(1S,2S)-1-(2-Bromo-4-hydr­oxy-3,5-dimethoxy­phen­yl)propane-1,2,3-triol

The title compond, C₁₁H₁₅BrO₆, is enanti­omerically pure. The chirality at the stereogenic centres was installed via a Sharpless asymmetric dihydroxy­lation reaction and was determined to be S in each case. The crystal structure contains inter­molecular hydrogen-bonding inter­actions.

Key indicators

• Single-crystal X-ray study
• T = 200 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.022
• wR factor = 0.032
• Data-to-parameter ratio = 13.8

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT061_ALERT_3_C Tmax/Tmin Range Test RR' too Large .............       0.82
PLAT125_ALERT_4_C No _symmetry_space_group_name_Hall Given .......          ?
PLAT164_ALERT_4_C Nr. of Refined C-H H-Atoms in Heavy-At Struct...         11
PLAT220_ALERT_2_C Large Non-Solvent    C     Ueq(max)/Ueq(min) ...       2.56 Ratio
PLAT431_ALERT_2_C Short Inter HL..A Contact  Br7    ..  O14     ..       3.25 Ang.

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           27.47
           From the CIF: _reflns_number_total               2906
           Count of symmetry unique reflns         1698
           Completeness (_total/calc)            171.14%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured      1208
           Fraction of Friedel pairs measured     0.711
           Are heavy atom types Z>Si present        yes
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C8     = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C10    = .          S
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints .......         44

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

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

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S1. Comment

In the stereoselective total synthesis of (+)-aiphanol, the enantiomer of the natural product (–)-aiphanol, the absolute stereochemistry on the 1,4-dioxane ring system was unequivocally determined (Banwell et al., 2005). To achieve this the absolute stereochemistry at the stereogenic centres of the key intermediate employed in the synthesis of (+)-aiphanol, compound (II), was determined through single-crystal X-ray analysis of its brominated derivative, compound (I).

Compound (II) was brominated with pyridinium hydrobromide perbromide then the methoxymethyl (MOM) protecting group was removed under acidic conditions. The crude product was recrystallized from methanol-DCM to afford the title compound (I) as pure colourless crystals.

Compound (I) is enantiometrically pure. The absolute structure of the crystal has been determined by refinement of the Flack parameter. The chirality at the stereogenic centres was determined to be S in each case.

All H atoms were observed in a difference electron-density map. They were then repositioned geometrically and their coordinates refined with restraints being applied to distances and bond angles. Intermolecular hydrogen-bonding interactions are observed between the O—H groups O9—H9 and O13—H13 with O11 and O9, respectively, of an adjacent molecule. Intermolecular hydrogen bonding interactions are also observed for O11—H11 with O14 and O16, and for O16—H16 with O13 and O17 of adjacent molecules.

Related literature

For related literature, see: Banwell et al. (2005); Sharpless et al. (1988).

S2. Experimental

Compound (II) was prepared via a Sharpless asymmetric dihydroxylation reaction (Sharpless et al., 1988) and was obtained in >95% e.e. as determined by chiral HPLC analysis (for experimental details see Banwell et al., 2005). A magnetically stirred solution of compound (II) (20 mg, 0.07 mmol) in DCM (5 ml) maintained at 291 K was treated, in one portion, with pyridinium hydrobromide perbromide (22 mg, 0.07 mmol) then stirred for 10 minutes after which TLC analysis indicated no starting material remained. Consequently, the reaction mixture was quenched with sodium bisulphite (0.5 ml of a 1 M aqueous solution) then treated with NaHCO₃ (2 ml of a saturated solution). The DCM layer was separated, and the aqueous layer extracted with additional DCM (2 x 5 ml). The combined organic phases were washed with brine (1 x 10 ml) then dried (Na₂SO₄), filtered and concentrated under reduced pressure and the residue subjected to high vacuum for 4 h. The resulting material (21 mg, 0.06 mmol) in MeOH (5 ml) was treated with HCl (1 drop of conc. material) and the ensuing mixture stirred magnetically at 291 K for 18 h. The methanol was then removed under reduced pressure, water (10 ml) was added to the residue and the product extracted with ethyl acetate (3 x 10 ml). The combined organic phases were then dried (Na₂SO₄), filtered, and concentrated under reduced pressure. The residue thus obtained was subjected to column chromatography (silica, 19:1 v/v ethyl acetate - methanol elution) to afford, after concentration of the appropriate fractions (R_f = 0.4), a white solid. Recrystallization (from methanol-DCM) of this material afforded compound (I) (18 mg, 93%) as colourless crystals, m.p. 446–446 K. [α]_D +51.2° (c 0.3, MeOH); ¹H NMR (300 MHz, CD₃OD) δ: 7.06 (s, 1H, ArH), 5.04 (d, J 3.8 Hz, 1H), 3.90 (s, 3H), 3.81 (s, 3H), 3.76 (m, 1H), 3.60 (m, 2H); ¹³C NMR (75 MHz, CD₃OD) δ: 148.4 (C), 144.6 (C), 139.9 (C), 132.2 (C), 108.3 (C), 107.6 (C), 75.0 (CH), 72.2 (CH), 63.8 (CH₂), 59.7 (OCH₃), 55.6 (OCH₃).

