Methyl (2′R,3′R)-6-deoxy-3,4-O-(2′,3′-di­methoxy­butane-2′,3′-diyl)-2-O-toluene-p-sulfonyl-α-L-mannopyran­oside

In the title compound, C₂₀H₃₀O₉S, (III), both six-membered rings adopt chair conformations, placing H3 and the 2-sulf­on­yl­oxy group in the antiperiplanar arrangement required for an E2 reaction. However, unlike other α-manno­pyran­oside-2-sulfonates, the 2-O-tri­fluoro­methyl­sulfonyl (tri­fluoro­methane­sulfonate) derivative, (II), underwent an S_N2 displacement with an azide ion to give methyl (2′R,3′R)-2-azido-2,6-di­deoxy-3,4-O-(2′,3′-di­methoxy­butane-2′,3′-diyl)-α-L-gluco­pyran­oside, (IV), in pref­erence to the E2 reaction.

Key indicators

• Single-crystal X-ray study
• T = 150 K
• Mean [sigma](C-C) = 0.005 Å
• R factor = 0.069
• wR factor = 0.122
• Data-to-parameter ratio = 18.6

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry

General Notes



REFLT_03
         From the CIF: _diffrn_reflns_theta_max           28.25
         From the CIF: _reflns_number_total               5177
         From the CIF: _diffrn_reflns_limit_ max hkl    9.   18.   24.
         From the CIF: _diffrn_reflns_limit_ min hkl   -9.  -18.  -24.
         TEST1: Expected hkl limits for theta max
         Calculated maximum hkl   11.   18.   24.
         Calculated minimum hkl  -11.  -18.  -24.
          ALERT: Expected hkl max differ from CIF values

REFLT_03
         From the CIF: _diffrn_reflns_theta_max           28.25
         From the CIF: _reflns_number_total               5177
         Count of symmetry unique reflns         3127
         Completeness (_total/calc)            165.56%
         TEST3: Check Friedels for noncentro structure
         Estimate of Friedel pairs measured      2050
         Fraction of Friedel pairs measured     0.656
         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.

---

S1. Comment

Bimolecular nucleophilic (S_N2) displacements on α-hexopyranoside 2-sulfonates are notoriously difficult to effect with charged nucleophiles (Richardson, 1969). Elimination reactions tend to be favoured with α-mannopyranoside 2-sulfonates (Binkley & Binkley, 1997) and are sometimes accompanied by more deep-seated rearrangements (Vos et al., 1984; Barnes et al., 1996). We reasoned that S_N2 displacements on a bicyclic 2-sulfonate, such as (II), stood a much better chance of success since the incipient 2,3-double bond at the ring junction would introduce appreciable torsional strain in the transition state of the competing E2 reaction. The butane-3,4-diacetal, (I), is accessible through the seminal work of Ley's group (Hense et al.,1997; Ley et al., 1997) and is readily transformed into the 2-sulfonates (II) and (III). Sulfonate (II), an oil, reacted readily with sodium azide in dimethylformamide at 343 K to give, principally, the azide (IV). An extremely labile (minor) product of this reaction was identified as the 2,3-unsaturated sugar, (V), by ¹H NMR spectroscopy. (III) and (IV) are crystalline. The structure of (III) is reported here; that of (IV) is given in the following paper (Barnes et al., 2002).

(III) did not react with sodium azide in DMF even at 423 K. The p-toluenesulfonate group at C2 would be much less reactive than the SO₂CF₃ group in (II). In addition, there will be some stabilization of (III) from the close approach of the methyl proton H16c to the centroid of the phenyl ring (3.237 Å). The presence of the sulfonate group made it possible to determine the absolute conformation of (III) by Flack's method (Flack, 1983). Fig. 1 shows that, as expected, (III) retains the conformation of (I). The same is presumably true of (II). Comparison with the structure of (IV) (Barnes et al., 2002) shows that in (IV) the original conformation is preserved at all centers except for inversion of the configuration at the reaction centre C2. Thus the hoped for S_N2 displacement had occurred. In (III), the torsion angle O2—C2—C3—H3 is 172.6(?)°, only slightly displaced from the ideal antiperiplanar arrangement favoured by E2 eliminations (Eliel & Wilen, 1994). In (IV), the torsion angles N11—C2—C3—H3 are 61.02(?) and 62.64(?)°, showing the change in configuration at C2. There are no unusual bond lengths or angles in either structure. [Please provide s.u. values for the three torsion angles above]

S2. Experimental

(III) was prepared conventionally from (I). Analysis of (III), found: C 53.69, H 6.74, S 7.31%; calculated: C 53.80, H 6.77, S 7.18%. [α]_D -121° (cl, MeOH). Crystals from diethyl ether/hexane.

S3. Refinement

All H atoms were introduced at calculated positions as riding atoms (C—H = 0.97–0.98 Å, using AFIX 37 for CH₃, AFIX 43 for aromatic CH and AFIX 13 for CH), with a displacement parameter equal to 1.2 (CH) or 1.5(CH₃) times that of the parent atom. On the basis of 2259 Friedel pairs, final refinement allowed the fraction contribution of the inverted enantiomer to vary (Bernardinelli & Flack, 1985; Flack, 1983), the absolute structure parameter quoted being the refined value of this contribution.

Computing details

Data collection: DENZO (Otwinowski & Minor, 1997) and COLLECT (Hooft,1998); cell refinement: DENZO and COLLECT; data reduction: DENZO and COLLECT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLUTON92 (Spek, 1992) and PLATON92 (Spek, 1992); software used to prepare material for publication: SHELXL97.

Figures

Fig. 1. The structure of (III) showing 50% probability displacement ellipsoids.

(2'R,3'R)-methyl 6-deoxy-3,4-O-(2',3'-dimethoxybutane- 2',3'-diyl)-2-O-toluene-p-sulfonyl-α-L-mannopyranoside

Crystal data

C20H30O9S	Dx = 1.327 Mg m^−3
Mr = 446.50	Melting point = 130–131 K
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 9970 reflections
a = 8.7709 (3) Å	θ = 3.0–28.3°
b = 14.0181 (10) Å	µ = 0.19 mm^−1
c = 18.1744 (13) Å	T = 150 K
V = 2234.6 (2) Å^3	Needle, colourless
Z = 4	0.25 × 0.10 × 0.05 mm
F(000) = 952

Data collection

Nonius KappaCCD area-detector diffractometer	3591 reflections with I > 2σ(I)
Radiation source: Enraf-Nonius FR591 rotating anode	Rint = 0.058
Graphite monochromator	θmax = 28.3°, θmin = 3.0°
Detector resolution: 9.091 pixels/mm pixels mm^-1	h = −9→9
ϕ and ω scans to fill Ewald sphere	k = −18→18
9970 measured reflections	l = −24→24
5177 independent 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)] = 0.069	H-atom parameters constrained
wR(F^2) = 0.122	w = 1/[σ^2(Fo^2) + (0.0139P)^2 + 2.7542P] where P = (Fo^2 + 2Fc^2)/3
S = 1.09	(Δ/σ)max = 0.007
5177 reflections	Δρmax = 0.31 e Å^−3
278 parameters	Δρmin = −0.33 e Å^−3
0 restraints	Absolute structure: Flack (1983)
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.00 (12)

Special details

Experimental. Cell measurement fields are not particularly relevant to the area detector data. Entire data set used to refine cell. Cell indexed from a 10 ° phi range.

