(±)-2′-Phenylcyclohexanespiro-4′-(azepano[1,2-b]isoxazolidine)

In the crystal structure of the racemic title isoxazolidine, C19H27NO, the relative stereochemistry between the phenyl group and the bridgehead H atom is shown to be syn. There are two molecules in the asymmetric unit, one of which is the 7R*,13R* enantiomer, and one of which is the 7S*,13S* enantiomer. These enantiomers adopt different orientations of the phenyl ring with respect to the isoxazolidine ring, with C—C—C—C torsion angles of 63.6 (4) and 86.8 (4)°, respectively. In both enantiomers, the six-membered ring adopts a chair conformation, while the seven-membered ring adopts a twist-chair conformation.

In the crystal structure of the racemic title isoxazolidine, C 19 H 27 NO, the relative stereochemistry between the phenyl group and the bridgehead H atom is shown to be syn. There are two molecules in the asymmetric unit, one of which is the 7R*,13R* enantiomer, and one of which is the 7S*,13S* enantiomer. These enantiomers adopt different orientations of the phenyl ring with respect to the isoxazolidine ring, with C-C-C-C torsion angles of 63.6 (4) and 86.8 (4) , respectively. In both enantiomers, the six-membered ring adopts a chair conformation, while the seven-membered ring adopts a twist-chair conformation.

Comment
The title isoxazolidine was prepared as part of a synthetic program (Brimble & Trzoss, 2004;Brimble et al. 2005;O'Connor et al., 2008 andGuéret et al., 2008) directed towards the synthesis of heterocycles related to the spiroimine unit of the spirolide family of shellfish toxins that were isolated from the culture of a toxic clone of the dinoflagellate Alexandrium ostenfeldii (Hu et al., 2001;MacKinnon et al., 2006 andCiminiello et al., 2007). With this idea in mind, a study of the thermal-promoted 1,3-dipolar cycloaddition of a novel 7,6-spironitrone to a range of alkenes was investigated. In particular, the addition of the 7,6-spironitrone to styrene proceeded regioselectively to afford the title racemic isoxazolidine. However, establishment of the exo or endo selectivity of this 1,3-dipolar cycloaddition was required and this could not be deduced from detailed NMR studies. The crystal structure of the cycloadduct ( Fig. 1) clearly indicates the syn stereochemistry between the phenyl group at C13 and the bridgehead proton at C7, thereby confirming that the 1,3-dipolar cycloaddition took place with exo selectivity.
The relative stereochemistry of the racemic isoxazolidine is shown to be 7R*,13R* and 7S*,13S* from the crystal structure. Apart from the opposite stereochemistry, the two molecules in the asymmetric unit also differ from each other in the orientation adopted by the phenyl ring relative to the adjacent isoxazolidine ring. This is shown by the different torsion angle adopted at C12-C13-C14-C15: for one enantiomer, the torsion angle is 63.6 (4)° while the torsion angle for the opposite enantiomer is 86.8 (4)°. In both molecules, the six-membered ring adopts a chair conformation while the seven-membered ring adopts a twist-chair conformation. A view of the molecular packing is depicted in Fig. 2.
Experimental 8-Azoniaspiro[5.6]dodec-7-en-8-olate (550 mg, 1.96 mmol) and styrene (905 µl, 7.9 mmol) were dissolved in toluene (10 ml) under an argon atmosphere and the solution was heated under reflux for 12 h. The reaction mixture was cooled to room temperature and the solvent was concentrated in vacuo. The residue was purified directly by flash chromatography (hexane-ethyl acetate 10:1) to give the title compound as a white solid (353 mg, 63%). Recrystallization from diethyl ether afforded white needles.

Refinement
H atoms were placed in calculated positions and were refined using a riding model (C-H = 0.93 or 0.97 Å), with U iso (H) = 1.2 or 1.5 times U eq (C). Two peaks are present in the final difference density: 1.21 eÅ -3 at a distance of 1.11 Å from O, and 1.02 eÅ -3 at a distance of 1.20 Å from C14.