(2R,4R)-4-(2-Eth­oxy-2-oxoeth­yl)-2,6,6-trimeth­yl-2-oxo-1,3,6,2[lambda]⁵-dioxaza­phospho­can-6-ium iodide

The title compound, C₁₁H₂₃NO₅P⁺·I^-, consists of an eight-membered cationic heterocyclic ring in a boat-chair conformation. The ring features a tetra­alkyl­ammonium N and a methyl­phospho­nate P atom. A -CH₂(CO)OC₂H₅ ester side chain at the C adjacent to oxygen produces two chiral centers at that substituted C atom and the P atom, both of which were determined to have absolute R,R configurations. A previously determined racemic bromide analog has exactly the same ring but with a -C₁₅H₃₁ side chain. In that structure, both chiral centers show the same relative R/S,R/S configurations, but the ring in the bromide analog is in a boat conformation.

Key indicators

• Single-crystal X-ray study
• T = 90 K, P = 0.0 kPa
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.016
• wR factor = 0.039
• Data-to-parameter ratio = 35.6

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT910_ALERT_3_C Missing # of FCF Reflections Below Th(Min) .....          2
PLAT912_ALERT_4_C Missing # of FCF Reflections Above STh/L=  0.600          9

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           33.72
           From the CIF: _reflns_number_total               6304
           Count of symmetry unique reflns         3574
           Completeness (_total/calc)            176.39%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured      2730
           Fraction of Friedel pairs measured     0.764
           Are heavy atom types Z>Si present        yes
PLAT005_ALERT_5_G No _iucr_refine_instructions_details in CIF ....          ?
PLAT791_ALERT_4_G Note: The Model has Chirality at P1     (Verify)          R
PLAT791_ALERT_4_G Note: The Model has Chirality at C3     (Verify)          R

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   2 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   4 ALERT level G = General information/check it is not something unexpected

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   4 ALERT type 4 Improvement, methodology, query or suggestion
   1 ALERT type 5 Informative message, check

---

S1. Comment

The title compound (I) is an analog of 2,6,6-trimethyl-2-oxo-1,3-dioxa- 6-azonia-2-phosphocyclooctane bromide (compound II, CSD code YEVZUU, Allen, 2002), originally targeted for use as a reaction-intermediate inhibitor of carnitine acyltransferase (Kumaravel et al., 1994; Kumaravel et al., 1995). Both compounds contain the same 8-membered cationic heterocyclic ring (C₇H₁₆NO₃P) with two chiral centers at C3 and P1, but with different side chains at C3.

Compound I crystallizes as the R,R enantiomer, whereas II crystallizes as a racemate with R/S,R/S relative configurations. In I, the ring is in the boat-chair conformation, the lowest energy conformer of paradigmatic cyclooctane (Chem3DPro, Cambridgesoft, 2010), but surprisingly the ring in II is in the boat conformation, which in cyclooctane is a higher energy conformer.

Related literature

For MM2 energy minimization, see Cambridgesoft (2010). For a description of the Cambridge Structural Database, see: Allen (2002). For the absolute configuration from Bijvoet pair analysis, see: Hooft et al. (2008). For the synthesis, see: Kumaravel et al. (1994); Hubieki et al. (1996). For a related structure, see: Kumaravel et al. (1995).

S2. Experimental

Synthesis of this class of compounds has been described (Kumaravel et al., 1994; Hubieki et al., 1996). A suitable single-crystal was kindly supplied by Dr. J. H. Rouden.

S3. Refinement

All H atoms were placed in calculated positions guided by difference maps. The C—H bond distances were constrained to the range from 0.98 to 1.00 Å, and U_iso= 1.2U_eq (1.5 for methyl groups), thereafter refined as riding. A torsional parameter was refined for each methyl group.

The absolute configuration was determined by analysis of Bijvoet pairs: the Flack (Flack, 1983) parameter = 0.006 (7), the Hooft (Hooft et al., 2008) parameter = 0.006 (6) and P2(true) = 1.000.

