Crystal structure of 2-[(1R,2R,4aS,8aS)-2-hydroxy-2,5,5,8a-tetramethyldecahydronaphthalen-1-yl]-N-(o-tolyl)acetamide

The title compound, C23H35NO2, is an amide derivative of the lactone (+)-sclareolide, and was synthesized from natural sclareol. In the molecular structure, the two six-membered rings (A and B) of the labdane skeleton are trans-fused, and adopt chair conformations. There is an intramolecular N—H⋯O hydrogen bond present forming an S(7) ring motif. In the crystal, O—H⋯O hydrogen bonds link the molecules into helical chains propagating along the b-axis direction. The chains are linked via C—H⋯π interactions, forming a three-dimensional structure.

Cg is the centroid of benzene ring C1-C6. The title compound, possessing an intact homodrimane skeleton, is an amide derivative of (+)-sclareolide, which was synthesized from natural sclareol (Barrero et al., 2004). The commercially available diterpene (-)-sclareol or the lactone derivative (+)-sclareolide make an ideal starting point for some biologically important natural products (Mohamad et al., 2005). Furthermore, the enantiometrically pure sclareolide provided the perfect tool to validate the absolute stereochemistry of certain chinensine family members, whose stereochemistry had been tentatively assigned based on comparisons to other biogenetically close compounds, such as coronarin E (Margaros & Vassilikogiannakis, 2007;Sy & Brown, 1997). Herein, we report on the first synthesis and crystal structure of the title compound.
The molecular structure of the title compound is shown in Fig. 1 (Table 1).
In the crystal, O-H···O hydrogen bonds link the molecules into zigzag chains propagating along the b axis direction (Table 1 and Fig. 2). The chains are linked via C-H···π interactions forming a three-dimensional structure (Table 1).

S2. Synthesis and crystallization
A solution of DIBAL-H (1.5 M in toluene, 2.58 ml, 3.87 mmol) was added to a cooled (273 K) solution of o-methylanilines (0.688 g, 4.0 mmol) in THF (1.7 ml) under nitrogen. The mixture was allowed to warm up and stirred at rt for 2 h. The concentration of the prepared DIBAL-H-o-CH 3 C 6 H 4 NH 2 complex was ca 0.88 M, and was used directly for aminolysis. To a solution of (+)-sclareolide (0.168 g, 0.67 mmol) in THF (2.5 ml) was added, under nitrogen at rt, the DIBAL-H-p-C 6 H 4 NH 2 complexe (3.8 ml, 3.35 mmol). After stirring at rt for 2 h, the reaction was cooled to 273 K, and then quenched with H 2 O (1.5 ml) and a 1 M aqueous solution of KHSO 4 (4 ml). The resulting mixture was extracted with CH 2 Cl 2 (3 × 10 ml). The combined organic layers were washed with brine, dried over Na 2 SO 4 and concentrated. The residue was purified by flash chromatography (200-300 m ilicon) with PE/EtOAc = 6:1 as eluant to give the title compound (215 mg, yield 90 %) as a white solid (Margaros & Georgios, 2007). Colourless crystals were obtained by slow evaporation of a solution in CH 2 Cl 2 .

S2.1. Refinement
Crystal data, data collection and structure refinement details are summarized in atoms and 1.2U eq (N,C) for other H atoms. The absolute configuration of the title compound is based on that of the starting reagent (+)-sclareolide.

Figure 1
A view of the molecular structure of the title compound, with atom labelling. Displacement ellipsoids are drawn at the 30% probability level. The intramolecular N-H···O hydrogen bonds is shown as a dashed line (see Table 1).

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 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 > σ(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.