S3. Refinement

All hydrogen atoms were observed in difference electron density maps prior to their inclusion. The alcohol H atoms were included at these locations and the other H atoms were added at calculated positions. Positional coordinates were refined for all H atoms with restraints being applied to distances and angles involving them.

Computing details

Data collection: COLLECT (Nonius, 1997); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997); 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: ORTEP-II (Johnson, 1976) in TEXSAN (Molecular Structure Corporation, 1992–1997); software used to prepare material for publication: CRYSTALS.

Figures

	Fig. 1. The Molecular Structure of compound (I), with the atom labeling scheme. Displacement ellipsoids are drawn at the 30% probability level and H atoms are drawn as spheres of small radii.
	Fig. 2. Unit cell packing diagram of C11H15BrO6. Hydrogen atoms are drawn as circles with small radii.

(1S,2S)-1-(2-Bromo-4-hydroxy-3,5-dimethoxyphenyl)propane- 1,2,3-triol

Crystal data

C11H15BrO6	Dx = 1.691 Mg m^−3
Mr = 323.14	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121	Cell parameters from 17028 reflections
a = 6.6489 (1) Å	θ = 2.6–27.5°
b = 11.2217 (2) Å	µ = 3.26 mm^−1
c = 17.0148 (4) Å	T = 200 K
V = 1269.51 (4) Å^3	Block, colourless
Z = 4	0.40 × 0.40 × 0.35 mm
F(000) = 656

Data collection

Nonius KappaCCD diffractometer	2498 reflections with I > 2.0σ(I)
Graphite monochromator	Rint = 0.045
ϕ and ω scans with CCD	θmax = 27.5°, θmin = 3.0°
Absorption correction: multi-scan (SORTAV; Blessing 1995, 1997)	h = −8→8
Tmin = 0.250, Tmax = 0.330	k = −14→14
23346 measured reflections	l = −22→22
2906 independent reflections

Refinement

Refinement on F^2	Only H-atom coordinates refined
Least-squares matrix: full	Method, part 1, Chebychev polynomial, (Carruthers & Watkin, 1979, Prince, 1982) [weight] = 1.0/[A0*T0(x) + A1*T1(x) ··· + An-1]*Tn-1(x)] where Ai are the Chebychev coefficients listed below and x = F /Fmax Method = Robust Weighting (Prince, 1982) W = [weight] * [1-(deltaF/6*sigmaF)^2]^2 Ai are: 13.6 13.2 3.26
R[F^2 > 2σ(F^2)] = 0.022	(Δ/σ)max = 0.016
wR(F^2) = 0.032	Δρmax = 0.52 e Å^−3
S = 1.02	Δρmin = −0.85 e Å^−3
2906 reflections	Extinction correction: Larson (1970), Equation 22
210 parameters	Extinction coefficient: 89 (2)
44 restraints	Absolute structure: Flack (1983), 1219 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.016 (7)
Hydrogen site location: inferred from neighbouring sites

