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Acta Crystallogr Sect E Struct Rep Online. 2010 January 1; 66(Pt 1): o217.
Published online 2009 December 19. doi:  10.1107/S1600536809051976
PMCID: PMC2980058

(4R)-Ethyl 4-(4-chloro­phen­yl)-2-hydr­oxy-5-oxo-2,3,4,5-tetra­hydro­pyrano[3,2-c]chromene-2-carboxyl­ate

Abstract

The title compound, C21H17ClO6, is optically pure and adopts an R configuration. It was obtained by an organocatalytic asymmetric Michael addition of 4-hydroxy­coumarin with (E)-ethyl 4-(4-chloro­phen­yl)-2-oxobut-3-enoate. The structure consists of a tetra­hydro­pyran unit fused to the coumarin ring ring system. The hydroxyl and phenyl groups are on the same side of the tetra­hydro­pyrane ring. The benzene ring is almost perpendicular to the coumarin ring [dihedral angle of 72.89 (3)°]. In the crystal structure, inter­molecular O—H(...)O hydrogen bonds are observed. An intra­molecular O—H(...)O contact also occurs.

Related literature

For general background to the use of coumarin derivatives as intermediates in organic and natural product synthesis, see: Fylaktakidou et al., (2004 [triangle]); Hoult et al., (1996 [triangle]). For a related structure, see: Zhang et al. (2009 [triangle]).

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Object name is e-66-0o217-scheme1.jpg

Experimental

Crystal data

  • C21H17ClO6
  • M r = 400.80
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-0o217-efi1.jpg
  • a = 5.4818 (3) Å
  • b = 14.8358 (7) Å
  • c = 11.3403 (6) Å
  • β = 94.6807 (15)°
  • V = 919.20 (8) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.25 mm−1
  • T = 296 K
  • 0.37 × 0.31 × 0.08 mm

Data collection

  • Rigaku RAXIS-RAPID diffractometer
  • Absorption correction: multi-scan (ABSCOR; Higashi, 1995 [triangle]) T min = 0.905, T max = 0.981
  • 8978 measured reflections
  • 3606 independent reflections
  • 3027 reflections with I > 2σ(I)
  • R int = 0.025

Refinement

  • R[F 2 > 2σ(F 2)] = 0.031
  • wR(F 2) = 0.080
  • S = 1.00
  • 3606 reflections
  • 256 parameters
  • 1 restraint
  • H-atom parameters constrained
  • Δρmax = 0.16 e Å−3
  • Δρmin = −0.20 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 1434 Friedel pairs
  • Flack parameter: 0.07 (6)

Data collection: PROCESS-AUTO (Rigaku, 2006 [triangle]); cell refinement: PROCESS-AUTO; data reduction: CrystalStructure (Rigaku, 2007 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 for Windows (Farrugia,1997 [triangle]); software used to prepare material for publication: WinGX (Farrugia, 1999 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809051976/zq2019sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809051976/zq2019Isup2.hkl

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

Acknowledgments

We thank Professor Jian-Ming Gu of Zhejiang University for his help.

supplementary crystallographic information

Comment

Coumarin derivatives are common found in a variety of natural products, and are used as versatile intermediates in organic and natural product synthesis (Fylaktakidou et al., 2004; Hoult et al., 1996). The title compound could be synthesized through an asymmetric Michael addition of 4-hydroxycoumarin with (E)-ethyl 4-(4-chlorophenyl)-2-oxobut-3-enoate, catalyzed by a tertiary-amine-squaramide catalyst. As part of our study in organocatalysis, the absolute structure of the title compound was determined, which adopts a R configuration. The structure consists of a tetrahydropyrane fused beside the coumarin ring. The hydroxyl and phenyl groups are on the same side of the tetrahydropyrane ring. The benzene ring is almost perpendicular to the coumarin ring with a dihedral angle of 72.89 (3)° between the mean planes. In addition, intermolecular O—H···O hydrogen bonds are observed in the crystal structure.

