Chiral tetraaminophosphonium carboxylate-catalyzed direct mannich-type reaction

Article abstract of DOI:10.1021/ja806311e

The cooperative asymmetric catalysis of chiral tetraaminophosphonium carboxylate (P,S)-1·OCOR has been established, and its synthetic utility has been successfully demonstrated by application to the highly enantioselective direct Mannich-type reaction of

Full text of DOI:10.1021/ja806311e

Published on Web 10/04/2008
Chiral Tetraaminophosphonium Carboxylate-Catalyzed Direct Mannich-Type
Reaction
Daisuke Uraguchi, Yusuke Ueki, and Takashi Ooi*
Department of Applied Chemistry, Graduate School of Engineering, Nagoya UniVersity, Nagoya 464-8603, Japan
Received August 16, 2008; E-mail: tooi@apchem.nagoya-u.ac.jp
Organic ion pair catalysis, particularly that involving chiral, nonracemic
onium salts, occupies a unique place in the recent development of organic
molecular catalysis,1 and its characteristic features have attracted significant
attention from industrial and academic communities. In the catalysis of
chiral quaternary onium salts, the cation structure is regarded as the most
important element for controlling reactivity and selectivity. Accordingly,
a catalyst manifold has been created for different types of reactions such
as a phase-transfer-catalyzed bond formation by the modification of a
cationic moiety.2 Although the anion part of the salts is essential for
Figure 1. Working hypothesis for the salt catalysis of 1·OCOR.
neutralizing the charge, it is hardly associated with the overall efficiency
and/or stereoselectivity in the targeted transformation because of the
multiple ion-exchange processes. Even in the case of chiral onium salts
bearing Lewis basic anions, their roles have been restricted to the activation
of silyl nucleophiles for initiating the catalysis.3,4 Thus, the inherent
synthetic relevance of incorporating tunable, functional anions to the parent
quaternary onium salts is yet to be explored.5 In this context, we are
interested in the possibility of establishing a novel catalysis of chiral
quaternary onium salts possessing an appropriate organic anion, which
can be controlled by not only the structural manipulation of the cation but
also that of the initial anion through its continuous participation in the
catalytic cycle. Here, we report such an asymmetric catalysis of chiral
tetraaminophosphonium carboxylate 1·OCOR and demonstrate its utility
in the highly enantioselective direct Mannich-type reaction of azlactones
(eq 1).
enolate anion, rendering the ion pair assembly with a defined hydrogen-
bonding network (A). Subsequent stereoselective bond formations with
imine would afford phosphonium sulfonamide B that could be rapidly
protonated by carboxylic acid to regenerate the chiral phosphonium
carboxylate.
Initial experiments to examine this hypothesis were conducted by
treating phenylalanine-derived azlactone 2a with N-tosyl imine 3a in the
presence of chiral aminophosphonium formate (M,S)-1·OCHO (2 mol%),
readily prepared from (M,S)-1·Cl through ion exchange, in THF at -40
°C (eq 2). After 3.5 h of stirring, the desired Mannich adduct 4a was
obtained near quantitatively with a syn/anti ratio of 1.3:1 (6% ee for the
major syn isomer). Interestingly, tuning the basicity of the anionic
component by changing it to acetate [(M,S)-1·OAc] and then to pivalate
[(M,S)-1·OPiv] led to a substantial rate enhancement though the stereo-
selectivities were virtually unaffected.7 This observation strongly suggested
the intervention of the expected protonation-deprotonation sequence.
Another intriguing observation was that the enantioselectivity was dramati-
cally improved by simply switching the chirality of the phosphorus center
of the catalyst, and syn-4a was obtained in 60% ee under the influence of
(P,S)-1·OPiv.13 The origin of this quantum leap of the enantioselectivity
could be ascribed to the difference in the hydrogen-bonding manner
depending on the P-spiro chirality of 1 as revealed by the single crystal
X-ray diffraction analyses of (M,S)- and (P,S)-1·Cl (Figure 2). While the
two N-H protons of the (M,S)-isomer are mutually disposed in opposite
directions and interact with Cl- and a water molecule, respectively, those
of the (P,S)-isomer are oriented on the same side, capturing the anion
simultaneously. The latter, more structured ion pairing assisted by the
double hydrogen bonding would be crucial for inducing high selectivity.
