Stereochemistry of Molecules in Crystals (part 1, 2)

Stereochemistry of Molecules in
Crystals (part 1, 2)
Fumio Toda
Okayama University of Science, Okayama, Japan
key word: solid state, host-guest complex
part 1: statistic aspect
part 2: dynamic aspect

host:
OH
Ph
OH
X
a: X = H
b: X = Cl (chiral)
X
Ph
OH
OH
Ph 2 C
CPh 2
OH
OH
rac, chiral
OH
OH
Ph 2 C
OH
R 2
O H
O H
Ph 2 C OH
rac, chiral
HOOC
COOH Ph Ph Br
COOH
O
Ph
rac, chiral
H-G complexation:
H/liq. G, H/gas G, H+G/solvent, H+G grinding

1) acetylacetone-enol form
part 1: statistic aspect
(I) stereoisomers in inclusion crystals
O
O
O
H
O
O
H
O
1
2
3
O
H
O
1.291
O
H
O
1.28-1.29
·
OH
OH
1.402
1.38-1.39
110 K, Bose 1998
Weber 1995
O
1.258
H
O
1.284
H
O O
1.263 1.323
H
O O
1.258 1.321
1.398 1.361
1.419 1.365
1.415 1.357
OH
Ph 2 C
OH
· H 2 O
(R, R)-(-)-
Me 2
O
O
H
H
OH
Ph 2 C
OH
CrystEngComm. 2003. 114-116.

O
1.258
H
O
1.284
H
O O
1.263 1.323
H
O O
1.258 1.321
1.398 1.361
OH
· H 2 O
1.419 1.365
O
(R, R)-(-)- Me 2
O
1.415 1
.
3
Ph 2 C OH
5
H
7
H
OH
Ph 2 C
OH
Fig. X-ray structures of inclusion complexes of acetylacetone.

2) acylic acid-monomeric s-trans form
H
H
O
H
O
O
O
H
Ph 2 C
OH
CPh 2
OH
s-trans
s-cis
host
Chem. Comm. 1998, 2502.

H
O
H
O
Ph 2 C
OH
CPh 2
OH
s-trans
host
(a)
(b)
1.20 Å
1.41 Å
1.38 Å
HO O
1.26 Å
46.5 º
HO
Fig. 3 X-Ray analytical data: (a) stereoview of the complex and (b) bond
lengths and dihedral angle for s-trans-acrylic acid in the complex.

H
O
H
O
OH
Ph 2 C
CPh 2
OH
s-trans
host
(a)
Host
O H
(b)
OH
OH
Host
H
O
HO
O
O
OH
O
H
Host
HO
O
O
OH
H
Host
O
O
HO
O
H
O
HO
O
Host
O
OH
O
H
Host
HO
O
O
O
OH
O
OH
Fig. 4 Schematic drawing: (a) a circle of three s-trans-acrylic acid molecules in
the complex and (b) a circle of three s-cis-acrylic acid molecules, both involving
disorder.

3) β-ionone
O
OH
O
hν
s-cis
retinal chromophore in rhodopsin
s-trans
host
OH
OH
O
HO
OH
s-trans
HO
Fig. X-ray structure of the 2:1 complex.

Ph 2 C
OH
(R, R)-(-)-
O
O
H
H
·
O
Ph 2 C
OH
s-cis
α-ionone
O
· O
H
H
ax-quasi-chair
eq-quasi-chair
Angew. Chem. Int. Ed. Engl. 1990, 662.
Pure Appl. Chem. 1990, 417.
Bio. Org. Chem. 1991, 157.

4) 1,2-dichloroethane
Ph
Ph
Br
Ph
O
(S)-(-)-2
H
Cl
H
Cl
H
Cl
Cl
H
yes
no
H
H
Cl
Cl
1a
trans
H
H
θ = 36 º
Cl
Cl
H
H H
H
(M)-1b
eclipsed
Cl···Cl
3.205 Å
(3.50 Å)
C=O ··· Cl
Fig. X-ray of a complex of (M)-1b.
Chem. Comm. 1997, 1227.

H
H
θ = 5(4) º
Cl
CH 3
H
H

5) halocyclohexane –- di-eq
eq
Cl
Cl
Cl
ax
Cl
Ph 2 C
OH
O H
(R, R)-(-)-
·
(-)- Cl
O
Cl
H
eq
Ph 2 C OH 90% ee
Supramol. Chem. 2001, 175.

5) halocyclohexane – eq
X
X
eq
ax
a: X = Cl; b: X = Br
F
F
rac -
O
O
OH
OH
·
eq
Cl
F
host
F

Cl
eq- C __ Cl streching ax- C __ Cl streching
732 685
F
F
rac -
O
O
OH
OH
F
host
F
inclusion compound
790 770 750 730 710 690 670
wavenumber (cm -1 )
Fig. IR spectra with using ATR (attenuated total reflection).

F
F
Cl
F
F
Fig. X-ray structure of the inclusion complex of eq-chlorocyclohexane.

F
F
rac -
O
O
OH
OH
·
eq
Br
F
host
F

F
F
rac -
O
O
OH
OH
·
eq
Br
F
host
F
bromocyclohexane
host
eq- C __ Br streching ax- C __ Br streching
687 659
F
F
Br
F
inclusion compound
790 770 750 730 710 690 670
wavenumber (cm -1 )
Fig. IR spectra with using ATR
(attenuated total reflection).
Chem. Comm. 2004, 2354.
F
Fig. X-ray structure.

5) halocyclohexane – ax
Cl
·
ax
host
Fig. X-ray structure of the complex.

·
ax
Cl
host
Fig. Packing diagram of ax-chlorocyclohexane complex which indicates the closest contacts.

·
ax
Cl
host
Fig. X-ray structure of normal and disordered ax-bromocyclohexane in the complex.

Cl
1,3-diaxial interaction (hydrogen
bond?)
2.905 Å
2.908 Å
Cl
H Cl
2.904 Å
2.881 Å
H
H
disordered
normal
Cl
2.939 Å
2.941 Å
H
H
Cl
van der Walls radius; H, 1.20 Å, Cl , 1.75 Å
A schematic structure of ax-chlorocyclohexane

Br
·
ax
host
Br
host
659
inclusion compound
687
790 770 750 730 710 690
wavenumber (cm -1 )
670
Fig. IR spectra with using the ATR.

·
ax
Cl
I (cps)
host
2 θ
·
ax
Br
host
I (cps)
2 θ
Fig . X-ray powder diffraction pattern
Chem. Comm. 2005, 3646.

6) cyclooctatrienone
O
O
11.9 kcal / mol
O
hν
hexane
21 days
solution
rac-
31%
Ph
OH
Cl
Cl
Ph
OH
·
2
O
hν
7 days
solid
(S, S)-(-)-
O
(-)-
56%
ee, not determined
7) cyclooctadienone
O
O
cycloctadienone
Ph
Cl
Cl
Ph
OH
OH
O
hν
pentane
rac-
O
1 h
solution
·
(S, S)-(-)-
O hν
(-)-
48 h
solid
Tetrahedron Lett. 1988, 653, J. Org. Chem. 1990, 4532.
O
10%
O
78% ee
55%

8) enantiomerization
Ph
tBu
C
OH
N
brucine
MeOH
Ph
tBu
O
+ HCN
MeOH
(+)-
(-)-
tBu
Ph
C
OH
N
MeO
MeO
N
N
OH
N
dil. HCl
tBu
·
(+)- Ph C
(+)-
Ph
tBu
C
OH
N
O
brucine
O
100% ee
100% yield
Chem. Lett. 1983, 661.

(II) stereoisomers in own crystals
1) neighboring group effect
HO O R
N
· HBr· Br 2 HO O R
H
Br
solid
HO O R
Br
H
H
Br
R = H, Me, Cl
H
Br H
solution
H
O
R
Acta Cryst. C53 1997, 620.

2) photochromism
O
Ph
Zn-ZnCl 2
O
Ph
Ph
H
Ph
O
THF-H 2 O
H
O
chiral
yellow
dark
hν
O
O
O
Ph
Ph
H
Ph
H
yellow
solution
Chem. Comm. 2000, 873.
Ph
H
O
H
triplet biradical
D = 13.78 G
E = 1.377 G
g xx = 2.0026
purple red

3) oxoamide, generation of chirality (i)
Me
Pr i
Me
N
OH
Ph
O
hν
Me
Pr i
N
O
Me
Ph
O
Me
Ph
O
O
N
Me
Pr i
hν
HO
Ph
O
Me
Me
N
Pr i
(+) in (+)-crystal in (-)-crystal
(-)
mirror
93% ee 93% ee
Chem. Comm. 1987, 1413
J. Am. Chem. Soc. 1989, 697.

4) succinamide, generation of chilality (ii)
Br
Ph 2 C O
O
Ph
Br 2 C C
2 MeNH 2
Ph 2 C O
Ph 2 C C
O
Br
Br
Ph 2 C
H
H
Ph 2 C
Br
O
O
N
Me
- 2 HBr
Ph 2 C
Ph 2 C
O
O
N
Me
Ph
O
Ph
O
N
Me
N
Me
Ph
(+)
O
Ph
(-)
O
hν
hν
Ph
O
Ph
O
N
Me
N
Me
H Ph
Ph
O
H Ph
Ph
O
(+)
(-)
Ph
O
Ph
O
Ph
H
Ph
(+)
O
N
Me
63% ee
Ph
H
Ph
(-)
O
N
Me
Supramol. Chem. 1994, 87.
Acta Cryst. B51 1995, 856.

Ph 2 C
Ph 2 C
O
O
N
Me
A
chiral
orange hexagonals
mp 260 ºC
B
rac
orange plates
302 ºC
C
rac
yellow plates
297 ºC
P2 1 Pbcn P2 1 /n