The Juliae-Colonna type asymmetric epoxidation reaction catalyzed by soluble Oligo-L-leucines containing an α-aminoisobutyric acid residue: Importance of helical structure of the catalyst on asymmetric induction

Article abstract of DOI:10.1246/cl.2000.366

Length-defined organic solvent soluble oligo-L-leucines containing an Aib residue were prepared by stepwise elongation and fragment condensation methods, and were used as catalysts in the Julia-Colonna asymmetric epoxidation reaction. The yield and enanti

Full text of DOI:10.1246/cl.2000.366

3
66
Chemistry Letters 2000
The Juliá-Colonna Type Asymmetric Epoxidation Reaction Catalyzed by Soluble
Oligo-L-leucines Containing an α-Aminoisobutyric Acid Residue:
Importance of Helical Structure of the Catalyst on Asymmetric Induction
Ryukichi Takagi, Akiko Shiraki, Toshiki Manabe, Satoshi Kojima, and Katsuo Ohkata*
Department of Chemistry, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739–8526
Received January 5, 2000; CL-000008)
Length-defined organic solvent soluble oligo-L-leucines
(
containing an Aib residue were prepared by stepwise elongation
and fragment condensation methods, and were used as catalysts
in the Juliá–Colonna asymmetric epoxidation reaction. The
yield and enantioselectivity rose by increasing the number of
amino acid units in the catalyst. The enantioselectivity was
very sensitive to the reaction solvent. The IR characteristic
bands (the amide I region) in CH Cl indicated the soluble cata-
1
2
2
fully characterized by MS (MALDI-TOF), H NMR and IR
lysts to be of helical structure in solution.
spectra. All the Boc-L-Leu –Aib–L-Leu -OBzl peptides pre-
m
n
pared here were soluble in a variety of organic solvents.
Epoxides are a widely used group of compounds in organic
synthesis.1 For this reason several approaches for enantioselec-
2
tive epoxidation have been developed. Juliá-Colonna asym-
metric epoxidation which utilizes poly-L-leucine as catalyst has
been established as a highly selective method of epoxidizing
2
d,3
enones
and has found application in natural product synthe-
4
5
sis. Our interest in the chemistry of small ring compounds
has attracted us to this very intriguing reaction, of which mech-
anistically little has been uncovered. The primary problem con-
cerning mechanistic examinations has been the insolubility of
the catalyst in ordinary solvents. One advance has been the
Epoxidation reactions of chalcone with the urea-hydrogen
peroxide adduct and DBU in the presence of soluble catalysts
6
introduction of cross-linked aminomethylpolystyrene support.
(
Boc-L-Leu –Aib–L-Leu -OBzl and TFA·H–L-Leu –Aib–L-
m n m
This paved the way for preparation of polymer-bound length-
defined catalysts, from which it was deduced that the chirality
of the N-terminus dictates the stereochemistry of the product
and that a certain number of consecutive amino acids of the
same chirality at this end are required for reasonable levels of
Leu -OBzl oligomers) were investigated at room temperature in
organic solvents. Table 1 shows the stereoselectivity in the
epoxidation catalyzed by Boc-L-Leu –Aib–L-Leu -OBzl (m =
4
having a free NH group. Both Boc-L-Leu –Aib–L-Leu -OBzl
and TFA·H–L-Leu –Aib–L-Leu -OBzl oligomers were effec-
n
11
m
n
, 6 and n = 4, 6) in THF and some N-deprotected oligomers
2
m
n
7
asymmetric induction. Still here, however, the state of the cat-
m
n
alysts has hampered spectroscopic examinations, and thus has
complicated speculations about the mechanism of the asymmet-
ric induction.
tive as catalysts from the viewpoint of both chemical yield and
stereoselectivity. The general trend was that the longer catalyst
gave better results, a tendency similarly observed in the epoxi-
In their early work, Juliá and Colonna had already suggest-
ed that α-helical structure might be important for asymmetric
induction in the epoxidation reaction under tri- and biphasic
7,8,9
dation reaction under tri- or biphasic conditions.
Contrary
to previous observations under heterogeneous tri- and biphasic
8
conditions where protection of the N-terminus as amides and
8
conditions, unfortunately they could not produce evidence to
9
carbamates lead to significant deterioration in reactivity, our
back it up. Our observation of IR spectra of length-defined
protected catalysts furnished comparable results with corre-
sponding unprotected catalysts. Coupled with the fact that
9
oligo-L-leucines in the solid state agreed with their suggestion.
Based on the report that the presence of even only a single α-
aminoisobutyric acid (Aib) residue placed in the mid-section of
oligo-L-amino acid chains promotes helix formation and greatly
improves the solubility of the oligomers towards organic sol-
vents,10 we prepared several length-defined oligo-L-leucines
containing an Aib residue, and have carried out the first exami-
nation of the Juliá–Colonna asymmetric epoxidation reaction
with soluble catalysts. Herein we disclose our results.
