(1S*,2S*,4S*)-3,3-Difluoro-2,4-dihydr­oxy-5,5-dimethyl­cyclo­oct-5(Z)-en-1-yl N,N-diethyl­carbamate

Fawcett, J.; Percy, J.M.; Pintat, S.; Smith, C.A.; Uneyama, E.

doi:10.1107/S1600536805024839

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 61| Part 10| October 2005| Pages o3319-o3321

doi:10.1107/S1600536805024839

(1S,2S,4S*)-3,3-Difluoro-2,4-dihydroxy-5,5-dimethylcyclooct-5(Z)-en-1-yl N,N-diethylcarbamate

John Fawcett,^a Jonathan M Percy,^a Stéphane Pintat,^b Clive A Smith ^c and Emi Uneyama ^a ^*

^aDepartment of Chemistry, University of Leicester, Leicester LE1 7RH, England, ^bGlaxoSmithKline Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow CM19 5AW, England, and ^cChroma Therapeutics Ltd, 93 Milton Park, Abingdon, Oxon OX14 4RY, England
^*Correspondence e-mail: jmp29@leicester.ac.uk

(Received 11 July 2005; accepted 3 August 2005; online 21 September 2005)

The structure of the title compound, C₁₅H₂₅F₂NO₄, is reported and reveals a pseudorotational relationship between the ring conformation of this compound and that of an isomeric by-product reported in the following paper.

Comment

Conformational equilibria in eight-membered carbocycles occur via two main processes, pseudorotation and ring inversion. The latter exchanges substituent groups between equatorial and axial environments in a pseudo-enantiomeric relationship. Ring inversion is usually the more energetically demanding process; barriers to inversion exchange of 7.3–8.5 kcal mol⁻¹ have been reported, with smaller barriers (ca 5 kcal mol⁻¹) (Servis & Noe, 1973 ) for the pseudorotation. [For early attempts to apply variable-temperature NMR to these phenomena, see Anderson et al. (1969 ) and St Jacques et al. (1966 ).] Recent work from our group has attempted to define these processes for a trio of difluorinated cyclooctenyl systems (Fawcett, Griffith et al., 2005 ). We were interested in observing a pseudorotational relationship between the ring conformations in the pair of reduction products (1) and (2), obtained upon treatment of a precursor ketone with sodium borohydride.

Product (1) (the major product) arises from the opposite sense of hydride attack, with the N,N-diethylcarbamoyl group retaining its original location (Fig. 1). Product (2), reported in the following paper (Fawcett, Percy et al., 2005 ), arises from reagent attack on the ring face which bears the hydroxyl group, followed by migration of the N,N-diethylcarbamoyl group on to the newly formed hydroxyl group (Balnaves et al., 1999 ). A comparison of the two molecules is shown in Fig. 2. O—H⋯O hydrogen bonding links molecules of (1) into chains along the b axis (Table 1).

Figure 1
The molecular structure of (1), showing the atom-numbering scheme and 50% displacement ellipsoids. H atoms have been omitted for clarity.

Figure 2
An overlay showing the relationship between the structures of compounds (1) and (2).

