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Stereoselective hydroboration of (-)-isopulegol and subsequent fractional crystallization furnishes the title compound, C10H20O2. The relative configuration of the stereogenic centres has been assigned by means of X-ray diffraction analysis since the monoterpenediol is employed as a versatile chiral building block in stereospecific natural product synthesis.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270199014122/na1422sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270199014122/na1422Isup2.hkl
Contains datablock I

CCDC reference: 140953

Comment top

The preparation of the title compound, (-)-(I), by hydroboration of (-)-isopulegol, (II), was first reported by Schulte-Elte & Ohloff (1967). In the meantime, (-)-(I) has found broad application as an optically active starting material in the synthesis of natural products, especially of the antimalarial drug artemisinin and a number of its analogues (Imakura et al., 1988; Constantino et al., 1996; Avery et al., 1990, 1994; Hui et al., 1997). Although the stereochemistryof (-)-(I) appears to be well established in the literature by NMR data and by the configuration of derivatives sythesized from it, the crystal structure of the important relay compound itself is still lacking. During our 18-step stereospecific preparation of the bis-abolane sesquiterpenes β-turmerone, (III), and β-sequiphellandrene, (IV) (Kreiser & Körner, 2000), we succeeded in determining the relative configuration of the vicinal asymmetric C atoms by X-ray diffraction analysis of their synthetic intermediate (-)-(I), since during further transformation, C2 and C2' of (-)-(I) become C1' and C6 in the corresponding sesquiterpenes. (-)-(I) was prepared from technical grade (-)-isopulegol, (II), of moderate enantiomeric and diastereomeric purity, but after repeated crystallization from Et2O, the material was identical in melting point and optical rotation with the data reported for (-)-(I) derived from highly pure (II). Therefore, the configuration given in Fig. 1 is most likely to be the absolute one. In the crystalline state, the cyclohexane part of (-)-(I) displays an almost perfect undistorted chair conformation since all the six torsion angles involving the three substituents (O1—C1—C2—C3, O1—C1—C6—C5, C2'—C2—C3—C4, C6—C1—C2—C2', C3—C4—C5—C5a and C5a—C5—C6—C1) are in the range 176.8 (3)–179.5 (3)°. Accordingly, the hydroxy, isopropyl and methyl substituents (O1, C2' and C5a, respectively) are found in ideal all-equatorial positions. Consequently, the relative arrangement of the hydroxy and isopropyl groups is anti, and of the hydroxy and the methyl groups is syn, in accordance with the predicted 1R,2S,5R stereochemistry. Considering that the stereogenic centres at C1 and C5 are going to be extinguished during the course of further synthetic manipulation, the most important aspect is the relative stereochemistry between C2 and C2', which can be deduced from Fig. 1. Provided that the configuration at C2 is S, that at C2' has to be R.

Experimental top

The preparation of (-)-(I) from (II) is described by Kreiser & Körner (2000). For the X-ray diffraction analysis, pure (I) (1.00 g, 5.80 mmol) was dissolved completely in the required amount of dry Et2O at reflux temperature. Thereafter, further Et2O (10 ml) was added and crystals [m.p. 377.5–378 K, [α]D295 = −19.6° (c = 2.67, CHCl3)] were grown slowly at 273 K.

Refinement top

The weighting scheme proposed by the refinement resulted in the low goodness-of-fit value.

Computing details top

Data collection: KappaCCD Software (Nonius, 1997); cell refinement: DENZO and SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO and SCALEPACK; program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL-Plus (Sheldrick, 1991); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997) and PARST95 (Nardelli, 1995).

