Modular ligands for asymmetric synthesis: Enantioselective catalytic CuII-mediated condensation reaction of ethyl pyruvate with Danishefsky's diene

Article abstract of DOI:10.1002/1521-3773(20020215)41:4<625::AID-ANIE625>3.0.CO;2-U

Only the correct order of addition of the components is required to prepare a variety of chiral Lewis acids. The complexes (for example, 4) formed by the condensation of chiral, nonracemic 1,2-diamines with ketones and subsequent addition of Cu(OTf)₂

Full text of DOI:10.1002/1521-3773(20020215)41:4<625::AID-ANIE625>3.0.CO;2-U

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[16] W. F. Marshall, E. U. Franck, J. Phys. Chem. Ref. Data 1981, 10, 295.
[17] An alternative but less likely mechanism is the direct attack of a water
molecule on the ester. Correlation of k1 with k1' and the concentration
of water suggests that about four molecules of water participate in the
transition state (k1 ˆ k1'[H2O]3.7).
in the reactants, the polar media must stabilize the reactants
more efficiently than the TS. Consequently, the hydrolysis
rate decreases with increasing water density.
In summary, we have demonstrated that the hydrolysis of
esters takes place exclusively by ionic mechanisms, whereby
hydroxide ions dissociated from SCW catalyze the reaction.
This mechanism is dominant in the initial stage of the
reaction, since the concentration of the generated carboxylic
acid is low. As the concentration of carboxylic acid increases
with the progress of the reaction, the mechanism would
change to the proton-catalyzed reaction if the concentration
of substrates were sufficiently high.[9] Our results clearly
indicate that one must consider the involvement of hydroxide
ions in other reactions in SCW, because dissociation of water
produces the same amount of protons and hydroxide ions.
[18] Addition of sodium hydroxide (4.8 Â 10À7 molLÀ1) enhanced the rate
of hydrolysis by a factor of about 2.5. However, the lack of data on the
dissociation constant of sodium hydroxide in SCW and the difficulties
in obtaining an accurate value of k3 prevented our making detailed
kinetic analyses.
[19] Because of the low solubility of 1 in water, we could not directly
compare the concentration effects.
[20] E. K. Euranto in The Chemistry of Carboxylic Acids and Esters (Ed.:
S. Patai), Interscience Publishers, London, 1969, pp. 505 588.
[21] J. W. Moore, R. G. Pearson, Kinetics and Mechanism, 3rd ed., Wiley,
New York, 1981.
Received: September 6, 2001 [Z17863]
[1] a) O. Kajimoto, Chem. Rev. 1999, 99, 355; b) P. E. Savage, Chem. Rev.
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[2] a) Green Chemistry. Frontiers in Benign Chemical Syntheses and
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Chem. 2001, 113, 216; Angew. Chem. Int. Ed. 2001, 40, 210; b) the
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287.
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c) M. Watanabe, H. Hirakoso, S. Sawamoto, T. Adshiri, M. Arai, J.
Supercrit. Fluids 1998, 13, 247; d) Y. Suzuki, H. Tagaya, T. Asou, J.
Kadokawa, K. Chiba, Ind. Eng. Chem. Res. 1999, 38, 1391; e) C.
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[8] S. D. Iyer, M. T. Klein, J. Supercrit. Fluids 1997, 10, 191. It is worth
mentioning that both carboxylic acid and ammonia generated by the
hydrolysis are suggested as possible catalysts.
Modular Ligands for Asymmetric Synthesis:
Enantioselective Catalytic CuII-Mediated
Condensation Reaction of Ethyl Pyruvate with
Danishefsky×s Diene**
Peter I. Dalko,* Lionel Moisan, and Janine Cossy*
The search for new catalysts for asymmetric synthesis is an
area of significant importance in modern organic synthesis,
and a number of spectacular advances have been reported in
recent years.[1, 2] However, there is still a need for simple and
À
readily available catalysts, particularly for C C bond-forming
processes.[3] A modular system that allows quick access to a
great diversity of ligands from simple components is valuable.
