6-[4-(tert-Butyl­dimethyl­sil­yloxy)phen­yl]-1-oxa­spiro­[2.5]hepta­ne

Wetzel, E.A.; Lindeman, S.; Donaldson, W.A.

doi:10.1107/S241431462400590X

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 9| Part 6| June 2024| x240590

https://doi.org/10.1107/S241431462400590X

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6-[4-(tert-Butyldimethylsilyloxy)phenyl]-1-oxaspiro[2.5]heptane

Edward A. Wetzel,^a Sergey Lindeman ^a and William A. Donaldson ^a ^*

^aDepartment of Chemistry, Marquette University, P. O. Box 1881, Milwaukee, WI 53201-1881, USA
^*Correspondence e-mail: william.donaldson@marquette.edu

Edited by W. T. A. Harrison, University of Aberdeen, United Kingdom (Received 11 June 2024; accepted 17 June 2024; online 21 June 2024)

The title compound, C₁₉H₃₀O₂Si, has triclinic (P $[\overline{1}]$ ) symmetry at 100 K. The O atom of the epoxide group has a pseudoaxial orientation and the dihedral angle between the cyclohexyl and benzene rings is 85.80 (8)°. The C—O—Si—C_t (t = tert-butyl) torsion angle is −177.40 (14)°. In the crystal, pairwise C—H⋯O links connect the molecules into inversion dimers featuring R²₂(8) loops.

Keywords: crystal structure; organic; spiroepoxide.

CCDC reference: 2363391

Structure description

Fumagillin and ovalicin, isolated from Aspergillus fumigatus and Pseudorotium ovalis, respectively, are sesquiterpene epoxides that exhibit anti-angiogenic activity. The key structural feature of both is a 1-oxospiro[2.5]heptane moiety. The structure of fumagillin was initially deduced by X-ray crystallographic analysis of its hydrolysis product fumagillol (McCorkindale & Sime, 1961 ) and the X-ray crystal structure of fumagillin was eventually reported (Halasz et al., 2000 $[Halász, J., Podányi, B., Vasvári-Debreczy, L., Szabó, A., Hajdú, F., Böcskei, Z., Hegedűs-Vajda, J., Győrb\?író, A. & Hermecz, I. (2000). Tetrahedron, 56, 10081-10085.]$ ). Preparation of the 1-oxospiro[2.5]heptane system by reaction of dimethylsulfoxonium methylide with substituted cyclohexanones generally proceeds with the formation of the exocyclic epoxide in which the oxygen atom has an axial orientation (Corey & Chaykovsky, 1965 ; Carlson & Behn, 1967 ). In connection with our studies on estrogen receptor beta-selective agonists (Hanson et al., 2018 ; Wetzel et al., 2022 ), we had the opportunity to prepare the title compound, C₁₉H₃₀O₂Si, and we now present its synthesis and crystal structure.

The title compound (Fig. 1) has an extended conformation with a transoid t-Bu—Si—O—Ar moiety. The cyclohexane ring has a chair conformation with the aryl substituent in an equatorial position and the epoxide oxygen atom in a pseudoaxial orientation. The C7—O1—Si1—C3 torsion angle is −177.40 (14)°. In the crystal, a weak C—H⋯O link (Fig. 2, Table 1) connects the molecules into inversion dimers featuring $[R_{2}^{2}]$ (8) loops.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C15—H15A⋯O2ⁱ	0.99	2.54	3.487 (2)	159
Symmetry code: (i) .

Figure 1
The molecular structure of the title compound showing 50% displacement ellipsoids.

Figure 2
Unit-cell packing of the title compound.

