(+)-Methyl (4R,5S)-4-[(R)-1-hydroxy­but-3-enyl]-5-2,2-di­methyl-tri­chloro­acet­amido-1,3-dioxane-5-carboxyl­ate

Ohba, S.; Sato, H.; Iida, M.; Chida, N.

doi:10.1107/S160053680301691X

(+)-Methyl (4R,5S)-4-[(R)-1-hydroxybut-3-enyl]-5-2,2-dimethyl-trichloroacetamido-1,3-dioxane-5-carboxylate

The title compound, C₁₄H₂₀Cl₃NO₆, was prepared in a synthetic study of myriocin derivatives. There are intramolecular N—H

O and intermolecular O—H

O hydrogen bonds, forming one-dimensional chains along the c axis.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S160053680301691X/lh6093sup1.cif Contains datablocks General, I
	Structure factor file (CIF format) https://doi.org/10.1107/S160053680301691X/lh6093Isup2.hkl Contains datablock I

CCDC reference: 222848

checkCIF report

Key indicators

Single-crystal X-ray study
T = 297 K
Mean (C-C) = 0.009 Å
R factor = 0.056
wR factor = 0.171
Data-to-parameter ratio = 11.0

checkCIF/PLATON results

No syntax errors found



Alert level B
PLAT242_ALERT_2_B Check Low    U(eq) as Compared to Neighbors ..          C24

Alert level C
PLAT220_ALERT_2_C Large Non-Solvent    C     Ueq(max)/Ueq(min) .       2.78 Ratio
PLAT340_ALERT_3_C Low Bond Precision on C-C bonds (x 1000) Ang..          9
PLAT431_ALERT_2_C Short Inter HL..A Contact:Cl1     .. O8      =       3.04 Ang.
PLAT431_ALERT_2_C Short Inter HL..A Contact:Cl3     .. O4      =       3.01 Ang.

Alert level G
REFLT03_ALERT_4_G  WARNING: Large fraction of Friedel related reflns may
                     be needed to determine absolute structure
           From the CIF: _diffrn_reflns_theta_max           27.50
           From the CIF: _reflns_number_total               2388
           Count of symmetry unique reflns         2248
           Completeness (_total/calc)            106.23%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured       140
           Fraction of Friedel pairs measured     0.062
           Are heavy atom types Z>Si present          yes

   0 ALERT level A = In general: serious problem
   1 ALERT level B = Potentially serious problem
   4 ALERT level C = Check and explain
   1 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   4 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
   1 ALERT type 4 Improvement, methodology, query or suggestion

Comment top

The title compound, (I), was prepared in a synthetic study on myriocin, which is a naturally occurring α-substituted α-amino acid derivative with potent immunosuppressive activity. Compound (I) would be a useful intermediate for the total synthesis of myriocin (Oishi et al., 2002), as well as its congeners, such as mycestericins (Sasaki et al., 1994). Since the geometry of (I) could not be fully determined based on the NMR experiments, an X-ray analysis has been carried out.

The dioxane ring of (I) shows a chair conformation, with the trichloroacetylamino group in an axial position (Fig. 1). The absolute configuration at atom C12, which came from that at C-2 of dimethyl L-tartrate, was confirmed with the reasonable Flack (1983) parameter. Consequently, the absolute configurations around other two chiral centers (C13 and C17 atoms) have been revealed. There are intramolecular N10—H10···O6 and intermolecular O6—H6···O9ⁱ [symmetry code: (i) y, 1 − x, z − 1/4] hydrogen bonds (Table 1), forming one-dimensional chains along the c axis (Fig. 2).

Experimental top

Treatment of methyl (4R,5S)-4-formyl-2,2-dimethyl-5-trichloroacetamido- 1,3-dioxane-5-carboxylate, prepared from dimethyl L-tartrate in 14-step reactions involving an Overman rearrangement (Sato et al., 2003), with allyltributyltin in the presence of MgBr₂ in CH₂Cl₂ afforded the title compound, (I). Crystals of (I) were grown from an ethyl acetate solution by slow evaporation (m.p. 371–372 K). The specific rotation [α]_D of (I) at 295 K is +56° (c = 1.0, CHCl₃).

Computing details top

Data collection: WinAFC Diffractometer Control Software (Rigaku, 1999); cell refinement: WinAFC Diffractometer Control Software; data reduction: TEXSAN (Molecular Structure Corporation, 2001); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: TEXSAN.

Figures top

	Fig. 1. The molecular structure of (I), with displacement ellipsoids plotted at the 40% probability level.
	Fig. 2. The projection of the crystal structure of (I) along the a axis, with thin lines indicating hydrogen bonding.

