(4R)-4-[(1R)-1,2-Dihydroxy­ethyl]-1-[(1R)-1-phenyl­ethyl]pyrrolidin-2-one

Blaser, A.; Boyd, P.D.W.

doi:10.1107/S1600536808027293

organic compounds

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Volume 64| Part 9| September 2008| Page o1851

doi:10.1107/S1600536808027293

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(4R)-4-[(1R)-1,2-Dihydroxyethyl]-1-[(1R)-1-phenylethyl]pyrrolidin-2-one

Adrian Blaser ^a and Peter D. W. Boyd ^b ^*

^aCancer Research Laboratory, The University of Auckland, Private Bag 92019, Auckland, New Zealand, and ^bDepartment of Chemistry, The University of Auckland, Private Bag 92019, Auckland, New Zealand
^*Correspondence e-mail: pdw.boyd@auckland.ac.nz

(Received 18 August 2008; accepted 25 August 2008; online 30 August 2008)

The title compound, C₁₄H₁₉NO₃, was obtained as one of the two isomers of a Sharpless asymmetric dihydroxylation reaction of (1S)-1-[(1R)-1-phenylethyl]-4-vinylpyrrolidin-2-one. The absolute stereochemistry of this isomer was determined from the known stereochemistry (R) at the bridge C atom between the phenyl and pyrrolidine rings. The molecules form one-dimensional tapes along the b axis via hydrogen bonding between the carbonyl O atom and the alcohol groups of neighbouring molecules. These assemble into sheets via interdigitative stacking of the phenyl rings and C—H⋯O interactions.

Related literature

For related literature see: Fava et al. (1999 ).

Experimental

Crystal data

C₁₄H₁₉NO₃
M_r = 249.30
Monoclinic, P 2₁
a = 6.1953 (1) Å
b = 8.2895 (2) Å
c = 13.2737 (1) Å
β = 103.353 (2)°
V = 663.25 (2) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 83 (2) K
0.28 × 0.18 × 0.10 mm

Data collection

Siemens SMART APEX CCD diffractometer
Absorption correction: none
4016 measured reflections
1461 independent reflections
1271 reflections with I > 2σ(I)
R_int = 0.040

Refinement

R[F² > 2σ(F²)] = 0.045
wR(F²) = 0.099
S = 1.01
1461 reflections
166 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3⋯O1ⁱ	0.82	1.96	2.743 (3)	158
O2—H2⋯O1ⁱ	0.82	1.93	2.738 (3)	170
Symmetry code: (i) x, y+1, z.

Data collection: SMART (Siemens, 1995 ); cell refinement: SAINT (Siemens, 1995); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPIII (Burnett & Johnson, 1996 ) and Mercury (Macrae et al., 2006 ); software used to prepare material for publication: WinGX (Farrugia, 1999 ).

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808027293/at2618sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808027293/at2618Isup2.hkl

checkCIF report

Comment top

The title compound (I) was obtained as one of the two isomers of a Sharpless asymmetric dihydroxylation reaction of (1S)-1-((1R)-1-phenylethyl)-4-vinylpyrrolidin-2-one (Fava et al.1999). The major isomer from the reaction was recrystallized to give a pure sample for X-ray analysis. The molecular structure of (I) is shown in Fig. 1. The assignment of the absolute stereochemistry is based on the known stereochemistry of C7 (R). This leads to the absolute configuration at C10 and C13 as R.

The molecules of (I) in the crystal form one dimensional tapes along the b axis via hydrogen bonding between the carbonyl oxygen, O1 and the two alcohol moieties O2—H and O3—H. These assemble by interdigitative stacking of phenyl rings between tapes and further connection by C11—H11B···O3, C5—H5···O2 interactions between adjacent molecules to form sheets near the b-c plane, Fig. 2 (Table 1).

