(3R,4S)-3,4-Isopropylidenedioxy-5-phenylsulfonylmethyl-3,4-dihydro-2H-pyrrole 1-oxide

Mari Fe Flores; P Garcia; Narciso M Garrido; Francisca Sanz; David Diez

doi:10.1107/S1600536811010737

. 2011 Apr 13;67(Pt 5):o1115. doi: 10.1107/S1600536811010737

(3R,4S)-3,4-Isopropylidenedioxy-5-phenylsulfonylmethyl-3,4-dihydro-2H-pyrrole 1-oxide

Mari Fe Flores ^a, P Garcia ^a, Narciso M Garrido ^a, Francisca Sanz ^b, David Diez ^a,^*

PMCID: PMC3089343 PMID: 21754431

Abstract

The title compound, C₁₄H₁₇NO₅S, was prepared by oxidation of (2R,3S,4R)-2-phenylsulfonylmethyl-1-hydroxy-3,4-isopropylidenedioxypyrrolidine. Its crystal structure confirms unequivocally its configuration. Two intermolecular C—H⋯O interactions help to establish the packing.

Related literature

For the preparation, see: Flores et al. (2010 ▶). For the standard oxidation of hydroxylamines to nitrones with manganese dioxide, see: Cicchi et al. (2001 ▶). For background to organocatalysts, see: Berkessel & Groger (2005 ▶); Macmillan (2008 ▶). For analogues of the organocatalyst l-proline, see: Andrey et al. (2004 ▶); Cobb et al. (2004 ▶); Tanaka et al. (2004 ▶); Wang et al. (2005 ▶).

Experimental

Crystal data

C₁₄H₁₇NO₅S
M _r = 311.35
Orthorhombic,
a = 5.6424 (2) Å
b = 15.5592 (7) Å
c = 16.9097 (8) Å
V = 1484.52 (11) Å³
Z = 4
Cu Kα radiation
μ = 2.14 mm⁻¹
T = 298 K
0.10 × 0.08 × 0.06 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2006 ▶) T _min = 0.815, T _max = 0.880
8018 measured reflections
2487 independent reflections
2159 reflections with I > 2σ(I)
R _int = 0.030

Refinement

R[F ² > 2σ(F ²)] = 0.034
wR(F ²) = 0.084
S = 1.06
2487 reflections
192 parameters
H-atom parameters constrained
Δρ_max = 0.14 e Å⁻³
Δρ_min = −0.15 e Å⁻³
Absolute structure: Flack (1983 ▶),
Flack parameter: 0.06 (2)

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

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811010737/bt5495sup1.cif

e-67-o1115-sup1.cif^{(17.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811010737/bt5495Isup2.hkl

e-67-o1115-Isup2.hkl^{(122.2KB, hkl)}

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
C4—H4⋯O4ⁱ	0.98	2.50	3.389 (2)	151
C12—H12⋯O3ⁱⁱ	0.93	2.51	3.270 (4)	139

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

The authors are grateful to the MICINN (CTQ2009–1172), Junta de Castilla y Leon for financial support (GR178 and SA001A09) and for the doctoral fellowships awarded to MFF.

supplementary crystallographic information

Comment

Recently there has been an enormous interest in organocatalysis (Berkessel & Groger et al. 2005 and Macmillan, 2008). Among the many known organocatalysts L-proline is perhaps the one which has been most studied. This fact has led to the appearance of many analogues (Andrey et al., 2004; Wang et al., 2005; Cobb et al., 2004; Tanaka et al., 2004). In our research group we have developed new organocatalyst using nitrones as starting material (Flores et al., 2010). This catalyst was obtained from chiral hydroxylamine (I) (Fig. 1). Here we communicate the oxidation of this compound into nitrone II and the crystal structure determination.

The crystal contains an unique molecule in the asymmetric unit (Fig. 2). The title molecule consists of a pyrroline-N-oxide ring with a phenylsulfonylmethylgroup and an isopropylidenedioxy group as susbtituents. All the bond lengths and angles are within the normal ranges. Statistically no diference is observed between the S1—O4 = 1.4310 (19) Å and S1—O5 = 1.4334 (18) Å distances suggesting that the two oxygen are very similar. The S1—C8 and S1—C9 bond lengths are 1.784 (2) Å and 1.755 (3) Å, respectively. The C—S—C and O—S—O angles are 104.02 (12)° and 119.46 (14)°, respectively. The large O—S—O angle and this deviation from the optimal 109.5° angle can be explained by the repulsion of the lone pairs of the oxygen placing the oxygen atoms as far away from each other as possible and thus minimizing the C—S—C angle. The molecule is twisted at the C—S bond being the C2—C8—S1—C9 torsion angle of -59.4 (7)°. The carbonyl group at atom N1 is desviated from the planar conformation with the pyrroline ring being the O3—N1—C3—C4 torsion angle of 165.9 (5)°.

Crystal packing (Fig. 3) is stabilized by two intermolecular C-H···O interactions. One occurs between the carbon atom (C4) of the isopropylidenedioxypyrroline group and the oxygen atom (O4) of the phenylsufonylmethyl group of the neighboring molecule oriented in the opposite direction along c axis with d(C4-H4···O4) = 3.389 (2) Å and <C4-H4···O4> = 151°. This leads to infinite molecular chains running along the [001] direction, which are joined each other along the b axis by another intermolecular interaction between the oxygen atom (O3) of the pyrroline group and the carbon atom (C12) of the phenyl group of the next molecule with d(C12-H3···O3) = 3.270 (1) Å and <C12-H3···O3> = 139°.

Experimental

The title N-oxide, (II), was obtained by spontaneous oxidation of (2R,3S,4R)-2-Phenylsulfonylmethyl-1-hydroxy-3,4-isopropylidenedioxypyrrolidine (I) (Flores et al. 2010) in a 30% of yield. Our attention was then turned to the synthesis of this nitrone because of the important role nitrones play in organic syntheses, particularly in the field of alkaloids, nitrogen containing natural products or bioactive analogues. Taking this into account we tried the standard oxidation of hydroxylamines to nitrones with manganese dioxide according to the methodology described by Cicchi et al. (2001). MnO₂ (107.2 mg, 1.11 mmol) was added to a solution of hydroxylamine I (234 mg, 0.74 mmol) in DCM (1.5 ml) at 0° C. The resulting mixture was stirred for 2 h, then it was filtered through celite; and concentrated. The resulting crude residue was purified by flash chromatography (silica gel, hexane/ EtAcO 1:1) to obtain the nitrone II (229 mg, 98%) (Flores et al., 2010). Well shaped colourless single crystals were obtained by crystallization from EtOAc/Et₂O. [α]_D²⁰ = +110.7 (c = 1.17, CHCl₃). IR (film): 3376 (broad), 3058, 2995, 2967, 1580 cm^{-1. 1}H NMR (200 MHz, CDCl₃, δ p.p.m.): 7.94 (2H, m, Horto), 7.69–7.58 (3H, m, Hmeta Hpara), 5.58 (1H, d, J = 6.2 Hz, H-4), 4.87 (1H, t, J = 6.2 and 12 Hz H-3), 4.04 (2H, d, J = 4.4 Hz, H-2), 3.96 (2H, s, 2H-1) 1.38 (3H, s, Me-acetonide), 1.37 (3H, s, Me-acetonide). ¹³C NMR (50 MHz, CDCl₃, δ p.p.m.): 139.7 (C—Ar), 134.62 (CH-para), 134.0 (C-5), 129.6 (2CH-meta), 128.1 (2CH-orto), 112.6 (C-acetonide), 80.8 (CH-4), 71.7 (CH-3), 68.1 (CH2–2), 52.1 (CH2–1), 27.2 (Me-acetonide), 25.8 (Me-acetonide). HRMS (EI): C₁₄H₁₇NO₅S requires (M+Na)⁺, 334.0725, found 334.0703.