Further optimization was made by examining the effect of the aromatic
substituents (Ar1, Ar2) in the substrates 2 and 3. With respect to azlactone
2, the introduction of more electron-donating, methoxy-substituted phenyl
groups enhanced enantioselectivity (entries 1-3, Table 1). This can be
At the outset of our study, we sought to employ our recently developed
[5,5]-P-spirocyclic tetraaminophosphonium framework as a primary
structure of the key onium ion and carboxylate as an organic counteranion.6
Considering the general basicity of the carboxylate anion,7 we selected
the direct and stereoselective Mannich-type reaction8 of oxazol-5-(4H)-
one (2), i.e., azlactone,9 with sulfonyl imine 3 to evaluate the salt
catalysis.10 We also recognized that this particular Mannich-type protocol
could provide new access to differently protected, optically active R,ꢀ-
diamino acids with an R-tetrasubstituted carbon stereocenter.11,12 In an
illustration of the expected catalytic cycle (Figure 1), a basic carboxylate
anion would abstract the active methine proton of azlactone to give the
corresponding chiral phosphonium enolate. To achieve high levels of
enantiocontrol, enforcing the geometrically identical ion pairing seemed
to be important. This led us to presume that use of a partially yet selectively
alkylated aminophosphonium cation such as 1 could minimize the mode
of the secondary interaction between the phosphonium cation and the
9
14088 J. AM. CHEM. SOC. 2008, 130, 14088–14089
10.1021/ja806311e CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Deprotection of syn-4h to R,ꢀ-Diamino Acid
Dihydrochloride (Ar1 ) 3,4,5-(CH3O)3-C6H2, Ar2 ) 2,5-xylyl)
4h (92% ee) with aqueous H2SO4 in THF quantitatively afforded the
corresponding carboxylic acid. Complete deprotection was then achieved
by simple acidic hydrolysis with hydrochloric acid at 100 °C, and
subsequent purification through an ion-exchange resin (Amberlite IR120,
H+ form) gave 6 in 87% yield (92% ee) (Scheme 1).16
Figure 2. ORTEP diagrams of (M,S)- and (P,S)-1·Cl (all calculated hydrogens
and a solvent molecule were omitted for clarity).
Table 1. Effect of Protective Groups (Ar1, Ar2) on
Stereoselectivitya (eq 1; R1 ) PhCH2, R2 ) PhCH2CH2)
In conclusion, the cooperative asymmetric catalysis of chiral tetraami-
nophosphonium carboxylate has been presented, and its synthetic utility
has been successfully demonstrated by the application to the highly
enantioselective direct Mannich-type reaction of azlactones with N-sulfonyl
imines. Further studies based on this concept will be reported in due course.
Ar1
(2)
Ar2
(3)
time yieldb
drc
(syn/anti) (%)
eed prod
entry
(h)
(%)
4
1
2
3
4
5
6
7e
4-CH3O-C6H4
4-tolyl
7
30
5
9
9
97
89
98
99
97
95
99
2.2:1
2.2:1
2.6:1
2.9:1
4.5:1
6.7:1
7.1:1
64 4b
65 4c
75 4d
93 4e
96 4f
95 4g
97
2-CH3O-C6H4
3,4,5-(CH3O)3-C6H2
mesityl
2,4-xylyl
2,5-xylyl
Acknowledgment. This work was supported by the Kurata Memo-
rial Hitachi Science and Technology Foundation, the Global COE Program
in Chemistry of Nagoya University, and a Grant-in-Aid for Scientific
Research on Priority Areas “Chemistry of Concerto Catalysis” from the
MEXT, Japan.