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
C1	0.9738 (4)	0.8151 (3)	0.7892 (2)	0.0220 (8)
H1	1.0716	0.8065	0.8144	0.031*
O1	0.9181 (3)	0.90663 (19)	0.80578 (15)	0.0271 (7)
C2	0.8577 (4)	0.7461 (3)	0.8229 (2)	0.0183 (8)
H2	0.8334	0.7654	0.8734	0.026*
O2	0.9276 (3)	0.65154 (17)	0.82271 (14)	0.0192 (6)
C3	0.7152 (4)	0.7450 (3)	0.77667 (19)	0.0173 (8)
H3	0.6634	0.8064	0.7829	0.024*
O3	0.6155 (3)	0.6718 (2)	0.80176 (13)	0.0219 (6)
C4	0.7474 (4)	0.7315 (3)	0.69643 (19)	0.0175 (8)
H4	0.7881	0.6673	0.6881	0.024*
O4	0.6060 (3)	0.74243 (19)	0.65738 (13)	0.0192 (6)
C5	0.8603 (4)	0.8054 (3)	0.6682 (2)	0.0209 (9)
H5	0.8157	0.8694	0.6717	0.029*
O5	0.9959 (3)	0.79962 (19)	0.71360 (13)	0.0224 (6)
C6	0.9095 (5)	0.7858 (3)	0.5902 (2)	0.0296 (10)
H6A	0.9772	0.8354	0.5740	0.041*
H6B	0.8216	0.7840	0.5588	0.041*
H6C	0.9612	0.7255	0.5881	0.041*
C7	1.0310 (5)	0.9802 (3)	0.7969 (2)	0.0361 (11)
H7A	1.1088	0.9728	0.8336	0.051*
H7B	0.9836	1.0416	0.8023	0.051*
H7C	1.0757	0.9754	0.7488	0.051*
C14	0.4713 (4)	0.6744 (3)	0.7649 (2)	0.0250 (9)
O14	0.3986 (3)	0.7623 (2)	0.78006 (16)	0.0357 (8)
C15	0.3821 (5)	0.7843 (4)	0.8563 (2)	0.0517 (16)
H15A	0.3082	0.7422	0.8779	0.072*
H15B	0.3486	0.8491	0.8616	0.072*
H15C	0.4783	0.7763	0.8806	0.072*
C16	0.3834 (5)	0.5883 (4)	0.7926 (2)	0.0420 (13)
H16A	0.4377	0.5311	0.7801	0.059*
H16B	0.2843	0.5871	0.7702	0.059*
H16C	0.3726	0.5923	0.8451	0.059*
C17	0.4938 (4)	0.6745 (3)	0.6798 (2)	0.0215 (9)
O17	0.5458 (3)	0.58073 (18)	0.66352 (14)	0.0268 (6)
C18	0.5788 (5)	0.5630 (3)	0.5873 (2)	0.0377 (12)
H18A	0.4850	0.5573	0.5604	0.053*
H18B	0.6359	0.5049	0.5829	0.053*
H18C	0.6374	0.6150	0.5678	0.053*
C19	0.3490 (4)	0.6998 (3)	0.6390 (2)	0.0276 (10)
H19A	0.3701	0.7044	0.5873	0.039*
H19B	0.3111	0.7598	0.6566	0.039*
H19C	0.2739	0.6511	0.6473	0.039*
S21	0.96432 (11)	0.60403 (7)	0.89998 (5)	0.0199 (2)
O22	1.0252 (3)	0.67532 (19)	0.94803 (14)	0.0275 (7)
O23	1.0534 (3)	0.52188 (19)	0.88131 (15)	0.0271 (7)
C24	0.7849 (4)	0.5673 (3)	0.9332 (2)	0.0178 (8)
C25	0.7267 (4)	0.4804 (3)	0.9110 (2)	0.0258 (9)
H25	0.7817	0.4413	0.8793	0.036*
C26	0.5846 (5)	0.4522 (3)	0.9369 (2)	0.0283 (10)
H26	0.5445	0.3937	0.9223	0.040*
C27	0.5017 (4)	0.5101 (3)	0.9843 (2)	0.0235 (9)
C28	0.5626 (4)	0.5977 (3)	1.0052 (2)	0.0264 (9)
H28	0.5074	0.6374	1.0364	0.037*
C29	0.7049 (4)	0.6266 (3)	0.9801 (2)	0.0232 (9)
H29	0.7456	0.6849	0.9946	0.032*
