(−)-(1S,5R)-2-Oxabicyclo­[3.3.1]nonan-3-one

Abstract

In the title compound, C₈H₁₂O₂, the cyclo­hexane ring exhibits a chair conformation and the δ-lactone ring is axially bonded to the cyclo­hexane ring. In the crystal, mol­ecules are linked by C—H⋯O hydrogen bonds, resulting in ribbons extending along [010].

Related literature

For the synthesis and confirmation of the absolute configuration of the title compound, see Olejniczak (2010 ▶); Wascholowski et al. (2008 ▶); Tzvetkov et al. (2006 ▶); Xu et al. (2002 ▶). For related structures see: Yokoyama et al. (2003 ▶); Schmidt et al. (1998 ▶); Finet et al. (2007 ▶); Militsina et al. (2005 ▶).

Experimental

Crystal data

• C₈H₁₂O₂

• M _r = 140.18

• Orthorhombic,

• a = 6.793 (2) Å

• b = 7.467 (2) Å

• c = 14.170 (4) Å

• V = 718.7 (4) ų

• Z = 4

• Mo Kα radiation

• μ = 0.09 mm⁻¹

• T = 100 K

• 0.30 × 0.14 × 0.10 mm

Data collection

• Kuma KM-4-CCD diffractometer

• 4925 measured reflections

• 935 independent reflections

• 685 reflections with I > 2σ(I)

• R _int = 0.051

Refinement

• R[F ² > 2σ(F ²)] = 0.043

• wR(F ²) = 0.096

• S = 1.04

• 935 reflections

• 92 parameters

• H-atom parameters constrained

• Δρ_max = 0.35 e Å⁻³

• Δρ_min = −0.16 e Å⁻³

Data collection: CrysAlis CCD (Oxford Diffraction, 2009 ▶); cell refinement: CrysAlis RED (Oxford Diffraction, 2009 ▶); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: XP (Bruker, 1999 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

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
C1—H1⋯O2i	1.00	2.58	3.224 (3)	122

Symmetry code: (i) .

supplementary crystallographic information

Comment

The titled compound, C₈H₁₂O₂, was prepared in a three step synthesis (Fig. 2). Racemic diethyl 2-(3-oxocyclohexyl)malonate (1) was synthesized as a product of Michael addition of diethyl malonate to cyclohex-2-en-1-one. (-)-Diethyl 2-((S)-3-oxocyclohexyl)malonate ((-)-1) (ee=98%) and (+)-diethyl 2-((1R, 3R)-3-hydroxycyclohexyl)malonate ((+)-2) (ee=99%) were isolated by micriobial bioreduction using Absidia coerulea AM 93. Hydroxydiester-(+)-2 was subjected to chemical lactonization, leading to (-)-(1S, 5R)-2-oxabicyclo[3.3.1]nonan-3-one ((-)-3) [for more details see Olejniczak, 2010].

The molecular structure of the title compound is shown in Fig. 1. Bond lengths and angles in (-)-3 are similar to those observed in related structures [Yokoyama et al., 2003; Schmidt et al., 1998; Finet et al., 2007]. As in these related structures, in (-)-3 the cyclohexane ring reveals chair conformation (Fig. 1) and the δ-lactone ring is axially bonded to the cyclohexane ring.

It is worth mentioning that the conformation of the δ-lactone ring differs a little from those observed in the related structures. According to the numbering scheme employed in this paper, the torsion angles C1 O2 C3 C4 and O2 C3 C4 C5 in the related structures are in the range -7.1 - 0.4 ° and 0.0 - 8.8 °, respectively, and in (-)-3 values of suitable torsion angles are equal to -18.1 (3) and 23.3 (4) °. However, the values of the torsion angles are similar to those, -17.5 and 25.5 °, observed in one of crystallographically unrelated molecules of 3,9,12a-trimethyl-5-oxotetradecahydro-3,6a- methanonaphtho[2,1-d]oxocine-9-carboxylic acid, in which δ-lactone ring axially bonded to cyclohexane ring is observed [Militsina et al., 2005].

The structure of (-)-3 is stabilized by weak intermolecular C—H···O hydrogen bonds and van der Waals contacts. Molecules of (-)-3 are linked by the C1—H1···O2(2-x, 0.5+y, 0.5-z) hydrogen bonds, resulting in ribbons extended along the [010] direction (Table 1, Fig. 3).