Computing details

Data collection: COLLECT (Bruker 2004); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO and SCALEPACK (Otwinowski & Minor, 1997), and SORTAV (Blessing, 1987, 1989); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures

Fig. 1. View of (I) (50% probability displacement ellipsoids)

(2R,4R)-4-(2-Ethoxy-2-oxoethyl)-2,6,6-trimethyl–2-oxo- 1,3,6,2λ⁵-dioxazaphosphocan-6-ium iodide

Crystal data

C11H23NO5P^+·I^−	F(000) = 816
Mr = 407.17	Dx = 1.706 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 3522 reflections
a = 7.4882 (2) Å	θ = 2.5–33.7°
b = 11.7438 (2) Å	µ = 2.14 mm^−1
c = 18.0235 (4) Å	T = 90 K
V = 1584.99 (6) Å^3	Prism, colourless
Z = 4	0.28 × 0.25 × 0.15 mm

Data collection

Nonius KappaCCD diffractometer	6304 independent reflections
Radiation source: sealed tube	6235 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.042
Detector resolution: 9 pixels mm^-1	θmax = 33.7°, θmin = 2.9°
CCD rotation images, thick slices scans	h = −11→11
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997)	k = −18→18
Tmin = 0.591, Tmax = 0.740	l = −27→28
26155 measured reflections

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F^2 > 2σ(F^2)] = 0.016	w = 1/[σ^2(Fo^2) + (0.0158P)^2 + 0.6491P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.039	(Δ/σ)max = 0.001
S = 1.05	Δρmax = 0.39 e Å^−3
6304 reflections	Δρmin = −0.66 e Å^−3
177 parameters	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0037 (2)
0 constraints	Absolute structure: Flack (1983), 2741 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.006 (7)
Secondary atom site location: difference Fourier map

Special details

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 > 2σ(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 (Ų)