Experimental

The precursor ketone was prepared as described in the literature (Fawcett, Griffith et al., 2005). Sodium borohydride (1.8 mmol, 70 mg) was added in five portions to a cold (273 K) solution of the ketone (1.8 mmol, 0.59 g) in ethanol (10 ml). After completion of the addition, the reaction mixture was allowed to warm to room temperature, stirred for 2 h at this temperature and poured over a mixture of ice and water (25 ml). HCl (10 ml of a 1 N solution) was added cautiously and the mixture was extracted with diethyl ether (3 × 25 ml). The combined organic extracts were dried (MgSO₄), filtered and concentrated under reduced pressure to leave a white solid (0.51 g). Purification by column chromatography (40% ethyl acetate in light petroleum) afforded the desired diol (1) as a white solid (0.43 g, 72%). R_F (40% ethyl acetate in light petroleum) 0.29; m.p. 388–389 K (found: C 56.17, H 7.71, N 4.29%; C₁₅H₂₅F₂NO₄ requires: C 56.06, H 7.84, N, 4.36%); ν_max(KBr)/cm⁻¹ 3460 (s br, O—H), 3356 (s br, O—H), 2977 (m, =C—H), 2877 (m, C—H), 1671 (s, C=O); ¹H NMR (250 MHz, CDCl₃): δ 5.83 (1H, dd, J = 18.5, 9.0 Hz, H-5), 5.53 (1H, t, J = 9.0, 9.0 Hz, H-4), 4.84 (1H, ddd, ³J_HF = 21.3, 8.0, 4.1 Hz, H-3), 4.48 (1H, d, J = 5.7 Hz, H-8), 4.18–4.04 (1H, m, H-1), 3.42–3.10 [5H, m, —OH and —N(CH₂CH₃)₂], 2.45 (1H, dd, J_gem = 13.8, J = 8.5 Hz, H-6a), 2.17 (1H, br s, —OH), 1.77 (1H, dd, J_gem = 13.8 Hz, J = 8.3 Hz, H-6b), 1.18–0.93 [12H, m, —N(CH₂CH₃)₂ and 2 × —CH₃]; ¹³C NMR (63 MHz, CDCl₃): δ 157.4, 131.4, 131.3 (d, ³J_CF = 6.6 Hz), 122.8 (dd, ¹J_CF = 253.1, 246.9 Hz), 87.4 (d, ³J_CF = 9.2 Hz), 70.8 (dd, ²J_CF = 23.9, 19.8 Hz), 68.4 (dd, ²J_CF = 23.9, 20.9 Hz), 42.8, 42.0, 39.8, 34.9, 30.4, 24.3, 14.5, 13.4; ¹⁹F NMR (235 MHz, CDCl₃): δ −118.5 (1F, dddd, J_gem = 241.5, ³J_HF = 21.2, 10.6, ⁴J_FH = 6.6 Hz), −122.1 (1F, dd, J_gem = 241.5, ³J_FH = 16.6 Hz); [HRMS (FAB, [M+H]⁺) Found: 322.18293, calculated for C₁₅H₂₆F₂NO₄: 322.18299]; m/z (FAB): 322 (100%, [M+H]⁺). An analytical sample was recrystallized by vapour diffusion (ethyl acetate/light petroleum) to afford colourless needles.

Crystal data

C₁₅H₂₅F₂NO₄
M_r = 321.36
Monoclinic, P n
a = 7.9651 (14) Å
b = 6.4632 (12) Å
c = 15.445 (3) Å
β = 90.136 (3)°
V = 795.1 (2) Å³
Z = 2
D_x = 1.342 Mg m⁻³
Mo Kα radiation
Cell parameters from 2104 reflections
θ = 2.6–24.7°
μ = 0.11 mm⁻¹
T = 150 (2) K
Block cut from needle, colourless
0.24 × 0.18 × 0.12 mm

Data collection

Bruker APEX CCD area-detector diffractometer
φ and ω scans
Absorption correction: none
5283 measured reflections
1403 independent reflections
1332 reflections with I > 2σ(I)
R_int = 0.041
θ_max = 25.0°
h = −9 → 9
k = −7 → 7
l = −18 → 18

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.082
wR(F²) = 0.230
S = 1.13
1403 reflections
203 parameters
H-atom parameters constrained
w = 1/[σ²(F_o²) + (0.1065P)² + 3.2641P] where P = (F_o² + 2F_c²)/3
(Δ/σ)_max = 0.003
Δρ_max = 0.37 e Å⁻³
Δρ_min = −0.45 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯O2ⁱ	0.84	2.18	2.816 (10)	133
Symmetry code: (i) x, y+1, z.

H atoms were positioned geometrically, with C—H = 0.95–1.00 Å and O—H = 0.84 Å, and treated as riding, with U_iso(H) = 1.2 or 1.5 (methyl and OH) times U_eq of the parent atom.

