Key tricyclic synthetic intermediates for the preparation of the sesquiterpenes α- and β-cedrene

A completely novel and direct route towards the synthesis of the natural sesquiterpenes α-cedrene and β-cedrene delivered the compounds (3β,3aβ,7β)-(±)-6,6-ethyl­ene­dioxy-3,8,8-tri­methyl-2,3,3a,4,5,6,7,8-octa­hydro-3a,7-methano­azulen-2-one, C₁₆H₂₂O₃, and (3β,3aβ,7β,8aα)-(±)-6,6-ethyl­ene­dioxy-3,8,8-tri­methyl-1,2,3,3a,4,5,6,7,8,8a-deca­hydro-3a,7-methano­azulen-2-one, C₁₆H₂₄O₃, at key stages of the preparative programme. Structural elucidation showed the latter compound to have added an H atom to the same face of the cyclo­pentenone ring as that occupied by the methyl substituent, and also allowed correct isomer identification for further reaction.

S1. Comment

In order to extend and illustrate our endeavours to develop further the efficiency (Kennedy et al., 2000; Ford et al., 2000) and applicability (Donkervoort et al., 1996) of the Khand cyclization reaction, we sought to utilize this annulation process strategically within routes towards the naturally ocurring sesquiterpenes α-cedrene, (Ia), and β-cedrene, (Ib). It was envisaged that use of these organocobalt-mediated methods would establish a direct and efficient pathway for the synthesis of the structurally demanding [5.3.1.0^1,5] tricyclic carbon skeleton of this family of natural species.

The cyclization precursors (IIa)/(IIb), prepared as an inseparable 2:1 mixture of geometric isomers, were employed in the key intramolecular Khand cyclization, and the products (IIIa) and (IIIb) were isolated in an excellent optimum combined yield of 95% (Kerr et al., 2001). Following separation, NMR spectroscopic studies could not fully identify each individual product with respect to the methyl group stereochemistry adjacent to the cyclopentenone carbonyl. Accordingly, the major component, (IIIa), was recrystallized and structural elucidation revealed the stereochemistry shown in Fig. 1. As this was not the required isomer, we were able to concentrate our synthetic endeavours on the tricyclic species, (IIIb), which was hydrogenated to give compound (IV), as shown in Fig. 2. In addition to showing the stereochemistry of the methyl group, the structure of (IV) also shows that the H atom introduced at the ring junction is syn to the methyl. Pleasingly, this stereochemical outcome was that desired for the continuation of the total synthesis programme. The crystal structure analyses of compounds (IIIa) and (IV) are presented here. \sch

Both structures (IIIa) and (IV) are comprised of discrete molecules, with all intermolecular distances being equal to at least the sum of van der Waal's radii. Interestingly, (IV) crystallizes in the chiral space group P2₁, raising the possibility of resolving the racemic mechanical mixture of crystals by utilizing seeding techniques.

The main differences in geometry between the two compounds are, as expected, centred around the double bond found in (IIIa) but not (IV). Not only is this C2—C3 bond shorter in (IIIa), but conjugation to the carbonyl group also causes significant changes to the C1—C2 and C1═O1 distances [1.328 (3), 1.471 (3) and 1.221 (2) Å, respectively, for (IIIa), and 1.533 (2), 1.513 (3) and 1.210 (2) Å, respectively, for (IV)]. The presence of an sp² hybridized atom at C3 also leads to a shortening of the C3—C4 and C3—C7 bonds. This shortening is more pronounced for C3—C4, which is within the cyclopentene ring, than it is for the aliphatic C3—C7 bond (see Tables 1 and 2). The bond lengths of the acetal group in (IIIa) are artificially shortened by a considerable degree of rotational motion (Fig. 1). A search of the Cambridge Structural Database (Release?; Allen & Kennard, 1993) found no cedrane-based fragments with a double bond such as that in (IIIa). However, several saturated analogues of (IV) were found, though none with a similarly placed ketone functionality. These gave geometric parameters consistent with those found for (IV) (for typical examples see Chen & Chang, 1996; Karlsson et al., 1973; Khan et al., 1985).

