Ethyl (4aR*,7S*,8S*,8aS*)-1-oxo-7-phenyl-3,4,4a,7,8,8a-hexa­hydro-1H-isochromene-8-carboxyl­ate

Abstract

In the title compound, C₁₈H₂₀O₄, both the tetra­hydro­pyran­one ring and the cyclo­hexene ring adopt envelope conformations. The crystal packing is stabilized by weak inter­molecular C—H⋯O hydrogen bonding.

Related literature

The title compound is a derivative of 1-oxo-hexa­hydro-1H-isochromene, which has been reported as a key inter­mediate towards the total syntheses of natural products such as eleutherobin and tetronothio­din, see: Kim et al. (2000 ▶); Jung et al. (2000 ▶); Page et al. (2003 ▶). For microwave-assisted intra­molecular Diels–Alder cyclo­addition, see: Wu et al. (2006 ▶, 2007 ▶); Wang et al. (2009 ▶).

Experimental

Crystal data

• C₁₈H₂₀O₄

• M _r = 300.34

• Orthorhombic,

• a = 15.5513 (12) Å

• b = 9.9178 (7) Å

• c = 21.1542 (17) Å

• V = 3262.7 (4) ų

• Z = 8

• Mo Kα radiation

• μ = 0.09 mm⁻¹

• T = 296 K

• 0.36 × 0.16 × 0.14 mm

Data collection

• Rigaku R-AXIS RAPID IP diffractometer

• 26140 measured reflections

• 3200 independent reflections

• 1627 reflections with I > 2σ(I)

• R _int = 0.075

Refinement

• R[F ² > 2σ(F ²)] = 0.069

• wR(F ²) = 0.197

• S = 1.00

• 3200 reflections

• 202 parameters

• 1 restraint

• H-atom parameters constrained

• Δρ_max = 0.35 e Å⁻³

• Δρ_min = −0.28 e Å⁻³

Data collection: PROCESS-AUTO (Rigaku, 1998 ▶); cell refinement: PROCESS-AUTO; data reduction: CrystalStructure (Rigaku/MSC, 2002 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

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⋯O4i	0.98	2.45	3.401 (4)	164
C5—H5A⋯O4i	0.97	2.48	3.412 (4)	161
C7—H7⋯O1ii	0.93	2.56	3.468 (5)	165
C13—H13⋯O2iii	0.93	2.59	3.356 (6)	140

Symmetry codes: (i) ; (ii) ; (iii) .

supplementary crystallographic information

Comment

The title compound, C₁₈H₂₀O₄, refers to the derivative of 1-oxo- hexahydro-1H-isochromenes, which has been reported as a key intermediate towards total syntheses of natural products such as eleutherobin (Kim et al., 2000; Jung et al., 2000) and tetronothiodin (Page et al., 2003). The title compound has recently been obtained during microwave-assisted intramolecular Diels-Alder cycloaddition along with a minor diastereomer with a 74:26 diastereomeric ratio (Wu et al., 2006, 2007; Wang et al., 2009). The compound has four stereogenic centers but crystallizes as a racemate as indicated by the centrosymmetric space group. We report here its crystal structure.

In the molecular structure of the title compound (Fig. 1), there are one pyranone ring and one cyclohexene ring. Both of the two rings C1-C2/C6-C9 and C2-C3/O2/C4-C6 adopt envelope conformation. The crystal packing is stabilized by weak non-classical intermolecular C—H···O hydrogen bonds (Table 1).

Experimental

A 10 mL pressured process vial was charged ethyl (3E,5E)-6-phenylhexa-3,5-dien-1-yl fumarate (172.0 mg, 0.57 mmol) followed by adding MeCN (4 mL). The loaded vial was then sealed with a cap containing a silicon septum and put into the cavity of a technical microwave reactor with the temperature measured by an IR sensor. After heating at 453 K for 1 h, the reaction mixture was concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, 20% EtOAc in petroleum ether) to furnish the title compound (95.0 mg, 52%), along with a minor diastereomer (32.0 mg, 19%), as colorless needles. mp 392-394 K (EtOAc-hexane). Single crystals, as a racemate, suitable for X-ray diffraction of the title compound were grown at ambient temperature in the mixed solvent of ethyl acetate and hexane (v:v = 10:1).