Experimental

Crystals suitable for X-ray structure analysis were obtained directly after purification by column chromatography by slow evaporation of the eluent (petroleum ether : aceton : iso-propanol : ethyl acetate (40:1:3:1) v/v) at room temperature.

Refinement

All H atoms were placed at calculated positions and were treated as riding atoms, with C—H distances of 0.99 - 1.00 Å. The absolute configuration of (-)-3 was choosen on the basis of known absolute configuration of particular substrates: The absolute configuration of (-)-1 was confirmed by comparison of its optical rotation with the literature data [Wascholowski et al., 2008; Tzvetkov et al., 2006; Xu et al., 2002]. The absolute configuration of the carbon atom bearing hydroxyl group in product (+)-2 was determined using the Mosher's ester [Olejniczak, 2010].

Figures

Fig. 1.

Selected view of (-)-3 (30% probability thermal ellipsoids).

Fig. 2.

Scheme of a three step synthesis of (-)-3.

Fig. 3.

Packing of (-)-3.

Crystal data

C8H12O2	F(000) = 304
Mr = 140.18	Dx = 1.295 Mg m−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 1754 reflections
a = 6.793 (2) Å	θ = 3.0–28.8°
b = 7.467 (2) Å	µ = 0.09 mm−1
c = 14.170 (4) Å	T = 100 K
V = 718.7 (4) Å3	Needle, colorless
Z = 4	0.30 × 0.14 × 0.10 mm

Data collection

Kuma KM-4-CCD diffractometer	685 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.051
graphite	θmax = 27.0°, θmin = 3.1°
ω scan	h = −8→8
4925 measured reflections	k = −9→9
935 independent reflections	l = −15→18

Refinement

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.043	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.096	H-atom parameters constrained
S = 1.04	w = 1/[σ2(Fo2) + (0.0507P)2] where P = (Fo2 + 2Fc2)/3
935 reflections	(Δ/σ)max = 0.004
92 parameters	Δρmax = 0.35 e Å−3
0 restraints	Δρmin = −0.16 e Å−3

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 (Ų)

	x	y	z	Uiso*/Ueq
C1	0.9078 (4)	0.4787 (3)	0.29810 (17)	0.0293 (6)
H1	1.0256	0.4916	0.2564	0.035*
O2	0.8893 (3)	0.2882 (2)	0.32719 (12)	0.0331 (5)
C3	0.7920 (4)	0.2414 (4)	0.40668 (17)	0.0302 (6)
O3	0.7539 (3)	0.0838 (2)	0.41770 (13)	0.0389 (5)
C4	0.7539 (4)	0.3815 (3)	0.48057 (18)	0.0300 (6)
H4A	0.8553	0.3693	0.5304	0.036*
H4B	0.6247	0.3561	0.5100	0.036*
C5	0.7535 (4)	0.5754 (3)	0.44672 (17)	0.0287 (6)
H5	0.7674	0.6561	0.5027	0.034*
C6	0.5660 (4)	0.6256 (4)	0.39356 (19)	0.0347 (7)
H6B	0.4509	0.6041	0.4349	0.042*
H6A	0.5695	0.7549	0.3782	0.042*
C7	0.5413 (4)	0.5192 (4)	0.30310 (17)	0.0344 (7)
H7B	0.4290	0.5683	0.2669	0.041*
H7A	0.5108	0.3931	0.3189	0.041*
C8	0.7258 (4)	0.5254 (4)	0.24230 (17)	0.0334 (6)
H8B	0.7115	0.4402	0.1892	0.040*
H8A	0.7407	0.6471	0.2155	0.040*
C9	0.9334 (4)	0.5985 (4)	0.38359 (19)	0.0302 (7)
H9B	0.9457	0.7250	0.3635	0.036*
H9A	1.0542	0.5648	0.4184	0.036*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
C1	0.0333 (15)	0.0256 (14)	0.0290 (14)	0.0004 (12)	0.0060 (13)	0.0044 (12)
O2	0.0360 (11)	0.0311 (10)	0.0322 (10)	0.0031 (8)	0.0082 (9)	−0.0003 (9)
C3	0.0285 (15)	0.0334 (16)	0.0286 (14)	0.0022 (12)	−0.0040 (12)	0.0043 (12)
O3	0.0434 (11)	0.0284 (10)	0.0451 (11)	−0.0025 (10)	−0.0047 (11)	0.0059 (9)
C4	0.0245 (14)	0.0393 (15)	0.0261 (12)	−0.0021 (14)	0.0014 (13)	0.0003 (11)
C5	0.0291 (14)	0.0297 (14)	0.0273 (13)	−0.0034 (13)	−0.0009 (13)	−0.0068 (11)
C6	0.0268 (15)	0.0336 (16)	0.0435 (17)	0.0048 (12)	0.0036 (13)	−0.0038 (13)
C7	0.0284 (14)	0.0368 (16)	0.0381 (17)	−0.0040 (12)	−0.0047 (12)	0.0040 (14)
C8	0.0429 (17)	0.0314 (14)	0.0259 (13)	−0.0055 (14)	−0.0033 (13)	0.0012 (11)
C9	0.0242 (14)	0.0312 (15)	0.0353 (16)	−0.0039 (12)	−0.0012 (12)	0.0037 (12)

