Relative configuration, absolute configuration and absolute structure of three isomeric 8-benzyl-2-[(4-bromophenyl)(hydroxy)methyl]-8-azabicyclo[3.2.1] octan-3-ones

organic compounds

Acta Crystallographica Section C

Crystal Structure

Communications

al., 2009; Lazny, Sienkiewicz, Olenski et al., 2012), as well as by

others for the synthesis of the nonnatural enantiomer of

cocaine (ent-cocaine) (Lee et al., 2000). However, the stereo-

selective syntheses of nortropinone aldols (Lazny et al., 2001;

Lazny & Nodzewska, 2003; Lazny et al., 2010) were not so

effective. Possible approaches to obtaining nor derivatives

have used synthetic equivalents of nortropinone, including

triazene derivatives (Lazny et al., 2001, 2010; Lazny &

Nodzewska, 2003), urethane derivatives (Lazny et al., 2010)

and polymer-supported analogues (Lazny et al., 2006, 2010;

Sienkiewicz & Lazny, 2010). We now report the crystal

structures of the three title stereoisomeric forms, (I)–(III), of a

promising newly prepared N-benzyl-protected derivative.

ISSN 0108-2701

Relative configuration, absolute

configuration and absolute structure

of three isomeric 8-benzyl-2-[(4-bromo-

phenyl)(hydroxy)methyl]-8-aza-

bicyclo[3.2.1]octan-3-ones

Krzysztof Brzezinski,* Ryszard Lazny, Aneta Nodzewska

and Katarzyna Sidorowicz

Institute of Chemistry, University of Bialystok, Hurtowa 1, 15-399 Bialystok, Poland

Correspondence e-mail: k.brzezinski@uwb.edu.pl

Received 16 October 2012

Accepted 24 January 2013

Online 19 February 2013

The title compounds, C₂₁H₂₂BrNO₂, are isomeric 8-benzyl-2-

[(4-bromophenyl)(hydroxy)methyl]-8-azabicyclo[3.2.1]octan-

3-ones. Compound (I), the (Æ)-exo,syn-(1RS,2SR,5SR,9SR)

isomer, crystallizes in the hexagonal space group R3, while

compounds (II) [the (+)-exo,anti-(1R,2S,5S,9R) isomer] and

(III) [the (Æ)-exo,anti-(1RS,2SR,5SR,9RS) isomer] crystallize

in the orthorhombic space groups P2₁2₁2₁and Pna2₁,

respectively. The absolute conﬁguration was determined for

enantiomerically pure (II). For the noncentrosymmetric

crystal of (III), its absolute structure was established. In the

crystal structures of (I) and (II), an intramolecular hydrogen

bond is formed between the hydroxy group and the

heterocyclic N atom. In the crystal structure of racemic

(III), hydrogen-bonded chains of molecules are formed via

intermolecular O—HÁ Á ÁO interactions. Additionally, face-to-

edge ꢀ–ꢀ interactions are present in the crystal structures of

(I) and (II). In all three structures, the piperidinone rings

adopt chair conformations and the N-benzyl substituents

occupy the equatorial positions.

Comment

By analogy with the recently reported spontaneous reaction

of an N-methyl derivative, i.e. tropinone, with aldehydes in the

presence of water, which surprisingly gave the other, atypical,

diastereomer (Lazny, Nodzewska, & Tomczuk, 2011; Lazny,

Nodzewska, Sidorowicz & Kalicki, 2012; Lazny, Ratkiewicz,

Nodzewska & Wysocka, 2012), we succeeded in converting a

much less reactive N-benzyl derivative and an aromatic

aldehyde to an aldol product. Based on NMR data, we iden-

tiﬁed (Lazny, Nodzewska, Sidorowicz & Kalicki, 2012), with

high probability, the major product of the reaction as the

exo,syn isomer. Analogous to previous reports, the major

product of the reaction promoted by a lithium amide (e.g.

lithium diisopropylamide, LDA) was assigned the likely

Tropane (8-methyl-8-azabicyclo[3.2.1]octane) and nortropane

(8-azabicyclo[3.2.1]octane) scaffolds can be found in

numerous natural alkaloids, many of which demonstrate a

range of biological activities (Lounasmaa, 1988; Lounasmaa &

Tamminen, 1993). Several tropane alkaloids and their non-

natural analogues have been synthesized in the quest for

interesting properties suitable for agrochemical and pharma-

ceutical applications (Singh, 2000; Zhao et al., 2000; Xu et al.,

2002; Pollini et al., 2006). Diastereomerically and enantio-

merically pure aldols of tropinone are key intermediates used

by us in the stereoselective syntheses of knightinol, alkaloid

KD-B (Majewski & Lazny, 1995) and ferrugine (Sienkiewicz et

Acta Cryst. (2013). C69, 303–306

doi:10.1107/S0108270113002503

# 2013 International Union of Crystallography 303

organic compounds

Figure 2

The molecular structure of (II), showing the atom-numbering scheme.

