Crystal structure of (1R,2S,4R,7R,8S,9R)-3,3-dichloro-8,9-epoxy-4,8,12,12-tetramethyltricyclo[5.5.0.0^2,4]dodecane

The title compound, C₁₆H₂₄Cl₂O, is built up from two fused six- and seven-membered rings which bear a di­chloro­cyclo­propane group and an ep­oxy group, respectively. In the mol­ecule, the six-membered ring adopts an envelope configuration with the C atom linking the ep­oxy ring at the flap, while the seven-membered ring adopts a boat–sofa conformation.

checkCIF/PLATON results

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Datablock: I


Alert level C
PLAT094_ALERT_2_C Ratio of Maximum / Minimum Residual Density ....       2.39 Report
PLAT338_ALERT_4_C Small Average Tau in cyclohexane C1     -C7           27.45 Degree
PLAT915_ALERT_3_C Low Friedel Pair Coverage ......................         89 %

Alert level G
PLAT791_ALERT_4_G The Model has Chirality at C1      (Chiral SPGR)          R Verify
PLAT791_ALERT_4_G The Model has Chirality at C2      (Chiral SPGR)          S Verify
PLAT791_ALERT_4_G The Model has Chirality at C4      (Chiral SPGR)          R Verify
PLAT791_ALERT_4_G The Model has Chirality at C7      (Chiral SPGR)          R Verify
PLAT791_ALERT_4_G The Model has Chirality at C8      (Chiral SPGR)          S Verify
PLAT791_ALERT_4_G The Model has Chirality at C9      (Chiral SPGR)          R Verify
PLAT910_ALERT_3_G Missing # of FCF Reflection(s) Below Th(Min) ...          4 Report

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   3 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   7 ALERT level G = General information/check it is not something unexpected

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   7 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Chemical context

Epoxides are valuable inter­mediates frequently used as versatile building blocks in organic synthesis (Qu et al., 2009). Thus, epoxides are important precursors in the synthesis of Anti­fungal products (Taylor et al., 1991) and different pheromones (Mori, 1989, Paddon-Jones et al., 1997). Besides, many natural products possess this functional group as an essential structural moiety for their biological activities (Yang, 2004; Vollhardt & Schore, 1996; Trost et al., 1983). Because of their widespread occurrence, biological and synthetic utilities, the synthesis of new epoxides has grown significantly.

In the aim of preparing new epoxides from natural products, we recently synthetise γ-Ep­oxy­himachalene 1 (scheme 1) from naturally occurred sesquiterpene γ-himachalene without crystallographic evidence of its absolute configuration as the product was oily. We therefore decided to transform it into a solid derivative by [2+1] cyclo­addition reaction of a dihalocarbene on the remaining cyclo­hexenic double bond.

The structure of the newly prepared 2 (scheme 2) has been established from its ¹H and ¹³C NMR spectral data. An X-ray structure analysis has allowed us to determine unambiguously its stereochemistry and deduce the absolute configuration of its oily precursor γ-Ep­oxy­himachalene 1.

S2. Structural commentary

Compound 2 is built up from two fused 6 and 7 membered rings (Fig. 1). The seven membered ring is bearing an ep­oxy group whereas the 6 membered ring bears a di­chloro­cyclo­propane. In the seven membered ring, the puckering parameters Q2= 0.9692 (15), Q2= 0.2716 (52) and φ2= 97.11, φ3= 74.34 agree with a boat sofa conformation (Boessenkool & Boeyens, 1980). The six membered ring displays an envelope conformation with the puckering parameters θ = 125.90° and φ2 = 118.89° (Cremer & Pople, 1975).

S3. Database survey

A search in the Cambridge Structural Database, version 5.36 reveals 9 hits with related structure having two fused 6 and 7 membered rings (Chiaroni et al., 1992, 1995; Chiaroni et al., 1996a,b,c; Sbai et al., 2002; Benharref et al., 2010; Oukhrib et al., 2013; Bimoussa et al., 2014 )

S4. Synthesis and crystallization

Thus, the di­chloro­carbene, generated at 0°C from an excess of CHCl₃ (0,93 mL, 11,59 mmol) and solid t-BuOK (1,3 g, 11,58 mmol), reacts in the presence of tri­ethyl­benzyl­ammonium chloride (100 mg, 0.439 mmol) as catalyst, with γ-Ep­oxy­himachalene 1 (0,650 g, 2,95 mmol) to give 22% yield (200 mg) of the cyclo­adduct C₁₆H₂₄OCl₂ 2.

