3,3 000 :5,6-Di- O -isopropylidene-3- C -hydroxy-methyl- D - allono -1,4-lactone: an organic structure containing large unoccupied voids

The Kiliani reaction of d-hamamelose with sodium cyanide, followed by acetonation, affords crystalline 3,3′:5,6-di-O-isopropyl­idene-3-C-hydroxy­methyl-d-allono-1,4-lactone, C13H20O7, a carbon-branched sugar with potential as an enanti­omerically pure carbohydrate scaffold. The lactone has one single free hydroxyl group unprotected, with six other functional groups protected in a single step as ketals or esters. The resulting crystal structure is unusual in that it contains large voids (544 A3) within which there is no evidence of included solvent.

The Kiliani reaction of d-hamamelose with sodium cyanide, followed by acetonation, affords crystalline 3,3 0 :5,6-di-O-isopropylidene-3-C-hydroxymethyl-d-allono-1,4-lactone, C 13 H 20 O 7 , a carbon-branched sugar with potential as an enantiomerically pure carbohydrate scaffold. The lactone has one single free hydroxyl group unprotected, with six other functional groups protected in a single step as ketals or esters. The resulting crystal structure is unusual in that it contains large voids (544 Å 3 ) within which there is no evidence of included solvent.

Comment
At present, there are very few accessible branched carbohydrate scaffolds (Lichtenthaler & Peters, 2004;Bols, 1996) for use in the synthesis of complex enantiomerically pure targets . The reactions of calcium oxide on Amadori 1-deoxyamino-ketoses (Hotchkiss et al., 2006) and the Kiliani reaction of cyanide with ketoses (Hotchkiss et al., 2004;Soengas et al., 2005) allow the preparation of 2-C-methyl and 2-C-hydroxymethyl lactones in relatively short sequences. However, syntheses of carbohydrates bearing a carbon branch at C-3 are very rare (Bream et al., 2006). One approach to such chirons is the Kiliani cyanide reaction on 2-C-hydroxymethyl sugars [such as hamamelose (1)] to produce 3-C-hydroxymethyl lactones [such as (2) and (4)]. The experimental details for the Kiliani reaction of d-hamamelose (1) with cyanide to give a mixture of the two branched sugar lactones (2) and (4), followed by treatment with dimethoxypropane to afford a separable mixture of the two diacetonides (3) and (5), have been reported in a previous paper (Parker et al., 2006). A significant number of ambiguities arise from the formation of possible lactones, the sites for the formation of cyclic ketals and the sizes of both the lactone and ketal rings. This is an area in which X-ray crystallography is needed to have any confidence at all in the structures of diacetonides obtained by this short procedure. The crystal structure of the altronodiacetonide (5), formed from the lactone (4) derived by cyclization of the branched C-3 0 hydroxymethyl group on to the carboxylic acid, has been established by X-ray crystallography (Parker et al., 2006). This paper firmly assigns the structure of the second crystalline product as the branched allono-lactone (3) formed from lactone formation from the C-4 hydroxyl group; the absolute configuration of (3) is determined by the use of d-ribose as the starting material for the synthesis. It is noteworthy that both lactones (3) and (5) have only the C-2 hydroxyl group unprotected; the sequence provides access to two sugars with seven functional groups but with six of the them protected in one simple step.
The component molecules have no unusual torsion angles, and show no evidence of internal strain. The relatively large anisotropic displacement parameters for the methyl groups and O atoms in the acetonide protecting group may indicate some ring fluxion (Fig. 1).
The crystal structure is unusual in that it contains substantial voids (544 Å 3 ) within which there is no evidence for included solvent (Fig. 2). The voids are big enough to have contained dichloromethane, but the maximum residual electron density is only 0.2 e Å À3 . We do not know if the voids in the dry crystals ever contained solvent, though generally solvent loss from organic crystals is associated with either a total loss of crystallinity, or at least a degradation of the crystal quality. In this case the crystals remained glass-clear.
The structure consists of a tight helix (Fig. 3), involving O-HÁ Á ÁO i hydrogen bonds (Table 1), which runs parallel to the c axis at ( 1 2 , 1 2 , z). The main parts of the molecule hang off this backbone like leaves from a tree. The tips of the 'leaves' of four separate helices meet to form a second helix at (0, 0, z). The 'leaves' of each pair of adjacent hydrogen-bonded helices (separated by z 2 because of the 4 1 axis) interleave along (0, 0, z), but there is no evidence for particularly strong interactions at these points.  The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitary radius.

Figure 2
Packing diagam of the title compound viewed along c. The residual electron density in the void has a maximum value of 0.22 e Å À3 . Hydrogen bonds are drawn as dotted lines

Experimental
The title compound, (3) (Prince, 1982;Watkin, 1994) Modified Chebychev polynomial (Watkin, 1994;Prince, 1982) (Á/) max = 0.010 Á max = 0.22 e Å À3 Á min = À0.21 e Å À3 Table 1 Hydrogen-bond geometry (Å , ). In the absence of significant anomalous scattering, Friedel pairs were merged and the absolute configuration assigned from the starting materials The H atoms were all 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 = 0.93-0.98, O-H = 0.82 Å and U iso (H) = 1.2 or 1.5 times U eq (parent atom)], after which the positions were refined with riding constraints.