Data collection: SMART (Bruker, 1997 ); cell refinement: SAINT (Bruker, 1999 ); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Sheldrick, 2000 ); software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks 1, global. DOI: 10.1107/S1600536805024839/cf6442sup1.cif

Structure factors: contains datablock 1. DOI: 10.1107/S1600536805024839/cf64421sup2.hkl

Comment top

Conformational equilibria in eight-membered carbocycles occur via two main processes, pseudorotation and ring inversion. The latter exchanges substituent groups between equatorial and axial environments in a pseudo-enantiomeric relationship. Ring inversion is usually the more energetically demanding process; barriers to inversion exchange of 7.3–8.5 kcal mol⁻¹ have been reported, with smaller barriers (ca 5 kcal mol⁻¹) (Servis & Noe, 1973) for the pseudorotation. [For early attempts to apply variable-temperature NMR to these phenomena, see Anderson et al. (1969) and St Jacques et al. (1966).] Recent work from our group has attempted to define these processes for a trio of difluorinated cyclooctenyl systems (Griffith et al., 2005). We were interested to observe a pseudorotational relationship between the ring conformations in the pair of reduction products (1) and (2), obtained upon treatment of a precursor ketone with sodium borohydride.

Product (1) (the major product) arises from the opposite sense of hydride attack, with the N,N-diethylcarbamoyl group retaining its original location (Fig. 1). Product (2), reported in the following paper (Fawcett, Percy et al., 2005), arises from reagent attack on the ring face which bears the hydroxyl group, followed by migration of the N,N-diethylcarbamoyl group on to the newly formed hydroxyl group (Balnaves et al., 1999). A comparison of the two molecules is shown in Fig. 2. O—H···O hydrogen bonding links molecules of (1) into chains along the b axis (Table 1).

Experimental top

The precursor ketone was prepared as described in the literature (Fawcett, Griffith et al., 2005). Sodium borohydride (1.8 mmol, 70 mg) was added in five portions to a cold (273 K) solution of the ketone (1.8 mmol, 0.59 g) in ethanol (10 ml). After completion of the addition, the reaction mixture was allowed to warm to room temperature, stirred for 2 h at this temperature and poured over a mixture of ice and water (25 ml). HCl (10 ml of a 1 N solution) was added cautiously and the mixture was extracted with diethyl ether (3 × 25 ml). The combined organic extracts were dried (MgSO₄), filtered and concentrated under reduced pressure to leave a white solid (0.51 g). Purification by column chromatography (40% ethyl acetate in light petroleum) afforded the desired diol (1) as a white solid (0.43 g, 72%). R_F (40% ethyl acetate in light petroleum) 0.29; m.p. 388–389 K (found: C 56.17, H 7.71, N 4.29%; C₁₅H₂₅F₂NO₄ requires: C 56.06, H 7.84, N, 4.36%); ν_max(KBr)/cm⁻¹ 3460 (s br, O—H), 3356 (s br, O—H), 2977 (m, ═C—H), 2877 (m, C—H), 1671 (s, C═O); ¹H NMR (250 MHz, CDCl₃): δ 5.83 (1H, dd, J = 18.5, 9.0 Hz, H-5), 5.53 (1H, t, J = 9.0, 9.0 Hz, H-4), 4.84 (1H, ddd, ³J_HF = 21.3, 8.0, 4.1 Hz, H-3), 4.48 (1H, d, J = 5.7 Hz, H-8), 4.18–4.04 (1H, m, H-1), 3.42–3.10 [5H, m, –OH and –N(CH₂CH₃)₂], 2.45 (1H, dd, J_gem = 13.8, J = 8.5 Hz, H-6a), 2.17 (1H, br s, –OH), 1.77 (1H, dd, J_gem = 13.8 Hz, J = 8.3 Hz, H-6 b), 1.18–0.93 [12H, m, –N(CH₂CH₃)₂ and 2 × –CH₃]; ¹³C NMR (63 MHz, CDCl₃): δ 157.4, 131.4, 131.3 (d, ³J_CF = 6.6 Hz), 122.8 (dd, ¹J_CF = 253.1, 246.9 Hz), 87.4 (d, ³J_CF = 9.2 Hz), 70.8 (dd, ²J_CF = 23.9, 19.8 Hz), 68.4 (dd, ²J_CF = 23.9, 20.9 Hz), 42.8, 42.0, 39.8, 34.9, 30.4, 24.3, 14.5, 13.4; ¹⁵F NMR (235 MHz, CDCl₃): δ −118.5 (1 F, dddd, J_gem = 241.5, ³J_HF = 21.2, 10.6, ⁴J_FH = 6.6 Hz), −122.1 (1 F, dd, J_gem = 241.5, ³J_FH = 16.6 Hz); [HRMS (FAB, [M+H]⁺) Found: 322.18293, calculated for C₁₅H₂₆F₂NO₄: 322.18299]; m/z (FAB): 322 (100%, [M+H]⁺). An analytical sample was recrystallized by vapour diffusion (ethyl acetate/light petroleum) to afford colourless needles.