9
20
a Unless otherwise noted, reactions were performed at -40 °C using
(P,S)-1·OPiv as a catalyst. See Supporting Information for details. b Isolated
yield. c Determined by 1H NMR analysis of crude reaction mixture.
d Enantiomeric excess of syn isomer, which was determined by chiral HPLC
analysis. Absolute configuration of 4g was determined to be (2S,3R) by X-ray
diffraction analysis after hydrolysis of azlactone, and the configurations of the
other products were assigned on the analogy. e Reaction was conducted at -50
°C.
Supporting Information Available: Representative experimental
procedures and spectral data of 1·OCOR and 2-6. Crystallographic data for
(M,S)- and (P,S)-1·Cl. This material is available free of charge via the Internet
at http://pubs.acs.org.
References
Table 2. Substrate Scope of the Direct Mannich-Type Reaction of
Azlactonea (eq 1; Ar1 ) 3,4,5-(CH3O)3-C6H2, Ar2 ) 2,5-xylyl)
(1) For reviews on organocatalysis, see: (a) Dalko, P. I.; Moisan, L. Angew.
Chem., Int. Ed. 2004, 43, 5138. (b) Pellissier, H. Tetrahedron 2007, 63,
9267. (c) Dondoni, A.; Massi, A. Angew. Chem., Int. Ed. 2008, 47, 4638.
(2) Asymmetric Phase Transfer Catalysis; Maruoka, K., Ed.; Wiley-VCH:
Weinheim, Germany, 2008.
R1
(2)
R2
(3)
time yieldb
drc
(syn/anti) (%)
eed prod
entry
(h)
(%)
4
(3) Nagao, H.; Kawano, Y.; Mukaiyama, T. Bull. Chem. Soc. Jpn. 2007, 80,
2406.
1
2
3
4
5
6
7
8
9
PhCH2
CH3
CH3(CH2)7
CH2dCH(CH2)8 21
PhCH2OCH2
PhCO2CH2
(CH3)2CHCH2
cHex
12
20
91
92
99
98
88
94
98
99
97
4.5:1
6.6:1
7.6:1
5.3:1
12:1
4.4:1
2.3:1
7.8:1
3.1:1
92 4h
96 4i
96 4j
95 4k
93 4l
95 4m
90 4n
96 4o
90 4p
(4) Ooi, T.; Maruoka, K. Acc. Chem. Res. 2004, 37, 526.
(5) Examples for chiral counteranion strategy in catalytic asymmetric
syntheses: (a) Mayer, S.; List, B. Angew. Chem., Int. Ed. 2006, 45, 4193.
(b) Hamilton, G. L.; Kang, E. J.; Mba, M.; Toste, F. D. Science 2007, 317,
496. (c) Rueping, M.; Antonchick, A. R.; Brinkmann, C. Angew. Chem.,
Int. Ed. 2007, 46, 6903. (d) Raheem, I. T.; Thiara, P. S.; Peterson, E. A.;
Jacobsen, E. N. J. Am. Chem. Soc. 2007, 129, 13404. (e) Wang, X.; List,
B. Angew. Chem., Int. Ed. 2008, 47, 1119. There are numbers of important
reports on anion effect in the catalysis of chiral amines, which involves
protonated ammonium salts; see for example : Mase, N.; Tanaka, F.; Barbas,
C. F., III Angew. Chem., Int. Ed. 2004, 43, 2420.
14
24
17
37
15
14
(CH3)2CHCH2 PhCH2CH2
CH3OCH2
a Reactions were performed at -50 °C with (P,S)-1·OPiv as a catalyst. See
(6) Uraguchi, D.; Sakaki, S.; Ooi, T. J. Am. Chem. Soc. 2007, 129, 12392.
(7) pKa values of selected carboxylic acids in water: formic acid, 3.75; benzoic
acid, 4.19; acetic acid, 4.76; pivalic acid, 5.03.