Experimental

A mixture of 4-hydroxycoumarin (0.1 mmol), (E)-ethyl 4-(4-chlorophenyl)-2-oxobut-3-enoate 2 (0.1 mmol) and the catalyst 3-((1S) -(6-methoxyquinolin-4-yl)(8-vinylquinuclidin-2-yl)methylamino) -4-((R)-1-phenylethylamino)cyclobut-3-ene-1,2-dione (0.0025 mmol) in ClCH2CH2Cl (1.0 ml) was stirred at room temperature for 3 h (monitored by TLC). The mixture was purified by column chromatography on silica gel, eluted by petroleum ether/EtOAc (10:1 to 3:1) to give the desired Michael adducts. Suitable crystals of the title compound were obtained by slow evaporation of a mixture solution of CH2Cl2 and iPrOH at room temperature.

Refinement

All hydrogen atoms were refined in calculated positions with C—H = 0.98 Å(sp), C—H = 0.97 Å (sp2), C—H = 0.96 Å (sp3), C—H = 0.93 Å (aromatic), O—H = 0.82 Å, and with Uiso(H) = 1.2Ueq of the carrier atoms.

Figures

Fig. 1.
The asymmetric unit of the structure of the title compound, with the atomic labeling scheme. Displacement ellipsoids are drawn at the 50% probability level.
Fig. 2.
The molecular packing of the title compound showing H-bridge interactions.

Crystal data

C21H17ClO6F(000) = 416
Mr = 400.80Dx = 1.448 Mg m3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ybCell parameters from 7553 reflections
a = 5.4818 (3) Åθ = 3.3–27.4°
b = 14.8358 (7) ŵ = 0.25 mm1
c = 11.3403 (6) ÅT = 296 K
β = 94.6807 (15)°Platelet, colorless
V = 919.20 (8) Å30.37 × 0.31 × 0.08 mm
Z = 2

Data collection

Rigaku RAXIS-RAPID diffractometer3606 independent reflections
Radiation source: rolling anode3027 reflections with I > 2σ(I)
graphiteRint = 0.025
Detector resolution: 10.00 pixels mm-1θmax = 27.4°, θmin = 3.3°
ω scansh = −7→6
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)k = −19→16
Tmin = 0.905, Tmax = 0.981l = −14→14
8978 measured reflections

Refinement

Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.031w = 1/[σ2(Fo2) + (0.0403P)2 + 0.110P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.080(Δ/σ)max < 0.001
S = 1.00Δρmax = 0.16 e Å3
3606 reflectionsΔρmin = −0.20 e Å3
256 parametersExtinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
1 restraintExtinction coefficient: 0.014 (2)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack (1983), 1434 Friedel pairs
Secondary atom site location: difference Fourier mapFlack parameter: 0.07 (6)

