2-C-Methyl-3,4-O-methyl­idene-d-arabinono-1,5-lactone

Bream, R.; Watkin, D.J.; Jones, N.A.; Jenkinson, S.F.; Fleet, G.W.J.

doi:10.1107/S1600536806035331

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 62| Part 10| October 2006| Pages o4356-o4358

https://doi.org/10.1107/S1600536806035331

2-C-Methyl-3,4-O-methylidene-D-arabinono-1,5-lactone

Richard Bream,^a ^* David J. Watkin,^a Nigel A. Jones,^b Sarah F. Jenkinson ^c and George W. J. Fleet ^c

^aDepartment of Chemical Crystallography, Chemical Research Laboratory, Mansfield Road, Oxford OX1 3TA, England, ^bDepartment of Organic Chemistry, Chemical Research Laboratory, Mansfield Road, Oxford OX1 3TA, England, and ^cDepartment of Organic Chemistry, Chemical Research Laboratory, Mansfield Road, Oxford OX1 3TA, England
^*Correspondence e-mail: Richard.Bream@pmb.oxon.org

(Received 25 August 2006; accepted 1 September 2006; online 8 September 2006)

The relative stereochemistry at C-2 of the title compound, C₇H₁₀O₅, was determined by X-ray crystallographic analysis of the arabinonolactone, which adopts a boat conformation with a flagpole hydroxyl group. Its absolute configuration was determined by the use of D-erythronolactone as the starting material.

Comment

Until recently, only linear carbohydrate chirons have been available as scaffolds for the synthesis of complex synthetic targets (Lichtenthaler & Peters, 2004 ). However, the Kiliani cyanide reaction on ketohexoses (Hotchkiss et al., 2004 ; Soengas et al., 2005 ) affords versatile intermediates with carbon branches at C-2 of the sugar for the synthesis of imino sugars and complex sugar amino acids with non-linear carbon chains (Simone et al., 2005 ). The Kiliani reaction on hamamelose provides access to carbohydrates with a branch at C-3 (Parker, Watkin, Simone & Fleet, 2006 ).

Carbohydrate building blocks with a C-2 methyl group can be formed by the reaction of cyanide on 1-deoxyketoses, themselves prepared by the addition of organometallic reagents to sugar lactones (Hotchkiss et al., 2006 ). Thus, reaction of the isopropylidene-protected D-erythronolactone, (1), with methyl magnesium bromide followed by sodium cyanide gave the arabino-protected derivative, (2), as the only 1,5-lactone isolated (Punzo et al., 2005a ). The potential of (2) as a route to sugar derivatives with a C-2 methyl group bearing a functional group at the tertiary centre is shown by its easy conversion to the branched arabinose, (3) (Punzo et al., 2005b ), the quaternary ribo-azide, (4) (Punzo, Watkin, Jenkinson, Cruz & Fleet, 2005 ), and the quaternary ribo-fluoride, (5) (Parker, Watkin, Mayes et al., 2006 ). The branched azidomethyl lactone, (6), has also been prepared from (2) and is a precursor to complex piperidine amino acids and iminosugars (Punzo et al., 2006 ).

In order to optimize the protecting group strategy for the synthesis of complex targets (and to investigate the diastereoselectivity of the Kiliani cyanide extension), the formaldehyde acetal of D-erythronolactone, (7), was treated with methyl magnesium bromide to give the 1-deoxy-D-ribulose, (8). The Kiliani reaction of (8) with sodium cyanide gave a single diastereomeric product, (9), as the only 1,5-lactone isolated (Jenkinson et al., 2006 ). This paper shows, by X-ray crystallography, that the arabinonolactone, (9), was formed in this reaction with none of the epimeric ribono diastereomer, (10), isolated.

The X-ray crystal structure determination shows that (9) is in a boat conformation (Fig. 1). The formation of (9) with the smaller hydroxyl group in the flagpole position may be due to the alternative product, (10), having the larger methyl group in the more hindered flagpole environment. The potential of (9) as a chiron is under investigation.