Computing details top

Data collection: SMART (Bruker, 1997); cell refinement: SAINT (Bruker, 1999); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Sheldrick, 2000); software used to prepare material for publication: SHELXTL.

Figures top

	Fig. 1. The molecular structure of (1), showing the atom-numbering scheme and 50% displacement ellipsoids. H atoms have been omitted for clarity.
	Fig. 2. An overlay showing the relationship between the structures of compounds (1) and (2).

(1S*,2S*,4S*)-3,3-Difluoro-2,4-dihydroxy-5,5-dimethylcyclooct-5(Z)-en-1-yl N,N-diethylcarbamate top

Crystal data top

C₁₅H₂₅F₂NO₄	F(000) = 344
M_r = 321.36	D_x = 1.342 Mg m⁻³
Monoclinic, Pn	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P -2yac	Cell parameters from 2104 reflections
a = 7.9651 (14) Å	θ = 2.6–24.7°
b = 6.4632 (12) Å	µ = 0.11 mm⁻¹
c = 15.445 (3) Å	T = 150 K
β = 90.136 (3)°	Block, colourless
V = 795.1 (2) Å³	0.24 × 0.18 × 0.12 mm
Z = 2

Data collection top

Bruker APEX CCD area-detector diffractometer	1332 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.041
Graphite monochromator	θ_max = 25.0°, θ_min = 2.6°
ϕ and ω scans	h = −9→9
5283 measured reflections	k = −7→7
1403 independent reflections	l = −18→18

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)] = 0.082	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.230	H-atom parameters constrained
S = 1.13	w = 1/[σ²(F_o²) + (0.1065P)² + 3.2641P] where P = (F_o² + 2F_c²)/3
1403 reflections	(Δ/σ)_max = 0.003
203 parameters	Δρ_max = 0.37 e Å⁻³
2 restraints	Δρ_min = −0.45 e Å⁻³

Crystal data top

C₁₅H₂₅F₂NO₄	V = 795.1 (2) Å³
M_r = 321.36	Z = 2
Monoclinic, Pn	Mo Kα radiation
a = 7.9651 (14) Å	µ = 0.11 mm⁻¹
b = 6.4632 (12) Å	T = 150 K
c = 15.445 (3) Å	0.24 × 0.18 × 0.12 mm
β = 90.136 (3)°

