(2R,5S)-2-Tri­chloro­methyl-3-oxa-1-aza­bi­cyclo­[3.3.0]­octane-4,8-dione

Punzo, F.; Watkin, D.J.; Pike, R.; Moloney, M.; Panchal, T.

doi:10.1107/S1600536804031605

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 61| Part 1| January 2005| Pages o42-o44

https://doi.org/10.1107/S1600536804031605

(2R,5S)-2-Trichloromethyl-3-oxa-1-azabicyclo[3.3.0]octane-4,8-dione

Francesco Punzo,^a ^*‡ David J. Watkin,^b Richard Pike,^c Mark Moloney ^c and Terry Panchal ^d

^aDipartimento di Scienze Chimiche, Facoltà di Farmacia, Università di Catania, Viale A. Doria 6, 95125, Catania, Italy, ^bDepartment of Chemical Crystallography, Chemical Research Laboratory, Mansfield Road, Oxford OX1 3TA, England, ^cDepartment of Organic Chemistry, Chemical Research Laboratory, Mansfield Road, Oxford OX1 3TA, England, and ^dMedicinal Chemistry II, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex CM19 5AW, England
^*Correspondence e-mail: francesco.punzo@chemistry.oxford.ac.uk

(Received 25 November 2004; accepted 30 November 2004; online 11 December 2004)

The crystal structure of the title bicyclic oxazolidindione, C₇H₆Cl₃NO₃, confirmed the absolute stereochemistry as 2R,5S.

Comment

Natural α-amino acids are at the core of many natural products (Ikota, 1992 ). (S)-pyroglutamic acid, in particular, forms the core of many excitatory amino acids, such as kaitocephalin (Watanabe et al., 2002 ) and kainic acid (Oppolzer & Thirring, 1982 ). Synthetic routes to these classes of compounds require stereochemical control at various positions around a pyrrolidine ring. Seebach's method of the so-called self-reproduction of chirality involves a dual protection of the amine and carboxylic acid of (S)-proline with pivaldehyde to give a bicyclic system (Seebach et al., 1983 ). The analogous protection of (S)-pyroglutamic acid was found to be unfavourable for pivaldehyde, the resulting product being particularly unstable (Dikshit et al., 1995 ). However, analogous protection of (S)-pyroglutamic acid with chloral (Amedjkouh & Ahlberg, 2002 ) provided the title compound, (3) (shown in Fig. 1 and Table 1), as an air-stable crystalline solid.

Figure 1
The molecular structure of (3), with displacement ellipsoids drawn at the 50% probability level. H-atom radii are arbitrary. Cl atoms are displayed in bright green.

Figure 2
Packing diagram of (3), viewed down the a axis.

Experimental

The title compound was prepared by the method described by Amedjkouh & Ahlberg (2002). Slow recrystallization from ethyl acetate gave colourless needle-like crystals. These tend to fracture when cut and therefore a large crystal was used. The multi-scan technique was used to correct for changes in the illuminated volume.

Crystal data

C₇H₆Cl₃NO₃
M_r = 258.49
Orthorhombic, P2₁2₁2₁
a = 6.0480 (1) Å
b = 10.1735 (3) Å
c = 15.5791 (4) Å
V = 958.57 (4) Å³
Z = 4
D_x = 1.791 Mg m⁻³
Mo Kα radiation
Cell parameters from 1485 reflections
θ = 5–30°
μ = 0.93 mm⁻¹
T = 190 K
Needle, colourless
0.80 × 0.20 × 0.20 mm

Data collection

Nonius KappaCCD diffractometer
ω scans
Absorption correction: none
2708 measured reflections
2692 independent reflections
2545 reflections with I > 2σ(I)
R_int = 0.028
θ_max = 30.0°
h = −8 → 8
k = −14 → 14
l = −21 → 21

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.027
wR(F²) = 0.064
S = 0.95
2692 reflections
128 parameters
H-atom parameters constrained
w = 1/[σ²(F²) + 0.02 + 0.49p] where p = [max(F_o²,0) + 2F_c²]/3
(Δ/σ)_max = 0.001
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.26 e Å⁻³
Absolute structure: Flack (1983 ), 1104 Friedel pairs
Flack parameter = 0.01 (6)

Table 1
Selected geometric parameters (Å, °)

C1—C2	1.544 (2)
C1—Cl12	1.7638 (16)
C1—Cl13	1.7617 (17)
C1—Cl14	1.7716 (16)
C2—N3	1.4352 (19)
C2—O6	1.4314 (19)
N3—C4	1.457 (2)
N3—C10	1.391 (2)
C4—C5	1.516 (2)
C4—C8	1.547 (2)
C5—O6	1.366 (2)
C5—O7	1.191 (2)
C8—C9	1.531 (3)
C9—C10	1.514 (3)
C10—O11	1.207 (2)

