lett.5, 4819–4822. [PubMed]
  • Saito, S., Ishikawa, T., Kuroda, A. & Moriwake, T. (1992). Tetrahedron, 48, 4067–4086.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • You, Z. W., Jiang, Z. X., Wang, B. L. & Qing, F. L. (2006). J. Org. Chem.71, 7261–7267. [PubMed]

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