Peptide-based ligands have been developed for Ti-catalyzed
additions of TMSCN to meso epoxides[4] and imines (Strecker
amino acid synthesis),[5] and Zr-catalyzed addition of dialkyl-
zincs to imines.[6] Recently, peptide-based phosphane ligands
have been shown to promote efficient Cu-catalyzed conjugate
addition.[7] Moreover, this class of ligands allows the regio-
and enantioselective formation of quaternary carbon centers
by using allylic reagents.[8] We report herein a simple and
efficient approach that leads to the generation of a great
diversity of asymmetric ligands from easily available compo-
nents.[9]
[9] P. Krammer, H. Vogel, J. Supercrit. Fluids 2000, 16, 189.
[10] T. Xiang, K. P. Johnston, J. Solution Chem. 1997, 26, 13.
[11] The observed decrease in the hydrolysis rate near the critical point
may also be attributed to the decrease in the ionic product of water
near the critical point. Similar results have been reported for the
hydrolysis of ethers: J. D. Taylor, J. I. Steinfeld, J. W. Tester, Ind. Eng.
Chem. Res. 2001, 40, 67.
[12] N. J. Turro, I. R. Gould, B. H. Baretz, J. Phys. Chem. 1983, 87, 531.
[13] Cylindrical stainless steel (SUS316) or quartz tubes were used as
reaction vessel. Similar results were obtained regardless of the vessel.
[14] The reaction also afforded benzaldehyde and acetophenone in 2 4%
yield. Ethylbenzene was unstable under the reaction conditions and
decomposed into various uncharacterized compounds. Stabilities of
alkyl-substituted benzenes have been already studied: J. Yu, S. Eser,
Ind. Eng. Chem. Res. 1998, 37, 4591.
The catalyst preparation is based on the condensation of
1,2-diamines[10] of type 1 with ketones or aldehydes 2
(Scheme 1), which affords imidazolidines 3 in solution in
equilibrium with the open form 4. The corresponding bis-
imine 5 and the starting diamine 1 are often present with
compounds 3 and 4 in the reaction mixture.[11] We anticipated
that chelating metals such as CuII would shift this equilibrium
toward the metallacyclic form 6 by forming a bidentate
complex (Scheme 1).[12] Although no precedent for the use of
[*] Dr. P. I. Dalko, Prof. Dr. J. Cossy, L. Moisan
¬
Laboratoire de Recherches Organiques associe au CNRS, ESCPI
10 rue Vauquelin, 75231 Paris Cedex 05
Fax : (‡33)1-40-79-46-60
[15] A flow reactor equipped with an HPLC pump (JASCO PU-1580) and
a pressure regulator (JASCO 880-81), connected by SUS316 tube
(2.2 mm inner diameter), was used. Similar equipment has already
been reported: B. M. Kabyemela, T. Adschiri, R. M. Malauan, K.
Arai, Ind. Eng. Chem. Res. 1997, 36, 1552.
E-mail: peter.dalko@espci.fr, janine.cossy@espci.fr
[**] The Association pour la Recherche contre le Cancer (ARC) (grant no.
7579) is gratefully acknowledged for financial support.
Angew. Chem. Int. Ed. 2002, 41, No. 4
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
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eral, a lower ee value was ob-
tained for dihydropyrone
when the premixing time was
reduced (see below).
R2
R2
R3
R2
R2
9
O
O
R3
R3
R3
H
R3
R1
R1
R1
R1
R2
R3
R1
R1
2
2
N
R1
R1
NH2
NH2
N
N
The condensation reaction
between 7 and 8 in the presence
of the chiral complexes derived
from diamines 1a and 1b
(10 mol%), carbonyl com-
pounds 2a f, and copper(ii) salt
at À728C afforded dihydropyr-
one 9 and the Mukaiyama aldol
product 10 (Scheme 2). At this
stage, the ee value of the pri-
mary cycloadduct 9 was deter-
mined[19] (Table 1), but unfortu-
nately the ee values of 10a and
10b could not be determined.