In the crystal structure, intermolecular O—H⋯O hydrogen bonds (Table 1) link the molecules into zigzag chains extending along the a axis (Fig. 2).

Figure 1
The molecular structure of the title compound, with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitrary radii.

Figure 2
The crystal packing, viewed down the a axis. Hydrogen bonds are shown as dashed lines.

Experimental

The title arabinono-1,5-lactone, (9), was obtained (Jenkinson et al.., 2006) by vapour diffusion of cyclohexane into a solution in ethyl acetate until crystals of a suitable size were formed (m.p. 373–375 K). [α]_D −126.0 (c 1.0, CHCl₃); ¹H NMR (400 MHz, CDCl₃, δ, p.p.m.): 1.67 (3H, s, Me), 3.04 (1H, s, OH), 4.25 (1H, d, J_3,4 = 7.9 Hz, H3), 4.46–4.50 (2H, m, H4, H5a), 4.82 (1H, s, OCH₂O), 4.97 (1H, dd, J_4,5 b = 1.9 Hz, J_5a,5 b = 12.0 Hz, H5b), 5.17 (1H, s, OCH₂O); ¹³C NMR (100 MHz, CDCl₃, δ, p.p.m.): 22.1 (Me), 68.7 (C5), 71.5 (C4), 72.2 (C3), 78.8 (C2), 94.9 (OCH₂O), 171.4 (CO).

Crystal data

C₇H₁₀O₅
M_r = 174.15
Orthorhombic, P 2₁ 2₁ 2₁
a = 6.8693 (3) Å
b = 7.0382 (3) Å
c = 15.7909 (7) Å
V = 763.45 (6) Å³
Z = 4
D_x = 1.515 Mg m⁻³
Mo Kα radiation
μ = 0.13 mm⁻¹
T = 150 K
Needle, colourless
0.50 × 0.20 × 0.20 mm

Data collection

Nonius KappaCCD area-detector diffractometer
ω scans
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997 ) T_min = 0.882, T_max = 0.974
1726 measured reflections
1032 independent reflections
784 reflections with I > 2σ(I)
R_int = 0.032
θ_max = 27.5°

Refinement

Refinement on F²
R[F² > 2σ(F²)] = 0.038
wR(F²) = 0.080
S = 1.00
1027 reflections
109 parameters
H-atom parameters constrained
w = 1/[σ²(F²) + (0.04P)² + 0.03P] where P = (max(F_o²,0) + 2F_c²)/3
(Δ/σ)_max < 0.001
Δρ_max = 0.36 e Å⁻³
Δρ_min = −0.34 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O11—H1⋯O7ⁱ	0.83	2.10	2.911 (2)	167
Symmetry code: (i) $[x+{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+1]$ .

A [sin(θ)/λ]² threshold of 0.01 was used to guard against the risk of including low angle reflections partially occluded by the beam stop. In the absence of significant anomalous scattering, 873 Friedel pairs were merged and the absolute configuration was assigned from the known starting material. All H atoms were located in a difference map, but those attached to C atoms were repositioned geometrically. The H atoms were initially refined with soft restraints on the bond lengths and angles to regularize their geometry (C—H in the range 0.93–98 Å, and O—H = 0.825 Å) and isotropic displacement parameters [U_iso(H) in the range 1.2–1.5U_eq of the parent atom], after which they were refined with riding constraints.

Data collection: COLLECT (Nonius, 2001 ); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO/SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003 ); molecular graphics: CAMERON (Watkin et al., 1996 ); software used to prepare material for publication: CRYSTALS.

Supporting information

Crystal structure: contains datablocks 9, global. DOI: https://doi.org/10.1107/S1600536806035331/cv2114sup1.cif

Structure factors: contains datablock 9. DOI: https://doi.org/10.1107/S1600536806035331/cv21149sup2.hkl

Computing details top

Data collection: COLLECT (Nonius, 2001); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO/SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003); molecular graphics: CAMERON (Watkin et al., 1996); software used to prepare material for publication: CRYSTALS.