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
Br7	0.28684 (4)	0.31423 (2)	0.730941 (16)	0.0364
O9	0.6736 (3)	0.1944 (2)	0.53031 (9)	0.0368
O11	0.9202 (2)	0.37486 (16)	0.58752 (10)	0.0278
O13	0.4452 (3)	0.48096 (16)	0.50205 (10)	0.0329
O14	1.0454 (2)	0.02665 (14)	0.76823 (11)	0.0306
O16	0.8140 (3)	0.06739 (16)	0.89022 (9)	0.0297
O17	0.4551 (2)	0.18876 (18)	0.87579 (9)	0.0319
C1	0.5309 (3)	0.22709 (17)	0.73816 (15)	0.0229
C2	0.6527 (3)	0.21166 (19)	0.67249 (13)	0.0222
C3	0.8289 (3)	0.14546 (19)	0.68246 (13)	0.0234
C4	0.8800 (3)	0.09653 (19)	0.75424 (13)	0.0229
C5	0.7574 (3)	0.11533 (19)	0.81937 (12)	0.0229
C6	0.5814 (3)	0.1798 (2)	0.81127 (12)	0.0237
C8	0.6077 (4)	0.2688 (2)	0.59378 (13)	0.0232
C10	0.7057 (4)	0.39041 (19)	0.58618 (12)	0.0212
C12	0.6538 (4)	0.4546 (2)	0.50984 (14)	0.0276
C15	1.1565 (4)	−0.0135 (3)	0.70203 (15)	0.0348
C18	0.4909 (5)	0.2920 (3)	0.92280 (18)	0.0540
H9	0.581 (3)	0.176 (3)	0.5096 (15)	0.0440*
H11	0.971 (4)	0.4368 (17)	0.5962 (16)	0.0330*
H13	0.391 (4)	0.4210 (18)	0.4890 (17)	0.0400*
H16	0.708 (3)	0.058 (2)	0.9095 (14)	0.0360*
H31	0.917 (2)	0.1332 (11)	0.6391 (9)	0.0283*
H81	0.463 (2)	0.2807 (16)	0.5883 (10)	0.0280*
H101	0.666 (3)	0.4388 (15)	0.6317 (9)	0.0256*
H121	0.726 (3)	0.5283 (14)	0.5102 (10)	0.0332*
H122	0.695 (3)	0.4028 (15)	0.4670 (10)	0.0332*
H151	1.258 (3)	−0.0688 (15)	0.7219 (11)	0.0419*
H152	1.216 (3)	0.0546 (15)	0.6763 (11)	0.0419*
H153	1.067 (3)	−0.0565 (18)	0.6689 (11)	0.0419*
H181	0.410 (3)	0.286 (2)	0.9696 (11)	0.0649*
H182	0.631 (3)	0.292 (2)	0.9376 (13)	0.0649*
H183	0.453 (4)	0.3617 (17)	0.8953 (12)	0.0649*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Br7	0.02617 (10)	0.03819 (12)	0.04482 (13)	0.01027 (12)	0.00424 (12)	0.00857 (14)
O9	0.0529 (12)	0.0345 (10)	0.0229 (8)	0.0013 (11)	−0.0115 (8)	−0.0090 (9)
O11	0.0190 (9)	0.0369 (10)	0.0275 (9)	−0.0057 (8)	−0.0009 (7)	−0.0011 (8)
O13	0.0293 (10)	0.0424 (11)	0.0268 (10)	0.0048 (8)	−0.0038 (8)	0.0048 (9)
O14	0.0298 (8)	0.0390 (9)	0.0231 (8)	0.0142 (7)	−0.0001 (9)	0.0054 (9)
O16	0.0275 (10)	0.0403 (10)	0.0212 (9)	0.0052 (8)	0.0036 (8)	0.0082 (7)
O17	0.0323 (8)	0.0352 (9)	0.0281 (8)	0.0025 (9)	0.0108 (7)	0.0022 (9)
C1	0.0169 (9)	0.0202 (10)	0.0316 (13)	0.0013 (8)	0.0005 (10)	0.0012 (10)
C2	0.0236 (11)	0.0214 (12)	0.0215 (11)	−0.0029 (8)	−0.0032 (9)	0.0020 (9)
C3	0.0231 (13)	0.0273 (12)	0.0197 (11)	0.0029 (9)	0.0005 (9)	0.0024 (9)
C4	0.0223 (10)	0.0223 (11)	0.0240 (14)	0.0030 (9)	−0.0015 (9)	0.0014 (9)
C5	0.0280 (15)	0.0213 (10)	0.0195 (11)	−0.0010 (9)	−0.0006 (9)	0.0031 (8)
C6	0.0247 (11)	0.0233 (11)	0.0229 (11)	−0.0024 (11)	0.0048 (9)	−0.0007 (11)
C8	0.0221 (11)	0.0247 (12)	0.0228 (12)	0.0025 (9)	−0.0041 (10)	0.0005 (10)
C10	0.0208 (10)	0.0238 (11)	0.0188 (11)	0.0015 (11)	−0.0013 (10)	−0.0012 (8)
C12	0.0284 (13)	0.0309 (13)	0.0234 (13)	−0.0001 (10)	0.0019 (10)	0.0035 (10)
C15	0.0343 (15)	0.0423 (16)	0.0279 (13)	0.0163 (12)	0.0023 (10)	0.0017 (11)
C18	0.075 (2)	0.048 (2)	0.0389 (17)	−0.0024 (18)	0.0217 (16)	−0.0141 (15)