Data collection top

Bruker APEX CCD area-detector diffractometer	1332 reflections with I > 2σ(I)
5283 measured reflections	R_int = 0.041
1403 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.082	2 restraints
wR(F²) = 0.230	H-atom parameters constrained
S = 1.13	Δρ_max = 0.37 e Å⁻³
1403 reflections	Δρ_min = −0.45 e Å⁻³
203 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
F1	0.6752 (7)	0.0571 (9)	0.2519 (4)	0.0344 (14)
F2	0.6142 (6)	0.1799 (8)	0.1254 (4)	0.0293 (12)
O1	0.7967 (8)	0.4476 (10)	0.2290 (4)	0.0285 (15)
H1	0.7144	0.4897	0.1998	0.043*
O2	0.6712 (8)	−0.2340 (10)	0.1225 (4)	0.0291 (15)
H2	0.7050	−0.3474	0.1024	0.044*
O3	0.8718 (8)	0.0997 (9)	0.0008 (4)	0.0249 (14)
O4	0.6287 (8)	−0.0565 (9)	−0.0385 (4)	0.0253 (14)
N1	0.6973 (9)	0.2608 (11)	−0.0879 (5)	0.0228 (16)
C1	0.8721 (11)	0.2781 (14)	0.1864 (6)	0.0243 (19)
H1A	0.9126	0.3248	0.1284	0.029*
C2	0.7432 (12)	0.1048 (15)	0.1735 (6)	0.026 (2)
C3	0.8118 (11)	−0.0981 (14)	0.1351 (6)	0.025 (2)
H3	0.8849	−0.1626	0.1805	0.030*
C4	0.9179 (11)	−0.0828 (13)	0.0516 (6)	0.0227 (19)
H4	0.8865	−0.2054	0.0155	0.027*
C5	1.1090 (11)	−0.0844 (14)	0.0577 (6)	0.0218 (19)
C5'	1.1659 (12)	−0.2867 (15)	0.1012 (7)	0.033 (2)
H5'1	1.1501	−0.2759	0.1640	0.050*
H5'2	1.2848	−0.3109	0.0887	0.050*
H5'3	1.0990	−0.4022	0.0788	0.050*
C5"	1.1791 (12)	−0.0842 (16)	−0.0346 (7)	0.032 (2)
H5"1	1.1315	−0.2007	−0.0670	0.047*
H5"2	1.3016	−0.0975	−0.0324	0.047*
H5"3	1.1490	0.0458	−0.0634	0.047*
C6	1.1867 (11)	0.1057 (15)	0.1063 (7)	0.029 (2)
H6A	1.3097	0.1034	0.0973	0.034*
H6B	1.1433	0.2334	0.0788	0.034*
C7	1.1546 (12)	0.1196 (14)	0.2009 (6)	0.026 (2)
H7	1.2371	0.0628	0.2386	0.032*
C8	1.0180 (12)	0.2062 (14)	0.2379 (6)	0.029 (2)
H8	1.0155	0.2214	0.2991	0.035*
C9	0.7223 (11)	0.0905 (15)	−0.0430 (5)	0.0227 (19)
C10	0.5307 (11)	0.2911 (17)	−0.1285 (6)	0.028 (2)
H10C	0.4777	0.1548	−0.1391	0.034*
H10D	0.5444	0.3612	−0.1850	0.034*
C10'	0.8155 (11)	0.4301 (14)	−0.0983 (6)	0.024 (2)
H10A	0.8889	0.4363	−0.0465	0.029*
H10B	0.7523	0.5617	−0.1014	0.029*
C11	0.4178 (12)	0.4201 (16)	−0.0708 (6)	0.030 (2)
H11D	0.4013	0.3486	−0.0156	0.045*
H11E	0.3090	0.4402	−0.0994	0.045*
H11F	0.4703	0.5550	−0.0603	0.045*
C11'	0.9211 (13)	0.411 (2)	−0.1756 (8)	0.041 (3)
H11A	0.9914	0.2876	−0.1708	0.061*
H11B	0.9927	0.5341	−0.1807	0.061*
H11C	0.8495	0.4002	−0.2271	0.061*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.044 (3)	0.033 (3)	0.027 (3)	−0.008 (3)	0.013 (2)	0.000 (2)
F2	0.018 (2)	0.031 (3)	0.039 (3)	0.006 (2)	−0.001 (2)	−0.002 (3)
O1	0.033 (4)	0.024 (3)	0.029 (3)	0.010 (3)	−0.002 (3)	−0.006 (3)
O2	0.026 (3)	0.021 (3)	0.040 (4)	−0.010 (3)	0.008 (3)	−0.007 (3)
O3	0.022 (3)	0.017 (3)	0.036 (3)	0.002 (3)	−0.007 (3)	0.001 (3)
O4	0.026 (3)	0.021 (3)	0.030 (3)	−0.002 (3)	−0.003 (3)	0.001 (3)
N1	0.030 (4)	0.015 (4)	0.024 (4)	0.006 (3)	−0.005 (3)	−0.003 (3)
C1	0.033 (5)	0.022 (4)	0.018 (4)	−0.004 (4)	0.006 (4)	−0.006 (4)
C2	0.028 (5)	0.019 (5)	0.030 (5)	0.005 (4)	−0.001 (4)	0.005 (4)
C3	0.025 (5)	0.022 (5)	0.029 (5)	0.000 (4)	−0.007 (4)	−0.001 (4)
C4	0.024 (4)	0.015 (4)	0.029 (5)	0.000 (3)	−0.004 (4)	0.003 (4)
C5	0.021 (4)	0.021 (4)	0.023 (4)	0.002 (4)	0.001 (4)	0.006 (4)
C5'	0.032 (5)	0.026 (5)	0.042 (6)	0.006 (4)	−0.007 (4)	0.013 (4)
C5"	0.025 (5)	0.033 (5)	0.036 (5)	0.000 (4)	0.005 (4)	−0.001 (4)
C6	0.014 (4)	0.029 (5)	0.044 (6)	−0.002 (4)	0.005 (4)	−0.002 (4)
C7	0.037 (5)	0.021 (4)	0.021 (5)	0.001 (4)	−0.009 (4)	0.003 (4)
C8	0.037 (5)	0.021 (5)	0.028 (5)	−0.007 (4)	−0.006 (4)	−0.002 (4)
C9	0.025 (4)	0.032 (5)	0.011 (4)	−0.004 (4)	−0.007 (3)	−0.004 (4)
C10	0.021 (4)	0.040 (6)	0.024 (4)	−0.002 (4)	−0.001 (4)	−0.006 (4)
C10'	0.024 (5)	0.023 (5)	0.027 (5)	0.008 (4)	−0.005 (4)	0.002 (4)
C11	0.025 (5)	0.033 (5)	0.032 (5)	0.006 (4)	0.008 (4)	0.009 (4)
C11'	0.023 (5)	0.051 (7)	0.047 (6)	−0.007 (5)	0.010 (5)	−0.009 (5)