Figures top
[Figure 1] Fig. 1. A view of the title compound showing the labelling of all non-H atoms. Displacement ellipsoids are shown at 50% probability levels and H atoms are drawn as circles of arbitrary radii.
(I) top
Crystal data top
C10H20O2F(000) = 192
Mr = 172.26Dx = 1.094 Mg m3
Monoclinic, P21Mo Kα radiation, λ = 0.71069 Å
a = 8.5710 (7) ÅCell parameters from 6694 reflections
b = 6.4665 (3) Åθ = 3.7–25.8°
c = 9.8502 (8) ŵ = 0.07 mm1
β = 106.783 (3)°T = 291 K
V = 522.69 (7) Å3Needle, colourless
Z = 20.30 × 0.08 × 0.05 mm
Data collection top
Nonius KappaCCD
diffractometer
1299 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.027
Graphite monochromatorθmax = 25.8°, θmin = 3.7°
Detector resolution: 19 vertical, 18 horizontal pixels mm-1h = 1010
360 frames via ω rotation (Δω = 1°) and 2 × 60 s per frame scansk = 77
6694 measured reflectionsl = 1111
1935 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.050Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.187H-atom parameters constrained
S = 0.72Calculated w = 1/[σ2(Fo2) + (0.1903P)2]
where P = (Fo2 + 2Fc2)/3
1935 reflections(Δ/σ)max < 0.001
112 parametersΔρmax = 0.21 e Å3
1 restraintΔρmin = 0.28 e Å3
Crystal data top
C10H20O2V = 522.69 (7) Å3
Mr = 172.26Z = 2
Monoclinic, P21Mo Kα radiation
a = 8.5710 (7) ŵ = 0.07 mm1
b = 6.4665 (3) ÅT = 291 K
c = 9.8502 (8) Å0.30 × 0.08 × 0.05 mm
β = 106.783 (3)°
Data collection top
Nonius KappaCCD
diffractometer
1299 reflections with I > 2σ(I)
6694 measured reflectionsRint = 0.027
1935 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0501 restraint
wR(F2) = 0.187H-atom parameters constrained
S = 0.72Δρmax = 0.21 e Å3
1935 reflectionsΔρmin = 0.28 e Å3
112 parameters
Special details top

Experimental. The data collection covered the whole sphere of reciprocal space. The crystal to detector distance was 2.8 cm. Crystal decay was monitored by repeating the initial frames at the end of data collection. Analysing the duplicate reflections there were no indications for any decay. The structure was solved by direct methods (Sheldrick, 1990) and successive difference Fourier syntheses.

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.

