Design of new chiral phase-transfer catalysts with dual functions for highly enantioselective epoxidation of α,β-unsaturated ketones

Article abstract of DOI:10.1021/ja048600b

A new chiral ammonium bromide, 1-Br, possessing diarylmethanol functionality as a substrate recognition site has been designed as a promising, dual-functioning catalyst for the highly enantioselective epoxidation of α,β-unsaturated ketones under mild phas

Full text of DOI:10.1021/ja048600b

Published on Web 05/18/2004
Design of New Chiral Phase-Transfer Catalysts with Dual Functions for Highly
Enantioselective Epoxidation of r,â-Unsaturated Ketones
Takashi Ooi, Daisuke Ohara, Masazumi Tamura, and Keiji Maruoka*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity, Sakyo, Kyoto 606-8502, Japan
Received March 11, 2004; E-mail: maruoka@kuchem.kyoto-u.ac.jp
Scheme 1
The catalytic asymmetric epoxidation of electron-deficient ole-
fins, particularly R,â-unsaturated ketones, has recently been the
subject of numerous investigations and a number of useful
methodologies involving different types of catalyst-reagent com-
binations have been elaborated.1 Among these, the method utilizing
chiral phase-transfer catalysis occupies a unique place, featuring
many advantages including operational simplicity, non-metal-
containing catalyst, and environmental consciousness.2 However,
successful examples have been very limited since the pioneering
work of Wynberg using alkylated cinchona alkaloids.3 In 1998,
Lygo showed the effectiveness of a catalyst incorporating a
9-anthracenylmethyl group in the epoxidation of mainly substituted
chalcones with commercially available sodium hypochlorite,4 and
the next year Corey reported that use of the same catalyst with
freshly prepared 65% potassium hypochlorite at lower temperature
(-40 °C) led to improved enantioselectivities.5 Despite such recent
Table 1. Structural Modification of 1 for Phase-Transfer Catalytic
Asymmetric Epoxidation of Chalconea
impressive progress,6 the full potential of this reaction is yet to be
realized in terms of both stereoselectivity and general applicability.
This situation is largely due to the lack of well-designed, finely
tunable chiral catalysts. Herein we wish to disclose our own solution
to this problem by introducing a new chiral quaternary ammonium
bromide with dual functions, which efficiently catalyzes the
epoxidation of a variety of R,â-unsaturated ketones with excellent
enantioselectivities under mild reaction conditions (Scheme 1).
Our prime concern in designing a suitable catalyst for phase-
transfer-catalyzed asymmetric epoxidation of R,â-unsaturated ke-
tones was to endow it with the ability to recognize the prochiral
enone for attaining sufficient reactivity and enantiofacial discrimi-
nation. To achieve this, we first planned to introduce certain
heteroatom-containing functionality as a substrate recognition site
and chose a diarylmethanol group with the expectation that it could
appropriately define the position of enones through hydrogen-
bonding interaction. With the steric demand of this functionality
in mind, we undertook the preparation of a new chiral quaternary
ammonium bromide, 1a, consisting of a flexible biphenyl subunit
with a diphenylhydroxymethyl substituent at the 3,3′-position and
a simple chiral binaphthyl structure. It was assumed that 1a adopted
a predominantly heterochiral (R,S) configuration around ambient
temperature,7 and its chiral efficiency was evaluated in the
epoxidation of chalcone using commercially available 13% sodium
hypochlorite (NaOCl). Thus, vigorous stirring of a mixture of
chalcone, 1a (3 mol %), and 13% NaOCl in toluene at 0 °C for 24
h gave rise to the corresponding epoxy ketone in 69% yield and
appreciable enantiomeric excess was attained (66% ee) (entry 1 in
Table 1). It should be noted that the reaction with catalyst 2 having
no hydroxy group under otherwise identical conditions resulted in
almost total loss of the catalytic activity and diminished stereose-
lectivity (3%, 46% ee) (entry 2).
c
entry
catalyst
% yieldb
%ee (config)d
1
2
3
4
5
6
1a
2
1b
1c
1d
1e
69
3
50
67
61
99
66 (RS,âR)
46 (RS,âR)
61 (RS,âR)
64 (RS,âR)
80 (RS,âR)
96 (RS,âR)
a The reaction (0.2 mmol scale) was carried out with 13% NaOCl (0.3
mL) in the presence of 3 mol % of 1 or 2 in toluene (0.6 mL) at 0 °C for
24 h. b Isolated yield. c Enantiopurity was determined by HPLC analysis
of epoxy chalcone using a chiral column (DAICEL Chiralcel OD).