(I) top

Crystal data top

C₁₄H₂₀Cl₃NO₆	D_x = 1.400 Mg m⁻³
M_r = 404.67	Melting point = 371–372 K
Tetragonal, P4₁	Mo Kα radiation, λ = 0.7107 Å
Hall symbol: P 4w	Cell parameters from 25 reflections
a = 9.1926 (8) Å	θ = 10.1–10.8°
c = 22.724 (2) Å	µ = 0.50 mm⁻¹
V = 1920.2 (3) Å³	T = 297 K
Z = 4	Block, colourless
F(000) = 840	0.55 × 0.45 × 0.45 mm

Data collection top

Rigaku AFC-7R diffractometer	R_int = 0.016
ω scans	θ_max = 27.5°
Absorption correction: integration (Coppens et al., 1965)	h = −4→11
T_min = 0.762, T_max = 0.815	k = 0→11
3009 measured reflections	l = −12→29
2388 independent reflections	3 standard reflections every 150 reflections
1963 reflections with I > 2σ(I)	intensity decay: 13.3%

Refinement top

Refinement on F²	w = 1/[σ²(F_o²) + (0.0963P)² + 1.4164P] where P = (F_o² + 2F_c²)/3
R[F² > 2σ(F²)] = 0.056	(Δ/σ)_max = 0.011
wR(F²) = 0.171	Δρ_max = 0.62 e Å⁻³
S = 1.05	Δρ_min = −0.51 e Å⁻³
2388 reflections	Absolute structure: Flack (1983), 140 Friedel pairs
218 parameters	Absolute structure parameter: 0.16 (13)
H-atom parameters not refined

Crystal data top

C₁₄H₂₀Cl₃NO₆	Z = 4
M_r = 404.67	Mo Kα radiation
Tetragonal, P4₁	µ = 0.50 mm⁻¹
a = 9.1926 (8) Å	T = 297 K
c = 22.724 (2) Å	0.55 × 0.45 × 0.45 mm
V = 1920.2 (3) Å³

Data collection top

Rigaku AFC-7R diffractometer	1963 reflections with I > 2σ(I)
Absorption correction: integration (Coppens et al., 1965)	R_int = 0.016
T_min = 0.762, T_max = 0.815	3 standard reflections every 150 reflections
3009 measured reflections	intensity decay: 13.3%
2388 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.056	H-atom parameters not refined
wR(F²) = 0.171	Δρ_max = 0.62 e Å⁻³
S = 1.05	Δρ_min = −0.51 e Å⁻³
2388 reflections	Absolute structure: Flack (1983), 140 Friedel pairs
218 parameters	Absolute structure parameter: 0.16 (13)

Special details top

Refinement. Refinement using reflections with F² > 0.0 σ(F²). The weighted R-factor (wR), goodness of fit (S) and R-factor (gt) are based on F, with F set to zero for negative F. The threshold expression of F² > 2.0 σ(F²) is used only for calculating R-factor (gt).

