3-tert-Butyl 5-methyl (2R,4S,5R)-2-(4-methoxyphenyl)-4-(3-nitrophenyl)-1,3-oxazolidine-3,5-dicarboxylate

Sara Montiel-Smith; Sylvain Bernès; Jesús Sandoval-Ramírez; Socorro Meza-Reyes; Joëlle Dubois

doi:10.1107/S160053681204192X

. 2012 Oct 20;68(Pt 11):o3146–o3147. doi: 10.1107/S160053681204192X

3-tert-Butyl 5-methyl (2R,4S,5R)-2-(4-methoxyphenyl)-4-(3-nitrophenyl)-1,3-oxazolidine-3,5-dicarboxylate

Sara Montiel-Smith ^a, Sylvain Bernès ^b,^*, Jesús Sandoval-Ramírez ^a, Socorro Meza-Reyes ^a, Joëlle Dubois ^c

PMCID: PMC3515246 PMID: 23284466

Abstract

The title molecule, C₂₃H₂₆N₂O₈, was synthesized in three steps starting from m-nitrocinnamic acid. The central oxazolidine ring adopts an almost perfect envelope conformation with the O atom as the flap [puckering parameter ϕ = 0.3 (6)°]. The dihedral angle formed by the benzene rings is 61.81 (9)°. In the crystal, molecules are connected into double chains parallel to [010] by C—H⋯O hydrogen bonds. The absolute configuration was assigned from the synthetic procedure.

Related literature

For the Sharpless asymmetric aminohydroxylation, see: Rudolph et al. (1996 ▶). For the synthesis of the phenylisoserine precursor of the title molecule, see: Montiel-Smith et al. (2002 ▶). For the stereocontrolled formation of the oxazolidine in the title molecule, see: Denis et al. (1994 ▶). For the structure of a related chiral N-Boc-protected oxazolidine, see: Tinant et al. (1996 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₂₃H₂₆N₂O₈
M _r = 458.46
Monoclinic,
a = 10.383 (1) Å
b = 6.0303 (6) Å
c = 18.7366 (17) Å
β = 95.591 (4)°
V = 1167.57 (19) Å³
Z = 2
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 298 K
0.60 × 0.16 × 0.16 mm

Data collection

Siemens P4 diffractometer
3169 measured reflections
2275 independent reflections
1628 reflections with I > 2σ(I)
R _int = 0.024
3 standard reflections every 97 reflections intensity decay: 0.5%

Refinement

R[F ² > 2σ(F ²)] = 0.039
wR(F ²) = 0.095
S = 1.02
2275 reflections
304 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 0.12 e Å⁻³
Δρ_min = −0.13 e Å⁻³

Data collection: XSCANS (Siemens, 1996 ▶); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Click here for additional data file.^{(30.4KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S160053681204192X/rz5008sup1.cif

e-68-o3146-sup1.cif^{(30.4KB, cif)}

Click here for additional data file.^{(111.8KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681204192X/rz5008Isup2.hkl

e-68-o3146-Isup2.hkl^{(111.8KB, hkl)}

Click here for additional data file.^{(8.8KB, cml)}

Supplementary material file. DOI: 10.1107/S160053681204192X/rz5008Isup3.cml

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

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C2—H2A⋯O15ⁱ	0.98	2.50	3.400 (4)	153
C5—H5A⋯O28ⁱⁱ	0.98	2.59	3.387 (4)	138
C26—H26A⋯O1ⁱⁱⁱ	0.93	2.59	3.252 (4)	128

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

This work was supported by the France–Mexico ECOS-ANUIES (M97–E02) agreement.

supplementary crystallographic information

Comment

The title compound is related to a project about new synthetic routes to obtain isoserines (α-hydroxy-β-amino acids). The stereocontrol of the synthesis is a key point, since chiral isoserines are found in bioactive substances, as in the side chain of the emblematic anti-cancer agent Paclitaxel, initially marketed under the brand name Taxol. We focused our efforts toward the synthesis of (2R,3S)-N-Boc-β-phenylisoserines (Montiel-Smith et al., 2002). Starting from commercially available m-nitrocinnamic acid, which was esterified in a first step, we probed various conditions for an asymmetric aminohydroxylation (Rudolph et al., 1996), and the best results were obtained by using tert-butyl-N-chlorocarbamate as the nitrogen source, (DHQ)₂PHAL (hydroquinine 1,4-phthalazinediyl diether) as chiral ligand, and K₂OsO₂(OH)₄ as catalyst. The desired phenylisoserine was eventually obtained with 81% ee (see compound 2c in Montiel-Smith et al., 2002). The title compound resulted from the protection of the amine and hydroxyl groups, via the formation of an oxazolidine (Fig. 1).

The molecular structure (Fig. 2) allowed to check for the configuration of chiral atoms C2 and C3 in the precursor isoserine 3, confirming that the chiral inductor (DHQ)₂PHAL affords the (2R,3S) isomer predominantly, as expected. The deduced configuration of the third stereocenter in the oxazolidine I, 2R, also agrees with literature data for related reactions (Denis et al., 1994). The substituents in the oxazolidine skeleton are arranged in such a way that steric hindrance is avoided. The oxazolidine exhibits a conformation very close to the ideal envelope conformation on O1, the puckering parameters (Cremer & Pople, 1975) being φ = 0.3 (6)° and q₂ = 0.331 (3) Å. The ring conformation is related to the substituents distribution. For instance, the X-ray structure for another N-Boc protected oxazolidine with a different absolute configuration, (2R,4R,5S), showed a twisted oxazolidine ring (Tinant et al., 1996).

The crystal structure (Fig. 3) is dominated by the stacking of bulky Boc groups, which are oriented along [100], with the molecules linked into double chains parallel to [010] by C—H···O hydrogen bonds (Table 1).

Experimental

The synthesis starting from commercially available m-nitrocinnamic acid 1 is depicted in Fig. 1. The two steps preparation of the phenylisoserine 3 has been published (Montiel-Smith et al., 2002; see compound 2c therein). The enantiospecific aminohydroxylation reaction was carried out using ^tBuOCONHCl as nitrogen source, reagent previously prepared in situ by reacting ^tBuOCONH₂ and ^tBuOCl in a NaOH solution. The last step to afford the title compound is a protection of the amine and hydroxyl groups of 3, via the formation of an oxazolidine, carried out by reacting 3 with 1-(dimethoxymethyl)-4-methoxybenzene in presence of pyridinium p-toluenesulfonate, in refluxing toluene. The isolated compound I was crystallized from AcOEt/heptane.