Quaternary ammonium dendrimers as Lewis base catalysts for Mukaiyama-Aldol reaction

Article abstract of DOI:10.1246/cl.2005.420

Surface-alkylated poly(propylene imine) dendrimer was treated with methyl iodide to afford quaternarized ammonium iodide dendrimer. The quaternarized dendrimer catalyzed the Mukaiyama-Aldol reaction of trimethylsilyl acetal with various aldehydes as a Lew

Full text of DOI:10.1246/cl.2005.420

420
Chemistry Letters Vol.34, No.3 (2005)
Quaternary Ammonium Dendrimers as Lewis Base Catalysts for Mukaiyama–Aldol Reaction
Tomoo Mizugaki, Casey E. Hetrick,y Makoto Murata, Kohki Ebitani, Michael D. Amiridis,y and Kiyotomi Kanedaꢀ
Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University,
1-3 Machikaneyama, Toyonaka, Osaka 560-8531
yDepartment of Chemical Engineering, University of South Carolina, Columbia, SC 29208, U.S.A.
(Received December 20, 2004; CL-041569)
Surface-alkylated poly(propylene imine) dendrimer was
treated with methyl iodide to afford quaternarized ammonium
iodide dendrimer. The quaternarized dendrimer catalyzed the
Mukaiyama–Aldol reaction of trimethylsilyl acetal with various
aldehydes as a Lewis base in apolar toluene solvent.
amino groups) was dissolved in 10 mL of DMF and then CH3I
(33.7 mmol, 10 equiv. to tertiary amino group) was added and
stirred at 50 ꢁC for 15 h under Ar.
After evaporation of DMF and excess CH3I, the residue was
washed with ether and dried in vacuo at 50 ꢁC to yield the cor-
responding quaternary ammonium iodide dendrimer (Q-G3-
C10(Iꢂ)) as shown in Figure 1.15 1H NMR (CDCl3, 400 MHz,
50 ꢁC): ꢀ ¼ 0:880 (t, J ¼ 6:79 Hz, –CH2CH3), 1.26 (br,
–(CH2)–), 1.60 (br –CH2CH3), 2.0–2.8 (br, –NþCH3), 3.2–4.2
(br, –Nþ(CH2)3–). Anal. Calcd for C262H538N30O16I14: C,
51.23; H, 8.83; N, 6.84. Found: C, 50.73; H, 9.13; N, 6.54. Q-
G3-C16(Iꢂ) was also prepared according to the above proce-
dure.16
Dendrimers are highly branched macromolecules with high-
ly congested peripheral end groups and hollow interiors.1 Vari-
ous organic molecules,2 metal complexes,3 and metal nanoparti-
cles4 can be encapsulated within voids in the dendrimers to con-
struct nanoreactors, which have received considerable attention
because of their unique catalyses.5
The catalytic performance of the quaternarized dendrimers
was examined in the Mukaiyama–Aldol reaction of 1-me-
thoxy-2-methyl-1-(trimethylsilyloxy)propene with benzalde-
hyde at 40 ꢁC in toluene. As shown in Table 1, an aldol product
was obtained in 98% yield within 12 h using Q-G3-C10(Iꢂ)
(Entry 1). The dendrimer modified with palmitoyl chloride
(Q-G3-C16(Iꢂ)) showed a low catalytic activity (Entry 2). The
Q-G3-C10(Iꢂ) dendrimer exhibited higher catalytic activity than
common quaternary ammonium iodides such as tetrabutylam-
monium iodide (TBAI) and tetraheptylammonium iodide
(THAI) (Entries 5 and 6).ꢂAs a Leꢂwis base catalyst, the iodide
anion was superior to BF4 or PF6 (Entries 3 and 4). No reac-
tion occurred using the non-quaternarized G3-C10 (Entry 7).
These results show that encapsulation of quaternary ammonium
iodides within alkylated PPI dendrimers efficiently promotes the
aldol reaction.
The Mukaiyama–Aldol reaction of silyl enolates with alde-
hydes is a powerful tool for selective carbon–carbon bond for-
mations and is classically promoted by Lewis acids through ac-
