(1R,2R)-2-(4-Methylenecyclohex-2-enyl)propyl (1R,4S)-camphanate

Esterification of a single diastereomer of 2-(4-methylene­cyclohex-2-enyl)propanol, (II), with (1R,4S)-(+)-camphanic acid [(1R,4S)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylic acid] leads to the crystalline title compound, C₂₀H₂₈O₄. The relative configuration of the camphanate was determined by X-ray diffraction analysis. The outcome clarifies the relative and absolute stereochemistry of the naturally occurring bisabolane sesquiterpenes [beta]-turmerone and [beta]-sesquiphellandrene, since we have converted (II) into both natural products via a stereospecific route.

S1. Comment

During the course of our investigation on the stereospecific synthesis (Kreiser & Körner, 1999) of β-turmerone, (III), [isolated from Curcuma longa by Golding et al. (1982)] and β-sesquiphellandrene, (IV), [isolated from Zingiber officinale by Connell & Sutherland (1966)] we tried hard to get hold of a crystalline synthetic intermediate because the natural compounds, like all known natural bisabolane-sesquiterpenes, are provided in an oily state. In our view X-ray diffraction analysis of a crystal appeared to be the only reliable proof for the relative configuration of the vicinal centres of chirality, which remain untouched until the final stage of the synthesis, since the interpretation of NMR-data had already led to contradictory assignments of (III). Compound (II) was prepared in a 13-step procedure from (-)-Isopulegol, (V), and esterified with both (-)- and (+)-camphanic acid, originally with the aim to determine its enantiopurity by means of NMR and high-pressure liquid chromatography techniques. We were able to crystallize (I) from 2-propanol and the result of the subsequent X-ray diffraction analysis is presented in Fig. 1. \sch

Based on the fact enantiomerically pure (1R,4S)-(+)-camphanic acid is involved and that the stereogenic centre C1'' is derived from (1R,2S,5R)-(-)-Isopulegol, (V), the absolute configuration of (I) could be assigned. In the solid state the cyclohexenyl ring of (I) adopts a half-chair conformation, being characterized by the almost planar arrangement of the four Csp² atoms along with the low C2''-C3''-C4''-C4a''-torsion angle of −172.2 (3)°. The substituted isopropyl group bound to the cyclohexane ring is found in a quasi-equatorial position. On the other hand the bicyclic part of the molecule does not display any surprising structural features, according to its conformational rigidity. To us the most valuable piece of information that can be deduced from Fig. 1 is the R configuration at C2' and the R configuration at C1'' of (I). The atoms C1' and C2 during further transformation of (II) become C1' and C6 in β-turmerone, (III), and β-sesquiphellandrene, (IV), respectively, and thus allow unambigous assignment for the latter compounds.

S2. Experimental

(I) was prepared by addition of (+)-camphanoyl chloride (572 mg, 2.64 mmol) in THF (2 ml) to a solution of (II) (200 mg, 1.32 mmol), 4-DMAP (40 mg, 0.33 mmol) and pyridine (2 ml) in THF (3 ml). After stirring at room temperature for 3 h, Et₂O (100 ml) was added, the solution was washed with saturated NaHCO₃ solution, H₂O and brine, dried (Na₂SO₄) and evaporated. The crude material was purified by column chromatography (cyclohexane:AcOEt = 10:1, R_f = 0.30). The pure ester (360 mg) was dissolved in 2-propanol (6.0 ml) at 313 K. The solution was cooled to 273 K within 1 h and crystals of (I) (m.p. 351–352 K) were grown by standing at this temperature for 24 h. The mother liquor was decanted, the crystals were washed with 2-propanol (1.0 ml) at 273 K and dried in vacuo.

S3. Refinement

Hydrogen atoms were placed in calculated positions using a riding model (including free rotation about C—C) with atomic displacement parameters fixed at 1.5 times those of the carrier atoms.