The mixture of 9 and 10 was
N
H
NH
NH2
R2
3
1
4
5
a: R1 = Ph
b: R1, R1 = -(CH2)4-
CuII
R2
R3
CuII
R1
R1
N
N
H2
6
Scheme 1. Condensation reaction between vicinal diamines and carbonyl compounds.
converted into the dihydropyrone 9 by treatment with a
catalytic amount of triflic acid, and the ee value of the
resulting dihydropyrone was measured (Table 1).[20]
this type of ligand in enantioselective catalytic reactions has
been reported, analogous reactions in the literature suggest
that these complexes may be active in a number of reac-
tions.[13]
Table 1. Condensation of 7 and 8 by using CuII complexes derived from
chiral amine.
To demonstrate the practical use of the catalyst system, a
condensation reaction between trans-1-methoxy-3-(trimethyl-
silyloxy)buta-1,3-diene (7; Danishefsky×s diene) and ethyl
pyruvate (8) was selected (Scheme 2).[14, 15] In this reaction,
Entry Amine 1 Ketone 2
1/2
9
yield [%] ee [%][a] ee [%][b]
1
2
3
4
5
6
7
8
9
(À)-1a
(À)-1a
(À)-1a
(À)-1a
(À)-1a
(‡)-1a
(À)-1a
(À)-1a
(À)-1a
none
0
cyclohexanone (2a) 1:1 7270
cyclopentanone (2b) 1:1 85
cyclobutanone (2c) 1:1 85
(À)-menthone (2d) 1:1 63
(À)-menthone (2d) 1:1 61
)
(92
OMe
OMe
OR
CO2Et
10
R = TMS
R = H
91
94
10
(92)
(ꢀ98)
O
a)
+
O
+
CO2Et
(10)
TMSO
O
CO2Et
O
12(17)
7
8
9
acetone (2e)
benzaldehyde (2 f)
benzaldehyde (2 f)
1:1 67
1:1 80
1:2 < 2
54
5
(70)
(18)
a:
b:
b)
10
(À)-1b cyclohexanone (2a) 1:1
0
Scheme 2. Reaction between Danishefsky×s diene and ethyl pyruvate by
using chiral CuII-derived catalysts. Reagents and conditions: a) CuII L*n
(10%), 4-ä molecular sieves, THF, À728C, 72h; b) CF 3COOH (cat.),
room temperature.
[a] The ee values after treatment with acid. [b] The ee values before
treatment with acid. Reaction conditions: THF, catalyst (10%), À728C,
4 ä molecular sieves, 72h.
As expected, the diamine copper(ii) triflate complex was
inefficient in mediating the reaction (Table 1, entry 1). When
ligands derived from diamine (À)-1a and cyclohexanone 2a
were used (Table 1, entry 2) the reaction afforded the hetero-
Diels Alder product 9 with high ee (92%). However, after
treatment with triflic acid, the enantiomeric excess of 9
proved to be lower (ee 70%).[20, 21] When the complexation
time (premixing) was reduced from the usual 16 h (Table 1,
entry 2) to 1 h, 9 was obtained in identical chemical yield, but
the ee value dropped from 70% to 49%.
Upon decreasing the ring size of the ketone component
from five to four carbon atoms, the ee value of cycloadduct 9,
before treatment with acid, increase from 92% (Table 1,
entry 3) to better than 98% (Table 1, entry 4). Likewise, the ee
value of 9 after treatment with acid increased from 91%
(Table 1, entry 3) to 94% (Table 1, entry 4). Somewhat
surprisingly, low enantioselectivity (10%) was observed when
(À)-menthone was used in combination either with the
(1R,2R)- or with the (1S,2S)-diphenylethylene diamine
dihydropyrone 9 can be formed through two distinct mech-
anistic pathways, that is, through a traditional hetero-Diels
Alder (HDA) cycloaddition reaction or by a Mukaiyama aldol
condensation pathway followed by cyclization.[16] It is gen-
erally accepted that the Mukaiyama aldol product 10 can
either be isolated, or may undergo a ring-closure reaction to
give dihydropyrone 9 under the reaction conditions or by
treatment with acid. Herein we show that complexes derived
from chiral diamines, carbonyl compounds, and CuII salts
catalyze both reaction pathways and afford the desired
adducts with high enantiomeric excesses.
The ligands were prepared by the condensation of amines 1
(Scheme 1) with ketones or aldehydes (see Table 1).[17] The
chiral Lewis acid catalysts were obtained by adding a
stoichiometric amount of Cu(OTf)2 to the reaction mixture,
which was allowed to stand for 16 h at room temperature
(premixing).[18] The premixing time significantly influenced
the enantioselectivity of the condensation reaction. In gen-
626
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161.9, 107.4, 82.9, 62.4, 44.8, 24.2, 14.1; MS (EI, 70 eV): m/z: 184 (27), 111
(100), 110 (24), 86 (12), 71 (89), 69 (25).
(Table 1, entries 5 and 6). This lack of selectivity may be a
consequence of the increased steric hindrance in the prox-
imity of the metal center in 6, which implies less selective
reaction paths. Interestingly, acyclic ketones such as acetone
2e were shown to be less selective than cyclic ketones
(Table 1, entry 7). Also, imidazolidines derived from diamine
and benzaldehyde 2 f resulted in low enantioselectivity
(Table 1, entry 8). Although bis-imines of type 5 were shown
earlier to be efficient in promoting enantioselective copper(ii)-
mediated HDA reactions,[2a] the bis-benzyl imine copper
complex derived from 1a and 2 f afforded only traces of a
nearly racemic product 9 under standard conditions (Table 1,
entry 9).[22] Furthermore, ligands derived from 1b and 2a
promoted neither the formation of the HDA adduct nor the
Mukaiyama aldol product (Table 1, entry 10).
The CuII/ligand stoichiometry was critical to the selectivity
and reactivity. This dependence was monitored on the HDA
adduct 9.[23] Whereas a 1:1 ratio of cyclohexylidene ligand
derived from (À)-1a, 2a, and Cu(OTf)2 afforded 9 in 92% ee,
an increase in the CuII/ligand ratio to 2:1 resulted in only 73%
ee. On the other hand, when a twofold molar excess of ligand
relative to the CuII salt was used, the catalytic activity of the
complex was inhibited.
Received: June 25, 2001
Revised: November 23, 2001 [Z17345]
[1] For leading references, see: a) Comprehensive Asymmetric Catalysis
(Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer, Heidelberg,
1999; b) Asymmetric Catalysis in Organic Synthesis (Ed.: R. Noyori),
Wiley, New York, 1994; c) Asymmetric Synthesis, 2nd ed. (Ed.: I.
Ojima), VCH, New York, 2000; d) ™Catalytic Asymmetric Synthesis∫:
Acc. Chem. Res. 2000, 33(6) (special issue); e) D. Astruc, Chimie
¬
Organometallique, EDP Sciences, Les Ulis, 2000; f) J. Seyden Penne,
Chiral Auxiliaires and Ligands in Asymmetric Synthesis, Wiley, New
York, 1995.
[2] a) J. S. Johnson, D. A. Evans, Acc. Chem. Res. 2000, 33, 325 335;
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Cappiello, Tetrahedron: Asymmetry 1998, 9, 1 45; d) E. J. Corey, C. J.
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[3] A. Berkessel, R. Riedl, J. Comb. Chem. 2000, 2, 215 219.
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Snapper, A. H. Hoveyda, Angew. Chem. 1996, 108, 1776 1779;
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[5] a) C. A. Krueger, K. W. Kuntz, C. D. Dzierba, W. G. Wirschun, J. D.
Gleason, M. L. Snapper, A. H. Hoveyda, J. Am. Chem. Soc. 1999, 121,
4248 4285; b) J. R. Porter, W. G. Wirschun, K. W. Kuntz, M. L.