S5. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. All H atoms attached to C atoms were fixed geometrically and treated as riding with C—H = 0.99 Å (methyl­ene), 0.98 Å (methyl), 0.95Å (methine) with U_iso(H) = 1.2U_eq(CH and CH₂) or U_iso(H) = 1.5U_eq(CH₃).

Related literature

For applications of epoxides, see: Qu et al. (2009); Taylor et al. (1991); Mori (1989); Paddon-Jones et al. (1997); Yang (2004); Vollhardt & Schore (1996); Trost et al. (1983). For related structures, see: Chiaroni et al. (1992, 1995, 1996a,b,c); Sbai et al. (2002); Benharref et al. (2010); Oukhrib et al. (2013); Bimoussa et al. (2014). For puckering parameters and ring conformation, see: Boessenkool & Boeyens (1980).

Structure description

Epoxides are valuable inter­mediates frequently used as versatile building blocks in organic synthesis (Qu et al., 2009). Thus, epoxides are important precursors in the synthesis of Anti­fungal products (Taylor et al., 1991) and different pheromones (Mori, 1989, Paddon-Jones et al., 1997). Besides, many natural products possess this functional group as an essential structural moiety for their biological activities (Yang, 2004; Vollhardt & Schore, 1996; Trost et al., 1983). Because of their widespread occurrence, biological and synthetic utilities, the synthesis of new epoxides has grown significantly.

In the aim of preparing new epoxides from natural products, we recently synthetise γ-Ep­oxy­himachalene 1 (scheme 1) from naturally occurred sesquiterpene γ-himachalene without crystallographic evidence of its absolute configuration as the product was oily. We therefore decided to transform it into a solid derivative by [2+1] cyclo­addition reaction of a dihalocarbene on the remaining cyclo­hexenic double bond.

The structure of the newly prepared 2 (scheme 2) has been established from its ¹H and ¹³C NMR spectral data. An X-ray structure analysis has allowed us to determine unambiguously its stereochemistry and deduce the absolute configuration of its oily precursor γ-Ep­oxy­himachalene 1.

Compound 2 is built up from two fused 6 and 7 membered rings (Fig. 1). The seven membered ring is bearing an ep­oxy group whereas the 6 membered ring bears a di­chloro­cyclo­propane. In the seven membered ring, the puckering parameters Q2= 0.9692 (15), Q2= 0.2716 (52) and φ2= 97.11, φ3= 74.34 agree with a boat sofa conformation (Boessenkool & Boeyens, 1980). The six membered ring displays an envelope conformation with the puckering parameters θ = 125.90° and φ2 = 118.89° (Cremer & Pople, 1975).

A search in the Cambridge Structural Database, version 5.36 reveals 9 hits with related structure having two fused 6 and 7 membered rings (Chiaroni et al., 1992, 1995; Chiaroni et al., 1996a,b,c; Sbai et al., 2002; Benharref et al., 2010; Oukhrib et al., 2013; Bimoussa et al., 2014 )

For applications of epoxides, see: Qu et al. (2009); Taylor et al. (1991); Mori (1989); Paddon-Jones et al. (1997); Yang (2004); Vollhardt & Schore (1996); Trost et al. (1983). For related structures, see: Chiaroni et al. (1992, 1995, 1996a,b,c); Sbai et al. (2002); Benharref et al. (2010); Oukhrib et al. (2013); Bimoussa et al. (2014). For puckering parameters and ring conformation, see: Boessenkool & Boeyens (1980).

Synthesis and crystallization

Thus, the di­chloro­carbene, generated at 0°C from an excess of CHCl₃ (0,93 mL, 11,59 mmol) and solid t-BuOK (1,3 g, 11,58 mmol), reacts in the presence of tri­ethyl­benzyl­ammonium chloride (100 mg, 0.439 mmol) as catalyst, with γ-Ep­oxy­himachalene 1 (0,650 g, 2,95 mmol) to give 22% yield (200 mg) of the cyclo­adduct C₁₆H₂₄OCl₂ 2.

Refinement details

Crystal data, data collection and structure refinement details are summarized in Table 1. All H atoms attached to C atoms were fixed geometrically and treated as riding with C—H = 0.99 Å (methyl­ene), 0.98 Å (methyl), 0.95Å (methine) with U_iso(H) = 1.2U_eq(CH and CH₂) or U_iso(H) = 1.5U_eq(CH₃).

