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

Alexander E Anderson; Kate L Edler; Raleigh W Parrott, II; Shawn R Hitchcock; Gregory M Ferrence

doi:10.1107/S1600536810009190

. 2010 Mar 24;66(Pt 4):o902–o903. doi: 10.1107/S1600536810009190

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

Alexander E Anderson ^a, Kate L Edler ^a, Raleigh W Parrott II ^a, Shawn R Hitchcock ^a, Gregory M Ferrence ^a,^*

PMCID: PMC2983802 PMID: 21580716

Abstract

The title compound, C₂₁H₂₇NO₂, exhibits hydrogen bonding between the phenolic H atom and the heterocyclic N atom. The absolute configuration of the molecule is known from the synthetic procedure.

Related literature

For related structures and background to the use of chiral oxazolidines as templates in asymmetric synthesis, see: Agami & Couty (2004 ▶); Campbell et al. (2010 ▶); Koyanagi et al. (2010 ▶); Parrott & Hitchcock (2007 ▶); Parrott et al. (2008 ▶). The synthesis of the title compound is described by Parrott & Hitchcock (2007 ▶). The absolute configuration assignment is based on both optical activity measurements and on the known stereochemistry of the commercially obtained optically pure ephedrine from which it was prepared (Parrott & Hitchcock, 2007 ▶). For geometry checks using Mogul, see: Bruno et al. (2004 ▶). For ring puckering analysis, see: Boeyens (1978 ▶); Cremer & Pople (1975 ▶); Spek (2009 ▶). For a description of the Jmol toolkit for the preparation of enhanced figures, see: McMahon & Hanson (2008 ▶).

Experimental

Crystal data

C₂₁H₂₇NO₂
M _r = 325.44
Monoclinic,
a = 8.3288 (8) Å
b = 9.8657 (9) Å
c = 11.4325 (11) Å
β = 91.667 (1)°
V = 939.00 (15) Å³
Z = 2
Mo Kα radiation
μ = 0.07 mm⁻¹
T = 140 K
0.55 × 0.27 × 0.27 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (APEX2; Bruker, 2008 ▶) T _min = 0.687, T _max = 0.746
9040 measured reflections
2284 independent reflections
2191 reflections with I > 2σ(I)
R _int = 0.017

Refinement

R[F ² > 2σ(F ²)] = 0.028
wR(F ²) = 0.074
S = 1.04
2284 reflections
221 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.21 e Å⁻³
Δρ_min = −0.14 e Å⁻³

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT (Bruker, 2008 ▶); data reduction: SAINT; program(s) used to solve structure: SIR2004 (Burla et al., 2005 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶), publCIF (McMahon & Westrip, 2008 ▶) and Mercury (Macrae et al., 2008 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810009190/zl2269sup1.cif

e-66-0o902-sup1.cif^{(21KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810009190/zl2269Isup2.hkl

e-66-0o902-Isup2.hkl^{(109.9KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Enhanced figure: interactive version of Fig. 2

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O20—H20⋯N3	0.90 (2)	1.79 (2)	2.6244 (16)	154.4 (19)

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Acknowledgments

This material is based upon work supported by the US National Science Foundation (CHE-0348158) (to GMF) and the American Chemical Society Petroleum Research Fund (to SRH & GMF). GMF thanks Matthias Zeller of the Youngstown State University Structure & Chemical Instrumentation Facility for the data collection and useful discussions. The diffractometer was funded by NSF grant 0087210, Ohio Board of Regents grant CAP-491, and YSU.

supplementary crystallographic information

Comment

Chiral oxazolidines are useful templates for conducting asymmetric syntheses (Agami & Couty, 2004). In order to explore the utility of these compounds in the catalytic asymmetric addition of diethylzinc to aldehydes, we prepared a series of oxazolidines from (1R,2S)-ephedrine, (1S,2S)-pseudoephedrine (Parrott & Hitchcock, 2007) and (1R,2S)-norephedrine (Parrott et al., 2008). In the course of synthesizing these oxazolidines, we were able to obtain crystals suitable for X-ray crystallographic analysis.

The title compound is structurally similar to two other oxazolidines published by Koyanagi et al. (2010) and Campbell et al. (2010). Despite these structural similarities, a Mogul geometry check (Bruno et al., 2004) reveals differences between the three structures. The C2—N3—C4 angle is found to be usual in the title compound (103.0 (1)°) and in Koyanagi et al. (106.0 (1)°), but not in Campbell et al. (106.2 (1)°), even though the last two angles are not significantly different. Another angle, C5—O1—C2, considered unusual in Mogul for both Koyanagi et al. and Campbell et al. (103.9 (1)° and 103.3 (1)°, respectively) is not unusual in the title compound (108.9 (1)°). These differences could be due to the difference in substituents on the N3 position in these compounds. The methyl substituent in the title compound occupies less space than the isopropyl substituent in the other two structures, allowing for more typical bond angles in the heterocycle of the title compound.

The difference in bond angles also appears in PLATON in the ring-puckering analysis of these compounds (Spek, 2009; Cremer & Pople, 1975; Boeyens, 1978). Koyanagi et al. and Campbell et al. report O1—C2—N3—C4—C5 ring conformations close to ¹E (Φ = 1.63 (17)° and -7.05 (19)°, respectively), with O1 as the flap apex, while the heterocycle conformation of the title compound is closer to an ³E conformation (Φ = 65.73 (20)°), resulting in N3 as the flap apex. Even with these differences, the distance between the hydrogen donor and acceptor in all three structures is virtually identical (2.6244 Å in the title compound compared to 2.6278 (16) Å and 2.6180 (17) Å in Koyanagi et al. and Campbell et al., respectively).

About the Jmol enhanced figure:

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; Koyanagi 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.

The Jmol enhanced figure included with this paper required substantial author hand-coding of Jmol scripts. To generate this enhanced figure, substantial author familiarity with Jmol script coding is required and generation of the figure is significantly more time-consuming. Strictly authoring with the Jmol toolkit GUI, without text editing any code, provides a relatively quick and easy means to prepare a decent enhanced figure, and is often sufficient. For advanced users, hand-coding Jmol scripts provides a much more versatile figure for the end-user. In particular, the orientation information of the structure can be eliminated from all radio buttons, buttons, and check boxes. This becomes a major advantage when the end-user toggles the figure to rotate or changes the orientation from the location dictated in the script. When a new option is selected, the figure will only change in the areas being highlighted. Another advantage of stripping the script of lines not related to the defined option is the ability to see more than one option at a time. For instance, in this enhanced figure, the thermal ellipse color may be viewed even when the atom style is not in the ellipse mode.

Experimental

The title compound was synthesized as previously reported (Parrott & Hitchcock, 2007). Single crystals were grown by vapor diffusion of hexane into a methylene chloride solution of the title compound.