Computing details

Data collection: KappaCCD Reference Manual (Nonius, 1998); 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 and PARST95 (Nardelli, 1995).

Figures

Fig. 1. View of the title compound showing the labelling of all non-H atoms. Displacement ellipsoids are shown at 50% probability levels. H atoms are drawn as circles of arbitrary radii.

(I)

Crystal data

C20H28O4	F(000) = 360
Mr = 332.42	Dx = 1.170 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71069 Å
a = 6.2171 (6) Å	Cell parameters from 12305 reflections
b = 12.5197 (9) Å	θ = 3.7–25.4°
c = 12.2224 (9) Å	µ = 0.08 mm^−1
β = 97.225 (5)°	T = 291 K
V = 943.79 (13) Å^3	Needle, colourless
Z = 2	0.30 × 0.10 × 0.10 mm

Data collection

Nonius KappaCCD diffractometer	1391 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.033
Graphite monochromator	θmax = 25.4°, θmin = 3.7°
Detector resolution: 19 vertical, 18 horizontal pixels mm^-1	h = 0→7
4 sets at different κ–angles with 386 frames via ϕ–rotation (Δϕ=1°) and two times 90 s per frame scans	k = 0→15
12305 measured reflections	l = −14→14
1810 independent reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.034	H-atom parameters constrained
wR(F^2) = 0.086	Calculated w = 1/[σ^2(Fo^2) + (0.0591P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 1.00	(Δ/σ)max < 0.001
1810 reflections	Δρmax = 0.17 e Å^−3
222 parameters	Δρmin = −0.12 e Å^−3
1 restraint	Extinction correction: SHELXL97 (Sheldrick, 1997), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.048 (11)

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.

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. The duplicate reflections did not indicate decay. The structure was solved by direct methods (Sheldrick, 1990) and successive difference Fourier syntheses. Refinement applied full-matrix least-squares methods (Sheldrick, 1997).

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

	x	y	z	Uiso*/Ueq
O1	0.7235 (2)	0.27193 (12)	0.22053 (14)	0.0626 (4)
O2	0.4656 (2)	0.05473 (13)	0.06938 (13)	0.0596 (4)
O3	0.4160 (3)	−0.11090 (16)	0.00454 (19)	0.0892 (6)
O4	0.3779 (3)	0.21985 (16)	0.1948 (2)	0.1008 (8)
C1	0.6519 (3)	0.11167 (18)	0.12694 (17)	0.0492 (5)
C1A	0.5636 (4)	0.20597 (18)	0.1836 (2)	0.0575 (6)
C1'	0.6601 (4)	0.37004 (18)	0.2709 (2)	0.0620 (6)
H1'1	0.6244	0.3558	0.3445	0.093*
H1'2	0.5337	0.4005	0.2274	0.093*
C1"	0.7822 (4)	0.5569 (2)	0.3172 (2)	0.0681 (7)
H1"	0.9081	0.6037	0.3159	0.102*
C2'	0.8481 (4)	0.4466 (2)	0.2762 (2)	0.0643 (6)
H2'	0.8828	0.4560	0.2008	0.096*
C2"	0.5999 (5)	0.6064 (2)	0.2418 (2)	0.0732 (7)
H2"	0.5946	0.5937	0.1666	0.110*
C3	0.5359 (4)	−0.0461 (2)	0.0509 (2)	0.0620 (6)
C3'	1.0500 (5)	0.4023 (3)	0.3447 (3)	0.0964 (10)
H3'1	1.0180	0.3867	0.4179	0.145*
H3'2	1.1644	0.4542	0.3484	0.145*
H3'3	1.0949	0.3381	0.3111	0.145*
C3"	0.4473 (5)	0.6666 (2)	0.2751 (2)	0.0792 (8)
H3"	0.3378	0.6917	0.2225	0.119*
C4	0.7723 (3)	−0.0509 (2)	0.09520 (19)	0.0583 (6)
C4A	0.8648 (5)	−0.1620 (2)	0.1077 (3)	0.0857 (9)
H4A1	0.7994	−0.1995	0.1636	0.129*
H4A2	1.0187	−0.1579	0.1286	0.129*
H4A3	0.8352	−0.1994	0.0389	0.129*
C4"	0.4410 (5)	0.6955 (2)	0.3881 (3)	0.0801 (8)
C4"A	0.2704 (7)	0.7463 (4)	0.4201 (4)	0.1309 (15)
H4"1	0.1525	0.7637	0.3686	0.196*
H4"2	0.2696	0.7644	0.4939	0.196*
C5	0.8780 (4)	0.0229 (2)	0.0140 (2)	0.0703 (7)
H5A	1.0349	0.0180	0.0265	0.105*
H5B	0.8289	0.0040	−0.0620	0.105*
C5"	0.6375 (6)	0.6660 (3)	0.4643 (2)	0.0914 (9)
H5"1	0.6015	0.6639	0.5393	0.137*
H5"2	0.7479	0.7203	0.4610	0.137*
C6	0.8012 (4)	0.1353 (2)	0.04064 (19)	0.0625 (6)
H6A	0.9217	0.1803	0.0702	0.094*
H6B	0.7236	0.1692	−0.0240	0.094*
C6"	0.7272 (5)	0.5580 (3)	0.4353 (2)	0.0865 (8)
H6"1	0.6209	0.5029	0.4439	0.130*
H6"2	0.8567	0.5422	0.4857	0.130*
C7	0.7708 (3)	0.02212 (18)	0.19793 (18)	0.0520 (5)
C7A	0.9954 (4)	0.0522 (2)	0.2552 (2)	0.0737 (7)
H7A1	1.0615	−0.0091	0.2928	0.111*
H7A2	0.9819	0.1083	0.3074	0.111*
H7A3	1.0840	0.0763	0.2012	0.111*