Computing details

Data collection: CrysAlis PRO (Agilent, 2014); cell refinement: CrysAlis PRO (Agilent, 2014); data reduction: CrysAlis PRO (Agilent, 2014); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2015); molecular graphics: ORTEPIII (Burnett & Johnson, 1996) and ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: SHELXL2013 (Sheldrick, 2015).

Figures

Fig. 1. Displacement ellipsoid plot of the title compound.

(1R,2S,4R,7R,8S,9R)-3,3-Dichloro-8,9-epoxy-4,8,12,12-tetramethyltricyclo[5.5.0.0^2,4]dodecane

Crystal data

C16H24Cl2O	F(000) = 324
Mr = 303.25	Dx = 1.319 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
a = 8.7706 (5) Å	Cell parameters from 4267 reflections
b = 10.5467 (4) Å	θ = 4.3–29.3°
c = 9.1639 (5) Å	µ = 0.42 mm^−1
β = 115.710 (7)°	T = 180 K
V = 763.75 (8) Å^3	Box, colourless
Z = 2	0.40 × 0.34 × 0.08 mm

Data collection

Agilent Xcalibur, Eos, Gemini ultra diffractometer	2945 independent reflections
Radiation source: Enhance (Mo) X-ray Source	2868 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.021
Detector resolution: 16.1978 pixels mm^-1	θmax = 26.4°, θmin = 3.2°
ω scans	h = −10→10
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2014)	k = −13→12
Tmin = 0.901, Tmax = 1.000	l = −11→11
7805 measured reflections

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.029	w = 1/[σ^2(Fo^2) + (0.0453P)^2 + 0.1659P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.076	(Δ/σ)max < 0.001
S = 1.05	Δρmax = 0.44 e Å^−3
2945 reflections	Δρmin = −0.18 e Å^−3
176 parameters	Absolute structure: Flack x determined using 1242 quotients [(I^+)-(I^-)]/[(I^+)+(I^-)] (Parsons et al., 2013)
1 restraint	Absolute structure parameter: −0.02 (2)

