(6R)-2-tert-Butyl-6-[(4R,5S)-3-isopropyl-4-methyl-5-phenyloxazolidin-2-yl]phenol

In the title compound, C23H31NO2, the lone pair on the nitrogen atom is oriented to facilitate intramolecular hydrogen bonding with the hydroxy group residing on the phenyl substituent. The five-membered ring adopts an envelope confornmation with the O atom at the flap. The absolute stereochemistry was verified by measurement of optical activity using a digital polarimeter.

In the title compound, C 23 H 31 NO 2 , the lone pair on the nitrogen atom is oriented to facilitate intramolecular hydrogen bonding with the hydroxy group residing on the phenyl substituent. The five-membered ring adopts an envelope confornmation with the O atom at the flap. The absolute stereochemistry was verified by measurement of optical activity using a digital polarimeter.

D-HÁ
Additional oxazolidine systems have been reported and studied (Parrott et al., 2008), where the phenyl substituent has a hydrogen atom alpha to the hydroxyl group. The torsion angles of the title compound mostly agree with this unsubstituted oxazolidine. Two minor differences arise that may be due to the sterically enhanced phenyl group. The oxazolidine compound previously reported (Parrott et al., 2008) contained a C21-C2-N3-C4 torsion angle being equal to 156.8 (2)°, while the corresponding title compound torsion angle of C4-N3-C2-C16 is equal to 147.10 (12)°. The second torsion angle of the reported oxazolidine (Parrott et al., 2008), C21-C2-N3-C31, is equal to -72.8 (3)°, whereas the title oxazolidine has a torsion angle equal to -87.85 (14)° at C13-N3-C2-C16. The molecular structure shown in Fig. 1 has one molecule in the asymmetric unit. A Mogul geometry check (Bruno et al., 2004) shows the only unusual bond length or bond angle to be the C5-O1-C2 angle with a value of 103.95 (11)° against a mean of 107.8°.
Ring puckering analysis using PLATON (Spek, 2009;Cremer & Pople, 1975;Boeyens, 1978) indicates Φ = 1.63 (17)°f or the O1-C2-N3-C4-C5 ring, which is consistent with a formal conformational assignment close to an idealized 1 E envelope with O1 being the flap apex. The crystal structure suggests that the isopropyl group on N3 has an anti-relationship with the substituents on C2, C4, and C5 due to the intramolecular H-bonding interaction between N3 and the hydroxyl group.
The donor to acceptor atom distance (2.6278 (16) Å) between O22-N3 is large enough to only support a weak H-bonding interaction. This interaction is further illustrated in the Jmol enhanced figure (Fig. 2).
About the Jmol enhanced figure: The procedure for recreating the Jmol figure is provided in the hopes that readers will find it useful for creating their own. We are reporting three related structures containing Jmol enhanced figures, one in this paper and the other two in other papers in this Journal (Campbell et al., 2010;Anderson et al., 2010). The Jmol enhanced figures were created to illustrate a range of author convenience versus end user experience, ranging from a purely GUI driven experience for the author resulting in a less functional figure for the end user to a more sophisticated use of the Jmol scripting by the author resulting in a more polished and versatile figure for the end user. The buttons, check boxes and radio buttons in the three examples visually appear to be identical; however, the underlying code they execute results in significantly different overall responses by the Jmol visualizer.
By strictly authoring with the Jmol toolkit GUI, without text editing any code, generation of the figure is relatively quick and easy. However, doing so results in a final figure which has some significant limitations. In particular, when the end user supplementary materials sup-2 manipulates the figure by, for example, a rotation, subsequent clicking of a radiobutton will result in the figure resetting to appear exactly as it appeared when the author saved the script. This includes all settings such as orientation and any other highlighting. This is the scenario illustrated by the Jmol enhanced figure associated with this Acta E article. The enhanced figure options were intentionally selected without any alteration of the structure's orientation, so that as long as the user does not move or rotate the structure, the molecule's orientation appears static.
The Jmol options were created as follows: Labels were added to atoms by navigating to the "label" sub-tab under the "select/label" tab and by checking the button "atom name" before turning the labels "on". The script was imported into a checkbox by navigating to the "checkbox" sub-tab under the "script" tab, and by clicking "import view".
The thermal displacement coloring was achieved by navigating to the "model" tab and by selecting "atomic displacement" next to the "colour" heading.
The color of particular atoms was changed by first selecting them. The atoms were selected by navigating to the "select/ label" tab, turning the "highlight selection" on, and picking "within area" under "selection mode". The color of the atoms was changed by navigating to the "atoms" sub-tab and picking a color from the drop down box next to the "colour" heading.
The various atom styles were selected by navigating to the "model" tab and by selecting the atom style of choice next to the "overall style" heading.
The hydrogen bond was displayed by navigating to the "measurements" sub-tab under the "select/label" tab. The "distance" option next to the "mode" heading was then selected, followed by the hydrogen and acceptor atoms.

Experimental
The title compound was synthesized in two steps. Optical activities were measured at 589 nm using a digital polarimeter as discribed for similar compounds in Parrott & Hitchcock (2007). The synthesis included reagents and solvents of reagent grade, which were used without further purification.
In the first step, to a flame dried, nitrogen purged flask was added (1S,2R)-norephedrine (10.1 g, 66.8 mmol), ethanol (100 ml), and acetone (7.4 ml, 100 mmol). The mixture was allowed to stir at room temperature for 24 hours. At that time the solution was cooled to 273 K and sodium borohydride (5.07 g, 134 mmol) was added and the mixture allowed to stir for 2 hours. The ethanol was removed under reduced pressure and the reaction quenched with sodium hydroxide (1M, 100 ml). The product was extracted with ethyl acetate (100 ml × 2), washed with brine, dried with magnesium sulfate, gravity filtered, and concentrated under reduced pressure. The amino alcohol was purified via recrystallization with hexanes: ethyl acetate (2:1) to afford (1-S,2R)-2-isopropylamino-1-phenyl-1-propanol as a white solid in 65% yield. Single crystals of the title compound were grown by vapor diffusion of hexane into a methylene chloride solution of the title compound.

Refinement
All non-H atoms were refined anisotropically without disorder. The absolute configuration of the title compound is based on the known stereochemistry of the commercially obtained optically pure norephedrine from which it was prepared and optical activity was measured as discribed for similar compounds in Parrott & Hitchcock (2007). All H atoms were initially identified through difference Fourier syntheses then, except for the O-H hydrogen atom, removed and included in the refinement in the riding-model approximation (C-H = 0.95, 0.98, and 1.00 Å for Ar-H, CH 3 and CH; Uiso(H) = 1.2Ueq(C) except for methyl groups, where Uiso(H) = 1.5Ueq(C)). The OH H atom was freely refined isotropically. In the absence of significant anomalous scattering effects, Friedel pairs were merged. Fig. 1. The molecular structure of the title compound with the atomic numbering scheme and intramolecular H-bonding. Displacement ellipsoids are drawn at the 50% probability level.