2-C-Methyl-3,4-O-methylidene-D-arabinono-1,5-lactone top

Crystal data top

C₇H₁₀O₅	D_x = 1.515 Mg m⁻³
M_r = 174.15	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P2₁2₁2₁	Cell parameters from 981 reflections
a = 6.8693 (3) Å	θ = 1–27°
b = 7.0382 (3) Å	µ = 0.13 mm⁻¹
c = 15.7909 (7) Å	T = 150 K
V = 763.45 (6) Å³	Needle, colourless
Z = 4	0.50 × 0.20 × 0.20 mm
F(000) = 368

Data collection top

Nonius KappaCCD area-detector diffractometer	784 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.032
ω scans	θ_max = 27.5°, θ_min = 2.6°
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997)	h = −8→8
T_min = 0.882, T_max = 0.974	k = −9→9
1726 measured reflections	l = −20→20
1032 independent reflections

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.038	H-atom parameters constrained
wR(F²) = 0.080	w = 1/[σ²(F²) + (0.04P)² + 0.03P] where P = (max(F_o²,0) + 2F_c²)/3
S = 1.01	(Δ/σ)_max = 0.000146
1027 reflections	Δρ_max = 0.36 e Å⁻³
109 parameters	Δρ_min = −0.34 e Å⁻³
0 restraints

Special details top

Experimental. [α]D -126.0 (c 1.0, CHCl₃); ¹H NMR (400 MHz, CDCl₃, δ, p.p.m.): 1.67 (3H, s, Me), 3.04 (1H, s, OH), 4.25 (1H, d, J_3,4 = 7.9 Hz, H3), 4.46–4.50 (2H, m, H4, H5a), 4.82 (1H, s, OCH₂O), 4.97 (1H, dd, J_{4,5 b} = 1.9 Hz, J_{5a,5 b} = 12.0 Hz, H5b), 5.17 (1H, s, OCH₂O); ¹³C NMR (100 MHz, CDCl₃, δ, p.p.m.): 22.1 (Me), 68.7 (C5), 71.5 (C4), 72.2 (C3), 78.8 (C2), 94.9 (OCH₂O), 171.4 (CO).