The conformation of the cedrene tricyclic skeleton is also affected by the introduction of an sp² atom at C3. Least changed is the six-membered ring C4/C9/C8/C12/C11/C10, which adopts a chair conformation in both compounds. The planarity forced upon C2, C3, C4 and C7 in (IIIa) by the sp² atom C3 is not perfect, as C3 lies slightly above the plane of the other three atoms, but it still has a marked effect on the five-membered rings C1/C2/C3/C4/C5 (ring A) and C3/C4/C9/C8/C7 (ring B). In (IIIa), there are two torsion angles around ring A that approach planarity [C1—C2—C3—C4 7.0 (3) and C3—C2—C1—C5 6.5 (2)°], which means that atoms C4 and C5 are twisted furthest from the ring plane. The torsion angles about ring A in (IV) show both an overall greater deviation from planarity (Table 2) and that C1 and C2 are the atoms twisted furthest out of the plane. The torsion angles about ring B for the two structures show that for both (IIIa) and (IV) the C4—C3—C7—C8 angle is flattest, but only for (IIIa) does it truly approach planarity [4.2 (3) and 11.24 (16)°, respectively]. The flattened conformation of (IIIa) leaves the methyl groups of C13 and C14 staggered with respect to C2 [C2—C3—C7—C13 57.0 (3)°], whilst in (IV), the methyl group of C13 approaches an eclipsed position [16.4 (2)°]. The strain inherent in these fused ring systems is shown by some large angular deviations from ideal geometry. Most notable are the widening of the C2—C3—C7 angles [to 135.2 (2) and 120.43 (15)° in (IIIa) and (IV), respectively], and of the C4—C5—C6 angle to 118.35 (15)° in (IV) and the C5—C4—C9 angle to 122.85 (18)° in (IIIa).

Related literature

For related literature, see: Allen & Kennard (1993); Chen & Chang (1996); Donkervoort et al. (1996); Ford et al. (2000); Karlsson et al. (1973); Kennedy et al. (2000); Kerr et al. (2001); Khan et al. (1985).

S2. Experimental

The syntheses and spectroscopic characterizations of compounds (IIIa) and (IV) are described in detail by Kerr et al. (2001). Crystals of both compounds were grown by slow recrystallization from petroleum ether/diethyl ether mixtures at room temperature.

S3. Refinement

All H atoms were treated as riding, with C—H = 0.93–1.00 Å. For compound (IV), the Freidel equivalents were merged prior to the final refinement.

Computing details

Data collection: MSC/AFC Diffractometer Control Software (Molecular Structure Corporation, 1988) for (IIIa); DENZO (Otwinowski & Minor, 1997) and COLLECT (Nonius, 1998) for (IV). Cell refinement: MSC/AFC Diffractometer Control Software for (IIIa); DENZO and COLLECT for (IV). Data reduction: TEXSAN (Molecular Structure Corporation, 1992) for (IIIa); DENZO and COLLECT for (IV). Program(s) used to solve structure: SIR92 (Altomare et al., 1994) for (IIIa); SHELXS97 (Sheldrick, 1990) for (IV). For both compounds, program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. The molecular structure of (IIIa) with 50% probability displacement ellipsoids and H atoms drawn as small spheres of arbitrary size.
	Fig. 2. The molecular structure of (IV) with 50% probability displacement ellipsoids and H atoms drawn as small spheres of arbitrary size.

(IIIa) (3β,3aβ,7β)-(±)-6,6-ethylenedioxy-3,8,8-trimethyl-2,3,3a,4,5,6,7,8- octahydro-3a,7-methanoazulen-2-one

Crystal data

C16H22O3	F(000) = 568
Mr = 262.34	Dx = 1.248 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71069 Å
a = 6.0402 (13) Å	Cell parameters from 21 reflections
b = 31.423 (4) Å	θ = 7.1–10.7°
c = 7.7111 (13) Å	µ = 0.09 mm^−1
β = 107.469 (15)°	T = 295 K
V = 1396.1 (4) Å^3	Tabular, colourless
Z = 4	0.50 × 0.40 × 0.15 mm

Data collection

Rigaku AFC-7S diffractometer	Rint = 0.061
Radiation source: fine-focus sealed tube	θmax = 26.0°, θmin = 2.6°
Graphite monochromator	h = 0→7
ω/2θ scans	k = 0→38
2977 measured reflections	l = −9→9
2721 independent reflections	3 standard reflections every 150 reflections
1522 reflections with I > 2σ(I)	intensity decay: 3.0%

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)] = 0.048	H-atom parameters constrained
wR(F^2) = 0.142	w = 1/[σ^2(Fo^2) + (0.0533P)^2 + 0.1589P] where P = (Fo^2 + 2Fc^2)/3
S = 1.01	(Δ/σ)max < 0.001
2721 reflections	Δρmax = 0.18 e Å^−3
176 parameters	Δρmin = −0.15 e Å^−3
0 restraints	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: 0.017 (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.

