Chiral 1,1′-binaphthyl-2,2′-diammonium salt catalysts for the enantioselective Diels-Alder reaction with α-acyloxyacroleins

Article abstract of DOI:10.1021/ol060490l

A diammonium salt of chiral 1,1′-binaphthyl-2,2′-diamine and trifluoromethanesulfonimide (Tf₂NH) shows excellent catalytic activity and enantioselectivity for the Diels-Alder reaction of α-acyloxyacroleins with cyclic dienes. For example, in th

Full text of DOI:10.1021/ol060490l

ORGANIC
LETTERS
2006
Vol. 8, No. 11
2229-2232
Chiral 1,1
Salt Catalysts for the Enantioselective
Diels Alder Reaction with
-Acyloxyacroleins
′-Binaphthyl-2,2′-diammonium
−
r
Akira Sakakura, Kenji Suzuki, Kazuhiko Nakano, and Kazuaki Ishihara*
Graduate School of Engineering, Nagoya UniVersity, Furo-cho, Chikusa-ku,
Nagoya 464-8603, Japan
ishihara@cc.nagoya-u.ac.jp
Received February 27, 2006
ABSTRACT
A diammonium salt of chiral 1,1
enantioselectivity for the Diels Alder reaction of
ammonium catalyst, the Diels Alder reaction of
′
-binaphthyl-2,2
′
-diamine and trifluoromethanesulfonimide (Tf2NH) shows excellent catalytic activity and
-acyloxyacroleins with cyclic dienes. For example, in the presence of 5 mol % of the
-(cyclohexanecarbonyloxy)acrolein with cyclopentadiene proceeded in EtCN at 75 C to
−
−
r
r
−
°
give the adducts in 88% yield with 92% exo and 91% ee. This catalyst can be easily prepared in situ by mixing the commercially available
chiral diamine and Tf2NH.
The enantioselective Diels-Alder reaction is one of the most
powerful organic transformations and is a versatile method
for the synthesis of many important chiral building blocks
for the total synthesis of bioactive natural products.1 Recently,
the development of methods based on metal-free organoca-
talysis has attracted great attention in this area.2-4 MacMillan
and co-workers reported the first enantioselective organo-
catalytic Diels-Alder reaction of dienes with R-unsubstituted
acroleins and 2-enones.2 Their catalysts, which were chiral
ammonium salts of HCl or HClO4 with secondary amines
derived from L-phenylalanine, gave good results for the
Diels-Alder reaction of R-unsubstituted acroleins and
2-enones. However, it is difficult to activate R-substituted
acroleins with the catalysts, probably because of poor
generation of the corresponding iminium cations. The
relatively greater bulkiness of the secondary amines was
(1) For review, see: Corey, E. J. Angew. Chem., Int. Ed. 2002, 41, 1650.
(2) (a) Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem.
Soc. 2000, 122, 4243. (b) Northrup, A. B.; MacMillan, D. W. C. J. Am.
Chem. Soc. 2002, 124, 2458.
(3) For chiral organocatalysts for Diels-Alder reactions, see: (a) Huang,
Y.; Unni, A. K.; Thadani, A. N.; Rawal, V. H. Nature 2003, 424, 146. (b)
Kim, K. H.; Lee, K. S.; Lee, D.-W.; Ko, D.-H.; Ha, D.-C. Tetrahedron
Lett. 2005, 46, 5991. (c) Lemay, M.; Ogilvie, W. W. Org. Lett. 2005, 7,
4141.
(4) For a recent review on hydrogen-bonding catalysis, see: Taylor, M.
S.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2006, 45, 1520.
10.1021/ol060490l CCC: $33.50
© 2006 American Chemical Society
Published on Web 04/26/2006

thought to be unfavorable for generating an iminium ion with
R-substituted acrolein.5
report a new organocatalyst, an ammonium salt of (S)-2,2′-
diamino-1,1′-binaphthyl (2) with trifluoromethanesulfonimide
(Tf2NH), for the enantioselective Diels-Alder reaction of
cyclic dienes with R-acyloxyacroleins (Figure 1).