Displacement ellipsoids are drawn at the 50% probability level. The

dashed line indicates the intramolecular hydrogen bond.

Figure 1

The molecular structure of (I), showing the atom-numbering scheme.

Displacement ellipsoids are drawn at the 50% probability level. The

dashed line indicates the intramolecular hydrogen bond.

exo,anti conﬁguration (Lazny et al., 2010; Lazny, Sienkiewicz,

Olenski et al., 2012), but the tentative assignments needed to

be conﬁrmed. In order to prepare an enantiomerically pure

N-benzyl analogue of tropinone aldol, we used known

enantioselective deprotonation with chiral lithium amide

bases (O’Brien, 1998; Simpkins & Weller, 2010). The proce-

dure gave an enantiomerically pure crystalline aldol (likely the

exo,anti isomer), the absolute structure of which reﬂects the

preferred enantio-differentiation of enantiotopic H atoms of

the N-benzyltropinone system by the chiral lithium amide

used (O’Brien, 1998; Simpkins & Weller, 2010; Majewski &

Lazny, 1995). From the asymmetric synthesis point of view, it is

essential to know the sense of the enantioselection. Therefore,

it is crucial not only to determine unambiguously the relative

structures of the aldols but also, more importantly, to deter-

mine positively the absolute conﬁguration of the product

resulting from the reaction of N-benzylnortropinone with the

speciﬁc enantiomeric form of the chiral reagent used.

Figure 3

The molecular structure of (III), showing the atom-numbering scheme.

Displacement ellipsoids are drawn at the 50% probability level.

Dauter & Brzezinski, 2012; Lazny, Sienkiewicz, Olenski et al.,

2012; Brzezinski et al., 2012; Jiang et al., 2012). The puckering

parameters of the six-membered heterocyclic ring are Q =

Based on the present crystallographic studies, the relative

conﬁguration of (I) was established. The absolute conﬁgura-

tion of (II) and the absolute structure of the crystal of (III)

were determined unequivocally based on anomalous diffrac-

tion effects, as conﬁrmed by the observed Flack parameters.

In the crystal structure of (I) (Fig. 1), the piperidinone ring

of the tropinone system adopts a distorted chair conformation

ꢀ

˚

0.643 (2) A, ꢁ = 27.07 (18) and ’ = 6.5 (4) for (II), and Q =

ꢀ

0.650 (3) A, ꢁ = 20.4 (3) and ’ = 3.5 (9) for (III).

In the crystal structure of (I), the piperidinone scaffold is

remarkably ﬂattened at the C3 pole of the ring. The strained

heterocyclic ring conformation is stabilized by an intra-

molecular O—HÁ Á ÁN hydrogen bond, as well as by intra-

ꢀ

˚

with puckering parameters Q = 0.6536 (18) A, ꢁ = 43.51 (17)

molecular [C15—H15Á Á ÁCg1, with C15Á Á ÁCg1 = 3.391 (2) A

and ’ = 5.8 (3)^ꢀ(Cremer & Pople, 1975). A chair conformation

of the piperidinone ring is observed in the crystal structures of

(II) and (III) (Figs. 2 and 3), as is observed in other N-methyl

and N-benzyl derivatives of tropinone and granatanone (Li et

al., 1993; Lazny, Wolosewicz, Zielinska et al., 2011; Lazny,

Nodzewska, Sidorowicz & Kalicki, 2012; Lazny, Wolosewicz,

and C15—H15Á Á ÁCg1 = 146^ꢀ] and intermolecular [C11—

˚

H11Á Á ÁCg2, with C11Á Á ÁCg2 = 3.455 (2) A and C11—

H11Á Á ÁCg2 = 152^ꢀ] face-to-edge C—HÁ Á Áꢀ interactions [the

symmetry-related molecule is at (y À 1, Àx + y, Àz + 1)]. For

(I) and (II), Cg1 and Cg2 are the centroids of C17–C22 and

C10–C15 rings, respectively. Additionally, the 4-bromophenyl

ꢁ

304 Brzezinski et al.

Three isomers of C₂₁H₂₂BrNO₂

Acta Cryst. (2013). C69, 303–306

organic compounds

group participates in the formation of short BrÁ Á ÁBr contacts

Experimental

˚

[3.5122 (3) A] with two symmetry-related molecules at (y À 1,

The reaction of 4-bromobenzaldehyde (0.093 g, 0.50 mmol) with

N-benzylnortropinone (0.215 g, 1.00 mmol) in water (1.25 ml)

admixed with an organic cosolvent [dimethylformamide (DMF),

0.25 ml], according to the literature procedure of Lazny, Nodzewska

& Tomczuk (2011), gave (I), which was crystallized from diethyl ether

[yield: 0.116 g, 58%; m.p. 428–429 K (decomposition)]. Crystals

suitable for X-ray diffraction analysis were obtained at room

temperature by slow evaporation from a heptane solution of (I).