Synthesis and crystallization

The reaction scheme is shown in Fig. 3. To a solution of potassium tert-butoxide (2.317 g, 20.65 mmol) in dimethylsulfoxide (DMSO) (10 ml) was added trimethylsulfoxonium iodide (5.00 g, 22.72 mmol). The solution was stirred for 30 min, and then a solution of 4-[(4-t-butyldimethylsilyloxy)phenyl]cyclohexanone (6.288 g, 20.65 mmol) in DMSO (50 ml) was added dropwise. The mixture was stirred for 24 h, and then partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO₄), and concentrated. Upon standing at room temperature overnight, colorless crystals formed. The crystals were filtered off to afford the title compound (5.262 g, 80%). Recrystallization from the mixed solvents of ethyl acetate/hexanes gave colorless flat prisms. ¹H NMR (400 MHz, CDCl₃) δ 7.08 (d, J = 8.0 Hz, 2H), 6.76 (d, J = 8.0 Hz, 2H), 2.68 (s, 2H), 2.54 (t, J = 8.2 Hz, 1H), 2.10–1.97 (m, 2H), 1.92–1.74 (m, 4H), 1.35 (d, J = Hz, 2H), 0.97 (s, 9H), 0.18 (s, 6H); ¹³C NMR (100 MHz, CDCl₃) δ 153.7, 139.3, 127.6, 119.8, 57.9, 53.9, 42.4, 33.2, 31.7, 25.6, 18.1, −4.4 p.p.m..

Figure 3
Reaction scheme.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₉H₃₀O₂Si
M_r	318.52
Crystal system, space group	Triclinic, P $[\overline{1}]$
Temperature (K)	100
a, b, c (Å)	7.3673 (3), 11.2285 (4), 12.5778 (5)
α, β, γ (°)	104.974 (4), 101.964 (4), 103.460 (4)
V (Å³)	937.09 (7)
Z	2
Radiation type	Cu Kα
μ (mm⁻¹)	1.13
Crystal size (mm)	0.74 × 0.43 × 0.07

Data collection
Diffractometer	Rigaku Oxford Diffraction SuperNova, Dual, Cu at home/near, Atlas
Absorption correction	Gaussian (CrysAlis PRO; Rigaku OD, 2018 $[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ )
T_min, T_max	0.184, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	16772, 3539, 3276
R_int	0.046
(sin θ/λ)_max (Å⁻¹)	0.612

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.046, 0.131, 1.10
No. of reflections	3539
No. of parameters	212
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.70, −0.35
Computer programs: CrysAlis PRO (Rigaku OD, 2018 $[Rigaku OD (2018). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ ), OLEX2.solve (Bourhis et al., 2015 ), SHELXL (Sheldrick, 2015 ), and OLEX2 (Dolomanov et al., 2009 ).

Structural data

CCDC reference: 2363391

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S241431462400590X/hb4478sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S241431462400590X/hb4478Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S241431462400590X/hb4478Isup3.cml

checkCIF report

Computing details top

6-[4-(tert-Butyldimethylsilyloxy)phenyl]-1-oxaspiro[2.5]heptane top

Crystal data top

C₁₉H₃₀O₂Si	Z = 2
M_r = 318.52	F(000) = 348
Triclinic, P1	D_x = 1.129 Mg m⁻³
a = 7.3673 (3) Å	Cu Kα radiation, λ = 1.54184 Å
b = 11.2285 (4) Å	Cell parameters from 9134 reflections
c = 12.5778 (5) Å	θ = 4.3–70.5°
α = 104.974 (4)°	µ = 1.13 mm⁻¹
β = 101.964 (4)°	T = 100 K
γ = 103.460 (4)°	Plate, colourless
V = 937.09 (7) Å³	0.74 × 0.43 × 0.07 mm

Data collection top

Rigaku Oxford Diffraction SuperNova, Dual, Cu at home/near, Atlas diffractometer	3539 independent reflections
Radiation source: micro-focus sealed X-ray tube, SuperNova (Cu) X-ray Source	3276 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.046
Detector resolution: 10.3756 pixels mm^-1	θ_max = 70.6°, θ_min = 3.8°
ω scans	h = −8→8
Absorption correction: gaussian (CrysAlisPro; Rigaku OD, 2018)	k = −13→13
T_min = 0.184, T_max = 1.000	l = −15→15
16772 measured reflections

Refinement top

Refinement on F²	Primary atom site location: iterative
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.046	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.131	w = 1/[σ²(F_o²) + (0.0862P)² + 0.2247P] where P = (F_o² + 2F_c²)/3
S = 1.10	(Δ/σ)_max < 0.001
3539 reflections	Δρ_max = 0.70 e Å⁻³
212 parameters	Δρ_min = −0.35 e Å⁻³
0 restraints

Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
Si1	0.40119 (5)	0.19395 (4)	0.24021 (3)	0.01921 (16)
O1	0.47620 (15)	0.22061 (11)	0.38036 (9)	0.0263 (3)
O2	1.64517 (17)	0.47505 (10)	0.88309 (10)	0.0292 (3)
C1	0.3887 (3)	0.02593 (17)	0.16096 (17)	0.0356 (4)
H1A	0.518022	0.014659	0.180830	0.053*
H1B	0.344470	0.010513	0.078168	0.053*
H1C	0.296937	−0.035756	0.182195	0.053*
C2	0.5762 (2)	0.31022 (18)	0.20005 (16)	0.0315 (4)
H2A	0.556202	0.395409	0.222952	0.047*
H2B	0.555172	0.279906	0.116802	0.047*
H2C	0.709501	0.316690	0.239220	0.047*
C3	0.1549 (2)	0.21993 (14)	0.21951 (13)	0.0220 (3)
C4	0.1760 (2)	0.35451 (16)	0.29980 (15)	0.0290 (4)
H4A	0.228450	0.359582	0.379644	0.044*
H4B	0.048251	0.368942	0.289519	0.044*
H4C	0.264834	0.420774	0.281404	0.044*
C5	0.0722 (2)	0.21241 (16)	0.09442 (15)	0.0287 (4)
H5A	0.156028	0.282682	0.077753	0.043*
H5B	−0.059390	0.220714	0.083054	0.043*
H5C	0.067239	0.129025	0.042720	0.043*
C6	0.0151 (2)	0.11714 (17)	0.24914 (17)	0.0327 (4)
H6A	0.000713	0.030972	0.198313	0.049*
H6B	−0.112221	0.132184	0.238917	0.049*
H6C	0.067749	0.122664	0.329095	0.049*
C7	0.6508 (2)	0.21980 (15)	0.44469 (12)	0.0208 (3)
C8	0.8018 (2)	0.33469 (14)	0.50020 (13)	0.0237 (3)
H8	0.788337	0.412995	0.488878	0.028*
C9	0.9723 (2)	0.33456 (14)	0.57228 (13)	0.0226 (3)
H9	1.075023	0.413377	0.609708	0.027*
C10	0.9962 (2)	0.22092 (14)	0.59095 (12)	0.0196 (3)
C11	0.8430 (2)	0.10703 (14)	0.53377 (13)	0.0212 (3)
H11	0.855594	0.028445	0.544784	0.025*
C12	0.6725 (2)	0.10593 (14)	0.46116 (13)	0.0222 (3)
H12	0.570384	0.027005	0.422645	0.027*
C13	1.1790 (2)	0.22081 (13)	0.67256 (12)	0.0200 (3)
H13	1.167369	0.128847	0.667431	0.024*
C14	1.1985 (2)	0.29503 (15)	0.79754 (13)	0.0228 (3)
H14A	1.206850	0.386201	0.804842	0.027*
H14B	1.080957	0.256789	0.818228	0.027*
C15	1.3792 (2)	0.29093 (15)	0.88093 (13)	0.0230 (3)
H15A	1.394933	0.347476	0.959145	0.028*
H15B	1.361595	0.201524	0.883051	0.028*
C16	1.5596 (2)	0.33507 (13)	0.84517 (13)	0.0214 (3)