C7B	0.6344 (4)	−0.0235 (2)	0.2833 (2)	0.0749 (7)
H7B1	0.6981	−0.0891	0.3124	0.112*
H7B2	0.4897	−0.0370	0.2486	0.112*
H7B3	0.6302	0.0270	0.3421	0.112*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0525 (8)	0.0486 (9)	0.0845 (11)	−0.0002 (7)	0.0000 (7)	−0.0088 (8)
O2	0.0414 (8)	0.0598 (9)	0.0754 (10)	−0.0012 (7)	−0.0012 (6)	−0.0106 (9)
O3	0.0662 (11)	0.0814 (13)	0.1176 (16)	−0.0146 (11)	0.0016 (11)	−0.0402 (12)
O4	0.0632 (12)	0.0742 (13)	0.173 (2)	−0.0173 (10)	0.0485 (12)	−0.0410 (13)
C1	0.0404 (11)	0.0488 (12)	0.0573 (13)	−0.0058 (9)	0.0019 (9)	0.0000 (10)
C1A	0.0536 (13)	0.0477 (12)	0.0729 (14)	−0.0059 (11)	0.0139 (10)	0.0001 (11)
C1'	0.0631 (14)	0.0470 (13)	0.0761 (16)	−0.0009 (11)	0.0095 (12)	−0.0073 (11)
C1"	0.0749 (16)	0.0550 (14)	0.0745 (17)	−0.0161 (13)	0.0093 (13)	−0.0092 (13)
C2'	0.0635 (14)	0.0571 (14)	0.0729 (15)	−0.0082 (12)	0.0110 (11)	−0.0050 (13)
C2"	0.108 (2)	0.0538 (14)	0.0573 (14)	−0.0019 (14)	0.0069 (14)	0.0009 (12)
C3	0.0504 (12)	0.0619 (14)	0.0744 (15)	−0.0076 (12)	0.0108 (11)	−0.0178 (13)
C3'	0.0666 (17)	0.085 (2)	0.135 (3)	0.0001 (15)	0.0021 (17)	−0.0207 (19)
C3"	0.1001 (19)	0.0560 (15)	0.0778 (18)	0.0091 (14)	−0.0027 (15)	−0.0082 (13)
C4	0.0461 (12)	0.0573 (13)	0.0726 (15)	0.0008 (11)	0.0118 (10)	−0.0077 (12)
C4A	0.0733 (17)	0.0658 (16)	0.120 (2)	0.0109 (14)	0.0205 (16)	−0.0117 (17)
C4"	0.0889 (18)	0.0599 (16)	0.092 (2)	−0.0061 (15)	0.0131 (15)	−0.0204 (15)
C4"A	0.110 (3)	0.129 (3)	0.154 (3)	−0.003 (3)	0.018 (2)	−0.072 (3)
C5	0.0593 (13)	0.0835 (18)	0.0706 (15)	−0.0009 (13)	0.0178 (11)	−0.0029 (14)
C5"	0.116 (2)	0.084 (2)	0.0729 (17)	−0.0096 (18)	0.0069 (16)	−0.0266 (16)
C6	0.0607 (14)	0.0683 (16)	0.0596 (14)	−0.0056 (12)	0.0123 (11)	0.0063 (12)
C6"	0.112 (2)	0.0803 (19)	0.0621 (16)	0.0102 (17)	−0.0080 (14)	−0.0122 (15)
C7	0.0457 (11)	0.0509 (12)	0.0593 (12)	−0.0029 (9)	0.0064 (9)	0.0012 (10)
C7A	0.0610 (14)	0.0773 (17)	0.0778 (16)	0.0015 (13)	−0.0113 (11)	0.0066 (14)
C7B	0.0873 (17)	0.0676 (16)	0.0732 (16)	−0.0029 (14)	0.0237 (14)	0.0136 (13)