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
O1	0.4059 (3)	−0.01602 (5)	0.7178 (2)	0.0581 (5)
O2	0.2944 (4)	0.21646 (5)	0.7625 (3)	0.0761 (6)
O3	0.1227 (4)	0.19061 (6)	0.9653 (3)	0.0815 (7)
C1	0.3382 (4)	0.02062 (7)	0.7164 (3)	0.0398 (5)
C2	0.3508 (4)	0.05474 (7)	0.5890 (3)	0.0413 (5)
H2	0.4117	0.0521	0.4921	0.050*
C3	0.2608 (3)	0.08994 (6)	0.6353 (3)	0.0334 (5)
C4	0.2031 (4)	0.08565 (6)	0.8116 (3)	0.0338 (5)
C5	0.2010 (4)	0.03721 (6)	0.8395 (3)	0.0373 (5)
H5	0.2807	0.0300	0.9665	0.045*
C6	−0.0401 (4)	0.01703 (7)	0.7789 (4)	0.0539 (7)
H6A	−0.1156	0.0241	0.6540	0.081*
H6B	−0.1303	0.0276	0.8530	0.081*
H6C	−0.0258	−0.0133	0.7917	0.081*
C7	0.1624 (4)	0.13113 (7)	0.5391 (3)	0.0422 (6)
C8	0.0592 (4)	0.15198 (7)	0.6824 (3)	0.0452 (6)
H8	−0.0763	0.1694	0.6212	0.054*
C9	−0.0155 (4)	0.11313 (7)	0.7733 (3)	0.0466 (6)
H9A	−0.0491	0.1209	0.8844	0.056*
H9B	−0.1493	0.0990	0.6918	0.056*
C10	0.3924 (4)	0.10675 (7)	0.9690 (3)	0.0453 (6)
H10A	0.3417	0.1068	1.0771	0.054*
H10B	0.5332	0.0899	0.9952	0.054*
C11	0.4463 (5)	0.15231 (7)	0.9267 (3)	0.0556 (7)
H11A	0.5296	0.1664	1.0392	0.067*
H11B	0.5470	0.1517	0.8497	0.067*
C12	0.2313 (5)	0.17780 (7)	0.8331 (3)	0.0541 (7)
C13	−0.0380 (5)	0.11880 (8)	0.3683 (3)	0.0651 (8)
H13A	0.0226	0.1025	0.2874	0.098*
H13B	−0.1107	0.1441	0.3077	0.098*
H13C	−0.1502	0.1021	0.4037	0.098*
C14	0.3359 (5)	0.15733 (8)	0.4728 (4)	0.0634 (8)
H14A	0.4644	0.1655	0.5750	0.095*
H14B	0.2605	0.1824	0.4114	0.095*
H14C	0.3913	0.1405	0.3904	0.095*
C15	0.1855 (8)	0.25013 (10)	0.8219 (6)	0.1173 (16)
H15A	0.0919	0.2664	0.7188	0.141*
H15B	0.3003	0.2690	0.8995	0.141*
C16	0.0364 (8)	0.23152 (10)	0.9246 (6)	0.1047 (13)
H16A	0.0494	0.2476	1.0346	0.126*
H16B	−0.1249	0.2309	0.8509	0.126*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0723 (12)	0.0379 (9)	0.0643 (12)	0.0130 (8)	0.0209 (10)	0.0006 (8)
O2	0.1065 (16)	0.0297 (9)	0.0880 (14)	−0.0054 (10)	0.0232 (12)	−0.0001 (9)
O3	0.1281 (19)	0.0504 (11)	0.0743 (13)	0.0276 (12)	0.0430 (13)	−0.0070 (10)
C1	0.0383 (12)	0.0361 (12)	0.0404 (12)	0.0000 (10)	0.0048 (10)	−0.0029 (9)
C2	0.0458 (13)	0.0441 (13)	0.0378 (12)	−0.0002 (10)	0.0183 (11)	−0.0026 (10)
C3	0.0332 (11)	0.0343 (11)	0.0314 (11)	−0.0045 (9)	0.0077 (9)	−0.0011 (8)
C4	0.0365 (12)	0.0321 (11)	0.0322 (11)	−0.0005 (9)	0.0092 (9)	−0.0002 (9)
C5	0.0403 (13)	0.0347 (11)	0.0336 (11)	−0.0018 (9)	0.0063 (10)	0.0030 (9)
C6	0.0526 (16)	0.0475 (14)	0.0625 (16)	−0.0104 (12)	0.0189 (13)	0.0029 (12)
C7	0.0503 (14)	0.0355 (12)	0.0387 (12)	−0.0018 (10)	0.0104 (10)	0.0037 (9)
C8	0.0410 (13)	0.0379 (12)	0.0535 (14)	0.0111 (10)	0.0090 (11)	0.0061 (10)
C9	0.0421 (13)	0.0473 (13)	0.0530 (14)	0.0069 (11)	0.0179 (11)	0.0037 (11)
C10	0.0527 (14)	0.0402 (12)	0.0371 (12)	0.0031 (10)	0.0047 (11)	−0.0053 (9)
C11	0.0612 (17)	0.0396 (13)	0.0524 (14)	−0.0023 (12)	−0.0034 (12)	−0.0089 (11)
C12	0.0733 (18)	0.0336 (12)	0.0555 (16)	0.0061 (12)	0.0195 (14)	−0.0032 (11)
C13	0.076 (2)	0.0574 (16)	0.0448 (14)	0.0011 (14)	−0.0082 (14)	0.0067 (12)
C14	0.080 (2)	0.0524 (15)	0.0622 (17)	−0.0088 (14)	0.0287 (15)	0.0100 (13)
C15	0.181 (5)	0.0385 (18)	0.131 (4)	0.018 (2)	0.046 (3)	0.001 (2)
C16	0.144 (4)	0.058 (2)	0.110 (3)	0.041 (2)	0.035 (3)	−0.0116 (19)