Refinement applied full-matrix least-squares methods (Sheldrick, 1997). Hydrogen atoms were placed in calculated position and refined with a riding model (including free rotation about C—C and O—C for one O—H–group and HFIX 83 for the other), and with Uiso constrained to be 1.5 times Ueq of the carrier atom.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.4074 (3)0.3324 (3)0.3519 (2)0.0543 (6)
H10.47050.28550.31090.081*
O1'0.4684 (3)0.2647 (3)0.3710 (2)0.0656 (7)
H1'0.50050.22250.45290.098*
C10.2435 (3)0.2921 (4)0.2697 (3)0.0454 (7)
H1A0.22430.36160.17790.068*
C1'0.4996 (4)0.1111 (5)0.2767 (4)0.0597 (9)
H1'10.57030.16840.22520.090*
H1'20.55460.00640.33120.090*
C20.2228 (4)0.0607 (4)0.2436 (3)0.0446 (7)
H20.24130.00480.33660.067*
C2'0.3418 (4)0.0407 (5)0.1731 (3)0.0500 (8)
H2'0.28760.16540.12550.075*
C30.0450 (4)0.0174 (6)0.1605 (3)0.0617 (9)
H3A0.02360.07640.06640.093*
H3B0.02930.13090.15000.093*
C3'0.3798 (5)0.0934 (6)0.0582 (4)0.0664 (10)
H3'10.44290.21120.10140.100*
H3'20.27980.13920.00750.100*
H3'30.44060.01360.00870.100*
C40.0773 (4)0.1048 (6)0.2308 (4)0.0667 (10)
H4A0.06590.03320.31970.100*
H4B0.18690.08040.16990.100*
C50.0532 (4)0.3351 (6)0.2591 (4)0.0596 (9)
H50.07490.40540.16740.089*
C5A0.1721 (5)0.4205 (9)0.3350 (5)0.0889 (14)
H5A10.15530.35100.42420.133*
H5A20.28190.39800.27720.133*
H5A30.15360.56600.35110.133*
C60.1249 (4)0.3767 (5)0.3423 (3)0.0541 (8)
H6A0.14130.52470.35480.081*
H6B0.14710.31470.43560.081*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0465 (12)0.0449 (12)0.0684 (14)0.0030 (9)0.0116 (10)0.0059 (10)
O1'0.0796 (17)0.0377 (11)0.0688 (15)0.0050 (10)0.0044 (13)0.0012 (10)
C10.0427 (16)0.0411 (15)0.0492 (16)0.0009 (13)0.0085 (14)0.0008 (12)
C1'0.059 (2)0.0380 (16)0.080 (2)0.0011 (14)0.0175 (17)0.0044 (15)
C20.0456 (17)0.0377 (16)0.0484 (16)0.0061 (13)0.0105 (14)0.0017 (13)
C2'0.0527 (18)0.0388 (15)0.0571 (18)0.0041 (12)0.0138 (15)0.0077 (13)
C30.057 (2)0.059 (2)0.066 (2)0.0104 (16)0.0123 (17)0.0158 (17)
C3'0.075 (2)0.065 (2)0.064 (2)0.0004 (17)0.0262 (19)0.0015 (16)
C40.045 (2)0.074 (2)0.079 (2)0.0092 (16)0.0149 (18)0.0065 (19)
C50.0513 (19)0.068 (2)0.0591 (19)0.0098 (17)0.0146 (15)0.0016 (16)
C5A0.064 (3)0.113 (4)0.096 (3)0.017 (2)0.033 (2)0.014 (3)
C60.0576 (19)0.0455 (16)0.0579 (18)0.0031 (14)0.0145 (15)0.0043 (14)
Geometric parameters (Å, º) top
O1—C11.429 (4)C3—H3A0.9700
O1—H10.8200C3—H3B0.9700
O1'—C1'1.437 (4)C3'—H3'10.9600
O1'—H1'0.8200C3'—H3'20.9600
C1—C61.505 (4)C3'—H3'30.9600
C1—C21.520 (4)C4—C51.518 (6)
C1—H1A0.9800C4—H4A0.9700
C1'—C2'1.510 (5)C4—H4B0.9700
C1'—H1'10.9700C5—C5A1.530 (5)
C1'—H1'20.9700C5—C61.534 (4)
C2—C2'1.536 (4)C5—H50.9800
C2—C31.533 (4)C5A—H5A10.9600
C2—H20.9800C5A—H5A20.9600
C2'—C3'1.534 (4)C5A—H5A30.9600
C2'—H2'0.9800C6—H6A0.9700
C3—C41.522 (5)C6—H6B0.9700
C1—O1—H1109.5H3A—C3—H3B107.7
C1'—O1'—H1'109.5C2'—C3'—H3'1109.5
O1—C1—C6110.7 (2)C2'—C3'—H3'2109.5
O1—C1—C2108.8 (2)H3'1—C3'—H3'2109.5
C6—C1—C2112.1 (3)C2'—C3'—H3'3109.5
O1—C1—H1A108.4H3'1—C3'—H3'3109.5
C6—C1—H1A108.4H3'2—C3'—H3'3109.5
C2—C1—H1A108.4C3—C4—C5111.9 (3)
O1'—C1'—C2'110.4 (3)C3—C4—H4A109.2
O1'—C1'—H1'1109.6C5—C4—H4A109.2
C2'—C1'—H1'1109.6C3—C4—H4B109.2
O1'—C1'—H1'2109.6C5—C4—H4B109.2
C2'—C1'—H1'2109.6H4A—C4—H4B107.9
H1'1—C1'—H1'2108.1C5A—C5—C6112.1 (3)
C1—C2—C2'115.9 (3)C5A—C5—C4111.7 (4)
C1—C2—C3108.7 (3)C6—C5—C4109.4 (3)
C2'—C2—C3111.6 (2)C5A—C5—H5107.8
C1—C2—H2106.7C6—C5—H5107.8
C2'—C2—H2106.7C4—C5—H5107.8
C3—C2—H2106.7C5—C5A—H5A1109.5
C1'—C2'—C3'109.2 (3)C5—C5A—H5A2109.5
C1'—C2'—C2113.9 (2)H5A1—C5A—H5A2109.5
C3'—C2'—C2113.7 (3)C5—C5A—H5A3109.5
C1'—C2'—H2'106.5H5A1—C5A—H5A3109.5
C3'—C2'—H2'106.5H5A2—C5A—H5A3109.5
C2—C2'—H2'106.5C1—C6—C5112.8 (2)
C4—C3—C2113.5 (3)C1—C6—H6A109.0
C4—C3—H3A108.9C5—C6—H6A109.0
C2—C3—H3A108.9C1—C6—H6B109.0
C4—C3—H3B108.9C5—C6—H6B109.0
C2—C3—H3B108.9H6A—C6—H6B107.8
O1—C1—C2—C2'55.7 (3)C1—C2—C3—C454.3 (4)
C6—C1—C2—C2'178.5 (2)C2'—C2—C3—C4176.8 (3)
O1—C1—C2—C3177.7 (2)C2—C3—C4—C555.1 (4)
C6—C1—C2—C355.0 (3)C3—C4—C5—C5A177.8 (3)
O1'—C1'—C2'—C3'170.2 (2)C3—C4—C5—C653.1 (4)
O1'—C1'—C2'—C261.5 (3)O1—C1—C6—C5179.3 (3)
C1—C2—C2'—C1'87.7 (3)C2—C1—C6—C557.6 (3)
C3—C2—C2'—C1'147.2 (3)C5A—C5—C6—C1179.5 (3)
C1—C2—C2'—C3'38.3 (3)C4—C5—C6—C155.1 (4)
C3—C2—C2'—C3'86.7 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1···O1i0.821.892.702 (3)170
Symmetry code: (i) x+1, y1/2, z+1.

