4 S * )-3 , 3-Difluoro-2 , 4-dihydroxy-5 , 5-dimethylcyclooct-5 ( Z )-en-1-yl N , N-diethylcarbamate

Conformational equilibria in eight-membered carbocycles occur via two main processes, pseudorotation and ring inversion. The latter exchanges substituent groups between equatorial and axial environments in a pseudo-enantiomeric relationship. Ring inversion is usually the more energetically demanding process; barriers to inversion exchange of 7.3–8.5 kcal mol 1 have been reported, with smaller barriers (ca 5 kcal mol ) (Servis & Noe, 1973) for the pseudorotation. [For early attempts to apply variable-temperature NMR to these phenomena, see Anderson et al. (1969) and St Jacques et al. (1966).] Recent work from our group has attempted to define these processes for a trio of difluorinated cyclooctenyl systems (Fawcett, Griffith et al., 2005). We were interested in observing a pseudorotational relationship between the ring conformations in the pair of reduction products (1) and (2), obtained upon treatment of a precursor ketone with sodium borohydride.

The structure of the title compound, C 15 H 25 F 2 NO 4 , is reported and reveals a pseudorotational relationship between the ring conformation of this compound and that of an isomeric byproduct reported in the following paper.

Comment
Conformational equilibria in eight-membered carbocycles occur via two main processes, pseudorotation and ring inversion. The latter exchanges substituent groups between equatorial and axial environments in a pseudo-enantiomeric relationship. Ring inversion is usually the more energetically demanding process; barriers to inversion exchange of 7.3-8.5 kcal mol À1 have been reported, with smaller barriers (ca 5 kcal mol À1 ) (Servis & Noe, 1973) for the pseudorotation. [For early attempts to apply variable-temperature NMR to these phenomena, see Anderson et al. (1969) and St Jacques et al. (1966).] Recent work from our group has attempted to define these processes for a trio of difluorinated cyclooctenyl systems (Fawcett, Griffith et al., 2005). We were interested in observing a pseudorotational relationship between the ring conformations in the pair of reduction products (1) and (2), obtained upon treatment of a precursor ketone with sodium borohydride.
Product (1) (the major product) arises from the opposite sense of hydride attack, with the N,N-diethylcarbamoyl group retaining its original location (Fig. 1). Product (2), reported in the following paper , arises from reagent attack on the ring face which bears the hydroxyl group, followed by migration of the N,N-diethylcarbamoyl group on to the newly formed hydroxyl group (Balnaves et al., 1999). A comparison of the two molecules is shown in Fig. 2. O-HÁ Á ÁO hydrogen bonding links molecules of (1) into chains along the b axis (Table 1).

Data collection
Bruker APEX CCD area-detector diffractometer ' and ! scans Absorption correction: none 5283 measured reflections 1403 independent reflections 1332 reflections with I > 2(I) Table 1 Hydrogen-bond geometry (Å , ). H atoms were positioned geometrically, with C-H = 0.95-1.00 Å and O-H = 0.84 Å , and treated as riding, with U iso (H) = 1.2 or 1.5 (methyl and OH) times U eq of the parent atom.

Figure 2
An overlay showing the relationship between the structures of compounds (1) and (2). structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Sheldrick, 2000); software used to prepare material for publication: SHELXTL. Conformational equilibria in eight-membered carbocycles occur via two main processes, pseudorotation and ring inversion. The latter exchanges substituent groups between equatorial and axial environments in a pseudo-enantiomeric relationship. Ring inversion is usually the more energetically demanding process; barriers to inversion exchange of 7.3-8.5 kcal mol −1 have been reported, with smaller barriers (ca 5 kcal mol −1 ) (Servis & Noe, 1973) for the pseudorotation.
[For early attempts to apply variable-temperature NMR to these phenomena, see Anderson et al. (1969) and St Jacques et al. (1966).] Recent work from our group has attempted to define these processes for a trio of difluorinated cyclooctenyl systems (Griffith et al., 2005). We were interested to observe a pseudorotational relationship between the ring conformations in the pair of reduction products (1) and (2), obtained upon treatment of a precursor ketone with sodium borohydride.
Product (1) (the major product) arises from the opposite sense of hydride attack, with the N,N-diethylcarbamoyl group retaining its original location (Fig. 1). Product (2), reported in the following paper , arises from reagent attack on the ring face which bears the hydroxyl group, followed by migration of the N,N-diethylcarbamoyl group on to the newly formed hydroxyl group (Balnaves et al., 1999). A comparison of the two molecules is shown in Fig. 2. O-H···O hydrogen bonding links molecules of (1) into chains along the b axis (Table 1).

S2. Experimental
The precursor ketone was prepared as described in the literature (Fawcett, Griffith et al., 2005). Sodium borohydride (1.8 mmol, 70 mg) was added in five portions to a cold (273 K) solution of the ketone (1.8 mmol, 0.59 g) in ethanol (10 ml).
After completion of the addition, the reaction mixture was allowed to warm to room temperature, stirred for 2 h at this temperature and poured over a mixture of ice and water (25 ml). HCl (10 ml of a 1 N solution) was added cautiously and the mixture was extracted with diethyl ether (3 × 25 ml). The combined organic extracts were dried (MgSO 4 ), filtered and concentrated under reduced pressure to leave a white solid (0.51 g). Purification by column chromatography (40% ethyl acetate in light petroleum) afforded the desired diol (1)

S3. Refinement
H atoms were positioned geometrically, with C-H = 0.95-1.00 Å and O-H = 0.84 Å, and treated as riding, with U iso (H) = 1.2 or 1.5 (methyl and OH) times U eq of the parent atom.

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.