Geometric parameters (Å, °)

C1—O2	1.486 (3)	C5—H5	1.0000
C1—C8	1.509 (3)	C6—C7	1.517 (4)
C1—C9	1.516 (4)	C6—H6B	0.9900
C1—H1	1.0000	C6—H6A	0.9900
O2—C3	1.352 (3)	C7—C8	1.522 (3)
C3—O3	1.215 (3)	C7—H7B	0.9900
C3—C4	1.502 (4)	C7—H7A	0.9900
C4—C5	1.526 (3)	C8—H8B	0.9900
C4—H4A	0.9900	C8—H8A	0.9900
C4—H4B	0.9900	C9—H9B	0.9900
C5—C9	1.524 (3)	C9—H9A	0.9900
C5—C6	1.526 (4)
O2—C1—C8	107.3 (2)	C7—C6—H6B	109.1
O2—C1—C9	110.7 (2)	C5—C6—H6B	109.1
C8—C1—C9	112.1 (2)	C7—C6—H6A	109.1
O2—C1—H1	108.9	C5—C6—H6A	109.1
C8—C1—H1	108.9	H6B—C6—H6A	107.9
C9—C1—H1	108.9	C6—C7—C8	111.8 (2)
C3—O2—C1	121.32 (19)	C6—C7—H7B	109.3
O3—C3—O2	117.5 (2)	C8—C7—H7B	109.3
O3—C3—C4	123.2 (2)	C6—C7—H7A	109.3
O2—C3—C4	119.0 (2)	C8—C7—H7A	109.3
C3—C4—C5	116.2 (2)	H7B—C7—H7A	107.9
C3—C4—H4A	108.2	C1—C8—C7	111.8 (2)
C5—C4—H4A	108.2	C1—C8—H8B	109.3
C3—C4—H4B	108.2	C7—C8—H8B	109.3
C5—C4—H4B	108.2	C1—C8—H8A	109.3
H4A—C4—H4B	107.4	C7—C8—H8A	109.3
C9—C5—C4	106.9 (2)	H8B—C8—H8A	107.9
C9—C5—C6	110.59 (19)	C1—C9—C5	108.1 (2)
C4—C5—C6	112.9 (2)	C1—C9—H9B	110.1
C9—C5—H5	108.8	C5—C9—H9B	110.1
C4—C5—H5	108.8	C1—C9—H9A	110.1
C6—C5—H5	108.8	C5—C9—H9A	110.1
C7—C6—C5	112.4 (2)	H9B—C9—H9A	108.4
C8—C1—O2—C3	−85.9 (3)	C4—C5—C6—C7	−63.5 (3)
C9—C1—O2—C3	36.8 (3)	C5—C6—C7—C8	−50.9 (3)
C1—O2—C3—O3	167.8 (2)	O2—C1—C8—C7	65.6 (3)
C1—O2—C3—C4	−18.1 (3)	C9—C1—C8—C7	−56.1 (3)
O3—C3—C4—C5	−162.9 (3)	C6—C7—C8—C1	50.3 (3)
O2—C3—C4—C5	23.3 (4)	O2—C1—C9—C5	−59.8 (3)
C3—C4—C5—C9	−46.0 (3)	C8—C1—C9—C5	60.0 (3)
C3—C4—C5—C6	75.9 (3)	C4—C5—C9—C1	64.0 (2)
C9—C5—C6—C7	56.2 (3)	C6—C5—C9—C1	−59.3 (3)

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1···O2i	1.00	2.58	3.224 (3)	122

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