Refinement

H atoms were placed in calculated positions with C—H = 0.93-0.98 Å, and refined in riding model with U_iso(H) = 1.5U_eq(C) for methyl and 1.2U_eq(C) for the others.

Figures

Fig. 1.

The molecular structure of the title compound with the atom numbering scheme. Displacement ellipsoids are drawn at 40% probability level. H atoms are presented as a small spheres of arbitrary radius.

Crystal data

C18H20O4	F(000) = 1280
Mr = 300.34	Dx = 1.223 Mg m−3
Orthorhombic, Pbca	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 12675 reflections
a = 15.5513 (12) Å	θ = 3.1–27.4°
b = 9.9178 (7) Å	µ = 0.09 mm−1
c = 21.1542 (17) Å	T = 296 K
V = 3262.7 (4) Å3	Needle, colorless
Z = 8	0.36 × 0.16 × 0.14 mm

Data collection

Rigaku R-AXIS RAPID IP diffractometer	1627 reflections with I > 2σ(I)
Radiation source: rolling anode	Rint = 0.075
graphite	θmax = 26.0°, θmin = 3.1°
Detector resolution: 10.00 pixels mm-1	h = −19→19
ω scans	k = −11→12
26140 measured reflections	l = −26→26
3200 independent reflections

Refinement

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.069	H-atom parameters constrained
wR(F2) = 0.197	w = 1/[σ2(Fo2) + (0.0698P)2 + 1.9409P] where P = (Fo2 + 2Fc2)/3
S = 1.00	(Δ/σ)max < 0.001
3200 reflections	Δρmax = 0.35 e Å−3
202 parameters	Δρmin = −0.28 e Å−3
1 restraint	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0067 (12)