7,8
NMe (in the place NH ) is also compatible, neither the
2
2
hydrogen-bonding ability of the hydrogen atom attached to
nitrogen nor the basicity of the nitrogen atom are involved in
the stereo-determining step, and thus the role of the N-terminus
seems to be minimal. The negative results with previous car-
8,9
bonyl protected catalysts could be due to unfavorable catalyst
conformations induced by the groups.
The solvent effect on the enantioselectivity is shown in
Table 2. The stereoselectivity was very sensitive to the reaction
solvent. The highest enantioselectivity was observed in THF.
The protected oligo-L-leucines (Boc-L-Leu –Aib–L-Leu -
m
n
OBzl) were prepared by the fragment condensation of Boc-L-
Leu -OH and TFA·H-Aib-L-Leu -OBzl as shown in Scheme 2
m
n
In CHCl solution, very low enantioselectivity was observed
3
1
0
by modifying reported procedures. The oligo-L-leucines were
although the epoxide was obtained in comparable yield. Since
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
367
(
1980). b) W. Zhang, J. L. Loebach, S. R. Wilson, and E. N.
Jacobsen, J. Am. Chem. Soc., 112, 2801 (1990). c) R. Irie, K. Noda,
Y. Ito, N. Matsumoto, and T. Katsuki, Tetrahedron Lett., 31, 7345
(
1990). d) S. Juliá, J. Masana, and J. C. Vega, Angew. Chem., Int.
Ed. Engl., 19, 929 (1980). e) D. Yang, Y.-C. Yip, M.-W. Tang, M.-
K. Wong, J.-H. Zheng, and K.-K. Cheung, J. Am. Chem. Soc., 118,
4
1
91 (1996). f) Y. Tu, Z.-X. Wang, and Y. Shi, J. Am. Chem. Soc.,
18, 9806 (1996). g) D. Enders, J. Zhu, and G. Raabe, Angew.
Chem., Int. Ed. Engl., 35, 1725 (1996). h) M. Bougauchi, S.
Watanabe, T. Arai, H. Sasaki, and M. Shibasaki, J. Am. Chem. Soc.,
1
19, 2329 (1997). i) C. L. Elston, R. F. W. Jackson, S. J. F.
MacDonald, and P. J. Murray, Angew. Chem., Int. Ed. Engl., 36, 410
1997). j) B. Lygo and P. G. Wainwright, Tetrahedron Lett., 39,
599 (1998). k) S. Watanabe, T. Arai, H. Sasaki, M. Bougauchi,
(
1
and M. Shibasaki, J. Org. Chem., 63, 8090 (1998).
3
4
For reviews on Juliá-Colonna epoxidation see: a) M. E. Lasterra-
Sanchez and S. M. Roberts, Curr. Org. Chem., 1, 187 (1997). b) S.
Ebrahim and M. Wills, Tetrahedron: Asymmetry, 8, 3163 (1997). c)
L. Pu, Tetrahedron: Asymmetry, 9, 1457 (1998).
a) J. R. Flisak, K. J. Gombatz, M. M. Holmes, A. A. Jamas, I.
Lantos, W. L. Mendelson, V. J. Navack, J. J. Remich, and L.
Snyder, J. Org. Chem., 58, 6247 (1993). b) R. J. J. Nel, P. S. van
Heerden, H. van Rensburg, and D. Ferreira Tetrahedron Lett., 39,
5
623 (1998). c) B. M. Adger, J. V. Barkley, S. Bergeron, M. W.
Cappi, B. E. Flowerdew, M. P. Jackson, R. McCague, T. C. Nugent,
and S. M. Roberts, J. Chem. Soc., Perkin Trans. 1, 1997, 3501. d)
M. W. Cappi, W.-P. Chen, R. W. Flood, Y.-W. Liao, S. M. Roberts,
J. Skidmore, J. A. Smith, and N. M. Williamson, Chem. Commun.,
1
998, 1159. e) W.-p. Chen and S. M. Roberts, J. Chem. Soc., Perkin
Trans. 1, 1999, 1043.
IR measurements indicated the homogeneous catalyst to be hel-
5
a) K. Ohkata, J. Kimura, Y. Shinohara, R. Takagi, and Y. Hiraga,
Chem. Commun., 1996, 2411. b) R. Takagi, J. Kimura, Y.
Shinohara, Y. Ohba, K. Takezono, Y. Hiraga, S. Kojima, and K.
Ohkata, J. Chem. Soc., Perkin Trans. 1, 1998, 689.
S. Itsuno, M. Sakakura, and K. Ito, J. Org. Chem., 53, 6047 (1990).
P. A. Bentley, M. W. Cappi, R. W. Flood, S. M. Robert, and J. A.
Smith, Tetrahedron Lett., 39, 9297 (1998).
a) S. Juliá, J. Gulixer, J. Masana. J. Rocas, S. Colonna, R.
