(2R)-8-Benzyl-2-[(S)-hy-droxy(phen-yl)meth-yl]-8-aza-bicyclo-[3.2.1]octan-3-one.

The crystal of the title compound, C(21)H(23)NO(2), was chosen from a conglomerate formed by a racemic mixture. An intra-molecular hydrogen bond is formed between hy-droxy group and heterocyclic N atom of the aza-bicyclo-[3.2.1]octan-3-one system. The crystal structure is stabilized by C-H⋯O inter-actions between aliphatic C-H groups and the carbonyl O atom. For the title chiral crystal, the highly redundant and accurate diffraction data set collected with low energy copper radiation gave a Flack parameter of 0.12 (18) for anomalous scattering effects originating from O atoms.

Related literature

For recent background literature on the chemistry of related tropane-derived aldols and their applications, including stereoselective syntheses of bioactive alkaloids, see: Lazny et al. (2011 ▶); Sienkiewicz et al. (2009 ▶) and references cited therein. For stereoselective syntheses of related nortropinone aldols, see: Lazny et al. (2001 ▶); Lazny & Nodzewska (2003 ▶). For a representative review of the biological activity of tropane derivatives, see: Singh (2000 ▶).

Experimental

Crystal data

C21H23NO2

M = 321.40

Orthorhombic,

a = 5.9354 (1) Å

b = 13.3091 (2) Å

c = 22.1511 (3) Å

V = 1749.82 (5) Å3

Z = 4

Cu Kα radiation

μ = 0.61 mm−1

T = 100 K

0.65 × 0.25 × 0.19 mm

Data collection

Oxford Diffraction SuperNova Dual diffractometer

Absorption correction: analytical (CrysAlis PRO; Agilent, 2011 ▶) T min = 0.75, T max = 0.89

32829 measured reflections

3323 independent reflections

3276 reflections with I > 2σ(I)

R int = 0.026

Refinement

R[F 2 > 2σ(F 2)] = 0.027

wR(F 2) = 0.070

S = 1.18

3323 reflections

218 parameters

H-atom parameters constrained

Δρmax = 0.16 e Å−3

Δρmin = −0.16 e Å−3

Absolute structure: Flack (1983 ▶), 1257 Friedel pairs

Flack parameter: 0.12 (18)

Data collection: CrysAlis PRO (Agilent, 2011 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXD (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and pyMOL (DeLano, 2002 ▶); software used to prepare material for publication: SHELXL97.

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811053190/gk2429sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811053190/gk2429Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536811053190/gk2429Isup3.cml

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

C21H23NO2	F(000) = 688
Mr = 321.40	Dx = 1.220 Mg m−3
Orthorhombic, P212121	Cu Kα radiation, λ = 1.54180 Å
Hall symbol: P 2ac 2ab	Cell parameters from 23874 reflections
a = 5.9354 (1) Å	θ = 3.3–73.6°
b = 13.3091 (2) Å	µ = 0.61 mm−1
c = 22.1511 (3) Å	T = 100 K
V = 1749.82 (5) Å3	Needle, colourless
Z = 4	0.65 × 0.25 × 0.19 mm

Oxford Diffraction SuperNova Dual diffractometer	3323 independent reflections
Radiation source: SuperNova (Cu) X-ray Source	3276 reflections with I > 2σ(I)
mirror	Rint = 0.026
Detector resolution: 10.4052 pixels mm-1	θmax = 73.6°, θmin = 3.9°
ω scans	h = −7→6
Absorption correction: analytical (CrysAlis PRO; Agilent, 2011)	k = 0→16
Tmin = 0.75, Tmax = 0.89	l = 0→27
32829 measured reflections

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.027	H-atom parameters constrained
wR(F2) = 0.070	w = 1/[σ2(Fo2) + (0.0283P)2 + 0.4297P] where P = (Fo2 + 2Fc2)/3
S = 1.18	(Δ/σ)max < 0.001
3323 reflections	Δρmax = 0.16 e Å−3
218 parameters	Δρmin = −0.16 e Å−3
0 restraints	Absolute structure: Flack (1983), 1257 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: 0.12 (18)

Geometry. All e.s.d.'s are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry.