First, we examined the Diels-Alder reaction of cyclo-
pentadiene (4 equiv) with methacrolein using chiral am-
monium salts of commercially available chiral aromatic
diamine 2 (5 mol %) and several Brønsted acids (HX, 9.5
mol %) in propionitrile (EtCN) at -75 °C (Table 1). The
Recently, we reported the enantioselective organocatalytic
Diels-Alder reaction with R-acyloxyacrolein.6 R-Acyloxy-
acrolein is an important alternative to R-haloacrolein7 and
has versatile synthetic utility as a dienophile.8 Our catalyst
is the chiral ammonium salt of pentafluorobenzenesulfonic
acid (C6F5SO3H)9 with the chiral triamine 1 bearing a primary
aliphatic amino group (Figure 1). The Diels-Alder reactions
Table 1. Diels-Alder Reaction of Cyclopentadiene with
Methacroleina
Figure 1. Chiral aliphatic triamine 1 including a primary amino
group and aromatic primary diamine 2.
entry
HX
time (h) yield (%) exo/endo eeb (%)
1
2
3
C6F5SO3H
TfOH
Tf2NH
15
6
6
8
27
13
90:10
97:3
97:3
45
39
61
of acyclic dienes and cyclohexadiene with R-(p-methoxy-
benzoyloxy)acrolein give the adducts with high enantiose-
lectivities. But unfortunately, the enantioselectivity for the
reaction of cyclopentadiene is up to 83% ee (20 mol % of
catalyst loading). In addition, the catalytic activity is not so
high (10∼20 mol % of catalyst is loaded at -20 °C to rt)
because of its relatively weak acidity. The adducts of
cyclopentadiene with R-acyloxyacrolein can be converted to
bicyclo[2.2.1]hept-5-en-2-one, which is a promising synthetic
intermediate for the total synthesis of several bioactive
compounds,10 and the development of a practical method for
the synthesis of the compound in an enantiomerically pure
form is strongly needed. To improve the catalytic activity
and the enantioselectivity for the Diels-Alder reaction of
cyclopentadiene, the use of the ammonium salt of a weakly
basic aromatic amine with a super Brønsted acid9 at a lower
reaction temperature would be desirable. In this paper, we
a The Diels-Alder reaction of cyclopentadiene (4 mmol) with methac-
rolein (1 mmol) in EtCN (2 mL) was carried out at -75 °C. b Enantiomeric
excess of the exo adduct.
ammonium salt of 2 and C6F5SO3H gave (2R)-exo adduct
as a major diastereomer in a conversion yield of 8% with
45% ee (entry 1). The use of trifluoromethanesulfonic acid
(TfOH) gave an enantioselectivity (39% ee) similar to that
of C6F5SO3H (entry 2). The use of other sulfonic acids such
as (+)-camphorsulfonic acid and 2,4,6-triisopropylbenzene-
sulfonic acid gave the adducts with low enantioselectivities
(<13% ee). On the other hand, ammonium salt of 2 and Tf2-
NH gave the Diels-Alder adduct with better enantioselec-
tivity (61% ee) (entry 3).
We then investigated several ammonium salts of N-
monosubstituted or N,N′-disubstituted 2,2′-diamino-1,1′-
binaphthyls and Tf2NH. But unfortunately, they all gave the
adduct with lower enantioselectivity (<13% ee).
(5) MacMillan failed to activate methacrolein with a secondary am-
monium salt: Kunz, R. K.; MacMillan D. W. C. J. Am. Chem. Soc. 2005,
127, 3240.
Next, we examined the Diels-Alder reaction of cyclo-
pentadiene (4 equiv) with R-acyloxyacroleins catalyzed by
the ammonium salt of 2 (5 mol %) and Tf2NH (9.5 mol %)
(Table 2). The Diels-Alder reaction with R-(p-methoxy-
benzoyloxy)acrolein, which gave the highest enantiomeric
excess (83%) in the Diels-Alder reaction of cyclopentadiene
catalyzed by the ammonium salt of 1 and C6F5SO3H,6 gave
the corresponding (2S)-exo adduct as a major diastereomer
with higher enantiomeric excess (94%) in moderate yield
(48%) (entry 1). This result prompted us to investigate the
Diels-Alder reaction of cyclopentadiene with several R-acyl-
oxyacroleins catalyzed by the ammonium salt of 2 and Tf2-
NH. After screening of several R-acyloxyacroleins, we found
that R-(cyclohexanecarbonyloxy)acrolein gave the corre-
sponding adduct with good enantioselectivity (86% ee) and
in good yield (80%) (entry 2). The use of the ammonium
(6) Ishihara, K.; Nakano, K. J. Am. Chem. Soc. 2005, 127, 10504.