¹H NMR (CDCl₃, 400 MHz): ꢂ 7.61 (br s, 1H), 7.49–7.44 (m, 3H),

7.40–7.32 (m, 2H), 7.30–7.26 (m, 2H), 6.80–6.74 (m, 2H), 4.88 (d, J =

2.2 Hz, 1H), 3.70–3.65 (m, 1H), 3.62 (d, J = 12.4 Hz, 1H), 3.49 (d, J =

12.4 Hz, 1H), 3.40–3.35 (m, 1H), 2.96 (dd, J = 17.0 Hz, 5.1 Hz, 1H),

2.48 (dt, J = 17.0 Hz, 1.7 Hz, 1H), 2.21–2.27 (m, 1H), 2.25–2.15 (m,

2H), 1.78–1.67 (m, 1H), 1.53–1.42 (m, 1H); ¹³C NMR (CDCl₃,

100 MHz): ꢂ 210.6, 142.4, 137.3, 131.2, 129.8, 129.1, 128.1, 127.2, 120.5,

75.6, 63.1, 59.9, 58.0, 57.4, 50.5, 27.1, 26.8.

Àx + y, Àz) and (x À y + 1, x + 1, Àz). The intramolecular O—

HÁ Á ÁN hydrogen bond is also observed in (II). Additionally,

intermolecular face-to-edge C—BrÁ Á Áꢀ interactions [the

1

3

symmetry-related molecule is at (x + , Ày + , Àz + 1)] are

2

present in the crystal structure of (II) [C13—Br13Á Á ÁCg1, with

ꢀ

˚

C13Á Á ÁCg1 = 5.372 (2) A and C13—Br13Á Á ÁCg1 = 151.83 (7) ].

The N-benzyl substituents of (I)–(III) are equatorial,

similar to the majority of crystal structures of N-alkyl-

nortropanes and the thermodynamic preference for tropanes

in solution (Lazny, Ratkiewicz, Nodzewska, Wynimko &

Siergiejczyk, 2012). Such a conﬁguration is strongly related to

the exo orientation of the bulky 4-bromophenyl(hydroxy)-

methyl groups at atom C2. The existence of the speciﬁc

N-alkyl invertomer can be explained by steric hindrance of the

C2 substituent in (I)–(III). Moreover in (I) and (II), an

intramolecular hydrogen bond is formed between heterocyclic

atom N8 and the OH group (Figs. 1 and 2); in (I), NÁ Á ÁO =

The reaction of 4-bromobenzaldehyde (0.330 g, 1.78 mmol) with

N-benzylnortropinone (0.333 g, 1.55 mmol) promoted with chiral

lithium (R)-N-benzhydryl-1-phenylethanamide (0.535 g, 1.86 mmol),

according to the literature procedure of Lazny, Sienkiewicz, Olenski

et al. (2012), followed by precipitation from a mixture of dichloro-

methane and hexane (1:8 v/v), gave (II) {yield: 0.470 g, 76%, 75% ee

[by ¹H NMR in the presence of (R)-(À)-1-(9-anthryl)-2,2,2-tri-

ﬂuoroethanol]} as a white solid. An analytical sample was recrys-

tallized from dichloromethane–hexane (1:8 v/v) [m.p. 404–405 K

(decomposition); ee ꢂ 98%; [ꢃ]_Dat 293 K = 37^ꢀ(c = 0.5, CHCl₃,

where c is the concentration in grams per 100 ml)]. Crystals suitable

for X-ray diffraction analysis were obtained at room temperature by

slow evaporation from a heptane solution of (II).

ꢀ

˚

2.7902 (19) A and N—HÁ Á ÁO = 149 , while in (II) the corre-

ꢀ

˚

sponding values are 2.682 (2) A and 157 (4) . As a result, in

the crystal structures of (I) and (II), the N-equatorial inver-

tomers are additionally stabilized and inversion to the N-axial

conformers is not possible. Similar conformations are

observed in solution. The H9C—C9—C2—H2 torsion angles

of À64.1^ꢀfor (I) and 56.7^ꢀfor (II) in the solid state corre-

spond, approximately, to the probable angles in solution,

estimated using the Karplus correlation of dihedral angles (52

and 58^ꢀ) and the observed vicinal coupling constants for

benzylic carbinol proton signals at 4.88 (d, J = 2.2 Hz) and

5.04 p.p.m (d, J = 2.8 Hz), respectively (Karplus, 1959, 1963;

Bifulco et al., 2007). This indicates similar conformations of (I)

and (II) in solution and in the solid state.

The reaction of 4-bromobenzaldehyde (0.213 g, 1.15 mmol) with

N-benzylnortropinone (0.215 g, 1.00 mmol) promoted with LDA

(lithium diisopropylamide; 1.20 mmol), according to the literature

procedure of Lazny, Sienkiewicz, Olenski et al. (2012), gave (III),

which was crystallized from a mixture of heptane and AcOEt (7:1 v/v)

[yield: 0.380 g, 95%; m.p. 421–423 K (decomposition)]. No additional

crystallization attempts were required prior to X-ray data collection.