Related literature top

For related literature see: Fava et al. (1999)

Experimental top

(4R)-4-[(1R)-1,2-Dihydroxyethyl]-1-[(1R)-1-phenylethyl]-2-pyrrolidinone (I): AD-mix-β (1.40 g, 1 mmol, Aldrich Cat. No. 392766) was dissolved in tert-butanol (5 ml) and water (5 ml). Methanesulfonamide (98 mg, 1 mmol) was added and cooled to 273 K, (1S)-1-((1R)-1-phenylethyl)-4-vinylpyrrolidin-2-one1 (216 mg, 1 mmol) was added and the reaction stirred for 24 h. Na₂SO₃ (1.5 g, 11.9 mmol) was added and stirred for another 90 minutes. The reaction was extracted with dichloromethane (4x100 ml), the combined organic layers were washed with 2 N KOH solution, dried (Na₂SO₄) and concentrated under reduced pressure. The residue was purified by chromatography, eluting with methanol/ethylacetate (3:7) to give the two isomers (4R)-4-[(1R)-1,2-dihydroxyethyl]-1-[(1R)-1-phenylethyl]-2-pyrrolidinone and (4R)-4-[(1S)-1,2-dihydroxyethyl]-1-[(1R)-1-phenylethyl]-2-pyrrolidinone (169 mg, 68%) in a ratio of 2:1. The title compound (I) was then obtained by recrystallization from ethylacetate as clear crystals. ¹H NMR (400 MHz, CDCl₃) δ 7.36–7.24 (m, 5 H), 5.47 (q, J=7.1 Hz, 1 H), 3.69 (dd, J=10.7, 2.8 Hz, 1 H), 3.67–3.60 (m, 1 H), 3.46 (dd, J=10.7, 7.0 Hz, 1 H), 3.35 (dd, J=10.0, 7.0 Hz, 1 H), 3.13 (dd, J=10.0, 8.0 Hz, 1 H), 2.66 (br s, 1 H), 2.46 (dd, J=15.2, 8.1 Hz, 1 H), 2.40–2.29 (m, 1 H), 2.26 (dd, J=15.2, 8.2 Hz, 1 H), 2.17 (br s, 1 H), 1.53 (t, J=7.1 Hz, 3 H). LCMS (APCI⁺) calcd for C₁₄H₁₉NO₃: 250 (MH⁺), found 250 (100%).

Computing details top

Data collection: SMART (Siemens, 1995); cell refinement: SAINT (Siemens, 1995); data reduction: SAINT (Siemens, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPIII (Burnett & Johnson, 1996) and Mercury (Macrae et al., 2006); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top

	Fig. 1. Structure of (I) showing 50% probability displacement ellipsoids for non-hydrogen atoms and hydrogen atoms as arbitary spheres.
	Fig. 2. Illustration of the arrangement of (I) into sheets.

(4R)-4-[(1R)-1,2-Dihydroxyethyl]-1-[(1R)-1- phenylethyl]pyrrolidin-2-one top

Crystal data top

C₁₄H₁₉NO₃	F(000) = 268
M_r = 249.30	D_x = 1.248 Mg m⁻³
Monoclinic, P2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 2597 reflections
a = 6.1953 (1) Å	θ = 1.6–26.4°
b = 8.2895 (2) Å	µ = 0.09 mm⁻¹
c = 13.2737 (1) Å	T = 83 K
β = 103.353 (2)°	Plate, colourless
V = 663.25 (2) Å³	0.28 × 0.18 × 0.10 mm
Z = 2

Data collection top

Siemens SMART APEX CCD diffractometer	1271 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.040
Graphite monochromator	θ_max = 26.4°, θ_min = 1.6°
ω scans	h = −7→7
4016 measured reflections	k = −10→10
1461 independent reflections	l = −7→16

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)] = 0.045	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.099	H-atom parameters constrained
S = 1.01	w = 1/[σ²(F_o²) + (0.0168P)² + 0.6853P] where P = (F_o² + 2F_c²)/3
1461 reflections	(Δ/σ)_max < 0.001
166 parameters	Δρ_max = 0.20 e Å⁻³
1 restraint	Δρ_min = −0.22 e Å⁻³