C17	1.5456 (2)	0.26890 (15)	0.72234 (13)	0.0232 (3)
H17A	1.539907	0.177436	0.711453	0.028*
H17B	1.663369	0.311268	0.703953	0.028*
C18	1.3644 (2)	0.27461 (14)	0.64068 (13)	0.0225 (3)
H18A	1.352443	0.223818	0.561100	0.027*
H18B	1.378788	0.365426	0.643765	0.027*
C19	1.7490 (2)	0.39772 (16)	0.93104 (15)	0.0285 (4)
H19A	1.865 (3)	0.394 (2)	0.9095 (18)	0.031 (5)*
H19B	1.758 (3)	0.4120 (18)	1.0091 (18)	0.024 (4)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Si1	0.0177 (2)	0.0210 (2)	0.0203 (3)	0.00703 (16)	0.00510 (16)	0.00808 (17)
O1	0.0212 (5)	0.0382 (6)	0.0223 (6)	0.0115 (5)	0.0069 (4)	0.0116 (5)
O2	0.0337 (6)	0.0184 (5)	0.0308 (6)	0.0041 (4)	0.0067 (5)	0.0055 (4)
C1	0.0330 (9)	0.0308 (9)	0.0370 (10)	0.0150 (7)	0.0022 (7)	0.0023 (7)
C2	0.0219 (8)	0.0424 (9)	0.0390 (10)	0.0118 (7)	0.0103 (7)	0.0245 (8)
C3	0.0176 (7)	0.0226 (7)	0.0274 (8)	0.0061 (5)	0.0066 (6)	0.0105 (6)
C4	0.0250 (8)	0.0288 (8)	0.0356 (9)	0.0123 (6)	0.0108 (7)	0.0089 (7)
C5	0.0227 (8)	0.0300 (8)	0.0316 (9)	0.0079 (6)	0.0020 (6)	0.0114 (7)
C6	0.0223 (8)	0.0334 (9)	0.0483 (11)	0.0068 (6)	0.0133 (7)	0.0220 (8)
C7	0.0196 (7)	0.0285 (7)	0.0164 (7)	0.0093 (6)	0.0062 (5)	0.0082 (6)
C8	0.0279 (8)	0.0219 (7)	0.0247 (8)	0.0096 (6)	0.0083 (6)	0.0105 (6)
C9	0.0226 (7)	0.0199 (7)	0.0234 (8)	0.0034 (5)	0.0053 (6)	0.0072 (6)
C10	0.0213 (7)	0.0212 (7)	0.0179 (7)	0.0072 (5)	0.0082 (6)	0.0064 (6)
C11	0.0242 (7)	0.0186 (7)	0.0226 (7)	0.0071 (5)	0.0089 (6)	0.0072 (6)
C12	0.0217 (7)	0.0220 (7)	0.0201 (7)	0.0032 (5)	0.0070 (6)	0.0043 (6)
C13	0.0211 (7)	0.0194 (7)	0.0206 (7)	0.0069 (5)	0.0066 (6)	0.0071 (6)
C14	0.0231 (7)	0.0267 (7)	0.0216 (8)	0.0092 (6)	0.0090 (6)	0.0090 (6)
C15	0.0252 (8)	0.0254 (7)	0.0200 (7)	0.0082 (6)	0.0072 (6)	0.0088 (6)
C16	0.0237 (7)	0.0183 (7)	0.0225 (8)	0.0072 (5)	0.0053 (6)	0.0073 (6)
C17	0.0209 (7)	0.0249 (7)	0.0230 (8)	0.0072 (6)	0.0073 (6)	0.0054 (6)
C18	0.0219 (7)	0.0270 (7)	0.0183 (7)	0.0065 (6)	0.0075 (6)	0.0063 (6)
C19	0.0250 (8)	0.0306 (8)	0.0254 (9)	0.0058 (6)	0.0040 (6)	0.0068 (7)