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

	x	y	z	U_iso*/U_eq
C1	0.5144 (3)	0.4702 (3)	0.40608 (13)	0.0239
C2	0.4191 (3)	0.5797 (3)	0.33348 (13)	0.0229
C3	0.2346 (3)	0.4823 (4)	0.29802 (14)	0.0265
C4	0.1759 (4)	0.3085 (4)	0.34774 (14)	0.0315
O5	0.1906 (2)	0.3444 (3)	0.43863 (9)	0.0308
C6	0.3551 (3)	0.4201 (3)	0.46975 (13)	0.0230
O7	0.3657 (2)	0.4406 (2)	0.54569 (9)	0.0280
O8	0.0852 (2)	0.6217 (2)	0.30591 (10)	0.0338
C9	0.1773 (4)	0.7974 (4)	0.32128 (16)	0.0299
O10	0.3496 (2)	0.7553 (2)	0.36642 (10)	0.0315
O11	0.5831 (2)	0.2984 (2)	0.36767 (10)	0.0312
C12	0.6764 (3)	0.5837 (4)	0.44681 (15)	0.0324
H21	0.5170	0.5978	0.2888	0.0257*
H31	0.2515	0.4494	0.2401	0.0317*
H41	0.0385	0.2805	0.3369	0.0378*
H42	0.2600	0.1971	0.3317	0.0373*
H91	0.2107	0.8636	0.2684	0.0341*
H92	0.0908	0.8822	0.3566	0.0339*
H121	0.7348	0.5108	0.4921	0.0481*
H122	0.7769	0.6091	0.4049	0.0476*
H123	0.6253	0.6978	0.4707	0.0472*
H1	0.6575	0.2398	0.3993	0.0572*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0250 (11)	0.0228 (14)	0.0239 (11)	0.0022 (11)	0.0032 (10)	0.0000 (10)
C2	0.0247 (10)	0.0235 (13)	0.0206 (11)	0.0009 (11)	0.0028 (10)	0.0011 (10)
C3	0.0299 (11)	0.0269 (14)	0.0227 (11)	0.0002 (12)	−0.0011 (10)	−0.0025 (11)
C4	0.0386 (13)	0.0316 (14)	0.0244 (12)	−0.0077 (13)	−0.0068 (12)	−0.0011 (11)
O5	0.0309 (8)	0.0378 (11)	0.0237 (8)	−0.0133 (8)	−0.0024 (7)	0.0046 (8)
C6	0.0265 (12)	0.0176 (12)	0.0250 (12)	−0.0003 (11)	0.0001 (10)	0.0041 (10)
O7	0.0286 (8)	0.0341 (11)	0.0215 (8)	0.0014 (8)	−0.0001 (7)	0.0006 (8)
O8	0.0281 (8)	0.0301 (10)	0.0432 (10)	−0.0002 (8)	−0.0045 (8)	0.0033 (9)
C9	0.0328 (12)	0.0281 (14)	0.0289 (12)	0.0040 (12)	−0.0023 (12)	0.0024 (11)
O10	0.0344 (9)	0.0251 (9)	0.0350 (9)	0.0041 (8)	−0.0080 (8)	−0.0047 (8)
O11	0.0373 (9)	0.0314 (10)	0.0248 (8)	0.0122 (8)	−0.0004 (8)	0.0007 (8)
C12	0.0245 (11)	0.0404 (16)	0.0324 (13)	−0.0055 (12)	−0.0027 (11)	0.0021 (12)

Geometric parameters (Å, º) top

C1—C2	1.529 (3)	C4—H42	1.006
C1—C6	1.528 (3)	O5—C6	1.342 (3)
C1—O11	1.432 (3)	C6—O7	1.210 (3)
C1—C12	1.514 (3)	O8—C9	1.410 (3)
C2—C3	1.545 (3)	C9—O10	1.414 (3)
C2—O10	1.423 (3)	C9—H91	0.983
C2—H21	0.984	C9—H92	1.010
C3—C4	1.508 (3)	O11—H1	0.825
C3—O8	1.426 (3)	C12—H121	0.966
C3—H31	0.951	C12—H122	0.972
C4—O5	1.461 (3)	C12—H123	0.954
C4—H41	0.979

C2—C1—C6	107.64 (17)	O5—C4—H42	110.0
C2—C1—O11	104.41 (17)	H41—C4—H42	110.6
C6—C1—O11	108.66 (18)	C4—O5—C6	119.11 (18)
C2—C1—C12	111.57 (19)	C1—C6—O5	116.98 (18)
C6—C1—C12	111.67 (18)	C1—C6—O7	125.5 (2)
O11—C1—C12	112.52 (18)	O5—C6—O7	117.47 (19)
C1—C2—C3	113.54 (19)	C3—O8—C9	107.19 (16)
C1—C2—O10	107.89 (17)	O8—C9—O10	106.18 (18)
C3—C2—O10	104.06 (17)	O8—C9—H91	112.0
C1—C2—H21	108.1	O10—C9—H91	109.4
C3—C2—H21	111.0	O8—C9—H92	110.4
O10—C2—H21	112.3	O10—C9—H92	109.7
C2—C3—C4	113.0 (2)	H91—C9—H92	109.1
C2—C3—O8	104.69 (17)	C2—O10—C9	106.17 (17)
C4—C3—O8	108.65 (18)	C1—O11—H1	111.7
C2—C3—H31	110.9	C1—C12—H121	109.8
C4—C3—H31	109.6	C1—C12—H122	109.3
O8—C3—H31	109.8	H121—C12—H122	107.8
C3—C4—O5	110.7 (2)	C1—C12—H123	110.0
C3—C4—H41	109.3	H121—C12—H123	107.9
O5—C4—H41	105.8	H122—C12—H123	112.1
C3—C4—H42	110.3

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O11—H1···O7ⁱ	0.83	2.10	2.911 (2)	167

Symmetry code: (i) x+1/2, −y+1/2, −z+1.