Geometric parameters (Å, º)

Br7—C1	1.8988 (19)	C3—C4	1.382 (3)
O9—C8	1.434 (3)	C3—H31	0.950 (15)
O9—H9	0.740 (16)	C4—C5	1.392 (3)
O11—C10	1.436 (3)	C5—C6	1.383 (3)
O11—H11	0.786 (16)	C8—C10	1.518 (3)
O13—C12	1.424 (3)	C8—H81	0.975 (15)
O13—H13	0.796 (16)	C10—C12	1.525 (3)
O14—C4	1.372 (2)	C10—H101	0.982 (15)
O14—C15	1.420 (3)	C12—H121	0.958 (16)
O16—C5	1.373 (2)	C12—H122	0.972 (15)
O16—H16	0.787 (16)	C15—H151	0.976 (15)
O17—C6	1.385 (2)	C15—H152	0.966 (16)
O17—C18	1.428 (3)	C15—H153	0.949 (16)
C1—C2	1.391 (3)	C18—H181	0.964 (16)
C1—C6	1.393 (3)	C18—H182	0.967 (16)
C2—C3	1.397 (3)	C18—H183	0.946 (17)
C2—C8	1.515 (3)
Br7···O14^i	3.250 (2)	O11···O16^v	2.817 (2)
Br7···C4^i	3.366 (2)	O11···O14^v	2.996 (2)
Br7···C5^i	3.498 (2)	O13···O16^i	2.696 (3)
Br7···O11^ii	3.516 (2)	O13···O17^i	3.193 (2)
Br7···O16^i	3.573 (2)	O13···C3^iv	3.531 (3)
O9···O13^iii	2.727 (3)	O14···C10^vi	3.349 (3)
O9···O11^iv	2.732 (2)	O17···C12^vii	3.349 (3)
O9···C8^iii	3.600 (3)	O17···C10^vii	3.574 (3)
C8—O9—H9	105 (2)	C2—C8—H81	109.7 (10)
C10—O11—H11	109 (2)	O9—C8—H81	108.0 (11)
C12—O13—H13	107 (2)	C10—C8—H81	107.0 (11)
C4—O14—C15	117.42 (19)	C8—C10—O11	108.41 (19)
C5—O16—H16	100 (2)	C8—C10—C12	113.56 (19)
C6—O17—C18	113.7 (2)	O11—C10—C12	107.2 (2)
Br7—C1—C2	120.65 (18)	C8—C10—H101	108.3 (10)
Br7—C1—C6	117.36 (16)	O11—C10—H101	108.7 (10)
C2—C1—C6	121.99 (19)	C12—C10—H101	110.5 (10)
C1—C2—C3	117.2 (2)	C10—C12—O13	113.5 (2)
C1—C2—C8	122.8 (2)	C10—C12—H121	106.7 (11)
C3—C2—C8	119.9 (2)	O13—C12—H121	108.1 (11)
C2—C3—C4	121.7 (2)	C10—C12—H122	107.0 (10)
C2—C3—H31	119.8 (10)	O13—C12—H122	109.3 (11)
C4—C3—H31	118.6 (10)	H121—C12—H122	112.3 (13)
C3—C4—O14	125.3 (2)	O14—C15—H151	106.6 (11)
C3—C4—C5	120.0 (2)	O14—C15—H152	108.8 (11)
O14—C4—C5	114.72 (19)	H151—C15—H152	112.1 (14)
C4—C5—O16	118.64 (19)	O14—C15—H153	107.9 (12)