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

	x	y	z	U_iso*/U_eq
Cl1	0.9478 (2)	0.4855 (3)	0.31714 (9)	0.0885 (7)
Cl2	0.9019 (4)	0.7523 (3)	0.3779 (1)	0.131 (1)
Cl3	0.6682 (2)	0.6126 (3)	0.3164 (1)	0.0864 (7)
O4	0.4651 (5)	0.4282 (5)	0.4821 (2)	0.0543 (10)
O5	0.4247 (4)	0.2631 (4)	0.4062 (2)	0.0411 (7)
O6	0.6421 (5)	0.1769 (5)	0.3241 (2)	0.055 (1)
O7	0.9048 (5)	0.1782 (6)	0.4394 (2)	0.077 (2)
O8	0.7717 (5)	0.1137 (5)	0.5168 (2)	0.063 (1)
O9	0.8516 (5)	0.5221 (6)	0.4619 (2)	0.063 (1)
N10	0.7042 (5)	0.3826 (5)	0.4054 (2)	0.0395 (9)
C11	0.3580 (6)	0.3434 (6)	0.4535 (3)	0.049 (1)
C12	0.5442 (5)	0.1758 (5)	0.4229 (2)	0.0357 (9)
C13	0.6635 (5)	0.2754 (6)	0.4504 (2)	0.0379 (10)
C14	0.5878 (6)	0.3485 (6)	0.5024 (2)	0.046 (1)
C15	0.2574 (9)	0.4508 (9)	0.4229 (4)	0.078 (2)
C16	0.2780 (7)	0.2450 (9)	0.4952 (3)	0.066 (2)
C17	0.5885 (6)	0.0846 (6)	0.3697 (2)	0.043 (1)
C18	0.4614 (8)	−0.0077 (7)	0.3486 (3)	0.061 (2)
C19	0.4043 (10)	−0.1111 (8)	0.3943 (3)	0.074 (2)
C20	0.275 (1)	−0.113 (1)	0.4146 (5)	0.098 (3)
C21	0.7939 (6)	0.1847 (7)	0.4673 (2)	0.047 (1)
C22	0.8868 (8)	0.018 (1)	0.5372 (4)	0.085 (2)
C23	0.7922 (6)	0.4931 (6)	0.4161 (2)	0.042 (1)
C24	0.8233 (6)	0.5869 (6)	0.3598 (3)	0.048 (1)
H6	0.6034	0.1549	0.2928	0.0552*
H10	0.6645	0.3716	0.3672	0.0471*
H12	0.5116	0.1112	0.4529	0.0427*
H14A	0.6532	0.4146	0.5207	0.0554*
H14B	0.5573	0.2775	0.5296	0.0554*
H15A	0.2158	0.5142	0.4515	0.0912*
H15B	0.3106	0.5058	0.3951	0.0912*
H15C	0.1817	0.3990	0.4035	0.0912*
H16A	0.2328	0.3032	0.5248	0.0782*
H16B	0.2060	0.1929	0.4743	0.0782*
H16C	0.3446	0.1802	0.5129	0.0782*
H17	0.6640	0.0202	0.3811	0.0520*
H18A	0.3833	0.0567	0.3383	0.0712*
H18B	0.4899	−0.0615	0.3155	0.0712*
H19	0.4712	−0.1798	0.4092	0.0883*
H20A	0.2461	−0.1815	0.4435	0.1129*
H20B	0.2033	−0.0438	0.4006	0.1129*
H22A	0.8598	−0.0287	0.5725	0.1001*
H22B	0.9028	−0.0574	0.5076	0.1001*
H22C	0.9746	0.0693	0.5420	0.1001*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.082 (1)	0.113 (2)	0.071 (1)	0.024 (1)	0.038 (1)	0.023 (1)
Cl2	0.196 (3)	0.081 (1)	0.115 (2)	−0.078 (2)	−0.020 (2)	0.010 (1)
Cl3	0.0588 (9)	0.103 (1)	0.098 (1)	0.0004 (9)	−0.0142 (10)	0.051 (1)
O4	0.061 (2)	0.057 (2)	0.046 (2)	0.005 (2)	0.005 (2)	−0.008 (2)
O5	0.041 (2)	0.049 (2)	0.033 (2)	0.005 (1)	−0.004 (1)	−0.001 (1)
O6	0.071 (2)	0.066 (2)	0.029 (2)	−0.019 (2)	0.000 (2)	−0.005 (2)
O7	0.057 (3)	0.111 (4)	0.062 (3)	0.022 (3)	0.013 (2)	0.021 (3)
O8	0.051 (2)	0.080 (3)	0.058 (3)	0.001 (2)	−0.003 (2)	0.032 (2)
O9	0.062 (3)	0.092 (3)	0.035 (2)	−0.029 (2)	−0.002 (2)	−0.012 (2)
N10	0.047 (2)	0.045 (2)	0.026 (2)	−0.008 (2)	−0.002 (2)	0.002 (2)
C11	0.039 (3)	0.058 (3)	0.050 (3)	0.010 (2)	0.000 (2)	−0.002 (2)
C12	0.039 (2)	0.041 (2)	0.026 (2)	−0.002 (2)	−0.002 (2)	−0.001 (2)
C13	0.042 (2)	0.047 (3)	0.024 (2)	−0.009 (2)	0.001 (2)	0.003 (2)
C14	0.055 (3)	0.055 (3)	0.027 (2)	−0.007 (2)	0.004 (2)	−0.006 (2)
C15	0.073 (5)	0.082 (5)	0.079 (5)	0.034 (4)	−0.009 (4)	−0.001 (4)
C16	0.046 (3)	0.093 (5)	0.059 (4)	0.011 (3)	0.016 (3)	0.001 (3)
C17	0.053 (3)	0.044 (2)	0.032 (2)	−0.001 (2)	0.003 (2)	−0.002 (2)
C18	0.086 (5)	0.056 (3)	0.042 (3)	−0.017 (3)	−0.008 (3)	−0.007 (3)
C19	0.107 (6)	0.054 (4)	0.060 (4)	−0.031 (4)	−0.003 (4)	0.000 (3)
C20	0.104 (7)	0.107 (7)	0.084 (6)	−0.050 (6)	0.002 (5)	0.003 (5)
C21	0.043 (3)	0.064 (3)	0.035 (2)	−0.011 (2)	−0.009 (2)	0.006 (2)
C22	0.067 (4)	0.100 (6)	0.087 (5)	0.002 (4)	−0.019 (4)	0.045 (5)
C23	0.045 (3)	0.049 (3)	0.032 (2)	−0.002 (2)	0.004 (2)	−0.006 (2)
C24	0.049 (3)	0.046 (3)	0.050 (3)	−0.008 (2)	−0.001 (2)	0.002 (2)