Refinement. Refinement of F2 against all reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2σ(F2) is used only for calculating R-factors etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F.

	x	y	z	Uiso*/Ueq
C1	0.8760 (2)	0.63105 (8)	0.16890 (5)	0.0158 (2)
H1	0.9172	0.6656	0.1304	0.019*
C2	0.8530 (2)	0.51680 (8)	0.15913 (5)	0.0153 (2)
H2	1.0031	0.4903	0.1462	0.018*
C3	0.7921 (2)	0.46720 (9)	0.21973 (5)	0.0169 (3)
O3	0.88275 (17)	0.38983 (7)	0.23623 (4)	0.0256 (2)
C4	0.6185 (2)	0.52123 (8)	0.25898 (5)	0.0177 (3)
H4A	0.6293	0.4967	0.3011	0.021*
H4B	0.4649	0.5066	0.2439	0.021*
C5	0.6612 (2)	0.63510 (8)	0.25734 (5)	0.0164 (2)
H5	0.5476	0.6719	0.2823	0.020*
C6	0.9079 (2)	0.65823 (10)	0.27939 (6)	0.0202 (3)
H6A	0.9603	0.6067	0.3084	0.024*
H6B	0.9166	0.7252	0.2987	0.024*
C7	1.0516 (2)	0.65523 (9)	0.21957 (6)	0.0204 (3)
H7A	1.1253	0.7208	0.2121	0.025*
H7B	1.1686	0.6024	0.2218	0.025*
N8	0.65350 (19)	0.66906 (7)	0.19242 (4)	0.0150 (2)
O9	0.45290 (16)	0.52672 (6)	0.12196 (4)	0.0204 (2)
H9	0.4614	0.5808	0.1414	0.031*
C9	0.6768 (2)	0.49154 (9)	0.10786 (5)	0.0165 (3)
H9C	0.7269	0.5263	0.0701	0.020*
C10	0.6686 (2)	0.38004 (9)	0.09495 (5)	0.0166 (3)
C11	0.8557 (3)	0.33441 (10)	0.06662 (5)	0.0210 (3)
H11	0.9814	0.3742	0.0551	0.025*
C12	0.8568 (3)	0.23166 (10)	0.05557 (6)	0.0238 (3)
H12	0.9833	0.2009	0.0369	0.029*
C13	0.6694 (3)	0.17393 (9)	0.07224 (6)	0.0241 (3)
H13	0.6699	0.1035	0.0652	0.029*
C14	0.4813 (3)	0.21910 (10)	0.09918 (6)	0.0226 (3)
H14	0.3537	0.1794	0.1093	0.027*
C15	0.4803 (2)	0.32179 (9)	0.11116 (5)	0.0196 (3)
H15	0.3539	0.3522	0.1301	0.023*
C16	0.6383 (2)	0.78046 (8)	0.19028 (5)	0.0171 (3)
H16A	0.7639	0.8098	0.2138	0.020*
H16B	0.4952	0.8022	0.2091	0.020*
C17	0.6486 (2)	0.81981 (8)	0.12530 (6)	0.0176 (3)
C18	0.4719 (3)	0.80051 (9)	0.08410 (6)	0.0212 (3)
H18	0.3449	0.7626	0.0969	0.025*
C19	0.4813 (3)	0.83679 (10)	0.02427 (6)	0.0252 (3)
H19	0.3614	0.8234	−0.0030	0.030*
C20	0.6690 (3)	0.89285 (10)	0.00518 (6)	0.0262 (3)
H20	0.6763	0.9177	−0.0350	0.031*
C21	0.8457 (3)	0.91194 (9)	0.04567 (6)	0.0265 (3)
H21	0.9729	0.9494	0.0326	0.032*
C22	0.8362 (3)	0.87590 (9)	0.10572 (6)	0.0227 (3)
H22	0.9564	0.8895	0.1328	0.027*