C30	0.3467 (5)	0.4799 (4)	1.0116 (3)	0.0411 (12)
H30A	0.2727	0.4891	0.9733	0.058*
H30B	0.3192	0.5175	1.0537	0.058*
H30C	0.3495	0.4137	1.0252	0.058*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.018 (2)	0.025 (2)	0.023 (2)	−0.0024 (18)	−0.0049 (17)	0.0031 (17)
O1	0.0286 (16)	0.0200 (15)	0.0328 (16)	−0.0066 (13)	−0.0034 (12)	−0.0007 (13)
C2	0.016 (2)	0.020 (2)	0.019 (2)	0.0024 (16)	−0.0028 (15)	0.0006 (16)
O2	0.0182 (15)	0.0211 (14)	0.0183 (13)	0.0032 (11)	−0.0006 (10)	0.0012 (11)
C3	0.0121 (19)	0.024 (2)	0.0155 (19)	−0.0031 (16)	0.0017 (15)	0.0032 (16)
O3	0.0147 (14)	0.0331 (16)	0.0179 (14)	−0.0053 (12)	−0.0019 (11)	0.0057 (13)
C4	0.016 (2)	0.019 (2)	0.0173 (19)	−0.0001 (15)	−0.0014 (15)	−0.0001 (16)
O4	0.0151 (13)	0.0245 (15)	0.0181 (14)	−0.0025 (11)	−0.0041 (11)	0.0022 (12)
C5	0.017 (2)	0.025 (2)	0.021 (2)	−0.0016 (16)	−0.0018 (16)	0.0037 (17)
O5	0.0150 (15)	0.0291 (16)	0.0230 (14)	−0.0029 (11)	−0.0005 (11)	0.0059 (12)
C6	0.028 (2)	0.040 (3)	0.021 (2)	−0.0077 (19)	0.0018 (18)	0.0039 (19)
C7	0.047 (3)	0.027 (2)	0.034 (2)	−0.016 (2)	−0.007 (2)	0.007 (2)
C14	0.017 (2)	0.038 (2)	0.020 (2)	−0.005 (2)	−0.0044 (17)	−0.0003 (17)
O14	0.0210 (15)	0.059 (2)	0.0274 (17)	0.0114 (15)	−0.0022 (13)	−0.0131 (15)
C15	0.030 (3)	0.093 (5)	0.032 (3)	0.010 (3)	−0.001 (2)	−0.027 (3)
C16	0.027 (3)	0.074 (4)	0.025 (2)	−0.024 (3)	−0.0055 (19)	0.009 (2)
C17	0.020 (2)	0.021 (2)	0.024 (2)	−0.0048 (16)	−0.0003 (16)	−0.0018 (17)
O17	0.0335 (16)	0.0216 (15)	0.0251 (15)	−0.0010 (13)	−0.0025 (13)	−0.0012 (11)
C18	0.048 (3)	0.033 (3)	0.032 (3)	0.007 (2)	0.001 (2)	−0.011 (2)
C19	0.021 (2)	0.036 (3)	0.025 (2)	−0.0054 (19)	−0.0008 (17)	−0.001 (2)
S21	0.0172 (5)	0.0205 (5)	0.0221 (5)	−0.0008 (4)	−0.0030 (4)	0.0032 (4)
O22	0.0273 (16)	0.0262 (15)	0.0291 (15)	−0.0064 (13)	−0.0077 (13)	0.0037 (12)
O23	0.0228 (15)	0.0238 (16)	0.0347 (17)	0.0039 (12)	−0.0017 (12)	0.0037 (13)
C24	0.016 (2)	0.020 (2)	0.018 (2)	−0.0004 (16)	−0.0014 (16)	0.0041 (16)
C25	0.029 (2)	0.023 (2)	0.025 (2)	−0.0006 (18)	0.0019 (18)	−0.0046 (19)
C26	0.032 (3)	0.025 (2)	0.029 (2)	−0.0075 (19)	−0.0011 (19)	0.0041 (19)
C27	0.019 (2)	0.030 (2)	0.022 (2)	−0.0023 (17)	0.0022 (16)	0.0062 (18)
C28	0.028 (2)	0.031 (2)	0.020 (2)	0.004 (2)	0.0044 (16)	0.0019 (18)
C29	0.029 (2)	0.022 (2)	0.018 (2)	−0.0042 (17)	−0.0011 (17)	0.0020 (17)
C30	0.029 (3)	0.058 (3)	0.037 (3)	−0.008 (2)	0.003 (2)	0.012 (3)