Geometric parameters (Å, º) top

F1—C2	1.363 (11)	C5'—H5'2	0.980
F2—C2	1.356 (11)	C5'—H5'3	0.980
O1—C1	1.412 (10)	C5"—H5"1	0.980
O1—H1	0.840	C5"—H5"2	0.980
O2—C3	1.437 (11)	C5"—H5"3	0.980
O2—H2	0.840	C6—C7	1.487 (13)
O3—C9	1.369 (11)	C6—H6A	0.990
O3—C4	1.463 (10)	C6—H6B	0.990
O4—C9	1.210 (11)	C7—C8	1.351 (14)
N1—C9	1.315 (12)	C7—H7	0.950
N1—C10'	1.453 (12)	C8—H8	0.950
N1—C10	1.480 (11)	C10—C11	1.517 (13)
C1—C8	1.482 (13)	C10—H10C	0.990
C1—C2	1.533 (13)	C10—H10D	0.990
C1—H1A	1.000	C10'—C11'	1.468 (14)
C2—C3	1.540 (12)	C10'—H10A	0.990
C3—C4	1.548 (13)	C10'—H10B	0.990
C3—H3	1.000	C11—H11D	0.980
C4—C5	1.524 (12)	C11—H11E	0.980
C4—H4	1.000	C11—H11F	0.980
C5—C5"	1.532 (13)	C11'—H11A	0.980
C5—C5'	1.538 (12)	C11'—H11B	0.980
C5—C6	1.567 (13)	C11'—H11C	0.980
C5'—H5'1	0.980