¹H NMR (CDCl₃, 400 MHz): ꢂ 7.50 (br s, 1H), 7.45–7.32 (m, 7H),

7.12–7.03 (m, 2H), 5.04 (d, J = 2.8 Hz, 1H), 3.74–3.63 (m, 3H), 3.60–

3.54 (m, 1H), 2.78 (dd, J = 16.0 Hz, 3.3 Hz, 1H), 2.40 (s, 1H), 2.38–2.15

(m, 3H), 1.72–1.58 (m, 2H); ¹³C NMR (CDCl₃, 100 MHz): ꢂ 208.0,

140.7, 137.4, 131.0, 129.0, 128.8, 127.8, 127.3, 121.0, 75.8, 65.0, 64.1,

58.9, 57.0, 51.5, 26.8, 26.4.

In the crystal structures of (I) and (II), the packing is based

mainly on weak intermolecular interactions. A different

mechanism is observed in (III), where the –OH group parti-

cipates in the formation of an intermolecular hydrogen bond

with carbonyl atom O3 from a symmetry-related molecule at

1

2

˚

(Àx + 2, Ày + 1, z À ) [OÁ Á ÁO = 2.874 (3) A and O—HÁ Á ÁO =

176^ꢀ]. Molecules related by 2₁axes form helices extending

along the c direction, and a different orientation of the OH

group at atom C9 is observed. However, due to the exo

conﬁguration of the substituent on the bicyclic system,

formation of the second N-benzyl invertomer is prevented

here by the close proximity of the (4-bromophenyl)-

(hydroxy)methyl group. The H9C—C9—C2—H2 torsion

angle of 170.2^ꢀin (III) corresponds to the conformation which

is disfavoured in solution, as indicated by the relevant vicinal

coupling constant (J = 2.8 Hz) which rules out such a value for

the torsion angle.

The obtained crystals of (I), (II) and (III) were rather large for the

microfocus beam, but due to their fragility, any manipulation (e.g.

cutting) was unfeasible prior to the diffraction experiments.

Isomer (I)

Crystal data

C₂₁H₂₂BrNO₂

M_r= 400.31

Trigonal, R3

a = 29.8145 (5) A

c = 10.2028 (2) A

˚

V = 7854.2 (4) A

Z = 18

Mo Kꢃ radiation

ꢄ = 2.36 mm^À1

T = 100 K

0.54 Â 0.46 Â 0.29 mm

˚

3

Note that the mode of stabilization of the N-alkyl group in

the equatorial position reported here is also likely to be

operational in other N-methyl-substituted tropinones and also

in N-benzylgranatanone derivatives (Lazny, Wolosewicz,

Zielinska et al., 2011; Lazny, Sienkiewicz, Olenski et al., 2012;

Lazny, Wolosewicz, Dauter & Brzezinski, 2012; Brzezinski et

al., 2012).

Data collection

Agilent SuperNova Dual

diffractometer

Absorption correction: analytical

(CrysAlis PRO; Agilent, 2011)

T_min= 0.434, T_max= 0.633

24029 measured reﬂections

4885 independent reﬂections

4130 reﬂections with I > 2ꢅ(I)

R_int= 0.033

ꢁ

Acta Cryst. (2013). C69, 303–306

Brzezinski et al.

Three isomers of C₂₁H₂₂BrNO₂305

organic compounds

program(s) used to reﬁne structure: SHELXL97 (Sheldrick, 2008);

molecular graphics: OLEX2 (Dolomanov et al., 2009); software used

to prepare material for publication: SHELXL97.

Reﬁnement

R[F²> 2ꢅ(F²)] = 0.033

wR(F²) = 0.081

S = 1.06

227 parameters

H-atom paramete_Àrs₃constrained

˚

Áꢆ_max= 0.52 e A

À3

˚

4885 reﬂections

Áꢆ_min= À0.67 e A

This work was supported by the University of Bialystok

(grant No. BST-125) and the National Science Centre, Poland

(grant No. NN204 546939). The X-ray diffractometer was

funded by EFRD as part of the Operational Programme

Development of Eastern Poland 2007–2013 (project No.

POPW.01.03.00-20-034/09-00).

Isomer (II)

Crystal data

3

˚

V = 1829.83 (2) A

Z = 4

C₂₁H₂₂BrNO₂

M_r= 400.31

Orthorhombic, P2₁2₁2₁

Mo Kꢃ radiation

ꢄ = 2.26 mm^À1

T = 100 K

0.52 Â 0.11 Â 0.09 mm

˚

a = 5.96905 (4) A

Supplementary data for this paper are available from the IUCr electronic

archives (Reference: GZ3222). Services for accessing these data are

described at the back of the journal.

˚

b = 14.76590 (9) A

˚

c = 20.76083 (13) A

Data collection

Agilent SuperNova Dual

diffractometer

Absorption correction: analytical

(CrysAlis PRO; Agilent, 2011)

T_min= 0.308, T_max= 0.816

67899 measured reﬂections

5359 independent reﬂections

5007 reﬂections with I > 2ꢅ(I)

R_int= 0.064

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R[F²> 2ꢅ(F²)] = 0.033

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5359 reﬂections

230 parameters

H atoms treated by a mixture of

independent and constrained

reﬁnement

Áꢆ_max= 0.64 e A

À3

˚

À3

˚

Áꢆ_min= À0.48 e A

Absolute structure: Flack (1983),

with 2292 Friedel pairs

Flack parameter: À0.011 (7)

isomer (III)

Crystal data

3

˚

V = 1800.22 (17) A

Z = 4

C₂₁H₂₂BrNO₂

M_r= 400.31

Orthorhombic, Pna2₁

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a = 9.0968 (4) A

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b = 32.0680 (18) A

¨

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c = 6.1711 (4) A

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diffractometer

Absorption correction: analytical

(CrysAlis PRO; Agilent, 2011)

T_min= 0.726, T_max= 0.870

9954 measured reﬂections

4327 independent reﬂections

3985 reﬂections with I > 2ꢅ(I)

R_int= 0.026

Reﬁnement

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R[F²> 2ꢅ(F²)] = 0.031

wR(F²) = 0.067

S = 1.06

4327 reﬂections

227 parameters

1 restraint

H-atom paramete_Àrs₃constrained

˚

Áꢆ_max= 0.34 e A

À3

˚

Áꢆ_min= À0.29 e A

Absolute structure: Flack (1983),

with 1887 Friedel pairs

Flack parameter: À0.020 (8)

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˚

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˚

constrained to idealized positions, with O—H = 0.84 A and U_iso(H) =

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Zhao, L., Johnson, K. M., Zhang, M., Flippen-Anderson, J. & Kozikowski, A. P .

(2000). J. Med. Chem. 43 , 3283–3294.

1.5U_eq(O). For (II), the hydroxy H atom was freely reﬁned.

For all compounds, data collection: CrysAlis PRO (Agilent, 2011);

cell reﬁnement: CrysAlis PRO; data reduction: CrysAlis PRO;

program(s) used to solve structure: SHELXD (Sheldrick, 2008);

ꢁ

306 Brzezinski et al.

Three isomers of C₂₁H₂₂BrNO₂

Acta Cryst. (2013). C69, 303–306

supplementary materials

Acta Cryst. (2013). C69, 303-306 [doi:10.1107/S0108270113002503]

Relative configuration, absolute configuration and absolute structure of three

isomeric 8-benzyl-2-[(4-bromophenyl)(hydroxy)methyl]-8-azabicyclo-

[3.2.1]octan-3-ones

Krzysztof Brzezinski, Ryszard Lazny, Aneta Nodzewska and Katarzyna Sidorowicz

(I) ( )-exo,syn-(1RS,2SR,5SR)-8-Benzyl-2- [(SR)-(4-bromophenyl)(hydroxy)methyl]-8-azabicyclo[3.2.1]octan-3-

one

Crystal data

C₂₁H₂₂BrNO₂

M_r= 400.31

Trigonal, R3

Hall symbol: -R 3

a = 29.8145 (5) Å

c = 10.2028 (2) Å

V = 7854.2 (4) Å³

Z = 18

D_x= 1.523 Mg m⁻³

Mo Kα radiation, λ = 0.71073 Å

Cell parameters from 11027 reflections

θ = 2.7–29.5°

µ = 2.36 mm⁻¹

T = 100 K

Prism, colourless

0.54 × 0.46 × 0.29 mm

F(000) = 3708

Data collection

Agilent SuperNova Dual

T_min= 0.434, T_max= 0.633

diffractometer (Cu at zero) with Atlas detector

Radiation source: SuperNova (Mo) X-ray

Source

Mirror monochromator

Detector resolution: 10.4052 pixels mm^-1

ω scans

24029 measured reflections

4885 independent reflections

4130 reflections with I > 2σ(I)

R_int= 0.033

θ_max= 29.6°, θ_min= 2.7°

h = −41→38

k = −41→40

l = −14→12

Absorption correction: analytical

(CrysAlis PRO; Agilent, 2011)

Refinement

Refinement on F²

Least-squares matrix: full

R[F²> 2σ(F²)] = 0.033

wR(F²) = 0.081

Secondary atom site location: difference Fourier

map

Hydrogen site location: inferred from

neighbouring sites

S = 1.06

4885 reflections

227 parameters

0 restraints

Primary atom site location: structure-invariant

direct methods

H-atom parameters constrained

w = 1/[σ²(F_o²) + (0.0333P)²+ 18.6115P]

where P = (F_o²+ 2F_c²)/3

(Δ/σ)_max= 0.004

Δρ_max= 0.52 e Å⁻³

Δρ_min= −0.66 e Å⁻³

Acta Cryst. (2013). C69, 303-306

sup-1

supplementary materials

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) 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.