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
C190.7695 (3)0.87640 (13)0.68614 (17)0.0368 (4)
O60.9549 (3)0.87424 (10)0.76723 (12)0.0456 (3)
O50.6200 (3)0.93532 (10)0.67137 (15)0.0542 (4)
C200.9886 (5)0.95257 (18)0.8444 (2)0.0577 (6)
H20A0.85330.95790.89400.069*
H20B0.99651.00720.79780.069*
C211.2228 (5)0.9388 (2)0.9187 (2)0.0677 (7)
H21A1.35640.93800.86900.081*
H21B1.21690.88250.96000.081*
H21C1.24580.98710.97490.081*
Cl10.78443 (13)0.72613 (6)−0.01510 (5)0.0714 (2)
O30.6428 (2)0.72598 (9)0.68482 (11)0.0369 (3)
C90.5060 (3)0.57839 (13)0.71703 (16)0.0345 (4)
O40.6019 (2)0.80479 (9)0.50872 (12)0.0396 (3)
H40.52590.85190.51550.047*
C100.6604 (3)0.63786 (12)0.65397 (16)0.0325 (4)
O20.6645 (3)0.45423 (9)0.60916 (14)0.0467 (4)
O10.9452 (3)0.47428 (10)0.48350 (16)0.0577 (5)
C141.0913 (3)0.72144 (15)0.31531 (17)0.0407 (4)
H141.23570.74200.35520.049*
C130.9207 (3)0.67714 (13)0.37856 (16)0.0334 (4)
C20.8067 (3)0.60639 (12)0.57288 (16)0.0335 (4)
C10.9793 (3)0.66573 (12)0.51166 (16)0.0332 (4)
H11.14060.63700.52220.040*
C80.3482 (4)0.60857 (15)0.79984 (18)0.0429 (5)
H80.34030.66950.81840.051*
C151.0524 (4)0.73588 (16)0.19483 (18)0.0459 (5)
H151.16880.76570.15400.055*
C50.3671 (5)0.42524 (15)0.7439 (2)0.0547 (6)
H50.37210.36440.72480.066*
C110.7569 (3)0.79097 (12)0.60903 (16)0.0320 (4)
C60.2158 (5)0.45589 (17)0.8250 (2)0.0603 (7)
H60.11840.41490.86180.072*
C160.8385 (4)0.70536 (14)0.13638 (18)0.0438 (5)
C170.6664 (4)0.65979 (16)0.19587 (19)0.0476 (5)
H170.52320.63880.15540.057*
C30.8158 (4)0.51022 (13)0.54999 (19)0.0421 (5)
C121.0021 (3)0.75658 (12)0.57806 (17)0.0334 (4)
H12A1.10860.74910.65000.040*
H12B1.07630.80070.52890.040*
C40.5140 (4)0.48726 (14)0.69059 (19)0.0414 (5)
C180.7094 (3)0.64567 (14)0.31706 (18)0.0409 (4)
H180.59440.61460.35730.049*
C70.2036 (4)0.54659 (17)0.8539 (2)0.0544 (6)
H70.09880.56580.90930.065*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C190.0424 (10)0.0289 (9)0.0403 (10)−0.0053 (9)0.0112 (8)0.0000 (8)
O60.0582 (8)0.0365 (8)0.0417 (8)−0.0048 (7)0.0013 (6)−0.0088 (6)
O50.0549 (9)0.0375 (8)0.0713 (11)0.0070 (7)0.0109 (8)−0.0129 (7)
C200.0693 (14)0.0498 (14)0.0545 (14)−0.0138 (12)0.0078 (11)−0.0206 (11)
C210.0677 (15)0.081 (2)0.0540 (15)−0.0195 (15)0.0045 (12)−0.0199 (14)
Cl10.0961 (5)0.0781 (5)0.0382 (3)0.0081 (4)−0.0048 (3)0.0010 (3)
O30.0452 (7)0.0252 (6)0.0418 (7)−0.0039 (6)0.0128 (5)0.0007 (6)
C90.0382 (9)0.0321 (10)0.0327 (9)−0.0038 (8)0.0006 (7)0.0047 (8)
O40.0399 (7)0.0346 (8)0.0433 (7)0.0059 (6)−0.0023 (6)−0.0007 (6)
C100.0375 (9)0.0238 (8)0.0355 (9)−0.0013 (7)−0.0008 (7)0.0009 (7)
O20.0616 (9)0.0260 (7)0.0541 (9)−0.0058 (6)0.0140 (7)−0.0031 (6)
O10.0745 (11)0.0333 (8)0.0688 (11)0.0064 (8)0.0263 (9)−0.0074 (7)
C140.0350 (9)0.0441 (11)0.0432 (10)−0.0005 (9)0.0046 (8)−0.0034 (10)
C130.0341 (8)0.0285 (9)0.0378 (10)0.0050 (8)0.0046 (7)−0.0021 (8)
C20.0368 (9)0.0256 (8)0.0377 (10)0.0003 (8)0.0015 (8)0.0005 (8)
C10.0315 (8)0.0297 (9)0.0383 (10)0.0030 (8)0.0024 (7)0.0011 (8)
C80.0523 (12)0.0357 (10)0.0410 (11)−0.0040 (9)0.0060 (9)0.0030 (8)
C150.0470 (11)0.0466 (12)0.0450 (11)0.0027 (10)0.0091 (9)0.0025 (10)
C50.0785 (15)0.0323 (11)0.0547 (14)−0.0159 (11)0.0145 (12)0.0029 (10)
C110.0353 (8)0.0246 (9)0.0361 (9)−0.0023 (8)0.0028 (7)0.0018 (7)
C60.0808 (17)0.0471 (14)0.0556 (14)−0.0241 (12)0.0221 (12)0.0057 (11)
C160.0553 (12)0.0407 (12)0.0353 (10)0.0113 (9)0.0035 (9)−0.0019 (8)
C170.0456 (11)0.0477 (13)0.0479 (12)0.0046 (11)−0.0057 (9)−0.0086 (10)
C30.0492 (12)0.0293 (10)0.0481 (12)−0.0005 (9)0.0062 (9)0.0004 (9)
C120.0320 (8)0.0309 (9)0.0374 (10)−0.0034 (7)0.0033 (7)−0.0021 (7)
C40.0518 (11)0.0322 (10)0.0400 (11)−0.0070 (9)0.0027 (9)0.0008 (8)
C180.0377 (10)0.0389 (11)0.0461 (11)−0.0004 (9)0.0043 (8)−0.0044 (9)
C70.0644 (14)0.0506 (13)0.0506 (13)−0.0086 (12)0.0198 (11)0.0060 (10)

Geometric parameters (Å, °)

C19—O51.201 (3)C14—H140.9300
C19—O61.314 (2)C13—C181.384 (3)
C19—C111.538 (3)C13—C11.527 (3)
O6—C201.457 (3)C2—C31.452 (3)
C20—C211.491 (3)C2—C11.503 (3)
C20—H20A0.9700C1—C121.544 (2)
C20—H20B0.9700C1—H10.9800
C21—H21A0.9600C8—C71.389 (3)
C21—H21B0.9600C8—H80.9300
C21—H21C0.9600C15—C161.376 (3)
Cl1—C161.747 (2)C15—H150.9300
O3—C101.359 (2)C5—C61.366 (4)
O3—C111.466 (2)C5—C41.393 (3)
C9—C41.386 (3)C5—H50.9300
C9—C81.401 (3)C11—C121.506 (2)
C9—C101.451 (3)C6—C71.388 (4)
O4—C111.379 (2)C6—H60.9300
O4—H40.8200C16—C171.381 (3)
C10—C21.352 (3)C17—C181.391 (3)
O2—C41.378 (2)C17—H170.9300
O2—C31.385 (3)C12—H12A0.9700
O1—C31.202 (3)C12—H12B0.9700
C14—C151.382 (3)C18—H180.9300
C14—C131.389 (3)C7—H70.9300
O5—C19—O6126.54 (19)C7—C8—H8120.3
O5—C19—C11121.49 (18)C9—C8—H8120.3
O6—C19—C11111.95 (17)C16—C15—C14118.80 (19)
C19—O6—C20116.98 (18)C16—C15—H15120.6
O6—C20—C21106.9 (2)C14—C15—H15120.6
O6—C20—H20A110.3C6—C5—C4118.5 (2)
C21—C20—H20A110.3C6—C5—H5120.8
O6—C20—H20B110.3C4—C5—H5120.8
C21—C20—H20B110.3O4—C11—O3108.53 (14)
H20A—C20—H20B108.6O4—C11—C12111.09 (15)
C20—C21—H21A109.5O3—C11—C12110.24 (14)
C20—C21—H21B109.5O4—C11—C19110.03 (15)
H21A—C21—H21B109.5O3—C11—C19102.12 (14)
C20—C21—H21C109.5C12—C11—C19114.36 (15)
H21A—C21—H21C109.5C5—C6—C7121.7 (2)
H21B—C21—H21C109.5C5—C6—H6119.2
C10—O3—C11116.05 (14)C7—C6—H6119.2
C4—C9—C8119.26 (17)C15—C16—C17121.02 (19)
C4—C9—C10117.16 (18)C15—C16—Cl1119.04 (17)
C8—C9—C10123.56 (18)C17—C16—Cl1119.94 (16)
C11—O4—H4109.5C16—C17—C18119.28 (18)
C2—C10—O3124.48 (16)C16—C17—H17120.4
C2—C10—C9121.85 (17)C18—C17—H17120.4
O3—C10—C9113.68 (16)O1—C3—O2116.45 (18)
C4—O2—C3121.76 (15)O1—C3—C2125.38 (19)
C15—C14—C13121.85 (17)O2—C3—C2118.17 (17)
C15—C14—H14119.1C11—C12—C1111.80 (14)
C13—C14—H14119.1C11—C12—H12A109.3
C18—C13—C14118.06 (17)C1—C12—H12A109.3
C18—C13—C1124.12 (17)C11—C12—H12B109.3
C14—C13—C1117.82 (15)C1—C12—H12B109.3
C10—C2—C3119.47 (17)H12A—C12—H12B107.9
C10—C2—C1122.87 (17)O2—C4—C9121.55 (17)
C3—C2—C1117.45 (17)O2—C4—C5117.07 (19)
C2—C1—C13115.59 (15)C9—C4—C5121.4 (2)
C2—C1—C12108.35 (15)C13—C18—C17120.96 (19)
C13—C1—C12112.80 (15)C13—C18—H18119.5
C2—C1—H1106.5C17—C18—H18119.5
C13—C1—H1106.5C8—C7—C6119.9 (2)
C12—C1—H1106.5C8—C7—H7120.1
C7—C8—C9119.3 (2)C6—C7—H7120.1
O5—C19—O6—C20−2.5 (3)O6—C19—C11—O379.70 (17)
C11—C19—O6—C20178.81 (17)O5—C19—C11—C12141.84 (19)
C19—O6—C20—C21−173.86 (19)O6—C19—C11—C12−39.4 (2)
C11—O3—C10—C211.5 (3)C4—C5—C6—C70.7 (4)
C11—O3—C10—C9−168.76 (14)C14—C15—C16—C17−1.0 (3)
C4—C9—C10—C2−0.1 (3)C14—C15—C16—Cl1178.24 (17)
C8—C9—C10—C2−178.63 (19)C15—C16—C17—C180.8 (3)
C4—C9—C10—O3−179.89 (16)Cl1—C16—C17—C18−178.46 (16)
C8—C9—C10—O31.6 (3)C4—O2—C3—O1177.8 (2)
C15—C14—C13—C181.2 (3)C4—O2—C3—C2−2.0 (3)
C15—C14—C13—C1−179.16 (19)C10—C2—C3—O1−177.1 (2)
O3—C10—C2—C3178.07 (17)C1—C2—C3—O1−2.2 (3)
C9—C10—C2—C3−1.7 (3)C10—C2—C3—O22.7 (3)
O3—C10—C2—C13.5 (3)C1—C2—C3—O2177.59 (16)
C9—C10—C2—C1−176.26 (16)O4—C11—C12—C1−60.5 (2)
C10—C2—C1—C13−114.25 (19)O3—C11—C12—C159.81 (19)
C3—C2—C1—C1371.1 (2)C19—C11—C12—C1174.18 (15)
C10—C2—C1—C1213.4 (2)C2—C1—C12—C11−44.01 (19)
C3—C2—C1—C12−161.21 (16)C13—C1—C12—C1185.26 (18)
C18—C13—C1—C27.8 (3)C3—O2—C4—C90.2 (3)
C14—C13—C1—C2−171.77 (17)C3—O2—C4—C5179.2 (2)
C18—C13—C1—C12−117.64 (19)C8—C9—C4—O2179.47 (18)
C14—C13—C1—C1262.8 (2)C10—C9—C4—O20.9 (3)
C4—C9—C8—C70.1 (3)C8—C9—C4—C50.5 (3)
C10—C9—C8—C7178.6 (2)C10—C9—C4—C5−178.09 (19)
C13—C14—C15—C160.0 (3)C6—C5—C4—O2−180.0 (2)
C10—O3—C11—O479.38 (18)C6—C5—C4—C9−0.9 (3)
C10—O3—C11—C12−42.5 (2)C14—C13—C18—C17−1.5 (3)
C10—O3—C11—C19−164.42 (14)C1—C13—C18—C17178.97 (18)
O5—C19—C11—O416.0 (2)C16—C17—C18—C130.5 (3)
O6—C19—C11—O4−165.19 (15)C9—C8—C7—C6−0.3 (3)
O5—C19—C11—O3−99.1 (2)C5—C6—C7—C8−0.1 (4)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
O4—H4···O2i0.822.272.9184 (19)136
O4—H4···O50.822.192.671 (2)118

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: ZQ2019).

References

  • Farrugia, L. J. (1997). J. Appl. Cryst.30, 565.
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