Crystal structure of (–)-methyl (R,E)-4-[(2R,4R)-2-amino-2-trichloromethyl-1,3-dioxolan-4-yl]-4-hydroxy-2-methylbut-2-enoate

In the title compound, the 1,3-dioxane ring has an envelope conformation. In the crystal, classical O—H⋯O and N—H⋯O hydrogen bonds link molecules into a sheet structure, and a weak intermolecular C—H⋯Cl interaction extends the sheet structure into a three-dimensional network.


Chemical context
Cyclic compounds often play a significant role, not only in controlling stereochemistry due to their conformational rigidity, but also as protecting groups in organic synthesis. On the basis of this concept, we have explored the utilization of cyclic orthoamides, prepared from allylic diol and triol with known conditions (Overman, 1974;1976), and have developed a new strategy for the total synthesis of a certain natural product (Nakayama, et al., 2013). The title compound is a structural isomer of a recently reported compound (Oishi et al., 2016).

Figure 3
The crystal packing of the title compound, viewed along the c axis, showing the sheet structure parallel to (001). The helical chain running along the b-axis direction is drawn as overlapped molecules. Yellow lines indicate the intermolecular N-HÁ Á ÁO hydrogen bonds. Only H atoms involved in the hydrogen bonds are shown for clarity. [Symmetry code: (ii) x -1, y, z.]

Figure 1
The molecular structure of the title compound, with the atom labelling. Displacement ellipsoids are drawn at the 50% probability level. The purple dotted line indicates the short intramolecular N-HÁ Á ÁCl contact (see Table 1). Only H atoms connected to N, O and chiral C atoms are shown for clarity.
For the cyclic orthoamide core with a trichloromethyl group on the central carbon atom, four structures are registered in the CSD. These are two derivatives (WEKWOY: Haeckel et al., 1994;and LAGMAK: Oishi et al., 2016) of 1,3-dioxolane (b), one derivative (WAXBEE: Metwally, 2011) of 1,3-oxathiolane (c), and one derivative (LIBHIO: Rondot et al., 2007) of 1,3-dioxane (d). The amino H atoms were refined as adopting an sp 2 configuration for WEKWOY and WAXBEE, while they were refined assuming an sp 3 configuration of the N atom for LIBHIO and LAGMAK, as in the present study. Each N-H bond of the amino group in LIBHIO is mostly eclipsed by the neighbouring C-Cl bonds of the trichloromethyl group, whereas those in the title compound are slightly tilted (Fig. 6). There is an intramolecular N-HÁ Á ÁCl interaction [H6AÁ Á ÁCl1 = 2.66 (4) Å ; N6-H6AÁ Á ÁCl1 = 115 (3) ] in the title compound (Table 1), while the corresponding geometries are 2.76 Å and 109 in LIBHIO. These amino groups may be oriented to avoid intramolecular non-bonding short contacts as well as to form classical intermolecular hydrogen bonds. The amino H atoms in LAGMAK are disordered according to the possible intramolecular N-HÁ Á ÁO and NÁ Á ÁH-O hydrogen bonds with the hydroxy group (Oishi et al., 2016).

Synthesis and crystallization
The title compound was afforded from l-threose, which can be prepared according to the reported procedure (Smith et al., 1992) from d-galactose (Kidena et al., 2017). Purification was carried out by silica gel column chromatography, and colourless crystals were obtained from a benzene solution under a hexane-saturated atmosphere, by slow evaporation at ambient temperature (m.p. 358-359 K

Figure 6
A projected diagram looking through the N atom of the amino group onto the C atom of the trichloromethyl group.

Special details
Experimental. IR (film): 3393, 3325, 2953, 1714, 1438, 1239, 1093, 1035, 825, 803, 749 cm -1  Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 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 (Å 2 )
x y z U iso */U eq