Geometric parameters (Å, º) top

Si1—O1	1.6580 (11)	C8—C9	1.389 (2)
Si1—C1	1.8629 (17)	C9—C10	1.399 (2)
Si1—C2	1.8570 (16)	C10—C11	1.394 (2)
Si1—C3	1.8804 (15)	C10—C13	1.515 (2)
O1—C7	1.3735 (18)	C11—C12	1.387 (2)
O2—C16	1.4567 (17)	C13—C14	1.536 (2)
O2—C19	1.446 (2)	C13—C18	1.536 (2)
C3—C4	1.538 (2)	C14—C15	1.533 (2)
C3—C5	1.537 (2)	C15—C16	1.507 (2)
C3—C6	1.536 (2)	C16—C17	1.502 (2)
C7—C8	1.391 (2)	C16—C19	1.461 (2)
C7—C12	1.386 (2)	C17—C18	1.532 (2)

O1—Si1—C1	109.67 (8)	C9—C10—C13	121.75 (13)
O1—Si1—C2	109.22 (7)	C11—C10—C9	117.59 (14)
O1—Si1—C3	103.07 (6)	C11—C10—C13	120.64 (13)
C1—Si1—C3	112.59 (8)	C12—C11—C10	121.44 (14)
C2—Si1—C1	109.20 (9)	C7—C12—C11	120.11 (14)
C2—Si1—C3	112.88 (7)	C10—C13—C14	111.57 (12)
C7—O1—Si1	128.73 (9)	C10—C13—C18	112.72 (12)
C19—O2—C16	60.42 (10)	C18—C13—C14	110.02 (12)
C4—C3—Si1	108.90 (10)	C15—C14—C13	111.77 (12)
C5—C3—Si1	109.90 (10)	C16—C15—C14	111.09 (12)
C5—C3—C4	109.25 (13)	O2—C16—C15	113.99 (12)
C6—C3—Si1	110.17 (10)	O2—C16—C17	114.06 (12)
C6—C3—C4	108.91 (13)	O2—C16—C19	59.43 (10)
C6—C3—C5	109.69 (13)	C17—C16—C15	115.08 (12)
O1—C7—C8	120.15 (13)	C19—C16—C15	120.42 (14)
O1—C7—C12	120.07 (13)	C19—C16—C17	120.66 (13)
C12—C7—C8	119.63 (14)	C16—C17—C18	111.04 (12)
C9—C8—C7	119.77 (14)	C17—C18—C13	111.41 (12)
C8—C9—C10	121.45 (14)	O2—C19—C16	60.15 (10)

O1—Si1—C3—C4	54.6 (1)	C8—C7—C12—C11	0.8 (2)
O1—Si1—C3—C5	174.2 (1)	C7—C12—C11—C10	−0.5 (2)
O1—Si1—C3—C6	−64.8 (1)	C9—C10—C13—C14	66.7 (2)
O1—C7—C8—C9	175.0 (1)	C9—C10—C13—C18	−57.7 (2)
O1—C7—C12—C11	−174.6 (1)	C11—C10—C13—C14	−111.7 (2)
C1—Si1—C3—C4	172.7 (1)	C11—C10—C13—C18	124.0 (2)
C1—Si1—C3—C5	−67.7 (1)	C8—C9—C10—C13	−177.9 (1)
C1—Si1—C3—C6	53.3 (1)	C12—C11—C10—C13	178.2 (1)
C2—Si1—C3—C4	−63.1 (1)	C13—C14—C15—C16	52.9 (2)
C2—Si1—C3—C5	56.5 (1)	C14—C15—C16—C17	−51.4 (2)
C2—Si1—C3—C6	177.5 (1)	C15—C16—C17—C18	52.0 (2)
C1—Si1—O1—C7	62.5 (1)	C16—C17—C18—C13	−54.1 (2)
C2—Si1—O1—C7	−57.2 (1)	C17—C18—C13—C14	56.7 (2)
C3—Si1—O1—C7	−177.40 (14)	C18—C13—C14—C15	−56.2 (2)
Si1—O1—C7—C8	95.0 (2)	O2—C16—C17—C18	−82.4 (2)
Si1—O1—C7—C12	−89.6 (2)	O2—C16—C15—C14	83.1 (2)
C7—C8—C9—C10	−0.2 (2)	C19—C16—C17—C18	−149.9 (1)
C8—C9—C10—C11	0.5 (2)	C19—C16—C15—C14	150.5 (1)
C9—C10—C11—C12	−0.2 (2)	C10—C13—C14—C15	177.9 (1)
C9—C8—C7—C12	−0.5 (2)	C10—C13—C18—C17	−178.07 (13)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C15—H15A···O2ⁱ	0.99	2.54	3.487 (2)	159

Symmetry code: (i) −x+3, −y+1, −z+2.

Funding information

Funding for this research was provided by: National Institutes of Health, National Institute of General Medical Sciences (grant No. R15GM118304 to William A. Donaldson).

References

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