Crystal structure of (2R*,3aR*)-2-phenyl­sulfonyl-2,3,3a,4,5,6-hexa­hydro­pyrrolo­[1,2-b]isoxazole

Hernández, Y.; Marcos, I.S.; Garrido, N.M.; Sanz, F.; Diez, D.

doi:10.1107/S2056989016019952

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Volume 73| Part 1| January 2017| Pages 85-87

https://doi.org/10.1107/S2056989016019952

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Crystal structure of (2R,3aR)-2-phenylsulfonyl-2,3,3a,4,5,6-hexahydropyrrolo[1,2-b]isoxazole

Yaiza Hernández,^a Isidro Marcos,^a Narciso M. Garrido,^a Francisca Sanz ^b and David Diez ^a ^*

^aDepartamento de Química Orgánica, Universidad de Salamanca, Plaza de los Caidos, 37008 Salamanca, Spain, and ^bServicio de Difracción de Rayos X, Universidad de Salamanca, Plaza de los Caidos, 37008 Salamanca, Spain
^*Correspondence e-mail: ddm@usal.es

Edited by C. Rizzoli, Universita degli Studi di Parma, Italy (Received 30 November 2016; accepted 15 December 2016; online 1 January 2017)

The title compound, C₁₂H₁₅NO₃S, was prepared by 1,3-dipolar cycloaddition of 3,4-dihydro-2H-pyrrole 1-oxide and phenyl vinyl sulfone. In the molecule, both fused five-membered rings display a twisted conformation. In the crystal, C—H⋯O hydrogen bonds link neighbouring molecules, forming chains running parallel to the b axis.

Keywords: crystal structure; hydrogen bonds; isoxazolidines; nitrones; sulfones.

CCDC reference: 1519195

1. Chemical context

1,3-Dipolar cycloaddition is one of the most useful reaction in organic synthesis (Pellissier, 2007 ). Nitrones have been used in the synthesis of many kinds of isoxazolidines (Falkowska et al., 2015 ) by 1,3-dipolar cycloaddition of nitrones with sulfones (Flores, García, Garrido, Nieto et al., 2012 ) and have demonstrate a range of biological activities including antibiotic, gene expression regulation and cancer cell cytotoxicity (Karyakarte et al., 2012 ). Our research group is interested in the synthesis of isoxazolidines such as the title compound, for application in organic synthesis (Flores et al., 2011a ,b ; Flores, García-García et al., 2012 ; Flores, García, Garrido, Sanz et al., 2012 ; Flores et al., 2013 ).

2. Structural commentary

The molecular structure of the title compound, which consists of an anisoxazol derivative with a phenyl sulfone group as substituent, is shown in Fig. 1. Both the fused five-membered rings assume a twist conformation, as indicated by puckering parameters Q = 0.338 (3) Å, φ = −73.5 (7)° for the pyrrole ring and Q = 0.209 (2) Å, φ = −97.5 (6)° for the isoxazole ring. The dihedral angle between the mean planes of the five-membered rings is 64.91 (10)°. All the bond lengths are within normal ranges. The C—S—C and O—S—O angles are 104.34 (9) and 118.54 (11)°, respectively. The large O—S—O angle, and its deviation from the ideal 109.5° angle, can be explained by the repulsion of the lone pairs of the oxygen atoms as far away from each other as possible minimizing the C—S—C angle. The C5—C6—S1—C7 torsion angle is 171.26 (15)°.

Figure 1
The molecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitrary radius.

3. Supramolecular features

In the extended structure of the title compound, intermolecular C—H⋯O hydrogen bonds involving the O1 isoxazole and the O3 phenyl sulfone O atoms as donors (Table 1) lead to molecular chains running parallel to the b axis (Fig. 2).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C6—H6⋯O3ⁱ	0.98	2.35	3.314 (3)	168
C11—H11⋯O1ⁱⁱ	0.93	2.49	3.364 (3)	157
Symmetry codes: (i) x, y-1, z; (ii) $[-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Figure 2
Crystal packing of the title compound viewed along the [100] direction, showing intermolecular hydrogen bonding (dashed lines).