Geometric parameters (Å, º) top

Cl1—C24	1.766 (6)	C13—C21	1.509 (7)
Cl2—C24	1.732 (6)	C14—H14A	0.951
Cl3—C24	1.750 (6)	C14—H14B	0.943
O4—C11	1.414 (7)	C15—H15A	0.951
O4—C14	1.422 (7)	C15—H15B	0.947
O5—C11	1.440 (7)	C15—H15C	0.952
O5—C12	1.413 (6)	C16—H16A	0.955
O6—C17	1.427 (6)	C16—H16B	0.945
O6—H6	0.820	C16—H16C	0.945
O7—C21	1.202 (7)	C17—C18	1.522 (9)
O8—C21	1.317 (7)	C17—H17	0.948
O8—C22	1.454 (10)	C18—C19	1.502 (10)
O9—C23	1.206 (6)	C18—H18A	0.960
N10—C13	1.469 (6)	C18—H18B	0.936
N10—C23	1.322 (7)	C19—C20	1.28 (1)
N10—H10	0.947	C19—H19	0.945
C11—C15	1.52 (1)	C20—H20A	0.945
C11—C16	1.503 (9)	C20—H20B	0.971
C12—C13	1.559 (7)	C22—H22A	0.943
C12—C17	1.526 (7)	C22—H22B	0.975
C12—H12	0.952	C22—H22C	0.943
C13—C14	1.527 (7)	C23—C24	1.569 (8)

C11—O4—C14	114.6 (4)	H16A—C16—H16B	109.5
C11—O5—C12	115.0 (4)	H16A—C16—H16C	109.5
C17—O6—H6	109.5	H16B—C16—H16C	110.3
C21—O8—C22	117.5 (5)	O6—C17—C12	109.9 (4)
C13—N10—C23	122.9 (4)	O6—C17—C18	111.6 (4)
C13—N10—H10	118.0	O6—C17—H17	108.4
C23—N10—H10	119.1	C12—C17—C18	110.6 (4)
O4—C11—O5	109.3 (4)	C12—C17—H17	108.8
O4—C11—C15	106.0 (5)	C18—C17—H17	107.4
O4—C11—C16	112.5 (5)	C17—C18—C19	113.8 (5)
O5—C11—C15	104.6 (5)	C17—C18—H18A	107.9
O5—C11—C16	111.7 (5)	C17—C18—H18B	109.5
C15—C11—C16	112.4 (5)	C19—C18—H18A	107.3
O5—C12—C13	108.7 (4)	C19—C18—H18B	108.5
O5—C12—C17	107.9 (4)	H18A—C18—H18B	109.8
O5—C12—H12	107.6	C18—C19—C20	125.9 (8)
C13—C12—C17	116.9 (4)	C18—C19—H19	116.4
C13—C12—H12	107.5	C20—C19—H19	117.7
C17—C12—H12	108.0	C19—C20—H20A	121.5
N10—C13—C12	107.1 (4)	C19—C20—H20B	120.0
N10—C13—C14	111.1 (4)	H20A—C20—H20B	118.4
N10—C13—C21	110.2 (4)	O7—C21—O8	123.8 (5)
C12—C13—C14	104.3 (4)	O7—C21—C13	124.6 (5)
C12—C13—C21	109.6 (4)	O8—C21—C13	111.6 (4)
C14—C13—C21	114.1 (4)	O8—C22—H22A	110.7
O4—C14—C13	109.8 (4)	O8—C22—H22B	108.6
O4—C14—H14A	108.3	O8—C22—H22C	110.7
O4—C14—H14B	109.5	H22A—C22—H22B	108.0
C13—C14—H14A	109.4	H22A—C22—H22C	110.7
C13—C14—H14B	109.8	H22B—C22—H22C	108.0
H14A—C14—H14B	110.0	O9—C23—N10	127.3 (5)
C11—C15—H15A	109.3	O9—C23—C24	120.0 (5)
C11—C15—H15B	109.7	N10—C23—C24	112.6 (4)
C11—C15—H15C	109.3	Cl1—C24—CL2	108.9 (3)
H15A—C15—H15B	109.7	Cl1—C24—CL3	106.9 (3)
H15A—C15—H15C	109.2	Cl1—C24—C23	106.0 (4)
H15B—C15—H15C	109.6	Cl2—C24—CL3	110.8 (3)
C11—C16—H16A	108.7	Cl2—C24—C23	111.4 (4)
C11—C16—H16B	109.3	Cl3—C24—C23	112.7 (4)
C11—C16—H16C	109.4

