Phase transfer of enantiopure werner cations into organic solvents: An overlooked family of chiral hydrogen bond donors for enantioselective catalysis

Article abstract of DOI:10.1002/chem.200800226

A study was conducted to investigate phase transfer of ennantiopure Werner cations into organic salts and their use as donors for chiral hydrogen enantioselective catalysis for organic reactions. The study involved developing an extensive aqueous chemistry of these salts and analogues with other diamines. An aqueous solution of a salt derived from racemic trans-1,2-cyclohexanediamine was treated with with a CH₂Cl₂ solution of NaBAr _f. It was observed that the aqueous phase decolorized, while an identical reaction gave an identical (Co(rac-chnx)₃)(BAr _f)₃ in 89% yield as a nonhydrate.

Full text of DOI:10.1002/chem.200800226

COMMUNICATION
DOI: 10.1002/chem.200800226
Phase Transfer of Enantiopure Werner Cations into Organic Solvents:
An Overlooked Family of Chiral Hydrogen Bond Donors for
Enantioselective Catalysis
[
a]
[a, b]
Carola Ganzmann and John A. Gladysz*
Werner salts of the chiral tris(ethylenediamine)-substitut-
A literature survey revealed scant data, the most relevant
3
+
ed octahedral cation [Co(en)3] , and related complexes,
have played important historical roles in the development of
of which involved the tetraphenylborate salt [Co(en) ]-
3
[6,7]
A
H
R
U
G
This complex, or the hexakis
A
H
R
U
G
4
3
[
1–3]
inorganic chemistry and stereochemistry.
As originally
logue, was reported as soluble in methanol, acetone, THF,
[2b]
[6b,c,7a]
described in 1912, the two enantiomers (I, II) can be sep-
and methanol/CH Cl 1:9.
Many salts with more lipo-
2
2
philic diamine ligands—such as trans-1,2-cyclohexanedia-
[5]
mine—have been described. However, these have largely
featured small inorganic anions, and we have not been able
to locate any mention of solubility in organic solvents out-
[8]
side of an occasional reference to a light alcohol. Accord-
ingly, we set out to study chiral Werner salts with highly lip-
ophilic anions, and communicate herein our initial results
with the tetrakis[(3,5-trifluoromethyl)phenyl]borate or
À
[9]
BArf anion.
As shown in Scheme 1, an orange aqueous solution of D-
[
10]
arated by recrystallization of the diastereomeric tartrate
salts. Chloride anion exchange then affords resolved enan-
tiomers of [Co(en) ]Cl . An extensive aqueous chemistry of
(À)-[Co(en) ]I ·H O
and a colorless CH Cl solution of
2 2
3
3
2
[9b]
NaBAr (1:3 mol ratio) were combined and stirred. As il-
lustrated in the photographs, the lower CH Cl phase turned
f
3
3
2
2
these salts, and analogues with other diamines, was subse-
orange, and the upper aqueous phase was nearly decolor-
ized. The solvent was removed from the former to give the
[4,5]
quently developed.
However, despite the ready availabili-
ty and low cost of these enantiopure building blocks, there
have been no applications in enantioselective organic syn-
theses. Towards this end, we posed the initial question as to
whether such Werner salts can be rendered soluble in organ-
ic solvents.
anion exchange product D-(À)-[Co(en) ]
A
T
E
N
orange powder in 87% yield, which was characterized by
1
13
[11]
NMR ( H, C), IR, and UV-visible spectroscopy.
Both
1
H NMR spectra and elemental analyses showed the product
to be a hydrate, for which fourteen water molecules best fit
the data (calcd for C102H B CoF N O (3081.07): C 39.76,
88
3
72
6
14
H 2.88, N 2.73; found C 39.87, H 2.77, N 2.66). The hydra-
tion level was reproducible, and presumably reflects a labile
second-coordination-sphere hydrogen bonding network,
which was viewed as an auspicious sign for catalysis
[
a] Dipl.-Chem. C. Ganzmann, Prof. Dr. J. A. Gladysz
Institut für Organische Chemie and
Interdisciplinary Center for Molecular Materials
Friedrich-Alexander-Universität
Erlangen-Nürnberg, Henkestrasse 42, 91054 Erlangen (Germany)
Fax : (+49)9131-8526865
E-mail: gladysz@chemie.uni-erlangen.de
(
below). Thermogravimetric analyses showed several mass
[12]
loss regimes, the first two with T/T values of 37.1/95.78C
i e
[
b] Prof. Dr. J. A. Gladysz
(3.4%, or 5.8H O) and 95.8/155.78C (13.3% cumulative
2
New permanent address:
loss), respectively.
Department of Chemistry, Texas A&M University
PO Box 30012, College Station, TX 77842-3012 (USA)
Fax : (+1)979-8455629
25
The [a]5 value for D-(À)-[Co(en) ]
A
H
R
U
G
89
much smaller than that of the corresponding iodide salt D-
(
(
À)-[Co(en) ]I ·H O (À9Æ18 (CH Cl ) versus À908
E-mail: gladysz@mail.chem.tamu.edu
3
3
2
2
2
[10] [13]
H O) ). As analyzed elsewhere, this is an expected con-
Supporting information for this article is available on the WWW
under http://www.chemistry.org or from the author.
2
sequence of the much heavier anion. For idealized salts
Chem. Eur. J. 2008, 14, 5397 – 5400
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5397

[
5a]
brated (H O, 1008C).
Inter-
2
estingly, the product exhibited
1
3
three chxn C NMR signals,
suggestive of a single diastereo-
mer. Of the two diastereomers
that would give only three sig-
nals, lel and ob , the former is
3
3
À1
much more stable (8.20 kJmol
or 1.96 kcalmol ).
À1 [16]
An analogous reaction was
conducted with a salt derived
from enantiopure R,R-chxn,
[5a]
[Co
A
H
R
N
(R,R-chxn) ]Cl ·4H O,
a
3
3
2
system for which only two dia-
stereomers (D-lel3 and L-ob3)
are possible. Workup gave [Co-
A
H
R
U
G
A
H
R
U
[17]
hydrate in 78% yield.
Since
only a single set of three chxn
1
3
C NMR signals was observed,
the product was tentatively as-
signed as the more stable D-lel3
diastereomer. Both [Co
A
C
H
T
R
E
U
N
G
(rac-
ACHTREUNG
(BAr ) ·9H O and [Co-
Scheme 1. Synthesis of D-(À)-[Co(en)
3
]
A
H
R
U
G
f
)
3
·14H
2
O.
chxn)3]
f
3
2
A
H
R
U
G
A
H
R
U
hibited solubility profiles very
composed of non-interacting cations and anions, a value of
similar to that of D-(À)-[Co(en) ]
A
T
E
N
3
À198 would be predicted. Besides CH Cl , D-(À)-[Co(en) ]-
can be confidently extrapolated that all trications of the
2
2
3
3
+
A
C
H
T
R
E
U
N
G
(BAr ) ·14H O was soluble in acetone, ethyl acetate, THF,
type [Co(1,2-diamine)3]
media.
can be solubilized in organic
f
3
2
DMSO, and alcohols. It was sparingly soluble in ether, and
insoluble in CHCl , toluene, and benzene.
There is currently much interest in chiral hydrogen bond
donors as enantioselective catalysts for organic reactions.
3
[18]
To confirm generality, the preceding protocol was applied
to two trans-1,2-cyclohexanediamine (chxn) complexes, as
depicted in Scheme 2. First, an aqueous solution of a salt de-
A variety of literature data suggests that many amine-substi-
tuted Werner cations are exceptional donors. For example,
hydrogen bonds between the anions and NH protons are
present in all of the numerous crystal structures of [Co(1,2-
diamine) ]X and similar species we have examined. In the
rived from racemic trans-1,2-cyclohexanediamine, [Co
ACHTREUNG
[14]
3
3
2
2
2
tion of NaBAr . The aqueous phase decolorized, and an
f
3
3
identical workup gave [Co
A
H
R
U
G
A
H
R
U
G
case of chiral anions, many chiral recognition phenomena
3
f 3
1
as a nonahydrate, as assayed by H NMR and microanaly-
have been documented. For example, diastereomeric salts
[
15]
3+
sis. Eight stereoisomers are possible (four diastereomers
and their enantiomers), which for the starting salt have been
independently isolated, characterized, and thermally equili-
derived from D-lel -[Co
A
H
R
U
G
or L-lel -[Co(S,S-
A
C
H
T
R
E
U
N
G
3
3
3
3
+
chxn)3] and the tartrate dianion have been crystallographi-
cally characterized, and exhibit multidentate hydrogen
[19]
bonding motifs.
The relative
strengths of these interactions
have been estimated computa-
tionally, and are weaker in the
more soluble diastereomer.
Similar structural studies have
been conducted with diastereo-
meric tartrate salts of the enan-
[20]
tiomeric cations I and II, per
Wernerꢁs original resolution.
Thus, we sought to conclude
this study with a brief proof of
principle. Recently, a variety of
chiral thioureas have been
found to be effective enantiose-
Scheme 2. Syntheses of trans-1,2-cyclohexanediamine complexes.
5398
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Chem. Eur. J. 2008, 14, 5397 – 5400

Enantioselective Catalysis
COMMUNICATION
[
[
1] G. B. Kauffman, Coord. Chem. Rev. 1974, 12, 105–149.
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3
+
Ber. 1911, 44, 1887–1898; b) for the first enantiopure [Co(en)
species, see A. Werner, Chem. Ber. 1912, 45, 121–130.
3
]
[
3] For treatments of the stereoisomers possible with chiral (rac) and
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symmetry; Springer, Berlin, 1979, Chapter IV; b) R. E. Tapscott,
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[
[
4] Y. Yoshikawa, K. Yamasaki, Coord. Chem. Rev. 1979, 28, 205–229.
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B. S. Sørensen, I. Creaser, H. Maegaard, U. Pfenninger, C. E. Schäff-
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1
1
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23–224; b) N. Nakayama, A. Miura, T. Komamura, Japanese
4
8
[
2
Scheme 3. Enantioselective catalysis of a Michael addition by a Werner
complex.
Patent 7234475, 1995 [Chem. Abstr. 1995, 124, 131660].
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[
[
lective catalysts for Michael additions, activating the accept-
[21,22]
or via hydrogen bonding.
As shown in Scheme 3, the
Michael addition of dimethyl malonate to 2-cyclopenten-1-
3
581.
one was attempted in the presence of 9 mol% of D-(À)-
[
10] J. A. Broomhead, F. P. Dwyer, J. W. Hogarth, Inorg. Synth. 1960, 6,
[
Co(en) ]
A
C
H
T
R
E
U
N
G
(BAr ) ·14H O in CH Cl at À408C, using a stoi-
183–186.
3
f
3
2
2
2
2
5
1
chiometric amount of NEt . Column chromatography gave
[11] [a]
D
=À9Æ1 (c=1.05 in CH
at d=7.72 (s, 24H; o), 7.58 (s, 12H; p); 4.69 (br s, 12H; NH
.98 (brs, 6H; CHH’), 2.76 (s, 30H; 15H
2
Cl
2
); H NMR (400 MHz, CD
2
Cl
2
2
):
),
3
BAr
2
f
the addition product III in 78% yield. As described in the
2
O), 2.66 ppm (s, 6H;
Supporting Information, analysis of the corresponding ethyl-
13
1
CHH’); C NMR (100.6 MHz, CD
2
Cl
2
): BAr
f
at d=161.8 (q, J-
[23]
ene glycol ketal by chiral HPLC indicated a 33% ee.
2
ACHTREUNG
A
T
E
N
J
(C,F)=30.1Hz; CCF ),
3
1
When an aqueous solution of the reaction residue was treat-
124.7 (q,
J
A
H
R
U
G
3
2
IR (thin film): n=3246 (NH
2
), 1613 (NH
2
), 1355, 1274, 1116, 891,
ed with a CH Cl2 solution of NaBAr , D-(À)-[Co(en) ]-
2
f
3
À1
8
37 cm ; UV/Vis (EtOH): lmax (e)=463 (170), 334 (255), 278
A
C
H
T
R
E
U
N
G
(BAr ) ·14H O was recovered in high yield (81% after re-
f 3 2
À1
3
À1
(
10702), 269 (13532 mol dm cm ).
crystallization (analytically pure), or 98% with minor
amounts of NEt /educts/III) and reused with similar results.
[
12] H. K. Cammenga, M. Epple, Angew. Chem. 1995, 107, 1284–1301;
Angew. Chem. Int. Ed. Engl. 1995, 34, 1171–1187.
3
Since cobalt
A
C
H
T
R
E
U
N
G
(III) Werner cations are substitution inert,
[13] M. A. Dewey, J. A. Gladysz, Organometallics 1993, 12, 2390–2392.
[
14] M. McCann, S. Townsend, M. Devereux, V. McKee, B. Walker, Poly-
asymmetric induction must take place via a second-coordi-
nation-sphere mechanism, possibly with the participation of
hydrogen-bonded water molecules. Although our ee value is
lower than those obtained with the best thiourea catalysts,
the latter normally incorporate a nitrogen base, such that
the more highly organized transition state assemblies IV
hedron 2001, 20, 2799–2806.
1
[
15] H NMR (400 MHz, CD
2
Cl
2H; p); 4.71(brs, 6H; N HH’), 4.09 (brs, 6H; NHH’), 2.90 (s, 21H;
10.5 H O), chxn at 2.23 (m, 12H), 1.74 (m, 6H), 1.44 (m, 6H),
2 f
): BAr at d=7.72 (s, 24H; o), 7.58 (s,
1
2
1
3
1.10 ppm (m, 6H); C NMR (100.6 MHz, CD
(
CCF
(
(
2
Cl
2
): BAr
J
f
at d=161.8
(C,F)=31.3 Hz;
3
J(C,F)=272.3 Hz; CF ), 117.6 (s; p); chxn at 61.5
1
2
ACHTREUNG
q,
J
A
H
R
U
G
1
[21]
3
), 124.7 (q,
s; NCH), 33.1(s; CH
NH
A
H
R
U
G
(
Scheme 3) are possible.
Accordingly, efforts to prepare
2
), 23.3 ppm (s; CH
2
); IR (thin film): n=1611
functionalized Werner complexes that feature this and other
design elements are in progress and will be reported in due
À1
2
), 1355, 1273, 1121, 889, 837 cm ; elemental analysis calcd (%)
for C114H B CoF N O : C 43.42, H 3.07, N 2.67; found: C 43.42, H
96
3
72
6
9
[24]
course.
2.97, N 2.78.
1
3
[
[
16] To our knowledge, no C NMR spectra of any salts of the formula
[
Co(trans-chxn)
3 3
]X have ever been reported. However, the stereo-
isomers of analogous rac and meso-2,3-butanediamine complexes
Acknowledgements
13
[3c]
exhibit distinctive C NMR spectra.
nomenclature refers to the orientation of the H
versus the three-fold axis of the CoN core (parallel or oblique).
The well-established lel/ob
NCÀCNH
bonds
2
2
We thank the Deutsche Forschungsgemeinschaft (DFG, GL 300/8-1; SPP
179) for support.
6
1
Reference structures with alternative R/S designations are provided
in the Supporting Information.
1
17] H NMR (400 MHz, CD
2
Cl
2 f
): BAr at d=7.72 (s, 24H; o), 7.57 (s,
Keywords: enantioselective catalysis · hydrogen bonds ·
Michael addition · phase-transfer catalysis · Werner complex
1
2H; p); 4.64 (brs, 6H; NHH’), 4.09 (brs, 6H; NHH’), 2.81(s, 23H;
2
11.5 H O), chxn at 2.23 (m, 12H), 1.74 (m, 6H), 1.44 (m, 6H),
Chem. Eur. J. 2008, 14, 5397 – 5400
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www.chemeurj.org
5399

J. A. Gladysz and C. Ganzmann
1
3
1
.10 ppm (m, 6H); C NMR (100.6 MHz, CD
2
Cl
2
): BAr
J
f
at d=161.8
(C,F)=30.1Hz;
), 117.6 (s; p); chxn at 61.6
), 23.3 ppm (s; CH ); IR (thin film): n=1611
), 1355, 1272, 1119, 889, 837 cm ; elemental analysis calcd (%)
10: C 43.18, H 3.11, N 2.65; found: C 43.27, H
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1
2
ACHTREUNG
(q,
J
A
C
H
T
R
E
U
N
G
(C,B)=50.0 Hz; i), 134.9 (s; o), 128.9 (q,
1
CCF
(
(
for C114
2
3
), 124.7 (q,
J(C,F)=272.5 Hz; CF
3
A
C
H
T
R
E
U
N
G
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NH
2
2
À1
2
98 3 6
H B CoF72N O
.72, N 2.63.
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[
[
1
[23] Other chiral metal complexes that catalyze enantioselective Michael
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II
volving a Co complex of a chiral 1,2-diamine and the other a hy-
1
990, 29, 3020–3026; b) T. Mizuta, K. Sasaki, H. Yamane, K.
2
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Received: February 5, 2008
Published online: April 30, 2008
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