4. Synthesis and crystallization

In the synthesis, 5 g of phenyl vinyl sulfone (II) (29.40 mmol) was added to a solution of 2 g of 3,4-dihydro-2H-pyrrole 1-oxide (I) (23.50 mmol) in toluene (75 mL) at room temperature. The resulting mixture was stirred for 6 h, then it was quenched with a saturated aqueous solution of NH₄Cl and the product was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na₂SO₄, filtered, and concentrated, yielding the crude product (III) (8.93 mmol, 38%). The resulting crude residue was purified by flash chromatography (silica gel, hexane/EtOAc 6:4 v/v) and crystallized from hexane/ethyl acetate solution. IR (film): 3436 (broad), 3068, 2946, 2868, 1442, 1377, 1307, 1148, 1074 cm^{−1. 1}H NMR (400 MHz, CDCl₃, δ p.p.m.): 7.99 (2H, d, J = 8.0 Hz, Hortho), 7.70 (1H, t, J = 7.9Hz, Hpara), 7.58 (2H, t, J = 8.0 Hz, Hmeta), 5.04 (1H, dd, J = 4.0 y 8.4 Hz, H-2), 3.85–3.81(1H, m, H-3a), 3.36–3.31 (1H, m, H_B-6), 3.23 (1H, ddd, J = 4.0, 7.0 y 12.4 Hz, H_B-3), 3.05 (1H, dt, J = 8.3 y 13.8 Hz, H_A-6), 2.50 (1H, ddd, J = 4.0, 8.4 y 12.4 Hz, H_A-3), 2.04–1.93 (2H, m, H_A-4 y H_A-5), 1.76–1.74 (1H, m, H_B-5), 1.60-1.57 (1H, m, H_B-4). ¹³CNMR (100 MHz, CDCl₃ δ p.p.m.): 136.7 (C-ipso), 133.9 (CH_para), 129.5 (2CH_meta),128.9 (2CH_ortho), 92.5 (CH-2), 65.5 (CH-3a), 57.3 (CH₂-6), 36.8 (CH₂-3), 30.8(CH₂-4), 23.8 (CH₂-5). HRMS (EI): C₁₂H₁₅NO₃NaS requires (M+Na)⁺, 276.0665, found 276.0682.

5. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. The hydrogen atoms were positioned geometrically, with C–H distances constrained to 0.93 Å (aromatic CH), 0.97 Å (methylene CH₂), 0.98 (methyne CH) and refined using a riding mode with U_iso(H) = 1.2U_eq(C).

Table 2
Experimental details

Crystal data
Chemical formula	C₁₂H₁₅NO₃S
M_r	253.31
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	298
a, b, c (Å)	12.5730 (4), 5.4443 (2), 18.2266 (6)
β (°)	97.754 (2)
V (Å³)	1236.22 (7)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	2.31
Crystal size (mm)	0.25 × 0.20 × 0.10

Data collection
Diffractometer	Bruker APEXII CCD area detector
Absorption correction	Multi-scan (SADABS; Bruker, 2006 )
T_min, T_max	0.603, 0.794
No. of measured, independent and observed [I > 2σ(I)] reflections	9571, 2074, 1949
R_int	0.032
(sin θ/λ)_max (Å⁻¹)	0.596

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.042, 0.109, 1.04
No. of reflections	2074
No. of parameters	154
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.23, −0.25
Computer programs: APEX2 and SAINT (Bruker 2006), SHELXS97, SHELXL97 and SHELXTL/PC (Sheldrick, 2008 ) and Mercury (Macrae et al., 2006 ).

Supporting information

CCDC reference: 1519195

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2056989016019952/rz5200sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989016019952/rz5200Isup2.hkl

checkCIF report

Computing details top

Data collection: APEX2 (Bruker 2006); cell refinement: SAINT (Bruker 2006); data reduction: SAINT (Bruker 2006); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: Mercury (Macrae et al., 2006); software used to prepare material for publication: SHELXTL/PC (Sheldrick, 2008).

(2R*,3aR*)-2-Phenylsulfonyl-2,3,3a,4,5,6-hexahydropyrrolo[1,2-b]isoxazole top

Crystal data top

C₁₂H₁₅NO₃S	F(000) = 536
M_r = 253.31	D_x = 1.361 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ybc	Cell parameters from 1548 reflections
a = 12.5730 (4) Å	θ = 8.7–66.1°
b = 5.4443 (2) Å	µ = 2.31 mm⁻¹
c = 18.2266 (6) Å	T = 298 K
β = 97.754 (2)°	Prismatic, colorless
V = 1236.22 (7) Å³	0.25 × 0.20 × 0.10 mm
Z = 4

Data collection top

Bruker APEXII CCD area detector diffractometer	2074 independent reflections
Radiation source: fine-focus sealed tube	1949 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.032
phi and ω scans	θ_max = 66.8°, θ_min = 8.5°
Absorption correction: multi-scan (SADABS; Bruker, 2006)	h = −14→13
T_min = 0.603, T_max = 0.794	k = −6→6
9571 measured reflections	l = −17→21

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.042	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.109	H-atom parameters constrained
S = 1.04	w = 1/[σ²(F_o²) + (0.048P)² + 0.5869P] where P = (F_o² + 2F_c²)/3
2074 reflections	(Δ/σ)_max < 0.001
154 parameters	Δρ_max = 0.23 e Å⁻³
0 restraints	Δρ_min = −0.25 e Å⁻³

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.