(7) (a) Corey, E. J.; Loh, T.-P. J. Am. Chem. Soc. 1991, 113, 8966. (b)
Marshall, J. A.; Xie, S. J. Org. Chem. 1992, 57, 2987. (c) Corey, E. J.;
Cywin, C. L. J. Org. Chem. 1992, 57, 7372. (d) Corey, E. J.; Loh, T.-P.
Tetrahedron Lett. 1993, 34, 3979. (e) Ishihara, K.; Qingzhi, G.; Yamamoto,
H. J. Org. Chem. 1993, 58, 6917. (f) Ishihara, K.; Yamamoto, H. J. Am.
Chem. Soc. 1994, 116, 1561. (g) Corey, E. J.; Guzman-Perez, A.; Loh,
T.-P. J. Am. Chem. Soc. 1994, 116, 3611. (h) Ishihara, K.; Kurihara, H.;
Yamamoto, H. J. Am. Chem. Soc. 1996, 118, 3049. (i) Ishihara, K.; Kurihara,
H.; Matsumoto, M.; Yamamoto, H. J. Am. Chem. Soc. 1998, 120, 6920. (j)
Corey, E. J.; Shibata, T.; Lee, T. W. J. Am. Chem. Soc. 2002, 124, 3808.
(8) Funk, R. L.; Yost, K. J., III. J. Org. Chem. 1996, 61, 2598.
(9) C6F5SO3H is a weaker Brønsted acid than TsOH. (a) Ishihara, K.;
Nakagawa, S.; Sakakura, A. J. Am. Chem. Soc. 2005, 127, 4168. (b)
Sakakura, A.; Nakagawa, S.; Ishihara, K. Tetrahedron 2006, 62, 422.
(10) (a) Greene, A. E.; Le Drian, C.; Crabbe´, P. J. Am. Chem. Soc. 1980,
102, 7583. (b) Salomon, R. G.; Sachinvala, N. D.; Roy, S.; Basu, B.;
Raychaudhuri, S. R.; Miller, D. B.; Sharma, R. B. J. Am. Chem. Soc. 1991,
113, 3085. (c) Marschner, C.; Baumgartner, J.; Griemgl, H. J. Org. Chem.
1995, 60, 5224. (d) Wang, G. T.; Wang, S.; Chen, Y.; Gentles, R.; Sowin,
T. J. Org. Chem. 2001, 66, 2052. (e) Zhu, X.-F.; Nydegger, F.; Gossauer,
A. HelV. Chim. Acta 2004, 87, 2245.
2230
Org. Lett., Vol. 8, No. 11, 2006

Table 2. Diels-Alder Reaction of Cyclopentadiene with
R-Acyloxyacroleinsa
Table 3. Diels-Alder Reaction of Dienes with
R-Acyloxyacroleinsa
eeb (%)
solvent yield (%) exo/endo [config]
entry
R
time (h) yield (%) exo/endo eeb (%)
entry diene
R
1
2
3c
4d
5d
p-MeOC6H4
c-C6H11
c-C6H11
c-C6H11
c-C5H9
28
24
24
24
24
48
80
72
88
95
93:7
94:6
91:9
92:8
92:8
94
86
71
91
88
1c
2
3
4c
5c
CHd
CHd
CHd
c-C6H11 EtCN
c-C6H11 EtNO2
c-C5H9 EtNO2
92
90
97
88
98
<1:>99 91 [2S]
<1:>99 91 [2S]
<1:>99 87 [2S]
70 [-]
DMBd c-C6H11 EtNO2
DMBd c-C5H9 EtNO2
65 [-]
a Unless otherwise noted, the Diels-Alder reaction of cyclopentadiene
(1.6 mmol) with R-acyloxyacrolein (0.4 mmol) in EtCN (0.8 mL) was
carried out at -75 °C. b Enantiomeric excess of the exo adduct. c The
reaction was conducted in the presence of 2 (5 mol %) and Tf2NH (5 mol
%). d The reaction was conducted in the presence of 10 mol % of water.
a Unless otherwise noted, the Diels-Alder reaction of dienes (1.6 mmol)
with R-acyloxyacroleins (0.4 mmol) in solvent (0.8 mL) was carried out at
-75 °C. b Enantiomeric excess of the major diastereomer. c The reaction
was conducted in the presence of 2 (10 mol %), Tf2NH (19 mol %), and
water (10 mol %). d See text.
salt of 2 (5 mol %) and Tf2NH (5 mol %) as a catalyst gave
a lower yield (72%) and enantioselectivity (71%) (entry 3).