C2—C1—Cl12	110.98 (10)
C2—C1—Cl13	108.10 (11)
Cl12—C1—Cl13	110.16 (9)
C2—C1—Cl14	108.76 (11)
Cl12—C1—Cl14	109.83 (9)
Cl13—C1—Cl14	108.97 (8)
C1—C2—N3	113.21 (12)
C1—C2—O6	108.34 (12)
N3—C2—O6	105.82 (11)
C2—N3—C4	110.58 (12)
C2—N3—C10	121.30 (13)
C4—N3—C10	112.34 (13)
N3—C4—C5	102.17 (14)
N3—C4—C8	105.25 (13)
C5—C4—C8	117.03 (14)
C4—C5—O6	109.41 (14)
C4—C5—O7	129.11 (18)
O6—C5—O7	121.44 (16)
C2—O6—C5	110.71 (12)
C4—C8—C9	102.61 (13)
C8—C9—C10	104.36 (14)
C9—C10—N3	106.57 (14)
C9—C10—O11	129.32 (16)
N3—C10—O11	124.11 (16)

The H atoms were all seen in a difference map but those attached to C atoms were repositioned geometrically. The H atoms were initially refined with soft restraints on the bonds to regularize their geometry [bond lengths to accepted values, angles either set by symmetry or to accepted values, and U_iso(H) dependent on the adjacent bonded atom], after which they were refined with riding constraints only. C—H = 0.93–0.98 Å and U_iso(H) = 1.2U_eq(C).

Data collection: COLLECT (Nonius, 1997–2001 ); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997 ); data reduction: DENZO/SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003 ); molecular graphics: CAMERON (Watkin et al., 1996 ); software used to prepare material for publication: CRYSTALS.

Supporting information

Crystal structure: contains datablocks 3, global. DOI: https://doi.org/10.1107/S1600536804031605/sj6035sup1.cif

Structure factors: contains datablock 3. DOI: https://doi.org/10.1107/S1600536804031605/sj60353sup2.hkl

Computing details top

Data collection: COLLECT (Nonius, 1997); cell refinement: DENZO/SCALEPACK; data reduction: DENZO/SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003); molecular graphics: CAMERON (Watkin et al., 1996); software used to prepare material for publication: CRYSTALS.

(2R,5S)-2-Trichloromethyl-3-oxa-1-azabicyclo[3,3,0]octane-4,8-dione top

Crystal data top

C₇H₆Cl₃NO₃	D_x = 1.791 Mg m⁻³
M_r = 258.49	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 1485 reflections
a = 6.0480 (1) Å	θ = 5–30°
b = 10.1735 (3) Å	µ = 0.93 mm⁻¹
c = 15.5791 (4) Å	T = 190 K
V = 958.57 (4) Å³	Needle, colourless
Z = 4	0.80 × 0.20 × 0.20 mm
F(000) = 520

Data collection top

Nonius KappaCCD diffractometer	2545 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.028
ω scans	θ_max = 30.0°, θ_min = 5.2°
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997)	h = −8→8
T_min = 0.83, T_max = 0.83	k = −14→14
2708 measured reflections	l = −21→21
2692 independent reflections

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.027	w = 1/[sigma²(F²) + 0.02 + 0.49p] where p = (max(F_o²,0) + 2F_c²)/3 Method = SHELXL 97 (Sheldrick, 1997)
wR(F²) = 0.064	(Δ/σ)_max = 0.001
S = 0.96	Δρ_max = 0.27 e Å⁻³
2692 reflections	Δρ_min = −0.26 e Å⁻³
128 parameters	Absolute structure: Flack, (1983), 1104 Friedel-pairs
0 restraints	Absolute structure parameter: 0.01 (6)
Primary atom site location: structure-invariant direct methods

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

	x	y	z	U_iso*/U_eq
C1	0.8490 (2)	0.15246 (16)	0.24808 (9)	0.0240
C2	0.8540 (2)	0.14921 (15)	0.14903 (9)	0.0205
N3	0.9665 (2)	0.03633 (13)	0.11515 (8)	0.0210
C4	1.1804 (3)	0.07368 (16)	0.07969 (10)	0.0247
C5	1.1657 (3)	0.22241 (17)	0.07900 (10)	0.0286
O6	0.9761 (2)	0.26093 (11)	0.11948 (7)	0.0252
O7	1.2939 (3)	0.30057 (14)	0.05136 (10)	0.0485
C8	1.1938 (3)	0.00394 (17)	−0.00842 (11)	0.0296
C9	1.0262 (3)	−0.10780 (18)	0.00128 (12)	0.0322
C10	0.8571 (3)	−0.05505 (15)	0.06413 (10)	0.0258
O11	0.6642 (2)	−0.08309 (13)	0.07187 (9)	0.0354
Cl12	1.11902 (7)	0.15831 (5)	0.29063 (3)	0.0363
Cl13	0.71158 (9)	0.01009 (4)	0.28416 (3)	0.0407
Cl14	0.69808 (8)	0.29265 (4)	0.28155 (3)	0.0352
H21	0.7008	0.1531	0.1278	0.0237*
H41	1.3021	0.0455	0.1181	0.0286*
H81	1.3388	−0.0319	−0.0172	0.0351*
H82	1.1486	0.0656	−0.0533	0.0354*
H91	1.1002	−0.1859	0.0264	0.0391*
H92	0.9571	−0.1357	−0.0533	0.0390*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0243 (7)	0.0219 (7)	0.0259 (6)	0.0005 (7)	0.0032 (5)	0.0002 (6)
C2	0.0194 (6)	0.0182 (6)	0.0240 (6)	0.0008 (6)	−0.0022 (5)	0.0006 (6)
N3	0.0192 (6)	0.0211 (6)	0.0227 (6)	0.0007 (5)	−0.0001 (5)	−0.0013 (5)
C4	0.0212 (7)	0.0296 (8)	0.0233 (7)	0.0000 (6)	0.0009 (6)	−0.0030 (6)
C5	0.0334 (9)	0.0304 (8)	0.0219 (7)	−0.0084 (7)	0.0034 (6)	−0.0047 (6)
O6	0.0324 (6)	0.0197 (5)	0.0235 (5)	−0.0020 (5)	0.0008 (5)	0.0012 (4)
O7	0.0617 (10)	0.0415 (7)	0.0423 (7)	−0.0242 (7)	0.0251 (7)	−0.0099 (6)
C8	0.0294 (8)	0.0336 (8)	0.0257 (7)	0.0051 (7)	0.0026 (6)	−0.0059 (6)
C9	0.0408 (10)	0.0271 (8)	0.0286 (8)	0.0018 (7)	−0.0021 (7)	−0.0071 (6)
C10	0.0301 (8)	0.0200 (7)	0.0272 (7)	−0.0006 (6)	−0.0058 (6)	0.0000 (6)
O11	0.0297 (6)	0.0305 (6)	0.0458 (7)	−0.0069 (5)	−0.0053 (5)	−0.0043 (5)
Cl12	0.03185 (19)	0.0504 (2)	0.02677 (17)	0.0041 (2)	−0.00816 (15)	−0.0008 (2)
Cl13	0.0530 (3)	0.02717 (19)	0.0420 (2)	−0.00685 (19)	0.0198 (2)	0.00310 (18)
Cl14	0.0385 (2)	0.02754 (19)	0.0396 (2)	0.00699 (17)	0.00566 (19)	−0.00887 (17)

Geometric parameters (Å, º) top

C1—C2	1.544 (2)	C4—H41	0.991
C1—Cl12	1.7638 (16)	C5—O6	1.366 (2)
C1—Cl13	1.7617 (17)	C5—O7	1.191 (2)
C1—Cl14	1.7716 (16)	C8—C9	1.531 (3)
C2—N3	1.4352 (19)	C8—H81	0.960
C2—O6	1.4314 (19)	C8—H82	0.978
C2—H21	0.985	C9—C10	1.514 (3)
N3—C4	1.457 (2)	C9—H91	0.993
N3—C10	1.391 (2)	C9—H92	0.989
C4—C5	1.516 (2)	C10—O11	1.207 (2)
C4—C8	1.547 (2)

C2—C1—Cl12	110.98 (10)	C8—C4—H41	111.354
C2—C1—Cl13	108.10 (11)	C4—C5—O6	109.41 (14)
Cl12—C1—Cl13	110.16 (9)	C4—C5—O7	129.11 (18)
C2—C1—Cl14	108.76 (11)	O6—C5—O7	121.44 (16)
Cl12—C1—Cl14	109.83 (9)	C2—O6—C5	110.71 (12)
Cl13—C1—Cl14	108.97 (8)	C4—C8—C9	102.61 (13)
C1—C2—N3	113.21 (12)	C4—C8—H81	110.425
C1—C2—O6	108.34 (12)	C9—C8—H81	109.705
N3—C2—O6	105.82 (11)	C4—C8—H82	108.963
C1—C2—H21	108.457	C9—C8—H82	111.198
N3—C2—H21	110.761	H81—C8—H82	113.404
O6—C2—H21	110.199	C8—C9—C10	104.36 (14)
C2—N3—C4	110.58 (12)	C8—C9—H91	109.562
C2—N3—C10	121.30 (13)	C10—C9—H91	109.503
C4—N3—C10	112.34 (13)	C8—C9—H92	114.037
N3—C4—C5	102.17 (14)	C10—C9—H92	111.890
N3—C4—C8	105.25 (13)	H91—C9—H92	107.434
C5—C4—C8	117.03 (14)	C9—C10—N3	106.57 (14)
N3—C4—H41	110.794	C9—C10—O11	129.32 (16)
C5—C4—H41	109.699	N3—C10—O11	124.11 (16)

Footnotes

‡Visiting scientist at the Department of Chemical Crystallography, Chemical Research Laboratory, Mansfield Road, Oxford OX1 3TA, England.

Acknowledgements

RP thanks the EPSRC for a grant and GlaxoSmithKline for a CASE award.

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