C1—O1—H1	109.5	H5"1—C5"—H5"2	109.5
C3—O2—H2	109.5	C5—C5"—H5"3	109.5
C9—O3—C4	116.6 (7)	H5"1—C5"—H5"3	109.5
C9—N1—C10'	126.2 (7)	H5"2—C5"—H5"3	109.5
C9—N1—C10	117.9 (8)	C7—C6—C5	116.7 (8)
C10'—N1—C10	115.7 (7)	C7—C6—H6A	108.1
O1—C1—C8	109.1 (7)	C5—C6—H6A	108.1
O1—C1—C2	110.0 (7)	C7—C6—H6B	108.1
C8—C1—C2	111.4 (8)	C5—C6—H6B	108.1
O1—C1—H1A	108.8	H6A—C6—H6B	107.3
C8—C1—H1A	108.8	C8—C7—C6	125.5 (8)
C2—C1—H1A	108.8	C8—C7—H7	117.2
F2—C2—F1	105.4 (7)	C6—C7—H7	117.2
F2—C2—C1	108.4 (7)	C7—C8—C1	122.3 (8)
F1—C2—C1	108.5 (7)	C7—C8—H8	118.9
F2—C2—C3	111.3 (7)	C1—C8—H8	118.9
F1—C2—C3	106.9 (7)	O4—C9—N1	126.5 (8)
C1—C2—C3	115.7 (7)	O4—C9—O3	122.7 (8)
O2—C3—C2	107.2 (7)	N1—C9—O3	110.7 (8)
O2—C3—C4	110.6 (7)	N1—C10—C11	110.8 (8)
C2—C3—C4	117.5 (8)	N1—C10—H10C	109.5
O2—C3—H3	107.0	C11—C10—H10C	109.5
C2—C3—H3	107.0	N1—C10—H10D	109.5
C4—C3—H3	107.0	C11—C10—H10D	109.5
O3—C4—C5	106.7 (7)	H10C—C10—H10D	108.1
O3—C4—C3	111.2 (7)	N1—C10'—C11'	113.6 (8)
C5—C4—C3	119.7 (7)	N1—C10'—H10A	108.8
O3—C4—H4	106.1	C11'—C10'—H10A	108.8
C5—C4—H4	106.1	N1—C10'—H10B	108.8
C3—C4—H4	106.1	C11'—C10'—H10B	108.8
C4—C5—C5"	107.9 (7)	H10A—C10'—H10B	107.7
C4—C5—C5'	109.0 (7)	C10—C11—H11D	109.5
C5"—C5—C5'	107.4 (8)	C10—C11—H11E	109.5
C4—C5—C6	114.7 (7)	H11D—C11—H11E	109.5
C5"—C5—C6	107.5 (7)	C10—C11—H11F	109.5
C5'—C5—C6	110.0 (8)	H11D—C11—H11F	109.5
C5—C5'—H5'1	109.5	H11E—C11—H11F	109.5
C5—C5'—H5'2	109.5	C10'—C11'—H11A	109.5
H5'1—C5'—H5'2	109.5	C10'—C11'—H11B	109.5
C5—C5'—H5'3	109.5	H11A—C11'—H11B	109.5
H5'1—C5'—H5'3	109.5	C10'—C11'—H11C	109.5
H5'2—C5'—H5'3	109.5	H11A—C11'—H11C	109.5
C5—C5"—H5"1	109.5	H11B—C11'—H11C	109.5
C5—C5"—H5"2	109.5

O1—C1—C2—F2	59.4 (9)	C3—C4—C5—C5'	59.3 (11)
C8—C1—C2—F2	−179.4 (7)	O3—C4—C5—C6	62.8 (9)
O1—C1—C2—F1	−54.5 (9)	C3—C4—C5—C6	−64.5 (11)
C8—C1—C2—F1	66.6 (9)	C4—C5—C6—C7	68.2 (10)
O1—C1—C2—C3	−174.7 (7)	C5"—C5—C6—C7	−171.7 (8)
C8—C1—C2—C3	−53.6 (10)	C5'—C5—C6—C7	−55.0 (10)
F2—C2—C3—O2	−51.6 (9)	C5—C6—C7—C8	−86.0 (12)
F1—C2—C3—O2	63.0 (9)	C6—C7—C8—C1	7.2 (15)
C1—C2—C3—O2	−176.0 (7)	O1—C1—C8—C7	−149.3 (9)
F2—C2—C3—C4	73.6 (10)	C2—C1—C8—C7	89.1 (10)
F1—C2—C3—C4	−171.7 (7)	C10'—N1—C9—O4	−175.1 (9)
C1—C2—C3—C4	−50.8 (11)	C10—N1—C9—O4	8.3 (13)
C9—O3—C4—C5	153.8 (7)	C10'—N1—C9—O3	5.7 (12)
C9—O3—C4—C3	−74.1 (9)	C10—N1—C9—O3	−170.9 (7)
O2—C3—C4—O3	96.4 (8)	C4—O3—C9—O4	2.5 (12)
C2—C3—C4—O3	−27.1 (11)	C4—O3—C9—N1	−178.3 (7)
O2—C3—C4—C5	−138.4 (8)	C9—N1—C10—C11	95.1 (10)
C2—C3—C4—C5	98.1 (10)	C10'—N1—C10—C11	−81.9 (10)
O3—C4—C5—C5"	−57.0 (9)	C9—N1—C10'—C11'	92.9 (11)
C3—C4—C5—C5"	175.8 (8)	C10—N1—C10'—C11'	−90.4 (10)
O3—C4—C5—C5'	−173.4 (7)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O2ⁱ	0.84	2.18	2.816 (10)	133