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
O3	0.16345 (14)	0.3940 (2)	0.39009 (15)	0.1040 (10)
C17	0.0706 (3)	0.3651 (6)	0.3998 (3)	0.146 (2)
H17A	0.0524	0.2860	0.3764	0.175*
H17B	0.0350	0.4414	0.3880	0.175*
C18	0.0687 (4)	0.3407 (8)	0.4701 (3)	0.205 (3)
H18A	0.0993	0.2591	0.4796	0.308*
H18B	0.0102	0.3325	0.4839	0.308*
H18C	0.0955	0.4150	0.4915	0.308*
O4	0.18555 (14)	0.1796 (2)	0.36346 (12)	0.0848 (8)
C1	0.30154 (17)	0.3380 (3)	0.35293 (14)	0.0588 (8)
H1	0.3083	0.4330	0.3645	0.071*
C9	0.36348 (18)	0.2519 (3)	0.39280 (14)	0.0642 (8)
H9	0.3484	0.1571	0.3860	0.077*
C16	0.21088 (19)	0.2931 (3)	0.36799 (15)	0.0660 (8)
C10	0.35139 (19)	0.2824 (3)	0.46291 (15)	0.0680 (8)
C8	0.4540 (2)	0.2708 (3)	0.37126 (18)	0.0765 (9)
H8	0.4978	0.2486	0.3993	0.092*
O2	0.27531 (18)	0.5007 (3)	0.20646 (13)	0.1045 (9)
C2	0.32050 (19)	0.3207 (3)	0.28126 (15)	0.0704 (9)
H2	0.3127	0.2249	0.2714	0.084*
C5	0.4213 (2)	0.5048 (4)	0.24889 (18)	0.0856 (10)
H5A	0.4050	0.5586	0.2853	0.103*
H5B	0.4803	0.5264	0.2381	0.103*
C7	0.4757 (2)	0.3170 (4)	0.31524 (19)	0.0837 (11)
H7	0.5340	0.3258	0.3065	0.100*
C6	0.4140 (2)	0.3561 (3)	0.26494 (16)	0.0730 (9)
H6	0.4293	0.3053	0.2268	0.088*
C15	0.3062 (2)	0.1947 (4)	0.50117 (18)	0.0838 (10)
H15	0.2835	0.1159	0.4842	0.101*
C3	0.2542 (3)	0.3978 (4)	0.24313 (18)	0.0886 (11)
O1	0.17953 (19)	0.3714 (4)	0.24613 (17)	0.1447 (14)
C11	0.3852 (2)	0.3990 (4)	0.48850 (19)	0.0886 (11)
H11	0.4150	0.4592	0.4629	0.106*
C14	0.2948 (3)	0.2231 (6)	0.5638 (2)	0.1138 (14)
H14	0.2636	0.1641	0.5891	0.137*
C13	0.3294 (4)	0.3388 (7)	0.5899 (2)	0.1200 (16)
H13	0.3222	0.3572	0.6326	0.144*
C4	0.3635 (3)	0.5372 (5)	0.1941 (2)	0.1098 (14)
H4A	0.3666	0.6330	0.1853	0.132*
H4B	0.3835	0.4893	0.1570	0.132*
C12	0.3746 (3)	0.4264 (5)	0.5521 (2)	0.1144 (15)
H12	0.3982	0.5043	0.5693	0.137*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O3	0.0557 (13)	0.0768 (15)	0.179 (3)	−0.0037 (11)	0.0323 (15)	−0.0228 (16)
C17	0.095 (3)	0.127 (4)	0.216 (7)	−0.015 (3)	0.045 (4)	−0.020 (4)
C18	0.146 (6)	0.258 (8)	0.211 (8)	−0.069 (5)	0.052 (5)	0.007 (7)
O4	0.0728 (15)	0.0589 (13)	0.123 (2)	−0.0162 (11)	−0.0052 (13)	−0.0008 (12)
C1	0.0494 (15)	0.0527 (15)	0.074 (2)	−0.0019 (13)	0.0044 (14)	−0.0056 (14)
C9	0.0597 (17)	0.0526 (15)	0.080 (2)	0.0045 (14)	0.0024 (16)	−0.0035 (15)
C16	0.0563 (17)	0.0572 (17)	0.084 (2)	−0.0022 (14)	−0.0007 (16)	0.0004 (16)
C10	0.0599 (18)	0.0660 (19)	0.078 (2)	0.0079 (15)	−0.0042 (16)	−0.0010 (17)
C8	0.0546 (18)	0.079 (2)	0.096 (3)	0.0106 (16)	0.0022 (18)	−0.0019 (19)
O2	0.095 (2)	0.116 (2)	0.103 (2)	−0.0024 (16)	−0.0076 (15)	0.0319 (17)
C2	0.068 (2)	0.0661 (18)	0.077 (2)	−0.0033 (16)	0.0021 (16)	−0.0063 (16)
C5	0.077 (2)	0.083 (2)	0.096 (3)	−0.0076 (19)	0.018 (2)	−0.002 (2)
C7	0.0534 (19)	0.091 (2)	0.106 (3)	0.0064 (17)	0.0163 (19)	−0.010 (2)
C6	0.068 (2)	0.074 (2)	0.077 (2)	0.0017 (16)	0.0155 (17)	−0.0103 (17)
C15	0.081 (2)	0.092 (2)	0.078 (2)	0.003 (2)	0.0015 (19)	0.011 (2)
C3	0.078 (2)	0.106 (3)	0.083 (2)	−0.007 (2)	−0.010 (2)	0.010 (2)
O1	0.0751 (19)	0.195 (3)	0.164 (3)	−0.024 (2)	−0.0326 (19)	0.072 (3)
C11	0.096 (3)	0.078 (2)	0.092 (3)	−0.001 (2)	−0.003 (2)	−0.015 (2)
C14	0.111 (3)	0.133 (4)	0.098 (4)	0.009 (3)	0.005 (3)	0.022 (3)
C13	0.127 (4)	0.155 (5)	0.078 (3)	0.037 (4)	0.003 (3)	−0.012 (3)
C4	0.099 (3)	0.111 (3)	0.119 (3)	−0.008 (3)	0.014 (3)	0.028 (3)
C12	0.128 (4)	0.109 (3)	0.106 (4)	0.014 (3)	−0.015 (3)	−0.031 (3)