	x	y	z	Uiso*/Ueq
I1	0.043921 (11)	0.959574 (7)	0.228805 (4)	0.01449 (2)
C1	0.36047 (17)	0.73826 (11)	0.14505 (7)	0.0118 (2)
H1A	0.4184	0.762	0.0982	0.014*
H1B	0.3399	0.808	0.1747	0.014*
C2	0.17996 (17)	0.68738 (12)	0.12605 (7)	0.0127 (2)
H2A	0.122	0.662	0.1726	0.015*
H2B	0.1042	0.7478	0.1042	0.015*
C3	0.59764 (16)	0.56554 (10)	0.06758 (7)	0.0098 (2)
H3	0.6129	0.6486	0.0573	0.012*
C4	0.53465 (16)	0.55152 (10)	0.14844 (6)	0.01054 (18)
H4A	0.4272	0.5024	0.149	0.013*
H4B	0.6293	0.5121	0.1769	0.013*
C5	0.66050 (17)	0.73081 (11)	0.19789 (7)	0.0135 (2)
H5A	0.6346	0.7997	0.2266	0.02*
H5B	0.7092	0.7522	0.1494	0.02*
H5C	0.7479	0.6842	0.2246	0.02*
C6	0.41775 (17)	0.63424 (12)	0.26270 (7)	0.0157 (2)
H6A	0.5067	0.59	0.2903	0.024*
H6B	0.3084	0.5892	0.2572	0.024*
H6C	0.3908	0.7045	0.2898	0.024*
C7	0.17486 (17)	0.50423 (12)	−0.06268 (7)	0.0133 (2)
H7A	0.0611	0.54	−0.0761	0.02*
H7B	0.1518	0.431	−0.0385	0.02*
H7C	0.2462	0.4919	−0.1075	0.02*
C8	0.77289 (16)	0.50631 (11)	0.05177 (7)	0.0119 (2)
H8A	0.7942	0.5088	−0.0024	0.014*
H8B	0.8696	0.5504	0.0758	0.014*
C9	0.78769 (17)	0.38388 (11)	0.07689 (7)	0.0118 (2)
C10	1.00454 (18)	0.23653 (11)	0.09371 (9)	0.0171 (2)
H10A	0.964	0.1762	0.0592	0.021*
H10B	0.9495	0.223	0.1429	0.021*
C11	1.2050 (2)	0.23625 (13)	0.09977 (8)	0.0180 (2)
H11A	1.2573	0.2507	0.0508	0.027*
H11B	1.2453	0.162	0.118	0.027*
H11C	1.2429	0.2959	0.1344	0.027*
N1	0.49050 (13)	0.66341 (9)	0.18714 (6)	0.01052 (17)
O1	0.46590 (12)	0.52051 (7)	0.01612 (4)	0.01006 (14)
O2	0.18599 (12)	0.59216 (8)	0.07507 (5)	0.01138 (16)
O3	0.32941 (13)	0.71123 (8)	−0.02761 (5)	0.01296 (17)
O4	0.66875 (13)	0.32687 (9)	0.10299 (6)	0.01603 (18)
O5	0.95505 (14)	0.34845 (8)	0.06562 (5)	0.01394 (16)
P1	0.29315 (4)	0.59443 (3)	−0.001033 (16)	0.00900 (5)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
I1	0.01306 (3)	0.01533 (4)	0.01509 (4)	0.00285 (3)	−0.00355 (3)	−0.00370 (3)
C1	0.0108 (5)	0.0117 (5)	0.0129 (5)	0.0012 (4)	−0.0012 (4)	−0.0008 (4)
C2	0.0098 (5)	0.0163 (6)	0.0121 (5)	0.0020 (4)	0.0004 (4)	−0.0031 (4)
C3	0.0081 (4)	0.0108 (5)	0.0105 (4)	0.0001 (3)	0.0001 (3)	0.0006 (4)
C4	0.0108 (4)	0.0110 (5)	0.0098 (4)	0.0004 (4)	−0.0003 (4)	0.0010 (3)
C5	0.0111 (5)	0.0154 (5)	0.0141 (5)	−0.0038 (4)	−0.0010 (4)	−0.0012 (4)
C6	0.0158 (5)	0.0223 (6)	0.0090 (5)	−0.0027 (4)	0.0016 (4)	0.0004 (4)
C7	0.0119 (5)	0.0172 (5)	0.0109 (5)	−0.0009 (4)	−0.0015 (4)	−0.0015 (4)
C8	0.0077 (4)	0.0122 (5)	0.0159 (5)	0.0005 (4)	0.0013 (4)	0.0026 (4)
C9	0.0107 (5)	0.0121 (5)	0.0125 (5)	0.0016 (4)	−0.0011 (4)	−0.0001 (4)
C10	0.0149 (6)	0.0109 (5)	0.0256 (6)	0.0038 (4)	−0.0005 (5)	0.0033 (4)
C11	0.0147 (6)	0.0216 (6)	0.0179 (6)	0.0048 (5)	−0.0014 (5)	0.0021 (5)
N1	0.0093 (4)	0.0133 (4)	0.0089 (4)	−0.0003 (3)	0.0002 (3)	−0.0006 (3)
O1	0.0089 (3)	0.0120 (4)	0.0093 (3)	0.0011 (3)	−0.0009 (3)	−0.0004 (3)
O2	0.0102 (4)	0.0143 (4)	0.0096 (4)	−0.0010 (3)	0.0013 (3)	−0.0013 (3)
O3	0.0144 (4)	0.0123 (4)	0.0121 (4)	0.0011 (3)	0.0003 (3)	0.0031 (3)
O4	0.0118 (4)	0.0152 (4)	0.0211 (4)	−0.0009 (3)	0.0010 (3)	0.0039 (4)
O5	0.0107 (4)	0.0121 (4)	0.0191 (4)	0.0023 (3)	0.0016 (4)	0.0026 (3)
P1	0.00772 (12)	0.01135 (13)	0.00792 (11)	0.00067 (10)	−0.00033 (10)	0.00100 (10)

Geometric parameters (Å, º)