An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F²against 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> σ(F²) is used

only for calculating R-factors(gt) 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, and R-factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²)

x

y

z

U_iso*/U_eq

C1

0.16570 (6)

0.1709

0.94796 (6)

0.9633

0.71283 (16)

0.6231

0.0114 (3)

0.014*

H1

C2

0.10840 (6)

0.0886

0.90755 (6)

0.9264

0.73507 (16)

0.7428

0.0123 (3)

0.015*

H2

C3

0.10052 (7)

0.14678 (7)

0.1439

0.87706 (7)

0.87775 (7)

0.8435

0.86202 (18)

0.92536 (17)

0.9117

0.0165 (3)

0.0157 (3)

0.019*

C4

H4A

H4B

C5

0.1453

0.8826

1.0210

0.019*

0.19969 (7)

0.2274

0.91966 (6)

0.9120

0.87456 (17)

0.9013

0.0137 (3)

0.016*

H5

C6

0.21288 (7)

0.2508

0.97402 (7)

0.9979

0.92092 (17)

0.9215

0.0162 (3)

0.019*

H6A

H6B

C7

0.1991

0.9727

1.0099

0.019*

0.18603 (7)

0.1571

0.99099 (6)

0.9935

0.81840 (17)

0.8587

0.0153 (3)

0.018*

H7A

H7B

C9

0.2110

1.0250

0.7800

0.018*

0.08391 (6)

0.0478

0.86743 (6)

0.8418

0.62219 (17)

0.6496

0.0135 (3)

0.016*

H9C

C10

C11

H11

C12

H12

C13

C14

H14

C15

H15

C16

H16A

H16B

C17

C18

H18

C19

H19

C20

0.07998 (6)

0.03816 (6)

0.0122

0.89204 (6)

0.90032 (7)

0.8891

0.49583 (17)

0.47817 (18)

0.5439

0.0130 (3)

0.0157 (3)

0.019*

0.03378 (7)

0.0052

0.92454 (7)

0.9300

0.36686 (19)

0.3563

0.0171 (3)

0.021*

0.07184 (7)

0.11339 (7)

0.1390

0.94069 (7)

0.93221 (7)

0.9430

0.27109 (17)

0.28452 (18)

0.2179

0.0164 (3)

0.0162 (3)

0.019*

0.11708 (6)

0.1453

0.90772 (6)

0.9016

0.39687 (17)

0.4062

0.0148 (3)

0.018*

0.24871 (6)

0.2712

0.95065 (7)

0.9379

0.66966 (17)

0.7052

0.0151 (3)

0.018*

0.2643

0.9877

0.6935

0.018*

0.24634 (6)

0.23544 (6)

0.2302

0.94546 (6)

0.89856 (7)

0.8704

0.52295 (17)

0.46486 (18)

0.5188

0.0129 (3)

0.0144 (3)

0.017*

0.23212 (7)

0.2243

0.89259 (7)

0.8604

0.33004 (18)

0.2920

0.0167 (3)

0.020*

0.24027 (7)

0.93395 (7)

0.25023 (18)

0.0170 (3)

Acta Cryst. (2013). C69, 303-306

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supplementary materials

H20

C21

H21

C22

H22

N8

0.2382

0.9300

0.1576

0.020*

0.25148 (7)

0.2572

0.98090 (7)

1.0092

0.30617 (18)

0.2519

0.0173 (3)

0.021*

0.25429 (6)

0.2617

0.98643 (6)

1.0185

0.44173 (18)

0.4795

0.0151 (3)

0.018*

0.19619 (5)

0.05746 (6)

0.11078 (5)

0.1418

0.92084 (5)

0.85040 (6)

0.83943 (5)

0.8582

0.72953 (14)

0.90646 (15)

0.60591 (13)

0.6286

0.0118 (3)

0.0310 (3)

0.0162 (3)

0.024*

O3

O9

H9O

Br13

0.068838 (8)

0.977249 (8)

0.12272 (2)

0.02544 (7)

Atomic displacement parameters (Å²)

U¹¹

U²²

U³³

U¹²

U¹³

U²³

C1

0.0141 (7)

0.0143 (7)

0.0211 (8)

0.0234 (9)

0.0187 (8)

0.0226 (8)

0.0208 (8)

0.0130 (7)

0.0116 (7)

0.0106 (7)

0.0121 (7)

0.0181 (8)

0.0148 (8)

0.0127 (7)

0.0113 (7)

0.0093 (7)

0.0129 (7)

0.0155 (8)

0.0153 (8)

0.0171 (8)

0.0125 (7)

0.0133 (6)

0.0223 (7)

0.0169 (6)

0.02526 (11)

0.0100 (7)

0.0116 (7)

0.0157 (8)

0.0139 (8)

0.0146 (7)

0.0141 (8)

0.0115 (7)

0.0113 (7)

0.0099 (7)

0.0156 (8)

0.0158 (8)

0.0143 (8)

0.0169 (8)

0.0151 (8)

0.0200 (8)

0.0158 (7)

0.0145 (7)

0.0177 (8)

0.0259 (9)

0.0203 (8)

0.0130 (7)

0.0128 (6)

0.0379 (8)

0.0127 (6)