d Absolute configuration was determined by comparison of the HPLC
retention time with that reported.6d
diphenylhydroxymethyl moiety subtly affected the reactivity and
selectivity of the epoxidation (entries 3 and 4), introduction of the
3,5-diphenylphenyl group as aromatic substituent (Ar) increased
the enantioselectivity to 80% ee (entry 5). Fascinatingly, further
structural modification by installing a 3,5-diphenylphenyl group
on the 4,4′-position of the binaphthyl subunit dramatically improved
not only the enantioselectivity but also the catalytic activity, and
epoxy chalcone was obtained quantitatively with 96% ee (entry
6).8
As shown in Figure 1, a successful single-crystal X-ray diffrac-
tion analysis of 1e-PF6 uncovered its distinctive three-dimensional
molecular architecture and established the heterochiral configura-
tion.9 The biphenyl and binaphthyl subunits of the core N-spiro
structure are nearly perpendicular, and this conformational informa-
tion is transmitted to each substituent, creating an attractive chiral
reaction cavity around the central nitrogen cation (blue). Impor-
tantly, hexafluorophosphate ion (green) is located inside the cavity
being surrounded by the radially spread 3,5-diphenylphenyl groups,
On the basis of these initial observations, we next pursued the
electronic and steric manipulations of this type of catalyst to enhance
the chiral recognition ability. Although electronic tuning of the
9
6844
J. AM. CHEM. SOC. 2004, 126, 6844-6845
10.1021/ja048600b CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
epoxidized cleanly with a high level of asymmetric inductions
(entries 5 and 6). Here, it is of interest that the catalyst 1d was
revealed to be superior for the epoxidation of the substrates with
an alkyl ketone moiety and that aliphatic R,â-unsaturated ketones
are amenable to this condition (entries 7-9). Moreover, â-ben-
zylidene-R-indanone and its tetralone analogue appeared to be good
candidates for this asymmetric transformation and virtually complete
stereochemical control has been realized (entries 10 and 11).
In summary, we have devised chiral quaternary ammonium
bromides that exhibit dual functions and allow practical highly
enantioselective epoxidation of various R,â-unsaturated ketones
under mild phase-transfer catalytic conditions. This system provides
ready access to a wide range of useful synthetic intermediates of
high enantiomeric purity. We believe the concept of the present
molecular design is applicable to the development of other
asymmetric phase-transfer reactions involving the addition of small
anionic nucleophiles being supplied as an aqueous inorganic salt
to prochiral electrophiles, which are difficult to achieve by the
conventional catalyst systems.
Figure 1. X-ray structure of 1e-PF6 (N, blue; O, red; PF6, green). Hydrogen
atoms and solvent molecules are omitted for clarity.
Table 2. Catalytic Asymmetric Epoxidation of R,â-Unsaturated
Ketones under Phase-Transfer Conditionsa
Acknowledgment. We gratefully acknowledge Dr. Kunihisa
Sugimoto (Rigaku Corporation) for the X-ray crystallographic
analysis. This work was partially supported by the Kurata Memorial
Hitachi Science and Technology Foundation and a Grant-in-Aid
for Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
Supporting Information Available: Physical characterization of
catalysts 1d and 1e and all new compounds (PDF); the crystallographic
data for 1e-PF6 (CIF). This material is available free of charge via the
Internet at http://pubs.acs.org.
References
(1) For recent excellent reviews, see: (a) Porter, M. J.; Skidmore, J. Chem.
Commun. 2000, 1215. (b) Nemoto, T.; Ohshima, T.; Shibasaki, M. J. Synth.
Org. Chem. Jpn. 2002, 60, 94.
(2) For recent representative reviews, see: (a) O’Donnell, M. J. In Catalytic
Asymmetric Synthesis; Ojima, I., Ed.; Verlag Chemie: New York, 1993;
Chapter 8. (b) Shioiri T.; Arai, S. In Stimulating Concepts in Chemistry;
Vogtle, F., Stoddart, J. F., Shibasaki, M., Eds.; WILEY-VCH: Weinheim,
2000; p 123. See also ref 1a.