Geometric parameters (Å, º)

C1—O5	1.404 (4)	C14—C16	1.518 (6)
C1—O1	1.406 (5)	C14—C17	1.559 (5)
C1—C2	1.532 (5)	O14—C15	1.426 (5)
O1—C7	1.439 (5)	C17—O17	1.422 (5)
C2—O2	1.460 (4)	C17—C19	1.513 (5)
C2—C3	1.506 (5)	O17—C18	1.436 (5)
O2—S21	1.587 (3)	S21—O22	1.431 (3)
C3—O3	1.423 (4)	S21—O23	1.432 (3)
C3—C4	1.497 (5)	S21—C24	1.762 (4)
O3—C14	1.432 (4)	C24—C29	1.382 (5)
C4—O4	1.437 (4)	C24—C25	1.381 (5)
C4—C5	1.522 (5)	C25—C26	1.389 (6)
O4—C17	1.429 (4)	C26—C27	1.390 (6)
C5—O5	1.449 (4)	C27—C28	1.392 (6)
C5—C6	1.508 (5)	C27—C30	1.508 (5)
C14—O14	1.414 (5)	C28—C29	1.389 (5)
O5—C1—O1	113.5 (3)	C16—C14—C17	113.2 (3)
O5—C1—C2	112.7 (3)	C14—O14—C15	115.1 (4)
O1—C1—C2	105.0 (3)	O17—C17—O4	109.6 (3)
C1—O1—C7	113.0 (3)	O17—C17—C19	112.6 (3)
O2—C2—C3	109.7 (3)	O4—C17—C19	106.4 (3)
O2—C2—C1	107.1 (3)	O17—C17—C14	104.3 (3)
C3—C2—C1	109.5 (3)	O4—C17—C14	111.7 (3)
C2—O2—S21	117.6 (2)	C19—C17—C14	112.3 (3)
O3—C3—C4	109.7 (3)	C17—O17—C18	115.1 (3)
O3—C3—C2	109.8 (3)	O22—S21—O23	120.18 (17)
C4—C3—C2	112.8 (3)	O22—S21—O2	108.83 (15)
C3—O3—C14	112.0 (3)	O23—S21—O2	103.80 (15)
O4—C4—C3	107.8 (3)	O22—S21—C24	109.18 (17)
O4—C4—C5	108.8 (3)	O23—S21—C24	109.47 (18)
C3—C4—C5	111.4 (3)	O2—S21—C24	104.11 (15)
C17—O4—C4	112.5 (3)	C29—C24—C25	121.5 (4)
O5—C5—C6	106.8 (3)	C29—C24—S21	119.3 (3)
O5—C5—C4	107.7 (3)	C25—C24—S21	119.2 (3)
C6—C5—C4	112.3 (3)	C24—C25—C26	119.0 (4)
C1—O5—C5	115.8 (3)	C25—C26—C27	120.8 (4)
O14—C14—O3	109.2 (3)	C26—C27—C28	119.0 (4)
O14—C14—C16	113.5 (4)	C26—C27—C30	120.7 (4)
O3—C14—C16	105.9 (3)	C28—C27—C30	120.3 (4)
O14—C14—C17	104.5 (3)	C29—C28—C27	120.8 (4)
O3—C14—C17	110.6 (3)	C24—C29—C28	119.0 (4)