Geometric parameters (Å, º)

O1—C1	1.221 (2)	C8—C12	1.538 (3)
O2—C15	1.394 (4)	C8—C9	1.541 (3)
O2—C12	1.429 (3)	C8—H8	0.980
O3—C16	1.387 (3)	C9—H9A	0.970
O3—C12	1.426 (3)	C9—H9B	0.970
C1—C2	1.471 (3)	C10—C11	1.525 (3)
C1—C5	1.527 (3)	C10—H10A	0.970
C2—C3	1.328 (3)	C10—H10B	0.970
C2—H2	0.930	C11—C12	1.512 (3)
C3—C4	1.508 (3)	C11—H11A	0.970
C3—C7	1.521 (3)	C11—H11B	0.970
C4—C9	1.531 (3)	C13—H13A	0.960
C4—C5	1.538 (3)	C13—H13B	0.960
C4—C10	1.545 (3)	C13—H13C	0.960
C5—C6	1.527 (3)	C14—H14A	0.960
C5—H5	0.980	C14—H14B	0.960
C6—H6A	0.960	C14—H14C	0.960
C6—H6B	0.960	C15—C16	1.486 (6)
C6—H6C	0.960	C15—H15A	0.970
C7—C14	1.536 (3)	C15—H15B	0.970
C7—C13	1.547 (3)	C16—H16A	0.970
C7—C8	1.566 (3)	C16—H16B	0.970
C15—O2—C12	108.3 (3)	C8—C9—H9B	112
C16—O3—C12	108.8 (2)	H9A—C9—H9B	109.4
O1—C1—C2	127.5 (2)	C11—C10—C4	112.96 (18)
O1—C1—C5	124.0 (2)	C11—C10—H10A	109
C2—C1—C5	108.22 (18)	C4—C10—H10A	109
C3—C2—C1	108.7 (2)	C11—C10—H10B	109
C3—C2—H2	126	C4—C10—H10B	109
C1—C2—H2	126	H10A—C10—H10B	107.8
C2—C3—C4	113.09 (18)	C12—C11—C10	113.0 (2)
C2—C3—C7	135.2 (2)	C12—C11—H11A	109
C4—C3—C7	110.71 (17)	C10—C11—H11A	109
C3—C4—C9	101.24 (17)	C12—C11—H11B	109
C3—C4—C5	103.21 (16)	C10—C11—H11B	109
C9—C4—C5	122.85 (18)	H11A—C11—H11B	108
C3—C4—C10	110.70 (18)	O3—C12—O2	105.36 (19)
C9—C4—C10	107.54 (18)	O3—C12—C11	108.7 (2)
C5—C4—C10	110.52 (16)	O2—C12—C11	110.1 (2)
C6—C5—C1	108.28 (17)	O3—C12—C8	109.7 (2)
C6—C5—C4	114.56 (18)	O2—C12—C8	110.98 (19)
C1—C5—C4	102.83 (16)	C11—C12—C8	111.72 (18)
C6—C5—H5	110	C7—C13—H13A	110
C1—C5—H5	110	C7—C13—H13B	110
C4—C5—H5	110	H13A—C13—H13B	110
C5—C6—H6A	110	C7—C13—H13C	110
C5—C6—H6B	110	H13A—C13—H13C	110
H6A—C6—H6B	110	H13B—C13—H13C	110
C5—C6—H6C	110	C7—C14—H14A	110
H6A—C6—H6C	110	C7—C14—H14B	110
H6B—C6—H6C	110	H14A—C14—H14B	110
C3—C7—C14	114.4 (2)	C7—C14—H14C	110
C3—C7—C13	107.07 (17)	H14A—C14—H14C	110
C14—C7—C13	106.8 (2)	H14B—C14—H14C	110
C3—C7—C8	101.06 (16)	O2—C15—C16	107.3 (3)
C14—C7—C8	117.81 (19)	O2—C15—H15A	110
C13—C7—C8	109.3 (2)	C16—C15—H15A	110
C12—C8—C9	107.34 (19)	O2—C15—H15B	110
C12—C8—C7	115.6 (2)	C16—C15—H15B	110
C9—C8—C7	102.85 (17)	H15A—C15—H15B	108.5
C12—C8—H8	110	O3—C16—C15	103.8 (3)
C9—C8—H8	110	O3—C16—H16A	111
C7—C8—H8	110	C15—C16—H16A	111
C4—C9—C8	100.46 (18)	O3—C16—H16B	111
C4—C9—H9A	112	C15—C16—H16B	111
C8—C9—H9A	112	H16A—C16—H16B	109
C4—C9—H9B	112
O1—C1—C2—C3	−179.2 (2)	C14—C7—C8—C9	−157.1 (2)
C5—C1—C2—C3	6.5 (2)	C13—C7—C8—C9	80.9 (2)
C1—C2—C3—C4	7.0 (3)	C3—C4—C9—C8	−43.9 (2)
C1—C2—C3—C7	−160.0 (2)	C5—C4—C9—C8	−157.83 (18)
C2—C3—C4—C9	−145.19 (19)	C10—C4—C9—C8	72.2 (2)
C7—C3—C4—C9	25.0 (2)	C12—C8—C9—C4	−74.5 (2)
C2—C3—C4—C5	−17.3 (2)	C7—C8—C9—C4	47.9 (2)
C7—C3—C4—C5	152.94 (16)	C3—C4—C10—C11	51.4 (3)
C2—C3—C4—C10	101.0 (2)	C9—C4—C10—C11	−58.3 (3)
C7—C3—C4—C10	−88.8 (2)	C5—C4—C10—C11	165.16 (19)
O1—C1—C5—C6	−69.3 (3)	C4—C10—C11—C12	42.2 (3)
C2—C1—C5—C6	105.2 (2)	C16—O3—C12—O2	24.0 (3)
O1—C1—C5—C4	169.1 (2)	C16—O3—C12—C11	141.9 (3)
C2—C1—C5—C4	−16.5 (2)	C16—O3—C12—C8	−95.6 (3)
C3—C4—C5—C6	−98.0 (2)	C15—O2—C12—O3	−11.8 (3)
C9—C4—C5—C6	14.9 (3)	C15—O2—C12—C11	−128.9 (3)
C10—C4—C5—C6	143.6 (2)	C15—O2—C12—C8	106.9 (3)
C3—C4—C5—C1	19.22 (19)	C10—C11—C12—O3	77.6 (3)
C9—C4—C5—C1	132.2 (2)	C10—C11—C12—O2	−167.5 (2)
C10—C4—C5—C1	−99.2 (2)	C10—C11—C12—C8	−43.7 (3)
C2—C3—C7—C14	−61.0 (3)	C9—C8—C12—O3	−59.0 (2)
C4—C3—C7—C14	131.8 (2)	C7—C8—C12—O3	−173.09 (17)
C2—C3—C7—C13	57.0 (3)	C9—C8—C12—O2	−175.06 (19)
C4—C3—C7—C13	−110.2 (2)	C7—C8—C12—O2	70.9 (2)
C2—C3—C7—C8	171.3 (2)	C9—C8—C12—C11	61.7 (3)
C4—C3—C7—C8	4.2 (2)	C7—C8—C12—C11	−52.4 (3)
C3—C7—C8—C12	84.9 (2)	C12—O2—C15—C16	−3.5 (4)
C14—C7—C8—C12	−40.5 (3)	C12—O3—C16—C15	−25.6 (4)
C13—C7—C8—C12	−162.46 (19)	O2—C15—C16—O3	17.9 (4)
C3—C7—C8—C9	−31.8 (2)

