[(2S,5R)-1-Methyl-5-phenyl­pyrrolidin-2-yl]diphenyl­methanol

Julio Zukerman-Schpector; Angélica Venturini Moro; Diogo S Lüdtke; Carlos Roque D Correia; Edward R T Tiekink

doi:10.1107/S1600536811023403

. 2011 Jun 25;67(Pt 7):o1807–o1808. doi: 10.1107/S1600536811023403

[(2S,5R)-1-Methyl-5-phenylpyrrolidin-2-yl]diphenylmethanol

Julio Zukerman-Schpector ^a,^*, Angélica Venturini Moro ^b, Diogo S Lüdtke ^c, Carlos Roque D Correia ^b, Edward R T Tiekink ^d

PMCID: PMC3151780 PMID: 21837179

Abstract

In the title compound, C₂₄H₂₅NO, the phenyl and diphenylmethanol substituents are syn to each other. The pyrrolidine ring has an envelope conformation with the flap atom being the C atom bearing the phenyl substituent. The hydroxy group forms an intramolecular hydrogen bond with the pyrrolidine N atom, and the phenyl rings lie to same side of the molecule. The crystal packing features C—H⋯π interactions. Two slightly displaced co-planar orientations were found for one of the phenyl rings; the major component had a site-occupancy factor of 0.782 (15).

Related literature

For background to the highly enantioselective addition of arylzinc reagents to aldehydes, see: Yoon & Jacobsen (2003 ▶), Taylor, et al. (2011 ▶). For related structures, see: Moro et al. (2010 ▶); Shabbir et al. (2009 ▶). For details of the synthetic protocols, see: Walsh & Kozlowski (2008 ▶); Paixão, et al. (2008 ▶). For ring conformational analysis, see: Cremer & Pople (1975 ▶).

Experimental

Crystal data

C₂₄H₂₅NO
M _r = 343.45
Orthorhombic,
a = 9.9672 (2) Å
b = 13.3376 (2) Å
c = 14.4369 (2) Å
V = 1919.22 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.07 mm⁻¹
T = 100 K
0.22 × 0.15 × 0.15 mm

Data collection

Bruker APEXII CCD diffractometer
24972 measured reflections
2262 independent reflections
1979 reflections with I > 2σ(I)
R _int = 0.039

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.092
S = 1.05
2262 reflections
255 parameters
H-atom parameters constrained
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.19 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and DIAMOND (Brandenburg, 2006 ▶); software used to prepare material for publication: MarvinSketch (Chemaxon, 2010 ▶) and publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811023403/hg5054sup1.cif

e-67-o1807-sup1.cif^{(24.6KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811023403/hg5054Isup2.hkl

e-67-o1807-Isup2.hkl^{(108.9KB, hkl)}

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

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

Cg is the centroid of the C6–C11 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O—H1O⋯N	0.84	2.02	2.648 (2)	132
C28—H28⋯Oⁱ	0.95	2.78	3.359 (7)	120
C17—H17⋯Cgⁱⁱ	0.95	2.92	3.776 (3)	150

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

Acknowledgments

We thank the Brazilian agencies FAPESP, CNPq (research fellowships to JZS, DSL and CRDC) and CAPES (808/2009 to JZS) for financial support.

supplementary crystallographic information

Comment

Chiral β-amino alcohols have found numerous applications in asymmetric catalysis in the past and continue to play a pivotal role in the development of new reactions and chiral ligands (Walsh & Kozlowski, 2008). One asymmetric reaction where chiral β-amino alcohol ligands have found enormous success is the enantioselective addition of organozinc reagents to carbonyl compounds, with particular emphasis in the alkylation of aldehydes by the addition of diethylzinc. A more challenging reaction is the asymmetric arylation reaction, since arylzinc reagents are more reactive than the dialkylzinc and the ligand turnover has to highly efficient in order to circumvent the uncatalyzed background reaction (Paixão et al., 2008). Considering the proline motif as a privileged framework for the development of asymmetric catalysts (Yoon & Jacobsen, 2003) we have recently described a new chiral ligand for the highly enantioselective addition of arylzinc reagents to aldehydes. The ligands were prepared by an straightforward synthetic sequence, with a Heck reaction of arenediazonium salts (Heck–Matsuda reaction) as the key step (Taylor et al., 2011). Herein, we describe the crystal structure analysis of a representative molecule, the title compound, (I).