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 > 2sigma(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 (Å²) top

	x	y	z	U_iso*/U_eq
S1	0.18509 (4)	0.20282 (9)	0.19580 (3)	0.0506 (2)
O1	0.27595 (12)	0.0779 (4)	0.33002 (8)	0.0780 (5)
O2	0.10289 (12)	0.0979 (4)	0.14263 (9)	0.0745 (5)
O3	0.17911 (13)	0.4582 (3)	0.21257 (10)	0.0722 (5)
N1	0.24857 (16)	0.2358 (4)	0.38806 (12)	0.0767 (6)
C1	0.2723 (3)	0.0922 (13)	0.45671 (19)	0.173 (3)
H1A	0.3095	−0.0579	0.4469	0.207*
H1B	0.3185	0.1863	0.4933	0.207*
C2	0.1731 (3)	0.0332 (7)	0.48481 (17)	0.1044 (11)
H2A	0.1821	0.0422	0.5384	0.125*
H2B	0.1487	−0.1303	0.4696	0.125*
C3	0.0964 (3)	0.2227 (6)	0.45154 (17)	0.0932 (9)
H3A	0.1018	0.3717	0.4810	0.112*
H3B	0.0231	0.1629	0.4466	0.112*
C4	0.13178 (19)	0.2665 (5)	0.37671 (14)	0.0653 (6)
H4	0.1134	0.4343	0.3602	0.078*
C5	0.08854 (17)	0.0856 (5)	0.31715 (13)	0.0669 (6)
H5A	0.0605	−0.0600	0.3385	0.080*
H5B	0.0322	0.1592	0.2824	0.080*
C6	0.18549 (16)	0.0244 (4)	0.27984 (11)	0.0548 (5)
H6	0.1848	−0.1510	0.2677	0.066*
C7	0.31162 (15)	0.1448 (4)	0.16793 (11)	0.0489 (5)
C8	0.3261 (2)	−0.0590 (5)	0.12636 (15)	0.0748 (7)
H8	0.2699	−0.1680	0.1129	0.090*
C9	0.4260 (3)	−0.0996 (6)	0.10473 (19)	0.0949 (9)
H9	0.4371	−0.2375	0.0766	0.114*
C10	0.5086 (2)	0.0610 (7)	0.12436 (18)	0.0902 (9)
H10	0.5754	0.0320	0.1095	0.108*
C11	0.4932 (2)	0.2622 (6)	0.16530 (18)	0.0843 (8)
H11	0.5495	0.3712	0.1783	0.101*
C12	0.39431 (18)	0.3066 (4)	0.18785 (14)	0.0650 (6)
H12	0.3839	0.4444	0.2162	0.078*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.0409 (3)	0.0501 (3)	0.0601 (3)	−0.00016 (19)	0.0047 (2)	0.0026 (2)
O1	0.0465 (8)	0.1268 (15)	0.0598 (9)	0.0238 (9)	0.0034 (7)	−0.0082 (10)
O2	0.0485 (8)	0.1031 (13)	0.0677 (9)	−0.0149 (8)	−0.0079 (7)	0.0020 (9)
O3	0.0706 (10)	0.0466 (8)	0.1034 (12)	0.0115 (7)	0.0265 (9)	0.0072 (8)
N1	0.0565 (12)	0.0980 (16)	0.0779 (13)	−0.0213 (11)	0.0169 (10)	−0.0249 (12)
C1	0.102 (3)	0.350 (8)	0.0652 (18)	0.079 (4)	0.0086 (18)	0.015 (3)
C2	0.146 (3)	0.098 (2)	0.0722 (17)	0.015 (2)	0.0272 (19)	0.0106 (16)
C3	0.094 (2)	0.111 (2)	0.0831 (18)	0.0098 (18)	0.0415 (17)	0.0043 (17)
C4	0.0646 (14)	0.0611 (13)	0.0743 (14)	0.0105 (11)	0.0250 (11)	0.0033 (11)
C5	0.0437 (11)	0.0849 (16)	0.0728 (14)	−0.0104 (11)	0.0101 (10)	0.0128 (12)
C6	0.0541 (11)	0.0495 (11)	0.0603 (12)	−0.0008 (9)	0.0062 (9)	−0.0008 (9)
C7	0.0446 (10)	0.0478 (11)	0.0539 (10)	−0.0008 (8)	0.0054 (8)	0.0021 (9)
C8	0.0772 (16)	0.0601 (14)	0.0901 (17)	−0.0040 (12)	0.0223 (13)	−0.0145 (13)
C9	0.104 (2)	0.0832 (19)	0.105 (2)	0.0252 (18)	0.0439 (18)	−0.0077 (17)
C10	0.0640 (16)	0.108 (2)	0.105 (2)	0.0248 (16)	0.0352 (15)	0.0315 (19)
C11	0.0447 (13)	0.100 (2)	0.108 (2)	−0.0088 (13)	0.0087 (13)	0.0152 (17)
C12	0.0512 (12)	0.0650 (14)	0.0782 (15)	−0.0091 (10)	0.0064 (11)	−0.0057 (11)