(IV) (3β,3aβ,7β,8aα)-(±)-6,6-ethylenedioxy-3,8,8-trimethyl- 1,2,3,3a,4,5,6,7,8,8a-decahydro-3a,7-methanoazulen-2-one

Crystal data

C16H24O3	F(000) = 288
Mr = 264.35	Dx = 1.284 Mg m^−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
a = 8.3280 (3) Å	Cell parameters from 17654 reflections
b = 8.3930 (3) Å	θ = 1.0–27.5°
c = 10.2120 (4) Å	µ = 0.09 mm^−1
β = 106.696 (2)°	T = 150 K
V = 683.70 (4) Å^3	Cut fragment, colourless
Z = 2	0.50 × 0.35 × 0.10 mm

Data collection

Nonius KappaCCD area-detector diffractometer	1579 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.030
Graphite monochromator	θmax = 27.5°, θmin = 3.5°
ϕ + ω scans to fill Ewald sphere	h = −10→10
5455 measured reflections	k = −10→10
1667 independent reflections	l = −13→13

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.031	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.080	H-atom parameters constrained
S = 1.07	w = 1/[σ^2(Fo^2) + (0.0438P)^2 + 0.1142P] where P = (Fo^2 + 2Fc^2)/3
1667 reflections	(Δ/σ)max < 0.001
175 parameters	Δρmax = 0.19 e Å^−3
1 restraint	Δρmin = −0.17 e Å^−3