Cl1—C24—C23—O9	101.0 (5)	O8—C21—C13—C12	−78.0 (5)
Cl1—C24—C23—N10	−75.9 (5)	O8—C21—C13—C14	38.5 (6)
Cl2—C24—C23—O9	−17.2 (7)	O9—C23—N10—C13	0.7 (9)
Cl2—C24—C23—N10	165.8 (4)	N10—C13—C12—C17	63.2 (5)
Cl3—C24—C23—O9	−142.4 (5)	C11—O4—C14—C13	60.4 (6)
Cl3—C24—C23—N10	40.6 (6)	C11—O5—C12—C13	−59.5 (5)
O4—C11—O5—C12	55.0 (6)	C11—O5—C12—C17	172.9 (4)
O4—C14—C13—N10	56.0 (5)	C12—O5—C11—C15	168.1 (5)
O4—C14—C13—C12	−59.1 (5)	C12—O5—C11—C16	−70.1 (5)
O4—C14—C13—C21	−178.7 (4)	C12—C13—N10—C23	172.9 (4)
O5—C11—O4—C14	−54.5 (6)	C12—C17—C18—C19	−59.5 (7)
O5—C12—C13—N10	−59.1 (5)	C13—N10—C23—C24	177.4 (4)
O5—C12—C13—C14	58.7 (5)	C13—C12—C17—C18	179.3 (4)
O5—C12—C13—C21	−178.7 (4)	C13—C21—O8—C22	177.8 (5)
O5—C12—C17—O6	65.6 (5)	C14—O4—C11—C15	−166.7 (5)
O5—C12—C17—C18	−58.0 (5)	C14—O4—C11—C16	70.1 (6)
O6—C17—C12—C13	−57.1 (6)	C14—C13—N10—C23	59.6 (6)
O6—C17—C18—C19	177.9 (5)	C14—C13—C12—C17	−179.0 (4)
O7—C21—O8—C22	−2.6 (9)	C17—C12—C13—C21	−56.4 (5)
O7—C21—C13—N10	−15.3 (8)	C17—C18—C19—C20	120.3 (9)
O7—C21—C13—C12	102.4 (6)	C21—C13—N10—C23	−67.9 (6)
O7—C21—C13—C14	−141.0 (6)	C21—C13—N10—C23	−67.9 (6)
O8—C21—C13—N10	164.3 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O6—H6···O9ⁱ	0.82	1.99	2.790 (5)	167
N10—H10···O5	0.95	2.58	2.798 (4)	93
N10—H10···O6	0.95	2.05	2.709 (4)	125

Symmetry code: (i) y, −x+1, z−1/4.

Experimental details

Crystal data
Chemical formula	C₁₄H₂₀Cl₃NO₆
M_r	404.67
Crystal system, space group	Tetragonal, P4₁
Temperature (K)	297
a, c (Å)	9.1926 (8), 22.724 (2)
V (Å³)	1920.2 (3)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.50
Crystal size (mm)	0.55 × 0.45 × 0.45

Data collection
Diffractometer	Rigaku AFC-7R diffractometer
Absorption correction	Integration (Coppens et al., 1965)
T_min, T_max	0.762, 0.815
No. of measured, independent and observed [I > 2σ(I)] reflections	3009, 2388, 1963
R_int	0.016
(sin θ/λ)_max (Å⁻¹)	0.650

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.056, 0.171, 1.05
No. of reflections	2388
No. of parameters	218
No. of restraints	?
H-atom treatment	H-atom parameters not refined
Δρ_max, Δρ_min (e Å⁻³)	0.62, −0.51
Absolute structure	Flack (1983), 140 Friedel pairs
Absolute structure parameter	0.16 (13)

Computer programs: WinAFC Diffractometer Control Software (Rigaku, 1999), WinAFC Diffractometer Control Software, TEXSAN (Molecular Structure Corporation, 2001), SIR92 (Altomare et al., 1994), SHELXL97 (Sheldrick, 1997), ORTEPII (Johnson, 1976), TEXSAN.