(1R,6R)-1-Methyl-8-azaspiro[5.6]dodecan-7-one

The crystal structure of the title compound, C12H21NO, has been investigated to establish the absolute stereochemistry at position 1. The absolute stereochemistry at the quaternary centre at position 6 is established to be R using an asymmetric Birch reductive alkylation reaction for which the stereochemical outcome is known. The crystal structure indicates the presence of two conformers of the bicyclic (1R,6R)-spirolactam ring system that differ in the conformation adopted by the six-membered ring. In one conformer, the methyl group adopts an axial position whereas in the other conformer, the same methyl group adopts an equatorial position. In both conformers, the seven-membered ring adopts a chair conformation. The two conformers of the bicyclic spirolactam are connected to each other via intermolecular N—H⋯O hydrogen bonds forming a heterodimer. The asymmetric unit contains two such dimers.

The crystal structure of the title compound, C 12 H 21 NO, has been investigated to establish the absolute stereochemistry at position 1. The absolute stereochemistry at the quaternary centre at position 6 is established to be R using an asymmetric Birch reductive alkylation reaction for which the stereochemical outcome is known. The crystal structure indicates the presence of two conformers of the bicyclic (1R,6R)-spirolactam ring system that differ in the conformation adopted by the six-membered ring. In one conformer, the methyl group adopts an axial position whereas in the other conformer, the same methyl group adopts an equatorial position. In both conformers, the seven-membered ring adopts a chair conformation. The two conformers of the bicyclic spirolactam are connected to each other via intermolecular N-HÁ Á ÁO hydrogen bonds forming a heterodimer. The asymmetric unit contains two such dimers. 3 restraints H-atom parameters constrained Á max = 0.46 e Å À3 Á min = À0.21 e Å À3 Table 1 Hydrogen-bond geometry (Å , ). Data collection: SMART (Siemens, 1995); cell refinement: SAINT (Siemens, 1995); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPIII (Burnett & Johnson, 1996); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and publCIF (Westrip, 2008).

Comment
The title spirolactam was prepared as part of a synthetic program directed towards the synthesis of spirolides A and C that were isolated from the culture of a toxic clone of the dinoflagellate Alexandrium ostenfeldii (Hu et al., 2001, MacKinnon et al., 2006, Ciminiello et al., 2007. The work demonstrates methodology to access enantiopure 7,6-spirolactams. The quaternary spirocyclic centre is generally considered a challenging stereocentre to be constructed in a stereoselective fashion in organic synthesis (Brimble et al., 2005;Brimble & Trzoss, 2004). By employing (S)-methoxypyrrolidine as a chiral auxiliary, a highly diastereoselective Birch reductive alkylation (Schultz et al., 1988 andPettus, 1997) furnished the alkylated product with the desired stereochemistry at the quaternary carbon which was then converted to the title spirolactam in several steps. Since the stereochemistry at C6 is known to be R, the absolute configuration at C1 has therefore been assigned as R.
The crystal structure indicates the presence of two conformers of the enantiopure bicyclic (1R,6R)-spirolactam. While in both conformers, the 7,6-bicyclic ring system adopts a chair-chair conformation, the methyl group (C13) adopts a differing position between the conformer. In one conformer, the methyl group (C13) adopts an axial position whereas in the other conformer, the same methyl group (C13B) adopts an equatorial position on their associated cyclohexane ring. In solution at room temperature, the two conformers are rapidly interconverting to each other as shown by the total lack of dynamic effects in the 1 H NMR spectrum at 400 MHz.
Each unit cell contains two heterodimers of the two chair-configured conformers of the bicyclic spirolactam. In each dimer, the axial and equatorial conformers are connected to each other by two adjacent intermolecular N-H···O hydrogen bonds ( Figure 1).

Refinement
Hydrogen atoms were placed in calculated positions and refined using the riding model [C-H 0.93-0.97 Å), with U iso (H) = 1.5 U eq (C). Fig. 1. The molecular structure and atom numbering scheme of the heterodimer of (1R,6R)-1methyl-8-azaspiro[5.6]dodecan-7-one. The respective methyl group (C13) adopts an axial or equatorial position on its associated cyclohexane ring as shown. Ellipsoids are drawn at the 50% probability level. H atoms are represented as small spheres of arbitrary radii. Hydrogen bonds are shown as dashed lines.

Special details
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 > σ(F 2 ) is used only for calculating Rfactors(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. Friedel pairs were merged as recommended for light atom structures in the checkCIF program.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )