Application of high pressure induced by water-freezing to the direct catalytic asymmetric three-component List-Barbas-Mannich reaction

Article abstract of DOI:10.1021/ja0372513

High pressure induced by water-freezing has been successfully applied to the direct catalytic asymmetric-three component List-Barbas-Mannich reaction, in which higher yield and better enantioselectivity can be realized than those from the reaction at room

Full text of DOI:10.1021/ja0372513

Published on Web 08/21/2003
Application of High Pressure Induced by Water-Freezing to the Direct
Catalytic Asymmetric Three-Component List-Barbas-Mannich Reaction
Yujiro Hayashi,*,† Wataru Tsuboi,† Mitsuru Shoji,† and Noriyuki Suzuki|
Department of Industrial Chemistry, Faculty of Engineering, Tokyo UniVersity of Science, Kagurazaka,
Shinjuku-ku, Tokyo 162-8601, Japan, and RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
Received July 14, 2003; E-mail: hayashi@ci.kagu.tus.ac.jp
Table 1. Mannich Reaction of Various Aldehydes, p-Anisidine,
and Acetone Catalyzed by L-Proline under Ambient Pressure and
High Pressure Induced by Water-Freezinga
High pressure is one of the factors that can effectively accelerate
many organic transformations,1 although its use in organic synthesis
is rather limited owing to the necessity for special high-pressure
apparatus. A new and easy method for generating high pressure is
desirable. We have been investigating the novel method of high
pressure induced by water-freezing, in which the high pressure (ca.
200 MPa) is easily achieved simply by freezing water (-20 °C) in
a sealed autoclave.2 The Michael reaction of alcohols with R,â-
enones2a and the Baylis-Hillmann reaction2b have been effectively
accelerated by this high pressure.
The Mannich reaction, on the other hand, is synthetically useful
for the construction of nitrogen-containing molecules.3 Recently
many excellent results have appeared describing catalytic asym-
metric variants of this reaction,4-6 among which is an elegant,
asymmetric, three-component Mannich reaction catalyzed by proline
reported independently by List4 and Barbas.5 Despite the high
enantioselectivity, there are limitations to List’s reaction: Yields
are generally insufficient when acetone is used as the Mannich
donor, while the Mannich acceptor should be electron-deficient and
highly reactive.
In this communication, we describe how our newly developed,
high-pressure method has been applied to the List-Barbas-
Mannich reaction, in the expectation that the effects of both high
pressure and low temperature would play pivotal roles; i.e. that
the yield and enantioselectivity would be improved due to the
negative activation volume of the three-component coupling reaction
and the lower temperature, respectively.
The Mannich reaction of p-bromobenzaldehyde, p-anisidine, and
acetone was investigated under high-pressure induced by water-
freezing, and it was found that the Mannich and aldol adducts were
obtained in 57% yield with 95% ee, and in 11% yield with 78%
ee, respectively.7 When the same reaction was performed under
ambient pressure at room temperature, the reaction proceeded
slowly, affording the Mannich adduct in 25% yield with 88% ee,
the aldol product in 10% yield with 74% ee, and 4-(p-bromophenyl)-
3-butene-2-one, the dehydrated product, in 12% yield.