Snapper, A. H. Hoveyda, J. Am. Chem. Soc. 2000, 122, 2657 2658;
c) N. S. Josephson, K. W. Kuntz, M. L. Snapper, A. H. Hoveyda, J.
Am. Chem. Soc. 2001, 123, 11594 11599.
[6] J. R. Porter, J. F. Traverse, A. H. Hoveyda, M. L. Snapper, J. Am.
Chem. Soc. 2001, 123, 984 985.
[7] S. J. Dergado, H. Mizutani, A. H. Hoveyda, J. Am. Chem. Soc. 2001,
123, 755 756.
[8] C. A. Luchaco-Cullis, H. Mizutani, K. E. Murphy, A. H. Hoveyda,
Angew. Chem. 2001, 113, 1504 1508; Angew. Chem. Int. Ed. 2001, 40,
1456 1460.
[9] For related catalyst systems, see: a) R. H. Crabtree, Chem. Commun.
1999, 1611 1616; b) M. T. Reetz, Angew. Chem. 2001, 113, 292 320;
Angew. Chem. Int. Ed. 2001, 40, 284 310; c) J. Long, J. Hu, X. Shen, B.
Ji, K. Ding, J. Am. Chem. Soc. 2002, 124, 10 11.
[10] a) Y. L. Bennani, S. Hanessian, Chem. Rev. 1997, 97, 3161 3195; b) D.
Lucet, T. Le Gall, C. Mioskowski, Angew. Chem. 1998, 110, 2 72 4
2772; Angew. Chem. Int. Ed. 1998, 37, 2580 2627.
The vicinal diamine ligands can be replaced by a chiral a-
aminoalcohol. Although this reaction was not optimized, a
reversal in enantioselectivity of the dihydropyrone 9 (67%
yield, 35% ee) from that of the Mukaiyama
Ph
aldol product 10 was observed when (R)-phen-
ylglycinol (11) was used.
NH2
OH
The foregoing three-component catalyst sys-
tems provide a simple and effective approach
for generating a variety of structurally diverse
11
chiral complexes for use in asymmetric synthesis. Important
structural features responsible for the catalytic activity are
unknown at the present time. The operational simplicity, easy
availability, low cost, stability, and diversity of potentially
active organometallic structures all contribute to the potential
usefulness of these catalysts.
[11] C. Chapuis, A. Gauvreau, A. Klaebe, A. Lattes, J. J. Perie, Bull. Soc.
Chim. Fr. 1973, 977 985.
Experimental Section
Diamine 1 (0.09 mmol, 0.1 equiv) and ketone 2 (0.09 mmol, 0.1 equiv) were
dissolved in a small amount of dichloromethane (2mL). After 4 h at room
temperature, the solvent was evaporated, and the residue was co-
evaporated twice with benzene. Cu(OTf)2 (32.6 mg, 0.09 mmol, 0.1 equiv)
and the ligand were introduced in a dry flask with a small amount of ground
4-ä molecular sieves (ca. 100 mg), and THF (1.5 mL) was added to the
solid through a cannula. The slurry was stirred under an inert atmosphere
of Ar for 16 h at room temperature. The slurry was cooled to À728C, ethyl
pyruvate (100 mL, 0.9 mmol, 1.0 equiv) and Danishefsky×s diene (215 mL,
1.3 mmol, 1.2equiv) were added in one portion through a syringe, and the
mixture was stirred for an additional 72h at À728C. Trifluoroacetic acid
(0.1 mL) was then introduced to the mixture, which was allowed to warm to
room temperature. After 12hours, the solution was neutralized with
saturated sodium bicarbonate, the organic phase was separated, and the
aqueous phase was extracted with dichloromethane (2 Â 10 mL). The
combined organic phases were dried over Na2SO4, the solvent was
evaporated, and the crude reaction mixture was purified on a short column
of silica gel (pentane/ethyl acetate 4:1 eluent). Rf ˆ 0,5 (silica gel, EtOAc/
[12] P. Braunstein, F. Naud, Angew. Chem. 2001, 113, 702 722; Angew.
Chem. Int. Ed. 2001, 40, 680 699.
[13] Reactions that are potentially mediated by complexes derived either
from bis-imines 5 or the starting diamines 1 should be kinetically
disfavored transformations. A similar principle has been developed
earlier in the generation of imine-based virtual combinatorial
libraries; see: Y. Huc, J.-M. Lehn, Proc. Nat. Acad. Sci. USA 1997,
94, 2106.
[14] For recent reviews on this topic, see: a) W. Carruthers, Cycloaddition
Reactions in Organic Synthesis, Pergamon, Elmsford, NY, 1990
(Tetrahedron Organic Chemistry Series, Vol. 8); b) D. L. Boger,
S. H. Weinreb, Hetero-Diels Alder Methodology in Organic Syn-
thesis, Academic Press, New York, 1987; c) H. Waldmann, Synthesis
1994, 535 551; d) L. F. Tietze, G. Kettschau, Top. Curr. Chem. 1997,
190, 1; d) K. A. J˘rgensen, Angew. Chem. 2000, 112, 3702 3733;
Angew. Chem. Int. Ed. 2000, 39, 3558 3588.
[15] a) M. Johannsen, S. Yao, K. A. J˘rgensen, Chem. Commun. 1997,
2169 2170; b) S. Yao, M. Johannsen, H. Audrain, R. G. Hazell, K. A.
J˘rgensen, J. Am. Chem. Soc. 1998, 120, 8599 8605; c) S. Yao, M.
Johannsen, H. Audrain, R. G. Hazell, K. A. J˘rgensen, J. Am. Chem.
Soc. 1998, 120, 8599 8605; d) M. Johannsen, S. Yao, A. Graven, K. A.
J˘rgensen, Pure Appl. Chem. 1998, 79, 1117; e) K. A. J˘rgensen, M.
pentane 1:1); IR (film): nÄ ˆ 1740, 1680, 1600 cmÀ1
;
1H NMR (CDCl3,
300 MHz): d ˆ 7.36 (d, J ˆ 5.9 Hz, 1H), 5.42(d, J ˆ 5.9 Hz, 1H), 4.22 (q, J ˆ
7.0 Hz, 2H), 3,00 (d, J ˆ 16.5 Hz, 1H), 2.68 (d, J ˆ 16.5 Hz, 1H), 1.66 (s,
3H), 1.27 (t, J ˆ 7.0 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d ˆ 190.1, 171.0,
Angew. Chem. Int. Ed. 2002, 41, No. 4
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
1433-7851/02/4104-0627 $ 17.50+.50/0
627

COMMUNICATIONS
Johannsen, S. Yao, H. Audrain, J. Thorhauge, Acc. Chem. Res. 1999,
32, 605 613.
phases gives rise to a sequence of different mesophase
morphologies. Hence, in dependence on the amphiphile
structure, its concentration, and the temperature, different
[16] For related aldol reactions, see: a) D. A. Evans, M. C. Kozlowski, J. A.
Murry, C. S. Burgey, K. R. Campos, B. T. Connell, R. J. Staples, J. Am.
Chem. Soc. 1999, 121, 669 685; b) D. A. Evans, C. S. Burgey, C. S.
Kozlowski, S. W. Tregay, J. Am. Chem. Soc. 1999, 121, 686 699; c) M.
Roberson, A. S. Jepsen, K. A. J˘rgensen, Tetrahedron 2001, 57, 907
913.
[17] Best results were obtained when the diamine and the carbonyl
compound were mixed in dichloromethane at room temperature
without an acid catalyst. The formation of the products was monitored
by 1H and 13C NMR spectroscopy.
[18] Other CuII salts such as Cu(SbF6)2, Cu(BF4)2, Cu(ClO4)2, Cu(OAc)2,
Cu(PF4)2 showed lower selectivity in this reaction.