	U11	U22	U33	U12	U13	U23
C1	0.0150 (6)	0.0132 (5)	0.0194 (6)	0.0009 (5)	0.0025 (5)	−0.0001 (4)
C2	0.0143 (6)	0.0129 (5)	0.0186 (5)	0.0017 (5)	−0.0010 (5)	−0.0008 (4)
C3	0.0174 (7)	0.0140 (5)	0.0192 (6)	−0.0017 (5)	−0.0041 (5)	−0.0006 (5)
O3	0.0324 (6)	0.0175 (4)	0.0269 (5)	0.0076 (4)	−0.0038 (4)	0.0032 (4)
C4	0.0197 (7)	0.0154 (5)	0.0178 (5)	0.0003 (5)	0.0000 (5)	0.0026 (4)
C5	0.0180 (7)	0.0157 (5)	0.0156 (5)	0.0014 (5)	0.0006 (5)	−0.0002 (4)
C6	0.0210 (8)	0.0187 (6)	0.0207 (6)	0.0000 (5)	−0.0046 (5)	−0.0004 (5)
C7	0.0147 (7)	0.0183 (6)	0.0283 (7)	0.0003 (5)	−0.0008 (5)	−0.0043 (5)
N8	0.0169 (6)	0.0120 (4)	0.0160 (5)	0.0020 (4)	0.0010 (4)	0.0004 (4)
O9	0.0178 (5)	0.0165 (4)	0.0269 (5)	0.0037 (3)	−0.0038 (4)	−0.0048 (4)
C9	0.0179 (7)	0.0157 (5)	0.0159 (5)	0.0005 (5)	0.0003 (5)	0.0004 (4)
C10	0.0207 (7)	0.0166 (5)	0.0126 (5)	0.0006 (5)	−0.0028 (5)	−0.0009 (4)
C11	0.0220 (7)	0.0223 (6)	0.0187 (6)	−0.0001 (5)	0.0002 (5)	−0.0029 (5)
C12	0.0260 (8)	0.0246 (6)	0.0209 (6)	0.0072 (6)	−0.0024 (6)	−0.0065 (5)
C13	0.0371 (9)	0.0155 (6)	0.0196 (6)	0.0019 (6)	−0.0052 (6)	−0.0030 (5)
C14	0.0309 (8)	0.0194 (6)	0.0175 (6)	−0.0055 (6)	−0.0018 (6)	0.0006 (5)
C15	0.0228 (7)	0.0197 (6)	0.0162 (5)	−0.0005 (5)	0.0008 (5)	−0.0012 (5)
C16	0.0188 (7)	0.0118 (5)	0.0206 (6)	0.0014 (5)	−0.0005 (5)	−0.0013 (4)
C17	0.0194 (7)	0.0110 (5)	0.0224 (6)	0.0034 (5)	0.0025 (6)	0.0002 (4)
C18	0.0228 (8)	0.0171 (6)	0.0238 (6)	0.0003 (5)	0.0003 (5)	0.0034 (5)
C19	0.0302 (8)	0.0218 (6)	0.0235 (6)	0.0036 (6)	−0.0033 (6)	0.0021 (5)
C20	0.0369 (9)	0.0192 (6)	0.0226 (6)	0.0066 (6)	0.0074 (6)	0.0049 (5)
C21	0.0261 (8)	0.0187 (6)	0.0347 (7)	0.0010 (6)	0.0113 (6)	0.0046 (5)
C22	0.0226 (8)	0.0153 (5)	0.0303 (7)	0.0009 (5)	0.0020 (6)	0.0007 (5)