C4—C5—C6	119.7 (2)	H151—C15—H153	108.1 (14)
O16—C5—C6	121.6 (2)	H152—C15—H153	112.9 (14)
C1—C6—O17	122.27 (19)	O17—C18—H181	108.3 (13)
C1—C6—C5	119.46 (19)	O17—C18—H182	107.9 (13)
O17—C6—C5	118.2 (2)	H181—C18—H182	109.0 (14)
C2—C8—O9	111.03 (19)	O17—C18—H183	110.4 (13)
C2—C8—C10	111.77 (19)	H181—C18—H183	108.3 (15)
O9—C8—C10	109.15 (19)	H182—C18—H183	112.9 (15)
Br7—C1—C2—C3	−179.4 (2)	O17—C6—C1—C2	−176.1 (2)
Br7—C1—C2—C8	4.1 (3)	O17—C6—C5—C4	175.0 (2)
Br7—C1—C6—O17	3.8 (3)	C1—C2—C3—C4	0.4 (3)
Br7—C1—C6—C5	179.8 (2)	C1—C2—C8—C10	90.4 (3)
O9—C8—C2—C1	−147.4 (2)	C1—C6—O17—C18	−91.3 (3)
O9—C8—C2—C3	36.2 (3)	C1—C6—C5—C4	−1.2 (3)
O9—C8—C10—O11	−58.7 (2)	C2—C1—C6—C5	−0.1 (3)
O9—C8—C10—C12	60.3 (3)	C2—C3—C4—C5	−1.7 (3)
O11—C10—C8—C2	64.6 (2)	C2—C8—C10—C12	−176.4 (2)
O11—C10—C12—O13	−177.4 (2)	C3—C2—C1—C6	0.5 (3)
O13—C12—C10—C8	62.9 (3)	C3—C2—C8—C10	−86.0 (3)
O14—C4—C3—C2	177.2 (2)	C3—C4—O14—C15	−10.0 (3)
O14—C4—C5—O16	2.1 (3)	C3—C4—C5—C6	2.1 (3)
O14—C4—C5—C6	−177.0 (2)	C4—C3—C2—C8	177.0 (2)
O16—C5—C4—C3	−178.8 (2)	C5—C4—O14—C15	169.0 (2)
O16—C5—C6—O17	−4.1 (3)	C5—C6—O17—C18	92.7 (3)
O16—C5—C6—C1	179.7 (2)	C6—C1—C2—C8	−176.0 (2)

Symmetry codes: (i) −x+1, y+1/2, −z+3/2; (ii) x−1, y, z; (iii) x+1/2, −y+1/2, −z+1; (iv) x−1/2, −y+1/2, −z+1; (v) −x+2, y+1/2, −z+3/2; (vi) −x+2, y−1/2, −z+3/2; (vii) −x+1, y−1/2, −z+3/2.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O9—H9···O11^iv	0.74 (2)	2.05 (3)	2.732 (2)	154 (2)
O11—H11···O14^v	0.79 (2)	2.52 (3)	2.996 (2)	120 (2)
O11—H11···O16^v	0.79 (2)	2.06 (2)	2.817 (2)	161 (3)
O13—H13···O9^iv	0.79 (2)	1.97 (2)	2.727 (3)	159 (3)
O16—H16···O17	0.78 (2)	2.30 (2)	2.759 (2)	118 (2)
O16—H16···O13^vii	0.78 (2)	2.01 (2)	2.696 (3)	146 (2)

Symmetry codes: (iv) x−1/2, −y+1/2, −z+1; (v) −x+2, y+1/2, −z+3/2; (vii) −x+1, y−1/2, −z+3/2.