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 (Ų)

	x	y	z	Uiso*/Ueq
O1	0.48780 (17)	−0.38785 (19)	0.53438 (12)	0.0344 (3)
O2	−0.39000 (14)	−0.31606 (19)	0.09467 (12)	0.0284 (3)
O3	−0.23261 (14)	−0.38265 (16)	−0.04680 (11)	0.0213 (3)
C1	0.3698 (2)	−0.3367 (2)	0.44531 (16)	0.0228 (4)
C2	0.2414 (2)	−0.2175 (2)	0.46290 (17)	0.0251 (4)
H2A	0.2696	−0.1084	0.4399	0.030*
H2B	0.2334	−0.2184	0.5578	0.030*
C3	0.07774 (19)	−0.2755 (2)	0.36180 (15)	0.0178 (3)
H3	0.0257	−0.3548	0.4104	0.021*
C4	0.12928 (19)	−0.3659 (2)	0.24538 (15)	0.0162 (3)
C5	0.32299 (19)	−0.3867 (2)	0.29559 (16)	0.0196 (3)
H5	0.3718	−0.3053	0.2466	0.024*
C6	0.3965 (2)	−0.5464 (3)	0.27365 (18)	0.0280 (4)
H6A	0.3591	−0.6284	0.3267	0.042*
H6B	0.5191	−0.5400	0.3037	0.042*
H6C	0.3587	−0.5741	0.1764	0.042*
C7	−0.0616 (2)	−0.1534 (2)	0.28849 (16)	0.0203 (3)
C8	−0.1065 (2)	−0.2061 (2)	0.13533 (16)	0.0182 (3)
H8	−0.1520	−0.1138	0.0740	0.022*
C9	0.06617 (19)	−0.2550 (2)	0.12185 (15)	0.0173 (3)
H9A	0.0559	−0.3118	0.0349	0.021*
H9B	0.1406	−0.1616	0.1282	0.021*
C10	0.0321 (2)	−0.5234 (2)	0.21179 (16)	0.0194 (3)
H10A	0.0553	−0.5729	0.1311	0.023*
H10B	0.0713	−0.5976	0.2899	0.023*
C11	−0.1575 (2)	−0.4974 (2)	0.18208 (17)	0.0219 (4)
H11A	−0.2170	−0.5930	0.1355	0.026*
H11B	−0.1845	−0.4855	0.2699	0.026*
C12	−0.22193 (19)	−0.3511 (2)	0.09335 (15)	0.0189 (3)
C13	0.0031 (3)	0.0192 (2)	0.2963 (2)	0.0288 (4)
H13A	0.0422	0.0527	0.3922	0.043*
H13B	−0.0878	0.0895	0.2463	0.043*
H13C	0.0960	0.0251	0.2555	0.043*
C14	−0.2077 (2)	−0.1542 (3)	0.35251 (18)	0.0290 (4)
H14A	−0.2968	−0.0835	0.3002	0.044*
H14B	−0.1678	−0.1167	0.4473	0.044*
H14C	−0.2515	−0.2627	0.3509	0.044*
C15	−0.5019 (2)	−0.3494 (3)	−0.03634 (17)	0.0279 (4)
H15A	−0.5447	−0.2496	−0.0857	0.034*
H15B	−0.5981	−0.4139	−0.0282	0.034*
C16	−0.3975 (2)	−0.4416 (2)	−0.10943 (17)	0.0241 (4)
H16A	−0.4043	−0.5577	−0.0946	0.029*
H16B	−0.4335	−0.4193	−0.2088	0.029*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0298 (7)	0.0395 (8)	0.0240 (6)	0.0062 (6)	−0.0083 (5)	−0.0033 (6)
O2	0.0147 (5)	0.0452 (9)	0.0235 (6)	0.0015 (6)	0.0028 (4)	−0.0075 (6)
O3	0.0173 (5)	0.0290 (7)	0.0153 (5)	0.0005 (5)	0.0008 (4)	−0.0031 (5)
C1	0.0195 (8)	0.0238 (9)	0.0216 (8)	−0.0059 (7)	0.0002 (6)	−0.0012 (7)
C2	0.0230 (8)	0.0283 (9)	0.0199 (8)	−0.0015 (7)	−0.0003 (6)	−0.0072 (7)
C3	0.0181 (7)	0.0203 (8)	0.0145 (7)	−0.0012 (6)	0.0040 (6)	−0.0012 (6)
C4	0.0160 (7)	0.0172 (8)	0.0143 (6)	0.0001 (6)	0.0025 (5)	−0.0003 (6)
C5	0.0159 (7)	0.0230 (8)	0.0181 (7)	−0.0009 (7)	0.0020 (6)	0.0008 (6)
C6	0.0212 (8)	0.0338 (11)	0.0251 (8)	0.0082 (8)	0.0006 (7)	−0.0033 (8)
C7	0.0195 (8)	0.0232 (9)	0.0172 (8)	0.0013 (7)	0.0039 (6)	−0.0029 (7)
C8	0.0196 (7)	0.0190 (8)	0.0153 (7)	0.0027 (6)	0.0038 (6)	0.0004 (6)
C9	0.0176 (7)	0.0180 (8)	0.0154 (7)	−0.0010 (6)	0.0035 (5)	0.0012 (6)
C10	0.0214 (8)	0.0166 (8)	0.0181 (7)	−0.0026 (7)	0.0023 (6)	−0.0001 (6)
C11	0.0190 (8)	0.0234 (9)	0.0214 (8)	−0.0053 (7)	0.0030 (6)	0.0011 (7)
C12	0.0143 (7)	0.0260 (9)	0.0156 (7)	−0.0002 (7)	0.0032 (5)	−0.0023 (7)
C13	0.0337 (10)	0.0208 (9)	0.0294 (9)	0.0028 (8)	0.0052 (7)	−0.0049 (7)
C14	0.0244 (9)	0.0423 (12)	0.0212 (8)	0.0052 (8)	0.0077 (7)	−0.0069 (8)
C15	0.0170 (7)	0.0385 (11)	0.0241 (8)	0.0002 (8)	−0.0009 (6)	−0.0013 (8)
C16	0.0197 (8)	0.0268 (9)	0.0211 (8)	−0.0026 (7)	−0.0016 (6)	−0.0030 (7)