(3) (a) Helder, R.; Hummelen, J. C.; Laane, R. W. P. M.; Wiering, J. S.;
Wynberg, H. Tetrahedron Lett. 1976, 1831. (b) Wynberg, H.; Greijdanus,
B. J. Chem. Soc., Chem. Commun. 1978, 427. (c) Hummelen, J. C.;
Wynberg, H. Tetrahedron Lett. 1978, 1089. (d) Wynberg, H.; Marsman,
B. J. Org. Chem. 1980, 45, 158. (e) Pluim, H.; Wynberg, H. J. Org. Chem.
1980, 45, 2498.
a Unless otherwise noted, the reaction (0.1 mmol scale) was conducted
with 13% NaOCl (0.15-1.8 mL) in the presence of 3 mol % of 1e in toluene
(0.3 mL) at 0 °C for the given reaction time. b Isolated yield. c Enantiomeric
excess was determined by HPLC analysis using a chiral column. d Absolute
configuration was determined by comparison of optical rotation to literature
value except for entry 5 (see the Supporting Information). e The reaction
was carried out at -20 °C. f Use of 1d as catalyst.
(4) (a) Lygo, B.; Wainwright, P. G. Tetrahedron Lett. 1998, 39, 1599. (b)
Lygo, B.; Wainwright, P. G. Tetrahedron 1999, 55, 6289. (c) Lygo, B.;
To, D. C. M. Tetrahedron Lett. 2001, 42, 1343.
and the hydroxy moiety (red) is situated right above the nitrogen
and sticks to the hexafluorophosphate ion. This strongly implies
that, after the in situ ion-exchange, hypochlorite ion would be
correctly positioned prior to the reaction and the expected hydrogen-
bonding interaction would indeed bring enones inside the cavity
to provide an ideal proximity to hypochlorite ion for the initial
conjugate addition process, resulting in efficient bond formation
with rigorous enantiofacial differentiation.
(5) Corey, E. J.; Zhang, F.-Y. Org. Lett. 1999, 1, 1287.
(6) For other important contributions, see: (a) Harigaya, Y.; Yamaguchi, H.;
Onda, M. Heterocycles 1981, 15, 183. (b) Baba, N.; Oda, J.; Kawaguchi,
M. Agric. Biol. Chem. 1986, 50, 3113. (c) Arai, S.; Tsuge, H.; Shioiri, T.
Tetrahedron Lett. 1998, 39, 7563. (d) Arai, S.; Tsuge, H.; Oku, M.; Miura,
M.; Shioiri, T. Tetrahedron 2002, 58, 1623. (e) Adam, W.; Rao, P. B.;
Degen, H.-G.; Levai, A.; Patonay, T.; Saha-Mo¨ller, C. R. J. Org. Chem.
2002, 67, 259. (f) Ye, J.; Wang, Y.; Liu, R.; Zhang, G.; Zhang, Q.; Chen,
J.; Liang, X. Chem. Commun. 2003, 2714. (g) Allingham, M. T.; Howard-
Jones, A.; Murphy, P. J.; Thomas, D. A.; Caulkett, P. W. R. Tetrahedron
Lett. 2003, 44, 8677.
(7) Ooi, T.; Uematsu, Y.; Kameda, M.; Maruoka, K. Angew. Chem., Int. Ed.
2002, 41, 1551. Control experiments revealed that a structurally rigid
heterochiral catalyst exhibited higher chiral efficiency than a homochiral
one in the present epoxidation. See the Supporting Information.
(8) The catalyst 1e can be recovered quantitatively by chromatographic
separation and reused for this epoxidation at least five times without
decrease of catalytic activity and enantioselectivity.
The general applicability of the present system has been
thoroughly investigated and the representative results are sum-
marized in Table 2. In the epoxidation of a series of differently
substituted chalcone derivatives, the corresponding epoxy ketones
were obtained almost quantitatively with excellent enantioselec-
tivities (entries 1-4). The substrates possessing an alkyl substituent
either on the double bond or on the carbonyl carbon were also
(9) For detailed crystallographic data, see the Supporting Information.
JA048600B
9
J. AM. CHEM. SOC. VOL. 126, NO. 22, 2004 6845