Experimental details

Crystal data
Chemical formulaC10H20O2
Mr172.26
Crystal system, space groupMonoclinic, P21
Temperature (K)291
a, b, c (Å)8.5710 (7), 6.4665 (3), 9.8502 (8)
β (°) 106.783 (3)
V3)522.69 (7)
Z2
Radiation typeMo Kα
µ (mm1)0.07
Crystal size (mm)0.30 × 0.08 × 0.05
Data collection
DiffractometerNonius KappaCCD
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
6694, 1935, 1299
Rint0.027
(sin θ/λ)max1)0.612
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.050, 0.187, 0.72
No. of reflections1935
No. of parameters112
No. of restraints1
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.21, 0.28

Computer programs: KappaCCD Software (Nonius, 1997), DENZO and SCALEPACK (Otwinowski & Minor, 1997), DENZO and SCALEPACK, SHELXS97 (Sheldrick, 1990), SHELXTL-Plus (Sheldrick, 1991), SHELXL97 (Sheldrick, 1997) and PARST95 (Nardelli, 1995).

Selected torsion angles (º) top
C6—C1—C2—C2'178.5 (2)C3—C4—C5—C5A177.8 (3)
O1—C1—C2—C3177.7 (2)O1—C1—C6—C5179.3 (3)
C2'—C2—C3—C4176.8 (3)C5A—C5—C6—C1179.5 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1'—H1'···O1i0.821.892.702 (3)170
Symmetry code: (i) x+1, y1/2, z+1.
 

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