Geometric parameters (Å, º) top

S1—O3	1.4277 (16)	C4—C5	1.511 (4)
S1—O2	1.4364 (16)	C4—H4	0.9800
S1—C7	1.763 (2)	C5—C6	1.511 (3)
S1—C6	1.813 (2)	C5—H5A	0.9700
O1—C6	1.391 (3)	C5—H5B	0.9700
O1—N1	1.440 (3)	C6—H6	0.9800
N1—C4	1.465 (3)	C7—C8	1.370 (3)
N1—C1	1.472 (5)	C7—C12	1.374 (3)
C1—C2	1.446 (5)	C8—C9	1.384 (4)
C1—H1A	0.9700	C8—H8	0.9300
C1—H1B	0.9700	C9—C10	1.367 (5)
C2—C3	1.485 (4)	C9—H9	0.9300
C2—H2A	0.9700	C10—C11	1.354 (5)
C2—H2B	0.9700	C10—H10	0.9300
C3—C4	1.510 (4)	C11—C12	1.382 (4)
C3—H3A	0.9700	C11—H11	0.9300
C3—H3B	0.9700	C12—H12	0.9300

O3—S1—O2	118.54 (11)	C3—C4—H4	109.8
O3—S1—C7	108.17 (9)	C5—C4—H4	109.8
O2—S1—C7	109.24 (10)	C6—C5—C4	103.48 (17)
O3—S1—C6	109.58 (10)	C6—C5—H5A	111.1
O2—S1—C6	106.06 (10)	C4—C5—H5A	111.1
C7—S1—C6	104.34 (9)	C6—C5—H5B	111.1
C6—O1—N1	110.65 (15)	C4—C5—H5B	111.1
O1—N1—C4	107.39 (17)	H5A—C5—H5B	109.0
O1—N1—C1	105.4 (3)	O1—C6—C5	107.19 (17)
C4—N1—C1	105.4 (2)	O1—C6—S1	110.63 (15)
C2—C1—N1	109.5 (3)	C5—C6—S1	110.59 (15)
C2—C1—H1A	109.8	O1—C6—H6	109.5
N1—C1—H1A	109.8	C5—C6—H6	109.5
C2—C1—H1B	109.8	S1—C6—H6	109.5
N1—C1—H1B	109.8	C8—C7—C12	120.9 (2)
H1A—C1—H1B	108.2	C8—C7—S1	119.84 (17)
C1—C2—C3	104.2 (3)	C12—C7—S1	119.31 (16)
C1—C2—H2A	110.9	C7—C8—C9	118.8 (3)
C3—C2—H2A	110.9	C7—C8—H8	120.6
C1—C2—H2B	110.9	C9—C8—H8	120.6
C3—C2—H2B	110.9	C10—C9—C8	120.6 (3)
H2A—C2—H2B	108.9	C10—C9—H9	119.7
C2—C3—C4	103.0 (2)	C8—C9—H9	119.7
C2—C3—H3A	111.2	C11—C10—C9	120.1 (2)
C4—C3—H3A	111.2	C11—C10—H10	119.9
C2—C3—H3B	111.2	C9—C10—H10	119.9
C4—C3—H3B	111.2	C10—C11—C12	120.4 (3)
H3A—C3—H3B	109.1	C10—C11—H11	119.8
N1—C4—C3	105.5 (2)	C12—C11—H11	119.8
N1—C4—C5	106.48 (18)	C7—C12—C11	119.2 (2)
C3—C4—C5	115.1 (2)	C7—C12—H12	120.4
N1—C4—H4	109.8	C11—C12—H12	120.4

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C6—H6···O3ⁱ	0.98	2.35	3.314 (3)	168
C11—H11···O1ⁱⁱ	0.93	2.49	3.364 (3)	157

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

Acknowledgements

The authors gratefully acknowledge help from A. Lithgow (NMR) and C. Raposo (MS) of the Universidad de Salamanca.

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