Geometric parameters (Å, º)

O1—C1A	1.327 (3)	C4—C7	1.554 (3)
O1—C1'	1.451 (3)	C4—C5	1.560 (3)
O2—C3	1.364 (3)	C4A—H4A1	0.9600
O2—C1	1.463 (2)	C4A—H4A2	0.9600
O3—C3	1.195 (3)	C4A—H4A3	0.9600
O4—C1A	1.193 (3)	C4"—C4"A	1.337 (5)
C1—C1A	1.506 (3)	C4"—C5"	1.486 (5)
C1—C6	1.519 (3)	C4"A—H4"1	0.9300
C1—C7	1.548 (3)	C4"A—H4"2	0.9300
C1'—C2'	1.506 (3)	C5—C6	1.534 (4)
C1'—H1'1	0.9700	C5—H5A	0.9700
C1'—H1'2	0.9700	C5—H5B	0.9700
C1"—C2"	1.502 (4)	C5"—C6"	1.522 (4)
C1"—C6"	1.525 (4)	C5"—H5"1	0.9700
C1"—C2'	1.542 (4)	C5"—H5"2	0.9700
C1"—H1"	0.9800	C6—H6A	0.9700
C2'—C3'	1.523 (4)	C6—H6B	0.9700
C2'—H2'	0.9800	C6"—H6"1	0.9700
C2"—C3"	1.315 (4)	C6"—H6"2	0.9700
C2"—H2"	0.9300	C7—C7A	1.528 (3)
C3—C4	1.502 (3)	C7—C7B	1.535 (3)
C3'—H3'1	0.9600	C7A—H7A1	0.9600
C3'—H3'2	0.9600	C7A—H7A2	0.9600
C3'—H3'3	0.9600	C7A—H7A3	0.9600
C3"—C4"	1.434 (4)	C7B—H7B1	0.9600
C3"—H3"	0.9300	C7B—H7B2	0.9600
C4—C4A	1.506 (4)	C7B—H7B3	0.9600
C1A—O1—C1'	116.09 (16)	H4A1—C4A—H4A2	109.5
C3—O2—C1	106.23 (16)	C4—C4A—H4A3	109.5
O2—C1—C1A	106.91 (15)	H4A1—C4A—H4A3	109.5
O2—C1—C6	106.08 (17)	H4A2—C4A—H4A3	109.5
C1A—C1—C6	117.14 (18)	C4"A—C4"—C3"	121.4 (3)
O2—C1—C7	102.13 (17)	C4"A—C4"—C5"	123.7 (3)
C1A—C1—C7	119.08 (18)	C3"—C4"—C5"	114.9 (2)
C6—C1—C7	103.86 (16)	C4"—C4"A—H4"1	120.0
O4—C1A—O1	124.4 (2)	C4"—C4"A—H4"2	120.0
O4—C1A—C1	125.5 (2)	H4"1—C4"A—H4"2	120.0
O1—C1A—C1	110.11 (17)	C6—C5—C4	103.94 (18)
O1—C1'—C2'	107.82 (18)	C6—C5—H5A	111.0
O1—C1'—H1'1	110.1	C4—C5—H5A	111.0
C2'—C1'—H1'1	110.1	C6—C5—H5B	111.0
O1—C1'—H1'2	110.1	C4—C5—H5B	111.0
C2'—C1'—H1'2	110.1	H5A—C5—H5B	109.0
H1'1—C1'—H1'2	108.5	C4"—C5"—C6"	111.8 (2)
C2"—C1"—C6"	109.6 (2)	C4"—C5"—H5"1	109.3
C2"—C1"—C2'	112.4 (2)	C6"—C5"—H5"1	109.3
C6"—C1"—C2'	114.6 (2)	C4"—C5"—H5"2	109.3
C2"—C1"—H1"	106.6	C6"—C5"—H5"2	109.3
C6"—C1"—H1"	106.6	H5"1—C5"—H5"2	107.9
C2'—C1"—H1"	106.6	C1—C6—C5	101.69 (18)
C1'—C2'—C3'	111.9 (2)	C1—C6—H6A	111.4
C1'—C2'—C1"	110.29 (18)	C5—C6—H6A	111.4
C3'—C2'—C1"	112.4 (2)	C1—C6—H6B	111.4
C1'—C2'—H2'	107.3	C5—C6—H6B	111.4
C3'—C2'—H2'	107.3	H6A—C6—H6B	109.3
C1"—C2'—H2'	107.3	C5"—C6"—C1"	111.2 (3)
C3"—C2"—C1"	124.4 (3)	C5"—C6"—H6"1	109.4
C3"—C2"—H2"	117.8	C1"—C6"—H6"1	109.4
C1"—C2"—H2"	117.8	C5"—C6"—H6"2	109.4
O3—C3—O2	120.9 (2)	C1"—C6"—H6"2	109.4
