(1R,3S)-Methyl 2-benzyl-6,7-dimeth­oxy-1-phenyl-1,2,3,4-tetra­hydro­isoquinoline-3-carboxyl­ate

Tricia Naicker; Michael McKay; Thavendran Govender; Hendrik G Kruger; Glenn E M Maguire

doi:10.1107/S1600536809050521

. 2009 Nov 28;65(Pt 12):o3278. doi: 10.1107/S1600536809050521

(1R,3S)-Methyl 2-benzyl-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylate

Tricia Naicker ^a, Michael McKay ^a, Thavendran Govender ^b,^*, Hendrik G Kruger ^a, Glenn E M Maguire ^a

PMCID: PMC2972025 PMID: 21578971

Abstract

In the title compound, C₂₆H₂₇NO₄, a precursor to novel chiral catalysts, the N-containing six-membered ring assumes a half-boat conformation. Various C—H⋯π interactions and intermolecular short contacts (C⋯H = 2.81–2.90 Å) link the molecules together in the crystal structure.

Related literature

For the synthesis, see: Chakka et al. (2009 ▶). For crystallograhic details of analogous molecules, see Alberch et al. (2004 ▶); Aubry et al. (2006 ▶). graphic file with name e-65-o3278-scheme1.jpg

Experimental

Crystal data

C₂₆H₂₇NO₄
M _r = 417.49
Triclinic,
a = 6.0199 (1) Å
b = 9.2592 (2) Å
c = 11.0429 (2) Å
α = 73.365 (1)°
β = 74.694 (1)°
γ = 75.737 (1)°
V = 559.05 (2) Å³
Z = 1
Cu Kα radiation
μ = 0.67 mm⁻¹
T = 173 K
0.22 × 0.12 × 0.08 mm

Data collection

Bruker Kappa Duo APEXII diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1997 ▶) T _min = 0.692, T _max = 0.753
7546 measured reflections
3561 independent reflections
3536 reflections with I > 2σ(I)
R _int = 0.012

Refinement

R[F ² > 2σ(F ²)] = 0.028
wR(F ²) = 0.077
S = 1.07
3561 reflections
281 parameters
3 restraints
H-atom parameters constrained
Δρ_max = 0.16 e Å⁻³
Δρ_min = −0.16 e Å⁻³
Absolute structure: Flack (1983 ▶), 1483 Friedel pairs
Flack parameter: −0.01 (14)

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: SAINT (Bruker, 2006 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶) and X-SEED (Barbour, 2001 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: ORTEP-3.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809050521/hg2607sup1.cif

e-65-o3278-sup1.cif^{(23.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809050521/hg2607Isup2.hkl

e-65-o3278-Isup2.hkl^{(171KB, hkl)}

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

Table 1. C—H⋯π interaction (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C19—H19A⋯Cg ⁱ	0.98	2.82	3.639 (2)	148

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Symmetry code: (i) Inline graphic . Cg is the centroid of the C21–C26 ring.

Acknowledgments

The authors wish to thank Dr Hong Su of the Chemistry Department at the University of Cape Town for his assistance with the crystallographic data collection.

supplementary crystallographic information

Comment

The title compound (2, Scheme 1) is a precursor in the synthesis of novel chiral ligands containing a tetrahydroisoquinoline backbone. We have recently reported the use of these ligands as successful catalysts for transfer hydrogenations reactions (Chakka et al., 2009).

Compound 2 was derived from commercially available L-DOPA and benzaldehyde. Diastereomers formed during the first step of the synthesis were separated to yield subsequent derivatives and the title compound and with the stereochemistry as illustrated in Figure 1. The absolute stereochemistry was confirmed to be R,S at C1 and C9 positions respectively.

From the crystal structure it is evident that the N-containing six membered ring assumes a half boat conformation (Figure 1). This differs from an analogous structure which assumes a half chair conformation (Aubry et al., 2006 and Alberch et al., 2004). A possible reason for this change in conformation could be either the introduction of a substitutent on the nitrogen or the trans position of the phenyl ring at the C1 position.

The molecule exhibits various intermolecular short contacts i.e. between the methyl ester hydrogen (H11C) and phenyl ring (C14) of a neighbouring molecule; H15 to C6 and C7 and H24 to C14 and C15.

The methoxy groups display different interactions. The first methoxy group at C4 position displays one interaction between H18B and O2, which is the ether oxygen of the other methoxy group. The second methoxy group at C5 position displays three interactions; the first being the above mentioned interaction with H18B and O2, the second being a short contact between O2 and H25, and the third being another CH-π the interaction between H19A and C25. The atoms involved in these short contacts are shown in Figure 2.

Experimental

To a solution of 1 (Scheme 1) (500 mg, 1.52 mmol) in acetonitrile (20 ml), solid K₂CO₃(635 mg, 4.58 mmol) was added followed by benzyl bromide (286 mg, 1.67 mmol) at ambient temperature. There after the reaction mixture was refluxed for 3 h. Completion of the reaction was monitored with TLC using hexane/ethyl acetate (60:40, R_f 1/2). The solvent was evaporated and 30 ml of ethylacetate was added, washed with 2 × 10 ml of water, the organic layer was separated, and dried over anhydrous MgSO₄. The solvent was evaporated under reduced pressure to afford crude product, which was purified by column chromatography using hexane/ethyl acetate (60:40) as the eluent to yield pure benzyl ester 2 (0.44 g, 90%) as a white solid.

¹H NMR (400 MHz/CDCl₃): δ = 7.44 (d, J = 1.16 Hz, 2H), 7.32–7.10 (m, 14H), 7.0–6.88 (m, 6H), 6.69 (s, 1H), 6.38 (s, 1H), 4.74 (s,1H), 4.21 (d, J = 13.60 Hz, 1H), 4.14 (q, J = 3.70, 12.74 Hz, 1H), 3.89 (s, 3H), 3.72 (s, 3H), 3.57 (s, 1H), 3.30–3.18 (m, 2H), 2.60 (dd, J = 3.60, 16.48 Hz, 1H).

Colourless crystals suitable for X-ray diffraction were obtained by slow evaporation of 2 in dichloromethane at room temperature.