0.02610 (11)

0.0104 (8)

0.0063 (6)

0.0068 (6)

0.0095 (7)

0.0104 (7)

0.0096 (7)

0.0092 (7)

0.0086 (7)

0.0052 (6)

0.0032 (6)

0.0046 (6)

0.0056 (6)

0.0054 (7)

0.0054 (6)

0.0065 (6)

0.0074 (6)

0.0058 (6)

0.0072 (6)

0.0092 (7)

0.0118 (7)

0.0102 (7)

0.0052 (6)

0.0073 (5)

0.0111 (7)

0.0084 (5)

0.00920 (8)

0.0004 (6)

0.0018 (6)

0.0042 (6)

0.0029 (6)

−0.0011 (6)

−0.0020 (6)

−0.0022 (6)

0.0019 (6)

−0.0012 (6)

0.0000 (6)

−0.0043 (7)

−0.0055 (6)

−0.0001 (6)

−0.0006 (6)

0.0001 (6)

0.0016 (6)

0.0026 (6)

0.0018 (6)

0.0004 (6)

0.0019 (6)

0.0008 (6)

0.0011 (5)

0.0108 (6)

−0.0024 (5)

−0.00645 (7)

0.0007 (6)

0.0004 (6)

0.0019 (6)

0.0025 (6)

0.0005 (6)

−0.0025 (6)

−0.0013 (6)

0.0001 (6)

−0.0027 (6)

−0.0016 (6)

−0.0023 (7)

−0.0015 (6)

−0.0029 (6)

−0.0031 (6)

−0.0020 (6)

0.0002 (6)

0.0016 (6)

−0.0040 (7)

−0.0015 (7)

0.0049 (7)

−0.0007 (6)

0.0008 (5)

0.0166 (7)

−0.0027 (5)

0.00505 (7)

C2

0.0112 (8)

0.0132 (8)

0.0113 (8)

0.0095 (8)

0.0119 (8)

0.0142 (8)

0.0149 (8)

0.0146 (8)

0.0183 (9)

0.0215 (9)

0.0131 (8)

0.0135 (8)

0.0158 (8)

0.0134 (8)

0.0131 (8)

0.0162 (9)

0.0179 (9)

0.0118 (8)

0.0156 (9)

0.0184 (9)

0.0103 (7)

0.0273 (8)

0.0203 (7)

0.02010 (11)

C3

C4

C5

C6

C7

C9

C10

C11

C12

C13

C14

C15

C16

C17

C18

C19

C20

C21

C22

N8

O3

O9

Br13

Geometric parameters (Å, º)

C1—N8

C1—C2

C1—C7

C1—H1

C2—C3

C2—C9

C2—H2

C3—O3

1.498 (2)

C11—C12

1.386 (3)

1.537 (2)

1.548 (2)

1.0000

C11—H11

C12—C13

C12—H12

C13—C14

C13—Br13

C14—C15

C14—H14

0.9500

1.388 (3)

0.9500

1.531 (2)

1.555 (2)

1.0000

1.390 (2)

1.8935 (18)

1.393 (2)

0.9500

1.210 (2)

Acta Cryst. (2013). C69, 303-306

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supplementary materials

C3—C4

1.514 (3)

1.532 (2)

0.9900

C15—H15

C16—N8

0.9500

C4—C5

1.491 (2)

1.503 (2)

0.9900

C4—H4A

C4—H4B

C5—N8

C16—C17

C16—H16A

C16—H16B

C17—C22

C17—C18

C18—C19

C18—H18

C19—C20

C19—H19

C20—C21

C20—H20

C21—C22

C21—H21

C22—H22

O9—H9O

0.9900

1.485 (2)

1.539 (2)

1.0000

0.9900

C5—C6

1.395 (2)

1.399 (2)

1.384 (3)

0.9500

C5—H5

C6—C7

1.548 (2)

0.9900

C6—H6A

C6—H6B

C7—H7A

C7—H7B

C9—O9

0.9900

1.394 (3)

0.9500

0.9900

1.389 (3)

0.9500

1.426 (2)

1.517 (2)

1.0000

C9—C10

C9—H9C

C10—C15

C10—C11

1.391 (3)

0.9500

1.395 (2)

1.399 (2)

0.9500

0.8400

N8—C1—C2

N8—C1—C7

C2—C1—C7

N8—C1—H1

C2—C1—H1

C7—C1—H1

C3—C2—C1

C3—C2—C9

C1—C2—C9

C3—C2—H2

C1—C2—H2

C9—C2—H2

O3—C3—C4

O3—C3—C2

C4—C3—C2

C3—C4—C5

C3—C4—H4A

C5—C4—H4A

C3—C4—H4B

C5—C4—H4B

H4A—C4—H4B

N8—C5—C4

N8—C5—C6

C4—C5—C6

N8—C5—H5

C4—C5—H5

C6—C5—H5

C5—C6—C7

C5—C6—H6A

C7—C6—H6A

C5—C6—H6B

107.26 (12)

106.04 (13)

