(2R,3S,4S,5R)-4-Hydroxy-3-iodo-5-methyl­tetra­hydro-2-furyl­methyl benzoate

The crystal structure determination of the title compound, C₁₃H₁₅IO₄, has allowed the relative stereochemistry between the tetrasubstituted C atoms on the tetra­hydro­furan moiety to be confirmed. The title compound is a precursor of the ionophoric antibiotic Aplasmomycin. The compound is involved in both intra- and intermolecular hydrogen bonding, the latter link the mol­ecules into chains running along the b axis.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.007 Å
• R factor = 0.027
• wR factor = 0.063
• Data-to-parameter ratio = 13.3

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry

General Notes



REFLT_03
         From the CIF: _diffrn_reflns_theta_max           25.03
         From the CIF: _reflns_number_total               2233
         Count of symmetry unique reflns         1446
         Completeness (_total/calc)            154.43%
         TEST3: Check Friedels for noncentro structure
         Estimate of Friedel pairs measured       787
         Fraction of Friedel pairs measured     0.544
         Are heavy atom types Z>Si present          yes
          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.

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S1. Comment

The title compound, (2), was synthesized as part of an ongoing synthetic project towards the synthesis of the C₂-symmetric boron-containing antibiotic Aplasmomycin (Scheme 1; Knight et al., 2000). Aplasmomycin and its congeners are metabolites of Streptomyces griseus and are a unique family of boron-containing ionophoric antibiotics which show activity against Gram-positive bacteria. To date, two total and two formal syntheses of Aplasmomycin have been reported (Corey et al., 1982; White et al., 1986; Nakata et al., 1986; Matsuda et al., 1990).

Tetrahydrofuran (1) differentially appended at the 2-, 4- and 5-positions is a crucial component of Aplasmomycin. The precursor to (1) in our prospective synthesis of the natural product required tetrahydrofuran (2). 3-Iodotetrahydrofuran, (2) was readily synthesized in three steps using commercially available hexa-2,4-dien-1-ol as the starting material. Esterification of this with benzoyl chloride yielded quantitatively the ester (2) (Scheme 2), reaction of which under Sharpless asymmetric dihydroxylation conditions (273 K, aqueous t-BuOH; 1:1, 0.004 eqⁿ K₂OsO₄, 0.01 eqⁿ DHQD-PHAL, 3 eqⁿ K₃Fe(CN)₆, 3 eqⁿ K₂CO₃, 1 eqⁿ MeSO₂NH₂) yielded diol (4) (55%). Finally, treatment of diol (4) under anhydrous conditions with 2 eqⁿ of iodine monobromide (263 K) gave (2) via a 5-endo-trig iodocyclization (Knight et al., 1999, 2000). Subsequent deiodination (Bu₃SnH, AlBN) and Mitsunobu mediated alcohol inversion (DIAD, PPh₃, p-nitrobenzoic acid) yielded precursor the tetrahydrofuran (1) (Scheme 2).

To our knowledge, this is the first reported crystal structure determination of a 2,3,4,5-tetrasubstituted furan appended with a hydroxymethyl group (esterified), an I atom, a hydroxyl and a methyl group. The X-ray determination was necessary to confirm the stereochemistry as NMR coupling constant data was ambiguous and NOE data only was considered insufficient upon which to base the subsequent synthetic plans.

The title molecule is involved in both intra- and intermolecular hydrogen bonding. An interaction between the hydroxyl H atom of O4 and the O atom of the tetrahydrofuran links the molecules into chains running along the b axis. The large deviation from linearity of this bond [132 (5)°] is a direct result of an additional competitive interaction between the same hydrogen and I1.

The tetrahydrofuran ring is puckered in an envelope form with C11 deviating by -0.640 (6) Å from the plane of the remaining four atoms. The conformation around the sp³ atoms C8 and C9 is almost perfectly staggered [O3—C9—C8—O2 = 173.2 (4)°] such that O3 and O2 adopt a trans configuration.

There are four chiral centres in the molecule all within the tetrahydrofuran ring; C9 = R, C10 = S, C11 = S and C12 = R.

S2. Experimental

To a 50 ml flame-dried round-bottomed flask equipped with a stirrer-bead and a suba-seal was added 500 mg (2.11 mmol) of (4). Diol (4) was dissolved in 25 ml of dry acetonitrile (Perrin & Armarego, 1988; acetonitrile refluxed and distilled from calcium hydride under argon, according to the procedure stated in the reference). To the cold (263 K) stirred solution, under argon, was added solid iodine monobromide in one portion (873 mg, 4.22 mmol, 2 equivalents). The resulting solution was stirred at 263 K in the dark under argon (flask wrapped in aluminium foil). After 16 h, TLC analysis indicated that all of the starting material had been consummed (eluent; ether: petrol, 1:1). The crude reaction mixture was stripped of the acetonitrile in vacuo (bath temperature no higher than 308 K) and replaced with 50 ml of dichloromethane. The dichloromethane solution was washed with water (3 x 50 ml), then with 2.5 M aqueous sodium thiosulfate (2 x 75 ml) and finally with saturated brine solution (50 ml) before being dried (MgSO₄), filtered and the solvent removed in vacuo. The crude product was purified via flash column chromatography (silica gel) using 1:1 pentane/ether as eluent. The title compound was obtained as a white solid (595 mg, 78%). Suitable crystals were grown by dissolving the purified product in a small amount of pure solvent and then allowing the solvent to evaporate slowly.

Computing details

Data collection: DENZO (Otwinoski & Minor, 1997) and COLLECT (Hooft, 1998); cell refinement: DENZO and COLLECT; data reduction: DENZO (Otwinoski & Minor, 1997), COLLECT (Hooft, 1998) and maXus (Mackay et al., 1998); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: CAMERON (Watkin et al., 1993); software used to prepare material for publication: WinGX (Farrugia, 1998).

Figures

Fig. 1. View of (I) (50% probability displacement ellipsoids) Fig. 2. Packing diagram of (I) showing the hydrogen-bonded chains viewed looking down the a axis.

(2R,3S,4S,5R)-4-Hydroxy-3-iodo-5-methyltetrahydro-2-furylmethyl benzoate

Crystal data

C13H15IO4	Dx = 1.774 Mg m^−3
Mr = 362.15	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121	Cell parameters from 4354 reflections
a = 4.797 (1) Å	θ = 3.1–25.0°
b = 11.886 (2) Å	µ = 2.37 mm^−1
c = 23.775 (5) Å	T = 293 K
V = 1355.6 (5) Å^3	Block, colourless
Z = 4	0.5 × 0.3 × 0.3 mm
F(000) = 712

Data collection

Nonius Kappa CCD area-detector diffractometer	2233 independent reflections
Radiation source: Nonius FR591 roating anode	2051 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.025
Detector resolution: 9.091 pixels per mm pixels mm^-1	θmax = 25.0°, θmin = 3.1°
Φ and ω scans to fill Ewald sphere	h = −4→4
Absorption correction: empirical (using intensity measurements) (SORTAV; Blessing, 1997)	k = −14→13
Tmin = 0.352, Tmax = 0.492	l = −28→28
4354 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.027	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.063	w = 1/[σ^2(Fo^2) + (0.0282P)^2 + 0.4539P] where P = (Fo^2 + 2Fc^2)/3
S = 1.05	(Δ/σ)max = 0.001
2233 reflections	Δρmax = 0.72 e Å^−3
168 parameters	Δρmin = −0.55 e Å^−3
0 restraints	Absolute structure: Flack (1983), 888 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.03 (3)

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 > 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 (Ų)

	x	y	z	Uiso*/Ueq
I1	0.40247 (7)	0.20383 (3)	0.852844 (15)	0.05541 (12)
O1	0.5551 (11)	0.6736 (3)	0.89771 (18)	0.0775 (14)
O2	0.4991 (7)	0.4940 (2)	0.87391 (14)	0.0472 (9)
O3	0.0307 (6)	0.4609 (3)	0.75426 (13)	0.0404 (7)
O4	−0.0168 (7)	0.2208 (3)	0.74347 (16)	0.0477 (9)
C1	0.8711 (11)	0.4210 (4)	0.95431 (19)	0.0453 (11)
C2	1.0587 (12)	0.3875 (4)	0.9944 (2)	0.0572 (13)
C3	1.1650 (12)	0.4635 (5)	1.0328 (2)	0.0594 (15)
C4	1.0786 (14)	0.5744 (5)	1.0309 (2)	0.0669 (17)
C5	0.8964 (12)	0.6080 (4)	0.9903 (2)	0.0569 (13)
C6	0.7911 (11)	0.5330 (4)	0.95095 (19)	0.0416 (11)
C7	0.6028 (11)	0.5756 (4)	0.90635 (19)	0.0442 (10)
C8	0.3295 (11)	0.5290 (4)	0.8267 (2)	0.0484 (13)
C9	0.1718 (9)	0.4273 (3)	0.80525 (18)	0.0347 (10)
C12	0.1404 (10)	0.3961 (4)	0.70741 (18)	0.0363 (10)
C10	0.3589 (10)	0.3286 (3)	0.78875 (19)	0.0350 (9)
C11	0.2269 (9)	0.2845 (3)	0.73469 (18)	0.0354 (9)
C13	−0.0690 (11)	0.3878 (4)	0.66103 (18)	0.0465 (11)
H1	0.7974	0.3687	0.9293	0.054*
H2	1.1151	0.3127	0.9958	0.069*
H3	1.2936	0.4403	1.0596	0.071*
H4	1.1446	0.6258	1.0572	0.08*
H5	0.8413	0.683	0.9889	0.068*
H8A	0.4467	0.5594	0.7971	0.058*
H8B	0.1995	0.587	0.8384	0.058*
H9	0.0352	0.4029	0.8334	0.042*
H10	0.5444	0.3581	0.7797	0.042*
H11	0.3624	0.2438	0.7115	0.042*
H12	0.3075	0.4338	0.693	0.044*
H13A	−0.2306	0.3482	0.6743	0.07*
H13B	0.011	0.3478	0.6299	0.07*
H13C	−0.1218	0.462	0.6492	0.07*
H04	0.010 (11)	0.169 (4)	0.763 (2)	0.044 (16)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
I1	0.0693 (2)	0.03275 (13)	0.0641 (2)	−0.00100 (16)	−0.01865 (18)	0.00937 (15)
O1	0.117 (4)	0.0328 (17)	0.083 (3)	−0.001 (2)	−0.051 (3)	−0.0026 (17)
O2	0.061 (2)	0.0270 (14)	0.0539 (19)	−0.0014 (13)	−0.0227 (15)	−0.0016 (13)
O3	0.0412 (19)	0.0332 (15)	0.0468 (17)	0.0098 (13)	−0.0074 (14)	−0.0061 (13)
O4	0.048 (2)	0.0351 (18)	0.060 (2)	−0.0117 (14)	−0.0146 (16)	0.0041 (16)
C1	0.053 (3)	0.037 (2)	0.046 (3)	−0.001 (2)	−0.004 (2)	−0.0019 (19)
C2	0.067 (4)	0.048 (3)	0.057 (3)	−0.001 (3)	−0.012 (3)	0.008 (2)
C3	0.058 (4)	0.071 (4)	0.049 (3)	−0.010 (3)	−0.014 (2)	0.017 (3)
C4	0.086 (5)	0.054 (3)	0.060 (3)	−0.012 (3)	−0.031 (4)	0.002 (3)
C5	0.071 (4)	0.038 (2)	0.062 (3)	−0.005 (3)	−0.019 (3)	−0.006 (2)
C6	0.048 (3)	0.039 (2)	0.038 (2)	−0.003 (2)	−0.001 (2)	0.0042 (19)
C7	0.051 (3)	0.033 (2)	0.048 (2)	0.000 (2)	−0.009 (2)	0.0000 (18)
C8	0.060 (4)	0.027 (2)	0.057 (3)	0.004 (2)	−0.019 (2)	−0.0029 (19)
C9	0.038 (3)	0.0286 (19)	0.037 (2)	−0.0003 (17)	−0.0046 (17)	0.0003 (17)
C10	0.029 (3)	0.0263 (18)	0.050 (2)	−0.0020 (16)	−0.0050 (19)	0.0010 (16)
C11	0.033 (2)	0.028 (2)	0.045 (2)	0.0030 (19)	−0.0024 (18)	−0.0029 (19)
C12	0.029 (3)	0.037 (2)	0.042 (2)	0.0019 (19)	0.0074 (19)	0.0040 (18)
C13	0.052 (3)	0.048 (2)	0.039 (2)	0.010 (2)	−0.007 (2)	0.0006 (19)

Geometric parameters (Å, º)

I1—C10	2.137 (4)	C5—C6	1.388 (6)
O2—C8	1.447 (5)	C7—O1	1.205 (5)
O3—C9	1.445 (5)	C7—O2	1.335 (5)
O3—C12	1.453 (5)	C7—C6	1.482 (7)
O4—C11	1.408 (5)	C9—C8	1.514 (6)
C1—C2	1.371 (7)	C9—C10	1.528 (6)
C1—C6	1.387 (6)	C10—C11	1.526 (6)
C2—C3	1.381 (7)	C12—C13	1.495 (6)
C3—C4	1.382 (8)	C12—C11	1.534 (6)
C5—C4	1.362 (7)
O1—C7—O2	122.2 (4)	C2—C1—C6	120.1 (5)
O1—C7—C6	124.6 (4)	C2—C3—C4	119.5 (5)
O2—C7—C6	113.1 (4)	C4—C5—C6	121.5 (5)
O2—C8—C9	108.2 (3)	C5—C6—C7	119.0 (4)
O3—C9—C8	107.2 (3)	C5—C4—C3	119.7 (5)
O3—C9—C10	105.8 (3)	C7—O2—C8	116.7 (3)
O3—C12—C13	110.9 (4)	C8—C9—C10	114.0 (4)
O3—C12—C11	103.4 (3)	C9—O3—C12	109.1 (3)
O4—C11—C10	113.9 (4)	C9—C10—I1	114.0 (3)
O4—C11—C12	107.6 (3)	C10—C11—C12	99.8 (3)
C1—C6—C5	118.5 (5)	C11—C10—C9	103.7 (3)
C1—C6—C7	122.5 (4)	C11—C10—I1	113.7 (3)
C1—C2—C3	120.8 (5)	C13—C12—C11	115.9 (4)
O3—C9—C8—O2	−173.2 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H04···O3^i	0.78 (5)	2.51 (5)	3.090 (4)	132 (5)
O4—H04···I1	0.78 (5)	2.88 (5)	3.294 (3)	115 (4)

Symmetry code: (i) −x, y−1/2, −z+3/2.