b
entry
aldehyde
MPa
°C
23
h
%
%ee
1c
2
p-nitrobenzaldehyde
p-nitrobenzaldehyde
p-nitrobenzaldehyde
p-nitrobenzaldehyde
p-bromobenzaldehyde
p-bromobenzaldehyde
benzaldehyde
benzaldehyde
1-naphthaldehyde
1-naphthaldehyde
0.1
0.1
50d
94
23 12 20d
90f
98f
91f
88g
95g
79g
93g
86f
93f
96
3
0.1 -20 12
5d
-20 12 58d
23 28 25e
-20 28 57e
23 72 12e
-20 72 99e
23 48 14d
-20 48 67d
4
200
0.1
200
0.1
200
0.1
200
0.1
0.1
200
0.1
200
0.1
200
5
6
7
8
9
10
11c 2-naphthaldehyde
23
35d
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
2-naphthaldehyde
2-naphthaldehyde
o-anisaldehyde
23 24 15d
-20 24 64d
23 24 25e
-20 24 61e
23 96 14e
-20 96 83e
89f
91f
92g
97g
63g
97g
o-anisaldehyde
m-anisaldehyde
m-anisaldehyde
p-anisaldehyde
0.1
0.1
200
0.1
23 96
40
0
p-anisaldehyde
p-anisaldehyde
3,4-dimethoxybenzaldehyde
3,4-dimethoxybenzaldehyde 200
N-acetyl-(4-formyl)aniline
N-acetyl-(4-formyl)aniline
2-furalaldehyde
2-furalaldehyde
cyclohexylcarbaldehyde
cyclohexylcarbaldehyde
4
20e
54g
94g
-20 96 99e
23 96
0
-20 96 65e
95g
0.1
200
0.1
200
0.1
200
23 24
0
-20 24 82d
92f
95f
23 41 65d
-20 41 95d >99f
23 40 23d
4f
-20 40 90d
84f
a The molar ratio of aldehyde:p-anisidine:L-proline ) 1:1.1:0.3, DMSO
was used as solvent. b Isolated yield. c Data of ref 4b. d The yield of the
Mannich adduct. e The two-step yield of the amino alcohol derived from
LiAlH4-reduction of the labile Mannich adduct, see Supporting Information
for details. f Enantiomeric excess was determined by chiral HPLC analysis
of the Mannich adduct. g Enantiomeric excess was determined by chiral
HPLC analysis of the anti-1,3-aminosilyl ether derived from the Mannich
adduct by the following procedure: (1) reduction with LiAlH4, (2) silylation
with TBSOTf and 2,6-lutidine, (3) separation of the anti- from the syn-
isomer. See the Supporting Information for details.
adducts are prone to racemize during purification, they were isolated
as the corresponding amino alcohols after reduction with LiAlH4.
For electron-deficient aldehydes such as p-nitro- and p-bro-
mobenzaldehydes, the yield at room temperature under 0.1 MPa is
only 20-25%, while it is 57-58% under water-freezing high-
pressure conditions, when the optical purity is 91-95% ee (entries
2-6). At low temperature (-20 °C) under 0.1 MPa, the reaction
proceeds very slowly, affording only a minute amount (5%) of the
Mannich adduct in very high optical purity (98% ee) (entry 3).
These results clearly indicate that high pressure decreases the optical
purity8 but increases the reaction rate, while lowering the temper-
ature decreases the reaction rate but increases the optical purity in
the reaction of p-nitrobenzaldehyde.
As the reaction under high pressure gave the Mannich product
in better yield and enantioselectivity without concomitant formation
of the R,â-enone, the present high-pressure method has been applied
to other aldehydes to investigate the generality of the reaction, the
results being summarized in Table 1. As some of the Mannich
The reactions of benzaldehyde, and 1- and 2-naphthaldehydes
under water-freezing high-pressure conditions afford Mannich
† Tokyo University of Science.
| RIKEN.
9
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10.1021/ja0372513 CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
adducts in good yield (64-99%) with excellent enantiomeric excess
(91-93% ee), in marked contrast to the reaction at room temper-
ature under 0.1 MPa, in which low yields (12-15%) and decreased
enantioselectivity (79-89% ee) are obtained (entries 7-13).
For electron-rich aldehydes, both yield and optical yield are low
at room temperature under 0.1 MPa, and in particular, no reaction
proceeds in the cases of p-anisaldehyde, 3,4-dimethoxybenzalde-
hyde, and N-acetyl-(4-formyl)aniline, while good yields (61-99%)
and excellent enantioselectivities (92-97% ee) have been realized
under water-freezing high-pressure conditions (entries 14-24).