C1—N8	1.5071 (16)	C10—C15	1.4068 (19)
C1—C2	1.5419 (15)	C10—C11	1.4127 (19)
C1—C7	1.5648 (18)	C11—C12	1.3893 (18)
C1—H1	1.0000	C11—H11	0.9500
C2—C3	1.5390 (16)	C12—C13	1.401 (2)
C2—C9	1.5801 (16)	C12—H12	0.9500
C2—H2	1.0000	C13—C14	1.401 (2)
C3—O3	1.2180 (15)	C13—H13	0.9500
C3—C4	1.5279 (18)	C14—C15	1.3923 (17)
C4—C5	1.5368 (15)	C14—H14	0.9500
C4—H4A	0.9900	C15—H15	0.9500
C4—H4B	0.9900	C16—C17	1.5329 (16)
C5—N8	1.5082 (14)	C16—H16A	0.9900
C5—C6	1.5742 (18)	C16—H16B	0.9900
C5—H5	1.0000	C17—C22	1.4091 (19)
C6—C7	1.5762 (18)	C17—C18	1.4140 (19)
C6—H6A	0.9900	C18—C19	1.4116 (18)
C6—H6B	0.9900	C18—H18	0.9500
C7—H7A	0.9900	C19—C20	1.406 (2)
C7—H7B	0.9900	C19—H19	0.9500
N8—C16	1.4861 (14)	C20—C21	1.403 (2)
O9—C9	1.4430 (16)	C20—H20	0.9500
O9—H9	0.8400	C21—C22	1.4151 (19)
C9—C10	1.5121 (16)	C21—H21	0.9500
C9—H9C	1.0000	C22—H22	0.9500
N8—C1—C2	107.58 (10)	O9—C9—H9C	107.8
N8—C1—C7	105.46 (9)	C10—C9—H9C	107.8
C2—C1—C7	111.25 (10)	C2—C9—H9C	107.8
N8—C1—H1	110.8	C15—C10—C11	120.07 (11)
C2—C1—H1	110.8	C15—C10—C9	121.20 (12)
C7—C1—H1	110.8	C11—C10—C9	118.73 (12)
C3—C2—C1	108.74 (9)	C12—C11—C10	120.33 (13)
C3—C2—C9	112.33 (10)	C12—C11—H11	119.8
C1—C2—C9	111.67 (9)	C10—C11—H11	119.8
C3—C2—H2	108.0	C11—C12—C13	119.32 (13)
C1—C2—H2	108.0	C11—C12—H12	120.3
C9—C2—H2	108.0	C13—C12—H12	120.3
O3—C3—C4	121.66 (11)	C12—C13—C14	120.62 (11)
O3—C3—C2	121.38 (12)	C12—C13—H13	119.7
C4—C3—C2	116.94 (10)	C14—C13—H13	119.7
C3—C4—C5	109.85 (10)	C15—C14—C13	120.37 (13)
C3—C4—H4A	109.7	C15—C14—H14	119.8
C5—C4—H4A	109.7	C13—C14—H14	119.8
C3—C4—H4B	109.7	C14—C15—C10	119.27 (13)
C5—C4—H4B	109.7	C14—C15—H15	120.4
H4A—C4—H4B	108.2	C10—C15—H15	120.4
N8—C5—C4	108.25 (9)	N8—C16—C17	111.62 (9)
N8—C5—C6	105.38 (10)	N8—C16—H16A	109.3
C4—C5—C6	109.80 (10)	C17—C16—H16A	109.3
N8—C5—H5	111.1	N8—C16—H16B	109.3
C4—C5—H5	111.1	C17—C16—H16B	109.3
C6—C5—H5	111.1	H16A—C16—H16B	108.0
C5—C6—C7	103.74 (10)	C22—C17—C18	118.94 (12)
C5—C6—H6A	111.0	C22—C17—C16	120.10 (12)
C7—C6—H6A	111.0	C18—C17—C16	120.96 (12)
C5—C6—H6B	111.0	C19—C18—C17	120.96 (13)
C7—C6—H6B	111.0	C19—C18—H18	119.5
H6A—C6—H6B	109.0	C17—C18—H18	119.5
C1—C7—C6	104.36 (10)	C20—C19—C18	119.68 (13)
C1—C7—H7A	110.9	C20—C19—H19	120.2
C6—C7—H7A	110.9	C18—C19—H19	120.2
C1—C7—H7B	110.9	C21—C20—C19	119.74 (12)
C6—C7—H7B	110.9	C21—C20—H20	120.1
H7A—C7—H7B	108.9	C19—C20—H20	120.1
C16—N8—C1	112.14 (10)	C20—C21—C22	120.66 (13)
C16—N8—C5	109.34 (9)	C20—C21—H21	119.7
C1—N8—C5	101.69 (9)	C22—C21—H21	119.7
C9—O9—H9	109.5	C17—C22—C21	120.02 (13)
O9—C9—C10	109.26 (11)	C17—C22—H22	120.0
O9—C9—C2	112.65 (9)	C21—C22—H22	120.0
C10—C9—C2	111.47 (10)

D—H···A	D—H	H···A	D···A	D—H···A
O9—H9···N8	0.84	1.99	2.7280 (13)	146
C6—H6B···O3i	0.99	2.61	3.3414 (15)	131
C7—H7A···O3i	0.99	2.52	3.2954 (15)	135
C16—H16A···O3i	0.99	2.60	3.5846 (16)	173

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O9—H9⋯N8	0.84	1.99	2.7280 (13)	146
C6—H6B⋯O3i	0.99	2.61	3.3414 (15)	131
C7—H7A⋯O3i	0.99	2.52	3.2954 (15)	135
C16—H16A⋯O3i	0.99	2.60	3.5846 (16)	173

Symmetry code: (i) .