The crystal structure analysis of (I) confirms the structure as having the expected syn relationship between the phenyl and the diphenylmethanol substituents, Fig. 1 (Moro et al., 2010; Shabbir et al., 2009). The pyrrolidine ring is in an envelope conformation with C1 out of the plane formed by the other four atoms, the ring puckering parameters being: q₂ = 0.379 (2) ° and φ₂ = 32.0 (3) ° (Cremer & Pople, 1975). The hydroxy group is orientated over the five-membered ring to facilitate the formation of an intramolecular O—H···N hydrogen bond, Table 1. The crystal packing is dominated by C—H···π interactions, Table 1. Globally. the pyrrolidine pack in the ab plane and are sandwiched by benzene rings along the c direction, Fig. 2.

Experimental

The starting (2S)-1-tert-butyl 2-methyl 5-argio-1H-pyrrole-1,2(2H,5H)-dicarboxylate was prepared as described in previous work (Moro et al., 2010). To a round-bottomed flask, under a hydrogen atmosphere, were added the Heck adduct ((2S))-1-tert-butyl 2-methyl 5-argio-1H-pyrrole-1,2(2H,5H)-dicarboxylate) (3 mmol) and dry methanol (60 ml), followed by the addition of Pd/C 10% (20% w/w, 0.18 g). The reaction was stirred at room temperature for 24 h. After this time, the crude reaction mixture was filtered in a plug of celite and concentrated under reduced pressure. The resulting product was used without further purification. To a round-bottomed flask, under an argon atmosphere, PhMgBr (5 equiv., 15 mmol) in THF (15 ml, 1 M solution) was added to a THF (10 ml) solution of the (2S)-1-tert-butyl 2-methyl 5-argiopyrrolidine-1,2-dicarboxylate (3 mmol) at room temperature, and the mixture was stirred for 4 h, before being quenched by careful addition of NaOH 2M. The heterogeneous mixture was filtered through a pad of Celite and washed with dichloromethane (3 x 50 ml). The combined organic phases were dried with MgSO₄, filtered and the solvent removed under vacuum. The resulting product was used without further purification. To a suspension of lithium aluminium hydride (1.14 g, 30 mmol) in THF (15 ml) in a round-bottomed flask, under an argon atmosphere and cooled to 273 K, a solution of the (2S,5R)-tert-butyl 2-(hydroxydiphenylmethyl)-5-phenylpyrrolidine-1-carboxylate in THF (5 ml) was added. The resulting mixture was refluxed for 12 h. After this time, the mixture was cooled to 273 K and NaOH (4M) was added. The mixture was filtered through a pad of Celite and washed with ethyl acetate. The organic layer was separated, and the filtrate was extracted with ethyl acetate (3 x 50 ml). The combined organic phases were dried with MgSO₄, filtered and the solvent removed under vacuum. The crude product was purified by flash chromatography in hexanes/ethyl acetate (95:05), to afford the 0.340 g (33%) of pure ((2S,5R)-1-methyl-5-phenylpyrrolidin-2-yl)diphenylmethanol (cis isomer) and 0.278 g (27%) of pure ((2S,5S)-1-methyl-5-phenylpyrrolidin-2-yl)diphenylmethanol (trans isomer) (60% combined yield). Suitable crystals for X-ray analysis were obtained by vapour diffusion from n-hexane/ethyl ether at 298 K. [α] _D²⁰ = +115 (c = 1.02, CHCl₃). ¹H NMR [CDCl₃, 500 MHz, δ (p.p.m.)]: 1.66 (s, 3H, N—CH₃), 1.68–1.83 (m, 2H, CH₂), 1.92–2.03 (m, 2H, CH₂), 3.54 (dd, J¹ = 10.8 Hz, J² = 6.0 Hz, 1H, CH), 3.89 (dd, J¹ = 9.8 Hz, J² = 4.0 Hz, 1H, CH), 4.97 (bs, 1H, OH), 7.09 (t, J = 7.0 Hz, 1H, Ar), 7.13 (t, J = 7.0 Hz, 1H, Ar), 7.19–7.33 (m, 9H, Ar), 7.58 (dd, J¹ = 8.5 Hz, J² = 1.0 Hz, 2H, Ar), 7.68 (dd, J¹ = 8.5 Hz, J² = 1.0 Hz, 2H, Ar). ¹³C NMR [CDCl₃, 125 MHz, δ (p.p.m.)]: 28.2, 34.5, 41.0, 72.5, 73.4, 77.8, 125.3, 125.4, 126.1, 126.2, 126.9, 127.2, 128.0, 128.1, 128.4, 142.6, 146.6, 148.0. IR (film, cm^-1): 3428, 3263, 1449. MS (ESI): 209, 167. HRMS (ESI) calc for C₂₄H₂₅NO + H: 344.2014, found: 344.2083.