Annuziata, and H. Molinari, J. Chem. Soc., Perkin Trans. 1, 1982,
1317. b) S. Colonna. H. Molinari, S. Banfi, S. Juliá, J. Masana, and
A. Alvarez, Tetrahedron, 39, 1635 (1983). c) S. Banfi, S. Colonna,
H. Molinari, S. Juliá, and J. Guixer, Tetrahedron, 40, 5207 (1984).
Manuscript in preparation.
ical even in CHCl , this experimental result can be ascribed to
3
the presence of a relatively fast background uncatalyzed epoxi-
dation process.12
6
7
Examination of the IR spectra of Boc-L-Leu –Aib–L-Leu -
6
6
OBzl, which exhibited the highest selectivity, showed a weak
-1
band at 3424 cm (w, free N-H stretching), and strong bands at
8
1
3
324 (s, hydrogen bonding N-H stretching) and 1661 cm- (s,
C=O stretching) in CH Cl solution, which can be assigned to
2
2
helical structure.13
We have demonstrated that soluble oligo-L-leucine cata-
lysts that show a high degree of helical conformational struc-
ture give results comparable to those of insoluble catalysts.
Therefore, we draw the conclusion that in general the segment
of the catalysts in the Juliá-Colonna reaction involved in the
asymmetric induction process assumes helical conformation.
This improvement in solubility of the catalyst brings in a new
dimension to the Juliá-Colonna reaction and should lead to fur-
ther understanding of the reaction.
9
1
0 M. Narita, K. Ishikawa, H. Sugasawa, and M. Doi, Bull. Chem. Soc.
Jpn., 58, 1731 (1985).
1 General method: To a mixture of chalcone 25 mg (0.12 mmol), cat-
alyst 0.030 mmol, urea-hydrogen peroxide adduct 12.5 mg (0.16
mmol) and 1 ml of THF, 0.1 ml of DBU (0.67 mmol) was added at 0
1
°
C. The mixture was allowed to warm to room temperature and
stirred for 24 h. The resulting mixture was extracted with CH Cl .
2
2
The combined extracts were washed with aqueous Na S O , water
and brine, dried over MgSO and evaporated. The crude product
was purified by preparative TLC [silica gel, petroleum ether : ether
2
2
3
4
=
10 : 1 (v/v)]. As the reaction progresses, the turbidity caused by
We are grateful to Professor Katsuyoshi Yoshizato and Mr.
Dan Kristensen, Hiroshima University, for the use of their
MALDI mass spectrometer, and Professor Kenichi Ohno of
Hiroshima University for IR spectra measurements. NMR, MS,
and CD spectra were measured at the Instrument Center for
Chemical Analysis, Hiroshima University.
the lowly soluble urea-hydrogen peroxide adduct decreases.
12 Uncatalyzed reactions in THF and CHCl solutions: By the same
3
procedure except without catalyst, the racemic epoxide was fur-
nished in 26 and 68% yield, respectively.
3 a) T. Miyazawa and E. J. Blout, J. Am. Chem. Soc., 83, 712 (1961).
b) D. F. Kennedy, M. Crisma, C. Toniolo, and D. Chapman,
Biochemistry, 30, 6541 (1991).
4 The CD spectrum of a trifluoroethanol solution of Boc-L-
Leu –Aib–L-Leu -OBzl in the absorption region of oligomer chro-
mophores displayed a negative CD band at 203 nm along with a
1
1
References and Notes
6
6
1
a) M. Bartok and K. L. Lang, “The Chemistry of Ethers, Crown
Ethers, Hydroxyl Groups and Their Sulphur Analogs, Supplement
E,” ed by S. Patai, John Wiley, New York (1980) vol. 2, p. 609. b)
A. S. Rao, S. K. Paknikar, and J. G. Kirtane, Tetrahedron, 39, 2323
shoulder centered near 222 nm with an R = [Θ] /[Θ] ratio of
222
203
0.5. In addition, the peak at 190 nm was positive with a further neg-
ative maximum at 181 nm. These spectral characteristics are
extremely similar to those of a reported oligopeptide with estab-
lished right-handed 310-helical conformation, thus implying the
presence of this structure: a) M. Manning and R. W. Woody,
Biopolymers, 31, 569 (1991). b) C. Toniolo, A. Polese, F.
Formaggio, M. Crisma, and J. Kamphuis, J. Am. Chem. Soc., 118,
(
“
1983). c) J. G. Smith, Synthesis, 1984, 629. d) E. G. Lewars, in
Comprehensive Heterocyclic Chemistry,” ed by A. R. Katritzky
and C. W. Rees, Pergamon, Oxford (1984), vol. 7, p. 95. e) I.
Erden, in “Comprehensive Heterocyclic Chemistry II,” ed by A.
Padwa, Elsevier, Oxford (1996), vol. 1A, p. 97.
2
744 (1996).
2
a) T. Katsuki and K. B. Sharpless, J. Am. Chem. Soc., 102, 5874