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	0.6765 (3)	1.0011 (2)	0.7612 (3)	0.0150 (5)
H1	0.5811	0.9485	0.6832	0.018*
C2	0.7132 (3)	1.0959 (2)	0.6554 (3)	0.0161 (5)
H2	0.7162	1.1866	0.6885	0.019*
C3	0.6463 (3)	1.0746 (2)	0.4760 (3)	0.0184 (5)
C4	0.8324 (3)	1.0632 (2)	0.5788 (3)	0.0183 (5)
C5	0.9157 (3)	0.9334 (3)	0.6122 (3)	0.0238 (5)
H5A	1.0399	0.9457	0.6641	0.029*
H5B	0.8860	0.8909	0.5070	0.029*
C6	0.8699 (3)	0.8432 (3)	0.7196 (3)	0.0222 (5)
H6A	0.7739	0.7896	0.6480	0.027*
H6B	0.9675	0.7863	0.7775	0.027*
C7	0.8220 (3)	0.9058 (2)	0.8456 (3)	0.0175 (5)
H7	0.7706	0.8360	0.8832	0.021*
C8	0.9699 (3)	0.9526 (3)	0.9984 (3)	0.0200 (5)
C9	0.9417 (3)	0.9677 (3)	1.1444 (3)	0.0234 (6)
H9	1.0197	1.0302	1.2236	0.028*
C10	0.7742 (3)	0.9537 (3)	1.1534 (3)	0.0266 (6)
H10A	0.7722	1.0173	1.2319	0.032*
H10B	0.7739	0.8692	1.2003	0.032*
C11	0.6069 (3)	0.9666 (3)	0.9990 (3)	0.0230 (6)
H11A	0.5167	0.9896	1.0317	0.028*
H11B	0.5778	0.8825	0.9461	0.028*
C12	0.6043 (3)	1.0642 (2)	0.8722 (3)	0.0189 (5)
C13	0.9439 (4)	1.1678 (3)	0.5645 (3)	0.0287 (6)
H13A	0.9746	1.1479	0.4762	0.043*
H13B	1.0468	1.1748	0.6664	0.043*
H13C	0.8823	1.2485	0.5416	0.043*
C14	1.1115 (3)	1.0267 (3)	0.9879 (3)	0.0278 (6)
H14A	1.1956	1.0487	1.0972	0.042*
H14B	1.0661	1.1045	0.9255	0.042*
H14C	1.1651	0.9752	0.9342	0.042*
C15	0.6951 (3)	1.1861 (2)	0.9559 (3)	0.0222 (5)
H15A	0.6600	1.2559	0.8774	0.033*
H15B	0.8178	1.1740	0.9988	0.033*
H15C	0.6658	1.2065	1.0449	0.033*
C16	0.4186 (3)	1.0978 (3)	0.7640 (3)	0.0294 (6)
H16A	0.3545	1.0200	0.7184	0.044*
H16B	0.4125	1.1533	0.6760	0.044*
H16C	0.3704	1.1415	0.8287	0.044*
O1	1.0269 (3)	0.85597 (19)	1.1245 (2)	0.0275 (4)
Cl1	0.52452 (8)	0.93841 (6)	0.38605 (7)	0.02818 (17)
Cl2	0.56482 (9)	1.20376 (6)	0.34222 (7)	0.03117 (18)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0159 (11)	0.0142 (11)	0.0135 (10)	−0.0016 (9)	0.0052 (9)	−0.0003 (9)
C2	0.0194 (12)	0.0136 (12)	0.0158 (11)	0.0011 (10)	0.0082 (9)	0.0008 (9)
C3	0.0220 (12)	0.0154 (11)	0.0155 (11)	0.0027 (10)	0.0060 (9)	0.0039 (9)
C4	0.0182 (12)	0.0205 (12)	0.0169 (11)	0.0013 (10)	0.0083 (9)	0.0011 (9)
C5	0.0258 (12)	0.0274 (14)	0.0212 (11)	0.0085 (12)	0.0130 (9)	0.0008 (12)
C6	0.0277 (14)	0.0172 (12)	0.0200 (11)	0.0075 (11)	0.0090 (10)	0.0018 (9)
C7	0.0223 (12)	0.0133 (12)	0.0173 (11)	0.0008 (9)	0.0089 (10)	0.0007 (9)
C8	0.0215 (12)	0.0190 (12)	0.0158 (10)	0.0055 (11)	0.0047 (9)	0.0038 (10)
C9	0.0276 (13)	0.0234 (14)	0.0155 (11)	0.0049 (11)	0.0060 (10)	0.0011 (10)
C10	0.0348 (14)	0.0279 (14)	0.0203 (11)	0.0043 (13)	0.0150 (11)	0.0035 (11)
C11	0.0285 (13)	0.0240 (14)	0.0216 (11)	−0.0017 (11)	0.0158 (10)	0.0012 (10)
C12	0.0198 (12)	0.0208 (13)	0.0183 (11)	−0.0004 (10)	0.0102 (9)	−0.0002 (10)
C13	0.0301 (14)	0.0327 (16)	0.0284 (13)	−0.0062 (13)	0.0175 (11)	−0.0007 (12)
C14	0.0215 (13)	0.0320 (15)	0.0251 (13)	−0.0017 (12)	0.0057 (11)	0.0026 (12)
C15	0.0309 (13)	0.0175 (13)	0.0213 (11)	0.0026 (11)	0.0142 (10)	−0.0009 (11)
C16	0.0222 (14)	0.0384 (16)	0.0296 (13)	0.0054 (13)	0.0132 (11)	0.0021 (13)
O1	0.0334 (11)	0.0271 (11)	0.0197 (9)	0.0117 (9)	0.0094 (8)	0.0075 (8)
Cl1	0.0305 (3)	0.0301 (3)	0.0191 (3)	−0.0081 (3)	0.0062 (2)	−0.0044 (3)
Cl2	0.0418 (4)	0.0283 (3)	0.0250 (3)	0.0152 (3)	0.0159 (3)	0.0122 (3)

Geometric parameters (Å, º)