Geometric parameters (Å, º)

O1—C1	1.210 (2)	C7—C8	1.564 (2)
O2—C15	1.421 (2)	C8—C12	1.533 (2)
O2—C12	1.4341 (19)	C8—C9	1.539 (2)
O3—C16	1.427 (2)	C8—H8	1.000
O3—C12	1.4329 (17)	C9—H9A	0.990
C1—C2	1.513 (3)	C9—H9B	0.990
C1—C5	1.524 (2)	C10—C11	1.536 (2)
C2—C3	1.533 (2)	C10—H10A	0.990
C2—H2A	0.990	C10—H10B	0.990
C2—H2B	0.990	C11—C12	1.529 (2)
C3—C7	1.568 (2)	C11—H11A	0.990
C3—C4	1.571 (2)	C11—H11B	0.990
C3—H3	1.000	C13—H13A	0.980
C4—C9	1.534 (2)	C13—H13B	0.980
C4—C10	1.536 (2)	C13—H13C	0.980
C4—C5	1.556 (2)	C14—H14A	0.980
C5—C6	1.517 (3)	C14—H14B	0.980
C5—H5	1.000	C14—H14C	0.980
C6—H6A	0.980	C15—C16	1.511 (3)
C6—H6B	0.980	C15—H15A	0.990
C6—H6C	0.980	C15—H15B	0.990
C7—C14	1.538 (2)	C16—H16A	0.990
C7—C13	1.539 (3)	C16—H16B	0.990
C15—O2—C12	109.17 (12)	C4—C9—H9A	112
C16—O3—C12	106.70 (12)	C8—C9—H9A	112
O1—C1—C2	126.49 (16)	C4—C9—H9B	112
O1—C1—C5	125.11 (17)	C8—C9—H9B	112
C2—C1—C5	108.38 (13)	H9A—C9—H9B	109
C1—C2—C3	103.41 (14)	C11—C10—C4	111.55 (14)
C1—C2—H2A	111	C11—C10—H10A	109
C3—C2—H2A	111	C4—C10—H10A	109
C1—C2—H2B	111	C11—C10—H10B	109
C3—C2—H2B	111	C4—C10—H10B	109
H2A—C2—H2B	109	H10A—C10—H10B	108
C2—C3—C7	120.43 (15)	C12—C11—C10	113.40 (13)
C2—C3—C4	106.24 (13)	C12—C11—H11A	109
C7—C3—C4	106.27 (12)	C10—C11—H11A	109
C2—C3—H3	108	C12—C11—H11B	109
C7—C3—H3	108	C10—C11—H11B	109
C4—C3—H3	108	H11A—C11—H11B	108
C9—C4—C10	107.72 (12)	O3—C12—O2	105.46 (12)
C9—C4—C5	114.65 (13)	O3—C12—C11	110.74 (14)
C10—C4—C5	113.99 (14)	O2—C12—C11	109.65 (13)
C9—C4—C3	103.05 (13)	O3—C12—C8	106.26 (12)
C10—C4—C3	110.11 (13)	O2—C12—C8	111.70 (14)
C5—C4—C3	106.73 (12)	C11—C12—C8	112.74 (13)
C6—C5—C1	113.18 (14)	C7—C13—H13A	110
C6—C5—C4	118.35 (15)	C7—C13—H13B	110
C1—C5—C4	104.00 (12)	H13A—C13—H13B	110
C6—C5—H5	107	C7—C13—H13C	110
C1—C5—H5	107	H13A—C13—H13C	110
C4—C5—H5	107	H13B—C13—H13C	110
C5—C6—H6A	110	C7—C14—H14A	110
C5—C6—H6B	110	C7—C14—H14B	110
H6A—C6—H6B	110	H14A—C14—H14B	110
C5—C6—H6C	110	C7—C14—H14C	110
H6A—C6—H6C	110	H14A—C14—H14C	110