References

Altomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst. 27, 435. CrossRef Web of Science IUCr Journals Google Scholar
Betteridge, P. W., Carruthers, J. R., Cooper, R. I., Prout, K. & Watkin, D. J. (2003). J. Appl. Cryst. 36, 1487. Web of Science CrossRef IUCr Journals Google Scholar
Hotchkiss, D. J., Jenkinson, S. F., Storer, R., Heinz, T. & Fleet, G. W. J. (2006). Tetrahedron Lett. 47, 315–318. Web of Science CrossRef CAS Google Scholar
Hotchkiss, D., Soengas, R., Simone, M. I., van Ameijde, J., Hunter, S., Cowley, A. R. & Fleet, G. W. J. (2004). Tetrahedron Lett. 45, 9461–9464. Web of Science CrossRef CAS Google Scholar
Jenkinson, S. F., Jones, N. A. & Fleet, G. W. J. (2006). In preparation. Google Scholar
Lichtenthaler, F. W. & Peters, S. (2004). C. R. Acad. Sci. Ser. IIc Chim. 7, 65–90. CAS Google Scholar
Nonius (2001). COLLECT. Nonius BV, Delft, The Netherlands. Google Scholar
Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307–326. New York: Academic Press. Google Scholar
Parker, S., Watkin, D., Mayes, B., Storer, R., Jenkinson, S. & Fleet, G. (2006). Acta Cryst. E62, o1208–o1210. Web of Science CSD CrossRef IUCr Journals Google Scholar
Parker, S. G., Watkin, D. J., Simone, M. I. & Fleet, G. W. J. (2006). Acta Cryst. E62, o3961–o3963. Web of Science CSD CrossRef IUCr Journals Google Scholar
Punzo, F., Watkin, D. J., Jenkinson, S. F., Cruz, F. P. & Fleet, G. W. J. (2005). Acta Cryst. E61, o511–o512. Web of Science CSD CrossRef IUCr Journals Google Scholar
Punzo, F., Watkin, D. J., Jenkinson, S. F., da Cruz, F. P. & Fleet, G. W. J. (2006). Acta Cryst. E62, o321–o323. Web of Science CSD CrossRef IUCr Journals Google Scholar
Punzo, F., Watkin, D. J., Jenkinson, S. F. & Fleet, G. W. J. (2005a). Acta Cryst. E61, o127–o129. Web of Science CSD CrossRef IUCr Journals Google Scholar
Punzo, F., Watkin, D. J., Jenkinson, S. F. & Fleet, G. W. J. (2005b). Acta Cryst. E61, o326–o327. Web of Science CSD CrossRef IUCr Journals Google Scholar
Simone, M. I., Soengas, R., Newton, C. R., Watkin, D. J. & Fleet, G. W. J. (2005). Tetrahedron Lett. 46, 5761–5775. Web of Science CSD CrossRef CAS Google Scholar
Soengas, R., Izumori, K., Simone, M. I., Watkin, D. J., Skytte, U. P., Soetaert, W. & Fleet, G. W. J. (2005). Tetrahedron Lett. 46, 5755–5759. Web of Science CrossRef CAS Google Scholar
Watkin, D. J., Prout, C. K. & Pearce, L. J. (1996). CAMERON. Chemical Crystallography Laboratory, University of Oxford, England. Google Scholar

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