{(1R,3S)-2-Benzyl-6,7-dimeth­oxy-1-phenyl-1,2,3,4-tetra­hydro­isoquinolin-3-yl}diphenyl­methanol

Tricia Naicker; Thavendran Govender; Hendrik G Kruger; Glenn EM Maguire

doi:10.1107/S1600536810005295

. 2010 Feb 17;66(Pt 3):o638. doi: 10.1107/S1600536810005295

{(1R,3S)-2-Benzyl-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinolin-3-yl}diphenylmethanol

Tricia Naicker ^a,^*, Thavendran Govender ^b, Hendrik G Kruger ^a, Glenn EM Maguire ^a

PMCID: PMC2983732 PMID: 21580394

Abstract

In the title compound, C₃₇H₃₅NO₃, a precursor to novel chiral catalysts, the N-containing six-membered ring assumes a half-chair conformation. Intermolecular C—H⋯O hydrogen bonds link the molecules in the crystal structure.

Related literature

For the synthesis of the title compound, see: Chakka et al. (2010 ▶). For related structures, see: Aubry et al. (2006 ▶). For a related structure with the same chiral centres and configuration, see: Naicker et al. (2009 ▶). For proline diaryl alcohols, see: Diner et al. (2008 ▶); Seebach et al. (2008 ▶).

Experimental

Crystal data

C₃₇H₃₅NO₃
M _r = 541.66
Monoclinic,
a = 11.9706 (5) Å
b = 10.1934 (4) Å
c = 13.1515 (5) Å
β = 116.546 (2)°
V = 1435.58 (10) Å³
Z = 2
Cu Kα radiation
μ = 0.62 mm⁻¹
T = 173 K
0.22 × 0.14 × 0.12 mm

Data collection

Bruker Kappa Duo APEXII diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2006 ▶) T _min = 0.876, T _max = 0.930
15262 measured reflections
2514 independent reflections
2451 reflections with I > 2σ(I)
R _int = 0.025

Refinement

R[F ² > 2σ(F ²)] = 0.025
wR(F ²) = 0.068
S = 1.10
2514 reflections
375 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.14 e Å⁻³
Δρ_min = −0.12 e Å⁻³

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 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and DIAMOND (Brandenburg, 1998 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, New_Global_Publ_Block. DOI: 10.1107/S1600536810005295/lx2135sup1.cif

e-66-0o638-sup1.cif^{(27.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810005295/lx2135Isup2.hkl

e-66-0o638-Isup2.hkl^{(123.5KB, hkl)}

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
C15—H15⋯O2ⁱ	0.95	2.44	3.385 (2)	171

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors wish to thank Dr Hong Su of the Chemistry Department of the University of Cape Town for her assistance with the crystallographic data collection and Dr M Bala of the School of Chemistry at University of KwaZulu-Natal for his assistance with preparation of this manuscript.

supplementary crystallographic information

Comment

The title compound (2, Fig. 3) is a precursor in the synthesis of novel chiral ligands involving a tetrahydroisoquinoline backbone. Recently, we have reported the application of these ligands as useful catalysts for transfer hydrogenation reactions (Chakka et al., 2010).

Compound 2 contains four phenyl rings and the absolute stereochemistry was confirmed to be R,S at C1 and C9 positions as shown in Fig. 1, respectively (Aubry et al., 2006). The crystal packing is stabilized by intermolecular C—H···O hydrogen bonds. The H atom of methanol does not form hydrogen bonds (Table 1 & Fig. 2). According to the Cambridge structural data base this is the first tetrahydroisoquinoline derivative with diaryl substitution at the C10 position. The structure displays a gauche or sc (synclinal) conformation around the O3—C10—C9—N1 bond with the OH group almost over the piperidine ring with a torsion angle of -77.0 (2)°. Due to the lack of analogous structures this observation was compared to proline diaryl alcohols (Seebach et al., 2008) which display a similar conformation around the exocyclic C9—C10 bond. Given the success of proline diaryl alcohols as a chiral catalyst (Diner et al., 2008) this comparison is particularly useful for catalysts bearing a tetrahydroisoquinoline framework as this feature could have a significant effect on the stereocontrol of the catalyst.

We recently reported a crystal structure of a similar molecule to the title compound (Naicker et al., 2009) which has an ester moiety at the C10 position and the N-containing six membered ring assumes a half boat conformation. The N-containing six membered ring in the title compound exists in a half chair conformation (see Fig. 1). A possible reason for this difference in conformation could be the introduction of large phenyl ring substitiuents at the C10 position. The efficiency of these tetrahydroisoquinoline catalysts is currently being tested in our laboratory.

Experimental

To a solution of compound 1 (Fig. 3) (500 mg, 1.19 mmol) in THF (10 ml), freshly prepared Grignard reagent of phenyl magnesium bromide (2.17 g, 11.9 mmol) was added under a nitrogen atmosphere at ambient temperature. Completion of the reaction was monitored with TLC by quenching 0.1 ml aliquots of the reaction mixture with saturated ammonium chloride solution at 0 °C using ethyl acetate/hexane as the solvent (40 : 60 R_f 0.5). Thereafter the reaction mixture was filtered and the solvent was evaporated under reduced pressure to afford the crude product. This was purified by column chromatography using ethyl acetate/hexane (40:60) as the eluent to yield 80 % (0.52 g) pure tetrahydroisoquinoline diphenyl alcohol 2 as a white solid. ¹H NMR (600 MHz,CDCl₃,δ, p.p.m): 7.38 (d, J = 7.26 Hz, 2H), 7.32–7.16 (m, 9H), 6.54 (s, 1H), 6.26 (s, 1H), 5.19 (s, 1H), 3.85–3.72 (m, 6H), 3.61 (s,6H), 3.23 (dd, J = 5.10, 15.66 Hz, 1H), 2.98 (dd, J = 3.00, 15.72, Hz, 1H). Light yellow crystals suitable for X-ray diffraction were obtained by slow evaporation of 2 in dichloromethane at room temperature.