H6B—C6—H6C	110	H14B—C14—H14C	110
C14—C7—C13	106.84 (16)	O2—C15—C16	104.55 (13)
C14—C7—C8	115.64 (14)	O2—C15—H15A	111
C13—C7—C8	107.35 (15)	C16—C15—H15A	111
C14—C7—C3	111.19 (15)	O2—C15—H15B	111
C13—C7—C3	112.97 (14)	C16—C15—H15B	111
C8—C7—C3	102.94 (13)	H15A—C15—H15B	109
C12—C8—C9	106.87 (13)	O3—C16—C15	102.54 (13)
C12—C8—C7	117.07 (13)	O3—C16—H16A	111
C9—C8—C7	101.75 (12)	C15—C16—H16A	111
C12—C8—H8	110	O3—C16—H16B	111
C9—C8—H8	110	C15—C16—H16B	111
C7—C8—H8	110	H16A—C16—H16B	109
C4—C9—C8	101.33 (12)
O1—C1—C2—C3	−143.48 (19)	C13—C7—C8—C9	82.17 (16)
C5—C1—C2—C3	34.84 (18)	C3—C7—C8—C9	−37.26 (16)
C1—C2—C3—C7	−147.82 (14)	C10—C4—C9—C8	74.09 (15)
C1—C2—C3—C4	−27.19 (18)	C5—C4—C9—C8	−157.87 (13)
C2—C3—C4—C9	−110.41 (14)	C3—C4—C9—C8	−42.31 (15)
C7—C3—C4—C9	18.98 (16)	C12—C8—C9—C4	−73.32 (14)
C2—C3—C4—C10	134.90 (14)	C7—C8—C9—C4	49.96 (16)
C7—C3—C4—C10	−95.71 (15)	C9—C4—C10—C11	−59.43 (16)
C2—C3—C4—C5	10.70 (18)	C5—C4—C10—C11	172.15 (12)
C7—C3—C4—C5	140.09 (14)	C3—C4—C10—C11	52.25 (16)
O1—C1—C5—C6	20.6 (3)	C4—C10—C11—C12	42.23 (18)
C2—C1—C5—C6	−157.73 (15)	C16—O3—C12—O2	−27.63 (18)
O1—C1—C5—C4	150.35 (18)	C16—O3—C12—C11	90.91 (16)
C2—C1—C5—C4	−27.99 (18)	C16—O3—C12—C8	−146.34 (13)
C9—C4—C5—C6	−110.04 (17)	C15—O2—C12—O3	8.7 (2)
C10—C4—C5—C6	14.8 (2)	C15—O2—C12—C11	−110.60 (16)
C3—C4—C5—C6	136.55 (15)	C15—O2—C12—C8	123.68 (16)
C9—C4—C5—C1	123.41 (15)	C10—C11—C12—O3	76.22 (17)
C10—C4—C5—C1	−111.78 (15)	C10—C11—C12—O2	−167.81 (13)
C3—C4—C5—C1	9.99 (18)	C10—C11—C12—C8	−42.68 (19)
C2—C3—C7—C14	−103.72 (18)	C9—C8—C12—O3	−62.21 (15)
C4—C3—C7—C14	135.66 (14)	C7—C8—C12—O3	−175.41 (13)
C2—C3—C7—C13	16.4 (2)	C9—C8—C12—O2	−176.73 (12)
C4—C3—C7—C13	−104.21 (16)	C7—C8—C12—O2	70.07 (18)
C2—C3—C7—C8	131.86 (15)	C9—C8—C12—C11	59.27 (16)
C4—C3—C7—C8	11.24 (16)	C7—C8—C12—C11	−53.93 (19)
C14—C7—C8—C12	−42.7 (2)	C12—O2—C15—C16	12.3 (2)
C13—C7—C8—C12	−161.78 (14)	C12—O3—C16—C15	34.46 (18)
C3—C7—C8—C12	78.79 (16)	O2—C15—C16—O3	−28.40 (19)
C14—C7—C8—C9	−158.70 (16)