C1—N1	1.5153 (16)	C6—H6C	0.98
C1—C2	1.5170 (18)	C7—P1	1.7723 (13)
C1—H1A	0.99	C7—H7A	0.98
C1—H1B	0.99	C7—H7B	0.98
C2—O2	1.4481 (16)	C7—H7C	0.98
C2—H2A	0.99	C8—C9	1.5115 (18)
C2—H2B	0.99	C8—H8A	0.99
C3—O1	1.4536 (15)	C8—H8B	0.99
C3—C8	1.5123 (17)	C9—O4	1.2095 (16)
C3—C4	1.5407 (16)	C9—O5	1.3361 (16)
C3—H3	1	C10—O5	1.4565 (16)
C4—N1	1.5239 (15)	C10—C11	1.505 (2)
C4—H4A	0.99	C10—H10A	0.99
C4—H4B	0.99	C10—H10B	0.99
C5—N1	1.5115 (16)	C11—H11A	0.98
C5—H5A	0.98	C11—H11B	0.98
C5—H5B	0.98	C11—H11C	0.98
C5—H5C	0.98	O1—P1	1.5883 (9)
C6—N1	1.5063 (16)	O2—P1	1.5893 (9)
C6—H6A	0.98	O3—P1	1.4780 (10)
C6—H6B	0.98
N1—C1—C2	117.20 (10)	P1—C7—H7C	109.5
N1—C1—H1A	108	H7A—C7—H7C	109.5
C2—C1—H1A	108	H7B—C7—H7C	109.5
N1—C1—H1B	108	C9—C8—C3	116.40 (10)
C2—C1—H1B	108	C9—C8—H8A	108.2
H1A—C1—H1B	107.2	C3—C8—H8A	108.2
O2—C2—C1	114.81 (10)	C9—C8—H8B	108.2
O2—C2—H2A	108.6	C3—C8—H8B	108.2
C1—C2—H2A	108.6	H8A—C8—H8B	107.3
O2—C2—H2B	108.6	O4—C9—O5	125.27 (12)
C1—C2—H2B	108.6	O4—C9—C8	126.10 (12)
H2A—C2—H2B	107.5	O5—C9—C8	108.63 (11)
O1—C3—C8	107.54 (10)	O5—C10—C11	106.31 (11)
O1—C3—C4	110.91 (9)	O5—C10—H10A	110.5
C8—C3—C4	113.25 (10)	C11—C10—H10A	110.5
O1—C3—H3	108.3	O5—C10—H10B	110.5
C8—C3—H3	108.3	C11—C10—H10B	110.5
C4—C3—H3	108.3	H10A—C10—H10B	108.7
N1—C4—C3	114.03 (9)	C10—C11—H11A	109.5
N1—C4—H4A	108.7	C10—C11—H11B	109.5
C3—C4—H4A	108.7	H11A—C11—H11B	109.5
N1—C4—H4B	108.7	C10—C11—H11C	109.5
C3—C4—H4B	108.7	H11A—C11—H11C	109.5
H4A—C4—H4B	107.6	H11B—C11—H11C	109.5
N1—C5—H5A	109.5	C6—N1—C5	107.93 (9)
N1—C5—H5B	109.5	C6—N1—C1	110.62 (10)
H5A—C5—H5B	109.5	C5—N1—C1	107.55 (10)
N1—C5—H5C	109.5	C6—N1—C4	107.23 (9)
H5A—C5—H5C	109.5	C5—N1—C4	109.11 (9)
H5B—C5—H5C	109.5	C1—N1—C4	114.23 (9)
N1—C6—H6A	109.5	C3—O1—P1	118.56 (7)
N1—C6—H6B	109.5	C2—O2—P1	123.39 (8)
H6A—C6—H6B	109.5	C9—O5—C10	117.83 (11)
N1—C6—H6C	109.5	O3—P1—O1	114.88 (5)
H6A—C6—H6C	109.5	O3—P1—O2	112.83 (5)
H6B—C6—H6C	109.5	O1—P1—O2	103.53 (5)
P1—C7—H7A	109.5	O3—P1—C7	116.32 (6)
P1—C7—H7B	109.5	O1—P1—C7	101.68 (6)
H7A—C7—H7B	109.5	O2—P1—C7	106.18 (6)
O2—P1—O1—C3	−68.45 (9)	C2—C1—N1—C6	−63.71 (13)
P1—O1—C3—C4	77.51 (10)	C2—C1—N1—C5	178.65 (10)
O1—C3—C4—N1	−111.53 (11)	C3—C4—N1—C6	175.54 (10)
C3—C4—N1—C1	52.59 (13)	C3—C4—N1—C5	−67.81 (12)
C4—N1—C1—C2	57.38 (13)	C8—C3—O1—P1	−158.16 (8)
N1—C1—C2—O2	−64.93 (14)	O4—C9—O5—C10	−6.70 (19)
C1—C2—O2—P1	−49.45 (14)	C8—C9—O5—C10	173.21 (11)
C2—O2—P1—O1	103.91 (10)	C11—C10—O5—C9	−159.32 (12)
C8—C3—C4—N1	127.45 (11)	C3—O1—P1—O3	55.03 (9)
O1—C3—C8—C9	−73.74 (13)	C3—O1—P1—C7	−178.47 (9)
C4—C3—C8—C9	49.16 (14)	C2—O2—P1—O3	−20.90 (11)
C3—C8—C9—O4	6.12 (19)	C2—O2—P1—C7	−149.44 (10)
C3—C8—C9—O5	−173.79 (11)