Higher temperature (40 °C) had no beneficial effect either on yield
or enantioselectivity as the Mannich product of p-anisaldehyde was
obtained in only 20% yield with lower enantiomeric excess (54%
ee), along with several unidentified products (entry 19), while the
Mannich adduct was obtained quantitatively and in 94% ee (entry
20), without any byproducts under our high-pressure conditions.
2-Furalaldehyde and aliphatic aldehydes such as cyclohexylcar-
baldehyde also react under water-freezing high-pressure conditions
to give Mannich adducts in good yield and high optical purity
(entries 25-28).
side reactions such as the formation of R,â-enone. An especially
noteworthy feature is that electron-rich, aromatic aldehydes, unre-
active substrates under ambient pressure, can be successfully
employed, affording the product in good yield. Moreover, by using
4-tert-butyldimethylsiloxyaniline, removal of the N-substituent can
be successfully performed without affecting any other oxidatively
labile, electron-rich aromatic groups, affording the syn- and anti-
1,3-amino alcohols, both of which are synthetically useful, in high
optical purity. Its high yield, excellent enantioselectivity, and
operational simplicity, combined with the availability and low cost
of the catalyst as well as the diversity of the accessible chemical
structures, mean the present reaction will prove useful in synthesis.
Acknowledgment. This work was supported by a Grant-in-Aid
for Scientific Research on Priority Areas (A) “Exploitation of Multi-
Element Cyclic Molecules” from the Ministry of Education, Culture,
Sports, Science and Technology, Japan. Y. H. thanks Dr. Kiyoshi
Hayakawa at the Kyoto Prefectural Comprehensive Center for small
and medium enterprises for instruction concerning the pressure
induced by water-freezing and a generous gift of autoclaves.
Supporting Information Available: Details of the experimental
procedure and chracterization and physical data of the products (PDF).
This material is available free of charge via the Internet at http://
pubs.acs.org.
Generally a small amount of R,â-enone product was observed
at ambient pressure, which was not formed at high pressure.
The predominant enantiomer formed is the same irrespective of
pressure, and its absolute stereochemistry is expected to be the same
as that determined by List and Barbas et al.4,5
References
Next 4-tert-butyldimethylsiloxyaniline was employed instead of
p-anisidine, because this N-substituent can be easily removed under
mild oxidative conditions. 4-tert-Butyldimethylsiloxyaniline reacts
even with highly electron-rich, unreactive, 3,4-dimethoxybenzal-
dehyde, affording the Mannich adduct with the same efficiency as
does p-anisidine. After reduction with LiAlH4, protection of the
hydroxyl group with TIPSOTf and 2,6-lutidine and separation of
the anti- and syn-isomers, the tert-butyldimethylsiloxyphenyl moiety
could be removed by our recently developed method using PhI-
(OCOCF3)29 to afford the 1,3-amino alcohol, without affecting the
electron-rich 3,4-dimethoxyphenyl moiety, while oxidative removal
with CAN or DDQ gave complex mixtures.10 As selective reduc-
tions of 1,3-aminoketones to both syn- and anti-1,3-amino alcohols
are known,11 the present procedure is one practical method for the
preparation of chiral 1,3-amino alcohols with either syn- or anti-
stereochemistry.
(1) Review, see: (a) Matsumoto, K.; Kaneko, M.; Katsura, H.; Hayashi, N,;
Uchida, T.; Acheson, R. M. Heterocycles 1998, 47, 1135. (b) Ciobanu,
M.; Matsumoto, K. Liebigs Ann. Recl. 1997, 623. (c) Matsumoto, K.;
Sera, A.; Uchida, T. Synthesis 1985, 1. (d) Matsumoto, K.; Sera, A.
Synthesis 1985, 999. (e) Jenner, G. Tetrahedron 2002, 58, 5185. (f) Jenner,
G. Tetrahedron 1997, 53, 2669. (g) Jenner, G. J. Phys. Org. Chem. 2002,
15, 1. (h) High-Pressure Chemistry; van Eldik, R., Klarner, F.-G., Eds.;
Wiley-VCH: Weinheim, 2002.