111.59 (13)

110.6

C15—C10—C9

C11—C10—C9

C12—C11—C10

C12—C11—H11

C10—C11—H11

C13—C12—C11

C13—C12—H12

C11—C12—H12

C12—C13—C14

C12—C13—Br13

C14—C13—Br13

C13—C14—C15

C13—C14—H14

C15—C14—H14

C14—C15—C10

C14—C15—H15

C10—C15—H15

N8—C16—C17

N8—C16—H16A

C17—C16—H16A

N8—C16—H16B

C17—C16—H16B

122.51 (15)

119.10 (15)

121.46 (16)

119.3

110.6

119.3

110.6

118.93 (16)

120.5

111.76 (14)

107.23 (13)

113.83 (13)

107.9

120.5

121.06 (16)

119.78 (13)

119.12 (14)

119.21 (16)

120.4

107.9

120.59 (16)

120.29 (17)

118.98 (15)

115.22 (14)

108.5

120.4

120.95 (16)

119.5

108.5

111.44 (14)

109.3

108.5

109.3

107.5

109.3

107.49 (14)

105.39 (13)

111.83 (14)

110.7

109.3

H16A—C16—H16B

C22—C17—C18

C22—C17—C16

C18—C17—C16

C19—C18—C17

C19—C18—H18

C17—C18—H18

C18—C19—C20

C18—C19—H19

108.0

118.45 (16)

121.52 (15)

120.02 (15)

121.02 (16)

119.5

110.7

103.59 (13)

111.0

119.5

111.0

119.81 (16)

120.1

111.0

Acta Cryst. (2013). C69, 303-306

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supplementary materials

C7—C6—H6B

H6A—C6—H6B

C1—C7—C6

111.0

C20—C19—H19

C21—C20—C19

C21—C20—H20

C19—C20—H20

C20—C21—C22

C20—C21—H21

C22—C21—H21

C21—C22—C17

C21—C22—H22

C17—C22—H22

C5—N8—C16

120.1

109.0

119.95 (16)

120.0

104.57 (13)

110.8

C1—C7—H7A

C6—C7—H7A

C1—C7—H7B

C6—C7—H7B

H7A—C7—H7B

O9—C9—C10

O9—C9—C2

120.0

110.8

119.88 (16)

120.1

110.8

120.1

108.9

120.88 (16)

119.6

112.70 (14)

110.56 (13)

112.19 (13)

107.0

119.6

C10—C9—C2

O9—C9—H9C

C10—C9—H9C

C2—C9—H9C

C15—C10—C11

110.92 (13)

101.24 (12)

111.80 (13)

109.5

C5—N8—C1

107.0

C16—N8—C1

107.0

C9—O9—H9O

118.38 (16)

(II) (+)-exo,anti-(1R,2S,5S)-8-Benzyl- 2-[(R)-(4-bromophenyl)(hydroxy)methyl]-8-azabicyclo[3.2.1]octan-3-one

Crystal data

C₂₁H₂₂BrNO₂

M_r= 400.31

F(000) = 824

D_x= 1.453 Mg m⁻³

Mo Kα radiation, λ = 0.71073 Å

Cell parameters from 28586 reflections

θ = 2.8–31.7°

Orthorhombic, P2₁2₁2₁

Hall symbol: P 2ac 2ab

a = 5.96905 (4) Å

b = 14.76590 (9) Å

c = 20.76083 (13) Å

V = 1829.83 (2) Å³

Z = 4

µ = 2.26 mm⁻¹

T = 100 K

Needle, colourless

0.52 × 0.11 × 0.09 mm

Data collection

Agilent SuperNova Dual

T_min= 0.308, T_max= 0.816

diffractometer (Cu at zero) with Atlas detector

Radiation source: SuperNova (Mo) X-ray

Source

Mirror monochromator

Detector resolution: 10.4052 pixels mm^-1

ω scans

67899 measured reflections

5359 independent reflections

5007 reflections with I > 2σ(I)

R_int= 0.064

θ_max= 30.0°, θ_min= 2.8°

h = −8→8

k = 0→20

l = 0→29

Absorption correction: analytical

(CrysAlis PRO; Agilent, 2011)

Refinement

Refinement on F²

Least-squares matrix: full

R[F²> 2σ(F²)] = 0.033

wR(F²) = 0.080

S = 1.04

5359 reflections

Hydrogen site location: inferred from

neighbouring sites

H atoms treated by a mixture of independent

and constrained refinement

w = 1/[σ²(F_o²) + (0.0364P)²+ 1.3126P]

where P = (F_o²+ 2F_c²)/3

230 parameters

0 restraints

Primary atom site location: structure-invariant

direct methods

Secondary atom site location: difference Fourier

map

(Δ/σ)_max= 0.002

Δρ_max= 0.64 e Å⁻³

Δρ_min= −0.48 e Å⁻³

Absolute structure: Flack (1983), with 2292

Friedel pairs

Flack parameter: −0.011 (7)

Acta Cryst. (2013). C69, 303-306

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