Geometric parameters (Å, °)

O3—C16	1.327 (4)	C2—C3	1.516 (5)
O3—C17	1.486 (5)	C2—C6	1.535 (4)
C17—C18	1.507 (8)	C2—H2	0.9800
C17—H17A	0.9700	C5—C4	1.501 (5)
C17—H17B	0.9700	C5—C6	1.518 (5)
C18—H18A	0.9600	C5—H5A	0.9700
C18—H18B	0.9600	C5—H5B	0.9700
C18—H18C	0.9600	C7—C6	1.485 (5)
O4—C16	1.197 (3)	C7—H7	0.9300
C1—C16	1.512 (4)	C6—H6	0.9800
C1—C9	1.539 (4)	C15—C14	1.367 (6)
C1—C2	1.554 (4)	C15—H15	0.9300
C1—H1	0.9800	C3—O1	1.192 (4)
C9—C8	1.491 (4)	C11—C12	1.382 (6)
C9—C10	1.525 (4)	C11—H11	0.9300
C9—H9	0.9800	C14—C13	1.382 (7)
C10—C15	1.379 (5)	C14—H14	0.9300
C10—C11	1.381 (4)	C13—C12	1.374 (6)
C8—C7	1.314 (4)	C13—H13	0.9300
C8—H8	0.9300	C4—H4A	0.9700
O2—C3	1.323 (4)	C4—H4B	0.9700
O2—C4	1.442 (5)	C12—H12	0.9300
C16—O3—C17	116.3 (3)	C1—C2—H2	106.9
O3—C17—C18	100.7 (4)	C4—C5—C6	109.6 (3)
O3—C17—H17A	111.6	C4—C5—H5A	109.7
C18—C17—H17A	111.6	C6—C5—H5A	109.7
O3—C17—H17B	111.6	C4—C5—H5B	109.7
C18—C17—H17B	111.6	C6—C5—H5B	109.7
H17A—C17—H17B	109.4	H5A—C5—H5B	108.2
C17—C18—H18A	109.5	C8—C7—C6	124.8 (3)
C17—C18—H18B	109.5	C8—C7—H7	117.6
H18A—C18—H18B	109.5	C6—C7—H7	117.6
C17—C18—H18C	109.5	C7—C6—C5	111.5 (3)
H18A—C18—H18C	109.5	C7—C6—C2	113.0 (3)
H18B—C18—H18C	109.5	C5—C6—C2	110.1 (3)
C16—C1—C9	107.8 (2)	C7—C6—H6	107.3
C16—C1—C2	110.5 (2)	C5—C6—H6	107.3
C9—C1—C2	110.8 (2)	C2—C6—H6	107.3
C16—C1—H1	109.3	C14—C15—C10	120.4 (4)
C9—C1—H1	109.3	C14—C15—H15	119.8
C2—C1—H1	109.3	C10—C15—H15	119.8
C8—C9—C10	112.9 (3)	O1—C3—O2	116.3 (4)
C8—C9—C1	110.7 (3)	O1—C3—C2	121.5 (4)
C10—C9—C1	110.2 (2)	O2—C3—C2	122.2 (3)
C8—C9—H9	107.6	C10—C11—C12	120.0 (4)
C10—C9—H9	107.6	C10—C11—H11	120.0
C1—C9—H9	107.6	C12—C11—H11	120.0
O4—C16—O3	123.6 (3)	C15—C14—C13	120.5 (5)
O4—C16—C1	124.5 (3)	C15—C14—H14	119.8
O3—C16—C1	111.8 (2)	C13—C14—H14	119.8
C15—C10—C11	119.4 (3)	C12—C13—C14	119.5 (4)
C15—C10—C9	120.6 (3)	C12—C13—H13	120.3
C11—C10—C9	120.0 (3)	C14—C13—H13	120.3
C7—C8—C9	124.2 (3)	O2—C4—C5	112.1 (3)
C7—C8—H8	117.9	O2—C4—H4A	109.2
C9—C8—H8	117.9	C5—C4—H4A	109.2
C3—O2—C4	122.4 (3)	O2—C4—H4B	109.2
C3—C2—C6	114.1 (3)	C5—C4—H4B	109.2
C3—C2—C1	109.5 (3)	H4A—C4—H4B	107.9
C6—C2—C1	112.0 (2)	C13—C12—C11	120.2 (4)
C3—C2—H2	106.9	C13—C12—H12	119.9
C6—C2—H2	106.9	C11—C12—H12	119.9
C16—O3—C17—C18	100.1 (5)	C8—C7—C6—C2	−7.3 (5)
C16—C1—C9—C8	168.7 (2)	C4—C5—C6—C7	175.1 (3)
C2—C1—C9—C8	47.7 (3)	C4—C5—C6—C2	−58.7 (4)
C16—C1—C9—C10	−65.7 (3)	C3—C2—C6—C7	160.7 (3)
C2—C1—C9—C10	173.3 (2)	C1—C2—C6—C7	35.6 (4)
C17—O3—C16—O4	−9.7 (6)	C3—C2—C6—C5	35.4 (4)
C17—O3—C16—C1	173.5 (3)	C1—C2—C6—C5	−89.8 (3)
C9—C1—C16—O4	−55.5 (4)	C11—C10—C15—C14	0.1 (5)
C2—C1—C16—O4	65.7 (4)	C9—C10—C15—C14	−179.3 (3)
C9—C1—C16—O3	121.3 (3)	C4—O2—C3—O1	−174.7 (4)
C2—C1—C16—O3	−117.5 (3)	C4—O2—C3—C2	7.5 (6)
C8—C9—C10—C15	−133.0 (3)	C6—C2—C3—O1	172.4 (4)
C1—C9—C10—C15	102.6 (3)	C1—C2—C3—O1	−61.2 (5)
C8—C9—C10—C11	47.5 (4)	C6—C2—C3—O2	−9.9 (5)
C1—C9—C10—C11	−76.9 (4)	C1—C2—C3—O2	116.5 (4)
C10—C9—C8—C7	−144.6 (3)	C15—C10—C11—C12	0.9 (5)
C1—C9—C8—C7	−20.5 (4)	C9—C10—C11—C12	−179.7 (3)
C16—C1—C2—C3	56.2 (3)	C10—C15—C14—C13	−1.0 (6)
C9—C1—C2—C3	175.6 (3)	C15—C14—C13—C12	0.8 (7)
C16—C1—C2—C6	−176.1 (2)	C3—O2—C4—C5	−31.0 (5)
C9—C1—C2—C6	−56.7 (3)	C6—C5—C4—O2	56.5 (4)
C9—C8—C7—C6	−0.5 (6)	C14—C13—C12—C11	0.2 (7)
C8—C7—C6—C5	117.3 (4)	C10—C11—C12—C13	−1.0 (6)

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1···O4i	0.98	2.45	3.401 (4)	164
C5—H5A···O4i	0.97	2.48	3.412 (4)	161
C7—H7···O1ii	0.93	2.56	3.468 (5)	165
C13—H13···O2iii	0.93	2.59	3.356 (6)	140

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