C1—C2	1.521 (3)	C9—O1	1.449 (3)
C1—C7	1.542 (3)	C9—C10	1.513 (4)
C1—C12	1.561 (3)	C9—H9	1.0000
C1—H1	1.0000	C10—C11	1.540 (4)
C2—C3	1.503 (3)	C10—H10A	0.9900
C2—C4	1.530 (3)	C10—H10B	0.9900
C2—H2	1.0000	C11—C12	1.545 (3)
C3—C4	1.494 (4)	C11—H11A	0.9900
C3—Cl2	1.764 (2)	C11—H11B	0.9900
C3—Cl1	1.766 (3)	C12—C15	1.532 (4)
C4—C13	1.517 (4)	C12—C16	1.536 (4)
C4—C5	1.519 (4)	C13—H13A	0.9800
C5—C6	1.542 (4)	C13—H13B	0.9800
C5—H5A	0.9900	C13—H13C	0.9800
C5—H5B	0.9900	C14—H14A	0.9800
C6—C7	1.538 (3)	C14—H14B	0.9800
C6—H6A	0.9900	C14—H14C	0.9800
C6—H6B	0.9900	C15—H15A	0.9800
C7—C8	1.520 (3)	C15—H15B	0.9800
C7—H7	1.0000	C15—H15C	0.9800
C8—O1	1.457 (3)	C16—H16A	0.9800
C8—C9	1.471 (3)	C16—H16B	0.9800
C8—C14	1.505 (4)	C16—H16C	0.9800
C2—C1—C7	112.96 (19)	O1—C9—C10	119.6 (2)
C2—C1—C12	113.1 (2)	C8—C9—C10	126.1 (2)
C7—C1—C12	115.62 (19)	O1—C9—H9	113.6
C2—C1—H1	104.6	C8—C9—H9	113.6
C7—C1—H1	104.6	C10—C9—H9	113.6
C12—C1—H1	104.6	C9—C10—C11	120.1 (2)
C3—C2—C1	120.6 (2)	C9—C10—H10A	107.3
C3—C2—C4	59.00 (16)	C11—C10—H10A	107.3
C1—C2—C4	121.3 (2)	C9—C10—H10B	107.3
C3—C2—H2	114.9	C11—C10—H10B	107.3
C1—C2—H2	114.9	H10A—C10—H10B	106.9
C4—C2—H2	114.9	C10—C11—C12	116.6 (2)
C4—C3—C2	61.39 (16)	C10—C11—H11A	108.2
C4—C3—Cl2	120.18 (19)	C12—C11—H11A	108.2
C2—C3—Cl2	119.53 (18)	C10—C11—H11B	108.2
C4—C3—Cl1	120.21 (18)	C12—C11—H11B	108.2
C2—C3—Cl1	120.14 (18)	H11A—C11—H11B	107.3
Cl2—C3—Cl1	108.85 (13)	C15—C12—C16	107.7 (2)
C3—C4—C13	117.1 (2)	C15—C12—C11	110.4 (2)
C3—C4—C5	119.9 (2)	C16—C12—C11	107.7 (2)
C13—C4—C5	113.6 (2)	C15—C12—C1	114.5 (2)
C3—C4—C2	59.62 (16)	C16—C12—C1	107.1 (2)
C13—C4—C2	118.0 (2)	C11—C12—C1	109.2 (2)
C5—C4—C2	118.4 (2)	C4—C13—H13A	109.5
C4—C5—C6	116.7 (2)	C4—C13—H13B	109.5
C4—C5—H5A	108.1	H13A—C13—H13B	109.5
C6—C5—H5A	108.1	C4—C13—H13C	109.5
C4—C5—H5B	108.1	H13A—C13—H13C	109.5
C6—C5—H5B	108.1	H13B—C13—H13C	109.5
H5A—C5—H5B	107.3	C8—C14—H14A	109.5
C7—C6—C5	116.5 (2)	C8—C14—H14B	109.5
C7—C6—H6A	108.2	H14A—C14—H14B	109.5
C5—C6—H6A	108.2	C8—C14—H14C	109.5
C7—C6—H6B	108.2	H14A—C14—H14C	109.5
C5—C6—H6B	108.2	H14B—C14—H14C	109.5
H6A—C6—H6B	107.3	C12—C15—H15A	109.5
C8—C7—C6	115.4 (2)	C12—C15—H15B	109.5
C8—C7—C1	116.08 (19)	H15A—C15—H15B	109.5
C6—C7—C1	109.83 (19)	C12—C15—H15C	109.5
C8—C7—H7	104.7	H15A—C15—H15C	109.5
C6—C7—H7	104.7	H15B—C15—H15C	109.5
C1—C7—H7	104.7	C12—C16—H16A	109.5
O1—C8—C9	59.31 (15)	C12—C16—H16B	109.5
O1—C8—C14	113.9 (2)	H16A—C16—H16B	109.5
C9—C8—C14	118.1 (2)	C12—C16—H16C	109.5
O1—C8—C7	111.4 (2)	H16A—C16—H16C	109.5
C9—C8—C7	117.4 (2)	H16B—C16—H16C	109.5
C14—C8—C7	120.5 (2)	C9—O1—C8	60.82 (15)
O1—C9—C8	59.88 (15)