Crystal data top

C₁₄H₁₉NO₃	V = 663.25 (2) Å³
M_r = 249.30	Z = 2
Monoclinic, P2₁	Mo Kα radiation
a = 6.1953 (1) Å	µ = 0.09 mm⁻¹
b = 8.2895 (2) Å	T = 83 K
c = 13.2737 (1) Å	0.28 × 0.18 × 0.10 mm
β = 103.353 (2)°

Data collection top

Siemens SMART APEX CCD diffractometer	1271 reflections with I > 2σ(I)
4016 measured reflections	R_int = 0.040
1461 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.045	1 restraint
wR(F²) = 0.099	H-atom parameters constrained
S = 1.01	Δρ_max = 0.20 e Å⁻³
1461 reflections	Δρ_min = −0.22 e Å⁻³
166 parameters

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
O3	0.1980 (4)	−0.0064 (3)	0.00048 (16)	0.0261 (5)
H3	0.2059	0.0736	−0.0348	0.039*
O1	0.3278 (5)	−0.7778 (3)	−0.12286 (19)	0.0277 (6)
O2	0.3068 (5)	−0.0804 (3)	−0.20720 (19)	0.0339 (6)
H2	0.3289	0.0108	−0.1832	0.051*
N1	0.4081 (4)	−0.5848 (3)	−0.2318 (2)	0.0200 (6)
C11	0.2531 (5)	−0.4926 (4)	−0.0993 (2)	0.0204 (6)
H11A	0.3554	−0.4685	−0.0339	0.024*
H11B	0.1070	−0.5120	−0.0869	0.024*
C7	0.5155 (5)	−0.6928 (4)	−0.2932 (2)	0.0216 (7)
H7	0.4748	−0.8031	−0.2784	0.026*
C13	0.3005 (6)	−0.1917 (4)	−0.1258 (3)	0.0231 (7)
H13	0.4473	−0.1964	−0.0784	0.028*
C9	0.4141 (6)	−0.4083 (4)	−0.2397 (3)	0.0231 (7)
H9A	0.3682	−0.3731	−0.3112	0.028*
H9B	0.5613	−0.3666	−0.2099	0.028*
C12	0.3308 (5)	−0.6349 (4)	−0.1506 (2)	0.0216 (7)
C1	0.4215 (5)	−0.6645 (4)	−0.4075 (2)	0.0222 (7)
C8	0.7661 (5)	−0.6810 (5)	−0.2569 (3)	0.0320 (8)
H8A	0.8137	−0.5754	−0.2721	0.048*
H8B	0.8341	−0.7605	−0.2922	0.048*
H8C	0.8089	−0.6998	−0.1837	0.048*
C10	0.2466 (6)	−0.3545 (4)	−0.1767 (3)	0.0217 (7)
H10	0.0983	−0.3499	−0.2228	0.026*
C6	0.5480 (6)	−0.6089 (4)	−0.4737 (2)	0.0297 (8)
H6	0.6968	−0.5842	−0.4474	0.036*
C14	0.1299 (6)	−0.1421 (4)	−0.0656 (2)	0.0236 (7)
H14A	−0.0084	−0.1162	−0.1142	0.028*