(2) (a) Hayashi, Y: Nishimura, K. Chem. Lett. 2002, 296. (b) Hayashi, Y.;
Okado, K.; Ashimine, I.; Shoji, M. Tetrahedron Lett. 2002, 43, 8683.
(3) Reviews: (a) Kleinmann, E. F. In ComprehensiVe Organic Synthesis:
Trost, B. M., Ed.; Pergamon Press: New York, 1991; Vol. 2, Chapter
4.1. (b) Arend, M.; Westermann, B.; Risch, N. Angew. Chem., Int. Ed.
1998, 37, 1045.
(4) (a) List, B. J. Am. Chem. Soc. 2000, 122, 9336. (b) List, B.; Pojarliev, P.;
Biller, W. T.; Martin, H. J. Am. Chem. Soc. 2002, 124, 827. Reviews,
see, (c) List, B. Synlett 2001, 1675. (d) List, B. Tetrahedron 2002, 58,
5573.
(5) (a) Notz, W.; Sakthivel, K.; Bui, T.; Zhong, G.; Barbas, C. F., III.
Tetrahedron Lett. 2001, 42, 199. (b) Cordova, A.; Notz, W.; Zhong, G.;
Betancort, J. M.; Barbas, C. F., III. J. Am. Chem. Soc. 2002, 124, 1842.
(c) Cordova, A.; Watanabe, S.; Tanaka, F.; Notz, W.; Barbas, C. F., III.
J. Am. Chem. Soc. 2002, 124, 1866. (d) Cordova, A.; Barbas, C. F., III.
Tetrahedron Lett. 2003, 44, 1923. (e) Cordova, A.; Barbas, C. F., III.
Tetrahedron Lett. 2002, 43, 7749. (f) Watanabe, S.; Cordova, A.; Tanaka,
F.; Barbas, C. F. III. Org. Lett. 2002, 4, 4519.
(6) Recent examples, see: (a) Kobayashi, S.; Kobayashi, J.; Ishitani, H.; Ueno,
M. Chem. Eur. J. 2002, 8, 4185. (b) Wenzel, A. G.; Jacobsen, E. N. J.
Am. Chem. Soc. 2002, 124, 12964 and references therein.
(7) See the Supporting Information for the precise experimental procedures.
(8) There are several reports describing the relationship between enantiose-
lectivity and pressure in asymmetric catalytic reactions. (a) Oishi, T.;
Oguri, H.; Hirama, M. Tetrahedron: Asymmetry 1995, 6, 1241. (b) Marko,
I. E.; Giles, P. R.; Hindley, N. J. Tetrahedron 1997, 53, 1015. (c) Hayase,
T.; Shibata, T.; Soai, K.; Wakatsuki, Y. Chem. Commun. 1998, 1271. (d)
Tietze, L. F.; Ott, C.; Frey, U. Liebigs Ann. 1996, 63. (e) Misumi, Y.;
Bulman, R. A.; Matsumoto, K. Heterocycles 2002, 56, 599. (f) Sera, A.;
Takagi, K.; Katayama, H.; Yamada, H.; Matsumoto, K. J. Org. Chem.
1988, 53, 1157.
In summary, the water-freezing induced-pressure method widens
the scope and generality of the List-Barbas-Mannich reaction,
giving both better yield and enantioselectivity, the increases of yield
and optical purity being due to the high pressure and low
temperature, respectively. High pressure and low temperature are
both essential for the success of this asymmetric catalytic reaction;
the former not only accelerates the reaction but also suppresses
(9) Hayashi, Y.; Tsuboi, W. Unpublished work.
(10) The p-methoxyphenyl protecting group on an amine can be easily removed
by oxidation with CAN. See ref 4b.
(11) Pilli, R. A.; Russowsky, D.; Dias, L. C. J. Chem. Soc., Perkin Trans. 1
1990, 1213.
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