O3—C3—C4	131.9 (2)	H6"1—C6"—H6"2	108.0
O2—C3—C4	107.3 (2)	C7A—C7—C7B	109.39 (19)
C2'—C3'—H3'1	109.5	C7A—C7—C1	114.99 (19)
C2'—C3'—H3'2	109.5	C7B—C7—C1	112.64 (18)
H3'1—C3'—H3'2	109.5	C7A—C7—C4	114.61 (18)
C2'—C3'—H3'3	109.5	C7B—C7—C4	113.0 (2)
H3'1—C3'—H3'3	109.5	C1—C7—C4	91.38 (17)
H3'2—C3'—H3'3	109.5	C7—C7A—H7A1	109.5
C2"—C3"—C4"	123.4 (3)	C7—C7A—H7A2	109.5
C2"—C3"—H3"	118.3	H7A1—C7A—H7A2	109.5
C4"—C3"—H3"	118.3	C7—C7A—H7A3	109.5
C3—C4—C4A	114.6 (2)	H7A1—C7A—H7A3	109.5
C3—C4—C7	99.35 (17)	H7A2—C7A—H7A3	109.5
C4A—C4—C7	120.2 (2)	C7—C7B—H7B1	109.5
C3—C4—C5	102.6 (2)	C7—C7B—H7B2	109.5
C4A—C4—C5	115.2 (2)	H7B1—C7B—H7B2	109.5
C7—C4—C5	102.23 (19)	C7—C7B—H7B3	109.5
C4—C4A—H4A1	109.5	H7B1—C7B—H7B3	109.5
C4—C4A—H4A2	109.5	H7B2—C7B—H7B3	109.5
C3—O2—C1—C1A	−159.93 (18)	C3—C4—C5—C6	69.7 (2)
C3—O2—C1—C6	74.3 (2)	C4A—C4—C5—C6	−165.1 (2)
C3—O2—C1—C7	−34.1 (2)	C7—C4—C5—C6	−33.0 (2)
C1'—O1—C1A—O4	−4.3 (4)	C4"A—C4"—C5"—C6"	142.5 (3)
C1'—O1—C1A—C1	176.21 (18)	C3"—C4"—C5"—C6"	−38.4 (4)
O2—C1—C1A—O4	11.9 (3)	O2—C1—C6—C5	−67.7 (2)
C6—C1—C1A—O4	130.6 (3)	C1A—C1—C6—C5	173.06 (19)
C7—C1—C1A—O4	−103.0 (3)	C7—C1—C6—C5	39.5 (2)
O2—C1—C1A—O1	−168.64 (17)	C4—C5—C6—C1	−3.5 (2)
C6—C1—C1A—O1	−49.9 (3)	C4"—C5"—C6"—C1"	57.9 (3)
C7—C1—C1A—O1	76.5 (2)	C2"—C1"—C6"—C5"	−45.5 (3)
C1A—O1—C1'—C2'	−163.5 (2)	C2'—C1"—C6"—C5"	−173.0 (2)
O1—C1'—C2'—C3'	−60.3 (3)	O2—C1—C7—C7A	170.58 (18)
O1—C1'—C2'—C1"	173.78 (19)	C1A—C1—C7—C7A	−72.0 (2)
C2"—C1"—C2'—C1'	−61.3 (3)	C6—C1—C7—C7A	60.4 (2)
C6"—C1"—C2'—C1'	64.8 (3)	O2—C1—C7—C7B	−63.2 (2)
C2"—C1"—C2'—C3'	173.1 (2)	C1A—C1—C7—C7B	54.2 (3)
C6"—C1"—C2'—C3'	−60.9 (3)	C6—C1—C7—C7B	−173.3 (2)
C6"—C1"—C2"—C3"	16.9 (4)	O2—C1—C7—C4	52.49 (17)
C2'—C1"—C2"—C3"	145.6 (3)	C1A—C1—C7—C4	169.87 (16)
C1—O2—C3—O3	−179.9 (2)	C6—C1—C7—C4	−57.68 (18)
C1—O2—C3—C4	−1.6 (2)	C3—C4—C7—C7A	−170.1 (2)
C1"—C2"—C3"—C4"	2.3 (5)	C4A—C4—C7—C7A	64.1 (3)
O3—C3—C4—C4A	−16.2 (4)	C5—C4—C7—C7A	−64.9 (2)
O2—C3—C4—C4A	165.6 (2)	C3—C4—C7—C7B	63.7 (2)
O3—C3—C4—C7	−145.7 (3)	C4A—C4—C7—C7B	−62.1 (3)
O2—C3—C4—C7	36.2 (2)	C5—C4—C7—C7B	168.88 (18)
O3—C3—C4—C5	109.4 (3)	C3—C4—C7—C1	−51.70 (19)
O2—C3—C4—C5	−68.7 (2)	C4A—C4—C7—C1	−177.5 (2)
C2"—C3"—C4"—C4"A	−172.2 (3)	C5—C4—C7—C1	53.51 (18)
C2"—C3"—C4"—C5"	8.7 (4)