H14B	0.1024	−0.2326	−0.0240	0.028*
C4	0.2361 (7)	−0.6207 (6)	−0.6180 (3)	0.0433 (10)
H4	0.1743	−0.6056	−0.6882	0.052*
C2	0.2008 (6)	−0.6969 (6)	−0.4493 (3)	0.0395 (10)
H2A	0.1129	−0.7347	−0.4063	0.047*
C5	0.4561 (7)	−0.5893 (5)	−0.5789 (3)	0.0370 (9)
H5	0.5444	−0.5548	−0.6227	0.044*
C3	0.1060 (7)	−0.6746 (7)	−0.5538 (3)	0.0491 (12)
H3A	−0.0438	−0.6959	−0.5801	0.059*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O3	0.0388 (14)	0.0189 (12)	0.0245 (11)	−0.0048 (12)	0.0151 (10)	−0.0050 (11)
O1	0.0460 (16)	0.0153 (12)	0.0264 (13)	−0.0007 (11)	0.0178 (12)	0.0004 (10)
O2	0.0633 (18)	0.0161 (12)	0.0291 (13)	−0.0033 (14)	0.0247 (13)	−0.0008 (10)
N1	0.0294 (15)	0.0130 (13)	0.0208 (13)	−0.0012 (12)	0.0121 (11)	−0.0019 (11)
C11	0.0293 (16)	0.0170 (15)	0.0176 (14)	−0.0016 (15)	0.0111 (12)	−0.0007 (14)
C7	0.0299 (17)	0.0168 (17)	0.0202 (15)	0.0016 (15)	0.0103 (13)	−0.0010 (13)
C13	0.0341 (18)	0.0166 (16)	0.0219 (16)	−0.0032 (15)	0.0135 (14)	−0.0008 (14)
C9	0.035 (2)	0.0168 (16)	0.0211 (16)	−0.0030 (15)	0.0134 (14)	−0.0025 (14)
C12	0.0269 (17)	0.0193 (16)	0.0196 (15)	−0.0028 (14)	0.0071 (13)	−0.0005 (14)
C1	0.0292 (17)	0.0180 (17)	0.0203 (15)	0.0016 (14)	0.0073 (13)	−0.0056 (14)
C8	0.0330 (19)	0.038 (2)	0.0248 (17)	0.0042 (18)	0.0050 (14)	−0.0050 (16)
C10	0.0309 (19)	0.0178 (16)	0.0191 (16)	−0.0010 (15)	0.0112 (14)	−0.0004 (13)
C6	0.041 (2)	0.0249 (19)	0.0255 (17)	−0.0037 (17)	0.0125 (15)	0.0010 (16)
C14	0.0327 (18)	0.0182 (16)	0.0225 (15)	−0.0025 (14)	0.0116 (13)	−0.0022 (14)
C4	0.059 (3)	0.044 (3)	0.0239 (17)	0.014 (2)	0.0029 (17)	−0.0049 (18)
C2	0.034 (2)	0.060 (3)	0.0269 (18)	−0.003 (2)	0.0112 (15)	−0.011 (2)
C5	0.063 (3)	0.0251 (19)	0.0269 (18)	0.001 (2)	0.0178 (18)	0.0022 (16)
C3	0.035 (2)	0.075 (4)	0.034 (2)	0.002 (2)	0.0001 (17)	−0.017 (2)