Supporting Information for details. b-d See footnotes in Table 1.
understood by assuming the formation of a tighter ion pair as a
consequence of the increased electron density on the oxygen of the enolate
of 3.14 Moreover, the subsequent screening of the sulfonyl substituent on
the imine nitrogen in the reactions with 3 possessing the 3,4,5-trimethox-
yphenyl moiety revealed its significant impact on the stereoselectivity. A
synthetically useful diastereoselectivity and an excellent enantioselectivity
were attained when 2,5-xylylsulfonyl imine was employed (entries 3-6).
Finally, decreasing the reaction temperature to -50 °C enabled the highest
level of stereochemical control (entry 7).
Experiments were then conducted to probe the scope of the present
(P,S)-1·OPiv-catalyzed, asymmetric direct Mannich-type protocol. The
representative results are listed in Table 2. A variety of aliphatic imines
having different substitution patterns are well accommodated,15 and even
the reaction with sulfonyl imine derived from acetaldehyde proceeds
smoothly in a highly stereoselective manner (entries 1-7). Not only
phenylalanine but also other R-amino acid derived azlactones are employ-
able as nucleophilic reacting partners (entries 8 and 9).
(8) For reviews on organocatalyzed Mannich-type reactions, see: (a) Ting, A.;
Schaus, S. E. Eur. J. Org. Chem. 2007, 5797. (b) Verkade, J. M. M.; van
Hemert, L. J. C.; Quaedflieg, P. J. L. M.; Rutjes, F. P. J. T. Chem. Soc.
ReV. 2008, 37, 29.
(9) (a) Fisk, J. S.; Mosey, R. A.; Tepe, J. J. Chem. Soc. ReV. 2007, 36, 1432.
(b) Cabrera, S.; Reyes, E.; Alemán, J.; Milelli, A.; Kobbelgaard, S.;
Jørgensen, K. A. J. Am. Chem. Soc. 2008, 130, 12031.
(10) Dalla Croce, P.; Ferraccioli, R.; La Rosa, C. J. Chem. Soc., Perkin Trans.
1 1994, 2499.
(11) Review on R,ꢀ-diamino acids: Viso, A.; de la Pradilla, R. F.; Garc´ıa, A.;
Flores, A. Chem. ReV. 2005, 105, 3167.
(12) Catalytic asymmetric synthesis of R-substituted R,ꢀ-diamino acids: (a)
Knudsen, K. R.; Jørgensen, K. A. Org. Biomol. Chem. 2005, 3, 1362. (b)
Chen, Z.; Morimoto, H.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc.
2008, 130, 2170. (c) Singh, A.; Johnston, J. N. J. Am. Chem. Soc. 2008,
130, 5866. (d) Uraguchi, D.; Koshimoto, K.; Ooi, T. J. Am. Chem. Soc.
2008, 130, 10878.
(13) Tetraaminophosphonium carboxylates without N-methyl groups were not
suitable for the present transformation in terms of the stereoselectivity.
(14) Similar observation was reported in the chiral quaternary ammonium salt-
catalyzed asymmetric phase-transfer alkylation: Corey, E. J.; Bo, Y.; Busch-
Petersen, J. J. Am. Chem. Soc. 1998, 120, 13000.
(15) This protocol is not effective for aromatic imines (R1 ) PhCH2, R2 ) Ph
in Table 2; 41 h, 98%, dr ) 1.1:1, 15% ee for major isomer).
(16) The conservation of enantiomeric purity was confirmed by HPLC analysis
after derivatization to the corresponding fully protected R,ꢀ-diamino acid
ester. See Supporting Information for details.
The Mannich adduct 4 can easily be converted into the corresponding
R,ꢀ-diamino acid dihydrochloride 6 in two steps without the loss of
enantiopurity. For instance, the treatment of diastereomerically pure syn-
JA806311E
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J. AM. CHEM. SOC. VOL. 130, NO. 43, 2008 14089