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

Experimental details

Crystal data
Chemical formula	C₁₅H₂₅F₂NO₄
M_r	321.36
Crystal system, space group	Monoclinic, Pn
Temperature (K)	150
a, b, c (Å)	7.9651 (14), 6.4632 (12), 15.445 (3)
β (°)	90.136 (3)
V (Å³)	795.1 (2)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.11
Crystal size (mm)	0.24 × 0.18 × 0.12

Data collection
Diffractometer	Bruker APEX CCD area-detector diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	5283, 1403, 1332
R_int	0.041
(sin θ/λ)_max (Å⁻¹)	0.594

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.082, 0.230, 1.13
No. of reflections	1403
No. of parameters	203
No. of restraints	2
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.37, −0.45

Computer programs: SMART (Bruker, 1997), SAINT (Bruker, 1999), SAINT, SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL (Sheldrick, 2000), SHELXTL.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O2ⁱ	0.84	2.18	2.816 (10)	133

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

Acknowledgements

The authors thank the Universities of Birmingham and Leicester, the EPSRC (project grant GR/K84882 for SP), GlaxoSmithKline (CASE studentship for SP) and Universities UK (ORS Award for EU).

References

Anderson, J. E., Glazer, E. S., Griffith, D. L., Knorr, R. & Roberts, J. D. (1969). J. Am. Chem. Soc. 91, 1386–1395. CrossRef CAS Web of Science Google Scholar
Balnaves, A. S., Gelbrich, T., Hursthouse, M. B., Light, M. E., Palmer, M. J. & Percy, J. M. (1999). J. Chem. Soc. Perkin Trans. 1, pp. 2525–2535. Web of Science CSD CrossRef Google Scholar
Bruker (1997). SMART. Version 5.622. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruker (1999). SAINT. Version 6.02. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Fawcett, J., Griffith, G. A., Percy, J. M., Pintat, S., Smith, C. A. & Uneyama, E. (2005). Org. Biomol. Chem. 3, 2701–2712. Web of Science CSD CrossRef PubMed Google Scholar
Fawcett, J., Percy, J. M., Pintat, S., Smith, C. A. & Uneyama, E. (2005). Acta Cryst. E61, o3322–o3323. Web of Science CSD CrossRef IUCr Journals Google Scholar
Servis, K. L. & Noe, E. A. (1973). J. Am. Chem. Soc. 95, 171–174. CrossRef CAS Web of Science Google Scholar
Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Göttingen, Germany. Google Scholar
Sheldrick, G. M. (2000). SHELXTL. Version 6.10. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
St Jacques, M., Brown, M. A. & Anet, F. A. L. (1966). Tetrahedron Lett. pp. 5947–5951. CrossRef Google Scholar

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Volume 61| Part 10| October 2005| Pages o3319-o3321

doi:10.1107/S1600536805024839

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organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

(1S*,2S*,4S*)-3,3-Di­fluoro-2,4-dihydr­­oxy-5,5-di­methyl­cyclo­oct-5(Z)-en-1-yl N,N-di­ethyl­carbamate

Comment

Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

(1S,2S,4S*)-3,3-Difluoro-2,4-dihydroxy-5,5-dimethylcyclooct-5(Z)-en-1-yl N,N-diethylcarbamate