Geometric parameters (Å, º) top

O3—C14	1.429 (4)	C9—H9A	0.9700
O3—H3	0.8200	C9—H9B	0.9700
O1—C12	1.242 (4)	C1—C2	1.378 (5)
O2—C13	1.428 (4)	C1—C6	1.385 (4)
O2—H2	0.8200	C8—H8A	0.9600
N1—C12	1.342 (4)	C8—H8B	0.9600
N1—C9	1.468 (4)	C8—H8C	0.9600
N1—C7	1.469 (4)	C10—H10	0.9800
C11—C12	1.496 (5)	C6—C5	1.390 (5)
C11—C10	1.532 (4)	C6—H6	0.9300
C11—H11A	0.9700	C14—H14A	0.9700
C11—H11B	0.9700	C14—H14B	0.9700
C7—C1	1.513 (4)	C4—C5	1.367 (6)
C7—C8	1.519 (5)	C4—C3	1.376 (6)
C7—H7	0.9800	C4—H4	0.9300
C13—C10	1.511 (5)	C2—C3	1.388 (5)
C13—C14	1.521 (4)	C2—H2A	0.9300
C13—H13	0.9800	C5—H5	0.9300
C9—C10	1.542 (5)	C3—H3A	0.9300

C14—O3—H3	109.5	C6—C1—C7	123.0 (3)
C13—O2—H2	109.5	C7—C8—H8A	109.5
C12—N1—C9	112.7 (3)	C7—C8—H8B	109.5
C12—N1—C7	123.2 (3)	H8A—C8—H8B	109.5
C9—N1—C7	123.1 (3)	C7—C8—H8C	109.5
C12—C11—C10	104.2 (2)	H8A—C8—H8C	109.5
C12—C11—H11A	110.9	H8B—C8—H8C	109.5
C10—C11—H11A	110.9	C13—C10—C11	113.5 (3)
C12—C11—H11B	110.9	C13—C10—C9	113.2 (3)
C10—C11—H11B	110.9	C11—C10—C9	103.3 (3)
H11A—C11—H11B	108.9	C13—C10—H10	108.9
N1—C7—C1	110.1 (3)	C11—C10—H10	108.9
N1—C7—C8	110.3 (3)	C9—C10—H10	108.9
C1—C7—C8	115.9 (3)	C1—C6—C5	121.0 (3)
N1—C7—H7	106.7	C1—C6—H6	119.5
C1—C7—H7	106.7	C5—C6—H6	119.5
C8—C7—H7	106.7	O3—C14—C13	113.2 (3)
O2—C13—C10	106.3 (3)	O3—C14—H14A	108.9
O2—C13—C14	111.5 (3)	C13—C14—H14A	108.9
C10—C13—C14	111.6 (3)	O3—C14—H14B	108.9
O2—C13—H13	109.1	C13—C14—H14B	108.9
C10—C13—H13	109.1	H14A—C14—H14B	107.8
C14—C13—H13	109.1	C5—C4—C3	120.1 (4)
N1—C9—C10	102.6 (3)	C5—C4—H4	119.9
N1—C9—H9A	111.2	C3—C4—H4	119.9
C10—C9—H9A	111.2	C1—C2—C3	121.9 (4)
N1—C9—H9B	111.2	C1—C2—H2A	119.1
C10—C9—H9B	111.2	C3—C2—H2A	119.1
H9A—C9—H9B	109.2	C4—C5—C6	120.0 (3)
O1—C12—N1	124.5 (3)	C4—C5—H5	120.0
O1—C12—C11	126.1 (3)	C6—C5—H5	120.0
N1—C12—C11	109.5 (3)	C4—C3—C2	119.3 (4)
C2—C1—C6	117.6 (3)	C4—C3—H3A	120.4
C2—C1—C7	119.3 (3)	C2—C3—H3A	120.4

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···O1ⁱ	0.82	1.96	2.743 (3)	158
O2—H2···O1ⁱ	0.82	1.93	2.738 (3)	170

Symmetry code: (i) x, y+1, z.

Experimental details

Crystal data
Chemical formula	C₁₄H₁₉NO₃
M_r	249.30
Crystal system, space group	Monoclinic, P2₁
Temperature (K)	83
a, b, c (Å)	6.1953 (1), 8.2895 (2), 13.2737 (1)
β (°)	103.353 (2)
V (Å³)	663.25 (2)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.28 × 0.18 × 0.10

Data collection
Diffractometer	Siemens SMART APEX CCD diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	4016, 1461, 1271
R_int	0.040
(sin θ/λ)_max (Å⁻¹)	0.626

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.045, 0.099, 1.01
No. of reflections	1461
No. of parameters	166
No. of restraints	1
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.20, −0.22

Computer programs: SMART (Siemens, 1995), SAINT (Siemens, 1995), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEPIII (Burnett & Johnson, 1996) and Mercury (Macrae et al., 2006), WinGX (Farrugia, 1999).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···O1ⁱ	0.82	1.96	2.743 (3)	158.3
O2—H2···O1ⁱ	0.82	1.93	2.738 (3)	169.7

Symmetry code: (i) x, y+1, z.

Acknowledgements

This work was supported by the Auckland Division of the Cancer Society of New Zealand, UniServices and the University of Auckland Research Committee.

References

Burnett, M. N. & Johnson, C. K. (1996). ORTEPIII. Report ORNL-6895. Oak Ridge National Laboratory, Tennessee, USA. Google Scholar
Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838. CrossRef CAS IUCr Journals Google Scholar
Fava, C., Galeazzi, R., Mobbili, G. & Orena, M. (1999). Heterocycles, 51, 2463–2470. CAS Google Scholar
Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453–457. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Siemens (1995). SMART and SAINT. Siemens Analytical X-ray Instruments Inc., Madison, Wisconsin, USA. Google Scholar