When the reaction with R-(cyclohexanecarbonyloxy)acrolein
was conducted in the presence of 10 mol % of water,11 the
yield and enantioselectivity were increased (88% yield and
91% ee) (entry 4). R-(Cyclopentanecarbonyloxy)acrolein also
gave good results (95% yield, 88% ee) (entry 5).
of acyclic dienes, such as 2,3-dimethylbutadiene (DMB),
gave the corresponding adducts in high (88-98%) yield with
moderate (65-70%) enantioselectivities (entries 4 and 5).
1
Next, a H NMR study was conducted to explore the
reaction mechanism. In the case of the present Diels-Alder
reaction, two reaction mechanisms can be proposed. One
reaction mechanism includes reversible formation of the
aldimine intermediate activated by a Brønsted acid, as
reported by us.6 The other is chiral Brønsted acid catalysis,
as reported by Rawal.14 Thus, we examined whether the
aldimine could be formed from R-acyloxyacrolein and 2‚
To explore the generality and scope of the Diels-Alder
reaction with R-acyloxyacroleins catalyzed by the ammonium
salt of 2 and Tf2NH, the Diels-Alder reaction of not only
cyclic dienes but also acyclic dienes was examined (Table
3). For the Diels-Alder reaction of cyclohexadiene (CH)
with R-(cyclohexanecarbonyloxy)acrolein in EtCN, 10 mol
% of the catalyst was used because the reactivity of
cyclohexadiene was lower than that of cyclopentadiene and
gave the corresponding (2S)-endo-adduct as a major dia-
stereomer (>99% de) in 92% yield with 91% ee (entry 1).
The use of EtNO2 as a solvent increased the reactivity, and
5 mol % of the catalyst was active enough for the Diels-
Alder reaction of cyclohexadiene (90% yield, 91% ee) (entry
2).12 R-(Cyclopentanecarbonyloxy)acrolein also gave good
results (97% yield, 87% ee) (entry 3). The Diels-Alder
adducts of cyclohexadiene with R-acyloxyacrolein can be
converted to bicyclo[2.2.2]oct-5-en-2-one, which is also
useful as a common intermediate for the total syntheses of
several bioactive compounds.13 The Diels-Alder reaction
1
1.9Tf2NH by an H NMR study. R-(Cyclohexanecarbonyl-
oxy)acrolein was mixed with 2 (1 equiv) and Tf2NH (1.9
1
equiv) in CD3CN and analyzed by H NMR. Three new
singlets corresponding to an aldimine proton (8.96 ppm,
-CHdNH+-) and protons of an exo-methylene group (6.68
and 6.60 ppm, CH2dC-) appeared in the spectra, which
suggested formation of the aldimine, albeit only a small
amount (ca. 5%). The fact that a catalytic amount of water
promoted the Diels-Alder reaction also suggested the
formation of the aldimine as an active intermediate.
According to an X-ray structural analysis of R-(p-meth-
oxybenzoyloxy)acrolein, the plane of the s-trans acrolein
moiety and the plane of the acyloxy group can be distorted
(Figure 2, top).15 A transition state was proposed on the basis
1
of the H NMR study and the X-ray structure of R-(p-
methoxybenzoyloxy)acrolein as shown in Figure 2 (bottom).
The present Diels-Alder reaction might proceed via TS-1
or TS-2. In each transition-state assembly, one of the amino
groups of the diamine forms the aldimine with R-acyloxy-
acrolein, and the other amino group forms the ammonium
salt with Tf2NH. In TS-1, the aldimine is activated by the
other molecule of Tf2NH to be the active dication intermedi-
(11) The reaction conducted in the presence of water (100 mol %) gave
similar results. When the reaction was carried out in the presence of more
than 500 mol % of water, solvent was partially frozen and the reactivity
was decreased.
(12) When the Diels-Alder reaction of cyclopentadiene with R-acy-
loxyacroleins was conducted in EtNO2, cyclopentadiene polymerized and
the Diels-Alder adducts were obtained with low enantioselectivity.
(13) (a) Evans, D. A.; Golob, A. M.; Mandel, N. S.; Mandel, G. S. J.
Am. Chem. Soc. 1978, 100, 8170. (b) Kozikowski, A. P.; Schemissing, R.