3]
lyotropic mesophases can result.[1 Arrays of alternating
layers yield smectic phases (SmA), regular arrangements of
cylinders give rise to hexagonal columnar phases (Colh), and
closed globular or nonglobular micelles can form cubic
mesophases (micellar cubic phases, CubI). Another type of
cubic mesophase, consisting of two mutually interwoven
networks of branched cylinders (bicontinuous cubic meso-
phases, CubV), occurs at the transition between smectic and
columnar organization (Figure 1). For each of the nonlamellar
mesophases two different types are possible. In normal phases
(type 1, positive curvature of the polar/apolar interface), the
stronger cohesive forces (hydrogen bonds) are located in the
continuum surrounding the aggregates. In the reversed (or
inverse) phases (type 2, negative interface curvature) they are
[19] The ee value of 9 was determined by chiral GC-MS on a Crompack
Chirasil-DEX CB column.
[20] No epimerization of 9 was observed after treatment with acid.
[21] The absolute configuration of the newly formed stereogenic center of
9 was found to be R in each case when the (1R,2R)-diphenylethylene
diamine ligand was used. The absolute configuration was determined
by comparison of the optical rotation of 9 with the literature value.[15c]
[22] The ligand was prepared by condensation of benzaldehyde (2 equiv)
with 1a followed by addition of Cu(OTf)2 (1 equiv).
[23] The reaction was quenched at À728C by using trifluoroacetic acid and
was allowed to stir at À108C for 1 h. This workup procedure allowed
the isolation of the HDA and aldol products. No interconversion
between the aldol and HDA products was observed under these
conditions.
A Thermotropic Mesophase Comprised of
Closed Micellar Aggregates of the Normal
Type**
Petra Fuchs, Carsten Tschierske,* Klaus Raith,
Kumar Das, and Siegmar Diele
The ability of amphiphilic molecules to self-organize in
aqueous systems with formation of micelles, vesicles, and
lyotropic mesophases is of great importance for numerous
applications of surfactants in several fields of science and
technology, and it is also a prerequisite for the development of
biological structures.[1, 2] In these polymolecular assemblies
the hydrophilic parts (together with the solvent molecules)
and the lipophilic parts of the amphiphiles are segregated into
nanoscopic compartments, whereby changing the degree of
curvature of the interfaces between the incompatible nano-
[*] Prof. Dr. C. Tschierske, Dr. P. Fuchs
Institute of Organic Chemistry
Martin-Luther-University Halle Wittenberg
Kurt-Mothes-Stra˚e 2, 06120 Halle (Germany)
Fax : (‡49)345-55-27223
E-mail: tschierske@chemie.uni-halle.de
Dr. S. Diele, Dr. K. Das
Institute of Physical Chemistry
Martin-Luther-University Halle Wittenberg
M¸hlpforte 1, 06120 Halle (Germany)
Fax : (‡49)345-55-27157
Figure 1. Dependence of the mesophase morphology of different poly-
hydroxy amphiphiles on the molecular structure. Abbreviations: CubI2
ˆ
reversed discontinuous (micellar) cubic mesophase with Pm3n lattice;
Colh2 ˆ reversed hexagonal columnar mesophase; CubV2 ˆ reversed bicon-
tinuous cubic mesophase with Ia3d lattice; SmA ˆ smectic A-phase;
CubV1 ˆ normal-type bicontinuous cubic mesophase with Ia3d lattice;
Colh1 ˆ normal-type hexagonal columnar mesophase; MI1 ˆ mesophase
comprised of discrete direct micelles with unknown lattice (the Im3m
lattice is shown as one of the possible structures).
Dr. K. Raith
Faculty of Pharmacy
Martin-Luther-University Halle Wittenberg (Germany)
[**] This work was supported by the Deutsche Forschungsgemeinschaft
and the Fonds der Chemischen Industrie.
628
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
1433-7851/02/4104-0628 $ 17.50+.50/0
Angew. Chem. Int. Ed. 2002, 41, No. 4