J. J. Org. Chem. 1983, 48, 1000. (c) Demuth, M.; Chandrasekhar, S.;
Schaffner, K. J. Am. Chem. Soc. 1984, 106, 1092. (d) Smith, A. B., III;
Empfield, J. R.; Rivero, R. A.; Vaccaro, H. A.; Duan, J. J.-W.; Sulikowski,
M. M. J. Am. Chem. Soc. 1992, 114, 9419.
(14) (a) Thadani, A. N.; Stankovic, A. R.; Rawal, V. H. Proc. Natl. Acad.
Sci. U.S.A. 2004, 101, 5846.
Org. Lett., Vol. 8, No. 11, 2006
2231

NH. Therefore, TS-2 should be less reactive than TS-1.
Indeed, the reaction catalyzed by the ammonium salt of 2
(5 mol %) and Tf2NH (5 mol %), which should proceed via
TS-2, gave the low reactivity and low enantioselectivity
(Table 2, entry 3). Therefore, it is suggested that the present
Diels-Alder reaction proceeded via TS-1.
In conclusion, we have developed the chiral ammonium
salt of binaphthyl-based diamine 2 with Tf2NH as a catalyst
for the enantioselective Diels-Alder reaction. The use of a
small amount (5 mol %) of this chiral ammonium catalyst
at a lower reaction temperature (-75 °C) allowed better
reactivity and enantioselectivity than with the ammonium
salt of triamine 1 with C6F5SO3H in the Diels-Alder reaction
of cyclic dienes with R-acyloxyacroleins. The ammonium
catalyst could be easily prepared in situ by mixing com-
mercially available 2,2′-diamino-1,1′-binaphthyl 2 and Tf2-
NH.
Acknowledgment. Financial support for this project was
provided by JSPS KAKENHI(15205021) and the 21st
Century COE Program of MEXT.
Figure 2. ORTEP plot of R-(p-methoxybenzoyloxy)acrolein (top)
and proposed transition-state assemblies (bottom). Counteranions
(Tf2N-) are omitted for clarity.
Supporting Information Available: Experimental pro-
cedures and full characterization of new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
ate. Moreover, the acyloxy group should be activated by a
linear intramolecular hydrogen bonding with a proton of the
ammonium group in the same molecule. In TS-1, the diene
should approach the si-face of the dienophile from the less-
hindered side to give the (2S)-exo adduct. On the other hand,
in TS-2, both the aldimine and the acyloxy group are
activated by the ammonium protons in the same molecule.
However, the two intramolecular hydrogen bondings of the
nitrogen of aldimine with a proton of the ammonium group
(N‚‚‚H-N) and the carbonyl oxygen of the acyloxy group
with a proton of the ammonium group (O‚‚‚H-N) are not
linear; therefore, these hydrogen bondings are weak, and
TS-2 is confomationally unstable. Moreover, the aldimine
of TS-2 is activated by the weakly acidic ammonium group,
while the aldimine of TS-1 is activated by superacidic Tf2-
OL060490L
(15) Crystal data for R-(p-methoxybenzoyloxy)acrolein: Bruker SMART
APEX diffractometer with CCD detector (graphite monochromator, Mo KR
radiation, λ ) 0.71073 Å). The structure was solved by direct methods and
expanded using Fourier techniques: formula C11H10O4, colorless, crystal
dimensions 0.20 × 0.20 × 0.20 mm3, monoclinic, space group P21(#4), a
) 6.437(2) Å, b ) 7.173(3) Å, c ) 22.181(8) Å, â ) 95.980(7)°, V )
1018.5(7) Å3, Z ) 4, and Dcalc ) 1.345 g cm-3, F(000) ) 432, µ ) 0.103
mm-1, T ) 223(2) K. 2635 reflections collected, 2022 independent
reflections with I > 2σ(I) (2θmax ) 29.07°), and 176 parameters were used
for the solution of the structure. The non-hydrogen atoms were refined
anisotropically. R1 ) 0.0542 and wR2 ) 0.1613, GOF ) 1.063. Crystal-
lographic data (excluding structure factors) for the structure reported in
this paper have been deposited with Cambridge Crystallographic Data
Centre. Copies of the data can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax: int. code + 44-
(1223)336-033; E-mail: deposit@ccdc.cam.ac.uk]. Supplementary publica-
tion no. CCDC-286812.
2232
Org. Lett., Vol. 8, No. 11, 2006