tivation of the aldehyde.6 Concerning dendrimer catalysts, Reetz
et al. have reported that Sc-containing dendrimer acted as effi-
cient heterogeneous catalysts for the aldol reaction.7 Recently,
several methods activating silyl enolate by Lewis bases such
as phosphoramide,8 CaCl2,9 and lithium amides10 were reported.
Also, quaternary ammonium fluorides11 and phosphines12 are
known to accelerate the aldol reaction in polar solvents by nucle-
ophilic cleavage of the O–Si bonds of silyl enolates.13 Herein,
we describe that an alkylated dendrimer having quaternary am-
monium iodides can catalyze the Mukaiyama–Aldol reaction of
silyl enolates with aldehydes in nonpolar solvents such as
toluene.
Poly(propylene imine) (PPI) dendrimer was selected be-
cause of the high density of tertiary amino groups within the den-
drimer. Primary amino groups on the periphery of the PPI den-
drimer were modified with decanoyl chloride (C10) or palmitoyl
chloride (C16) to give the corresponding alkylated dendrimers.14
Figure 1 shows a typical procedure for synthesis of the quater-
narized ammonium iodide dendrimer as follows: the third gener-
ation alkylated dendrimer (G3-C10 1 g, 3.37 mmol of tertiary
Table 2 shows typical examples of the Mukaiyama–Aldol
Table 1. Mukaiyama–Aldol reaction catalyzed by various
dendrimersa
OSiMe3
OSiMe3
CO2Me
CHO
cat.
+
40oC, toluene
OMe
Entry
Catalyst
Q-G3-C10(Iꢂ)
Conv./%b
Yield/%b
n
n
C
C
HN
O
O
O
1
2
3
4
5c
6c
7
98
32
9
6
11
2
98
32
9
6
10
2
O
NH
C
C
n
n
NH
Q-G3-C16(Iꢂ) ꢂ
HN
I-
O
O
HN
+
-
n
+
C
H3
CH3
C
n
I
N
+
C
N
NH
I- I-
CH3
Q-G3-C10(PF6 ꢂ
Q-G3-C10(BF4
N(n-Hep)4I
N(n-Bu)4I
G3-G10
)
)
I-
O
C
+
N
H
N
H
+
+
-
N
COCl
CH
3 N
N
I
N
C
O
+
n
n
CH3
N
CH3
O
H3C
I-
n
CH3I
DMF
n = 8, 14
NH2
N
H
-
+
I
H3C
n
16
excess NEt3
O
C
CH3
N
- H3C
I
+
-
I-
16
C
O
N
N
H
+
N
I-
+
n
N
I
n
+
N
N
H
G
3
PPI dendrimer
H3C
G -C
3
10, 16
O
CH3
I-
H3C
+
N
HN
NH
O
-
+
I
N
C
C
n
no reaction
no reaction
—
—
CH3
n
NH
C
HN
C
O
NH
C
HN
n
8
none
O
C
O
n
O
n
n
aReaction conditions: dendrimer 0.0036 mmol (0.05 mmol of
Iꢂ), benzaldehyde 0.5 mmol, silyl enolate 0.7 mmol, toluene
2 mL, 12 h, Ar atmosphere. bBased on benzaldehyde.
cTetraalkylammonium salts 0.05 mmol.
-
Q-G -C
(I )
3
10,16
Figure 1. Preparation of quaternary ammonium iodide dendri-
mer.
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.3 (2005)
421
Table 2. Mukaiyama–Aldol reaction of trimethylsilyl enolate
with various aldehydes catalyzed by Q-G3C10(Iꢂ)a
OSiMe3
dendrimer acts as a nanoreactor encapsulating a Lewis base cat-
alyst for the Mukaiyama–Aldol reaction of the trimethylsilyl
enolate with aldehydes. The high catalytic activity for the
Mukaiyama–Aldol reaction in toluene is ascribed to the highly
dense quaternary ammonium iodide within the dendrimer.
Q-G3-C10(I-)
OSiMe3
CO2Me
R-CHO +
R
60 oC, toluene
OMe
Time /h
Conv. /%b
Yield /%b
Entry
Aldehyde
This work was supported by a Grant-in-Aid for Scientific
Research from JSPS. We thank the center of excellence
(21COE) program ‘Creation of Integrated Ecochemistry’ of
Osaka University.
CHO
1
2
8
3
98
98
99
>99
Cl
CHO
CHO
O2N
8
3
88
88
MeO
Me
CHO
4
5
8
8
8
98
98
98
References and Notes
>99
CHO
CHO
1
2
3
For a book on dendrimers: ‘‘Dendrimers and Other Dendritic
´
Polymers,’’ ed. by J. M. J. Frechet and D. A. Tomalia, John Wiley
& Sons, New York (2001).
a) M. E. Piotti, F. Rivera, R. Bond, C. J. Hawker, and J. M. J.
Frechet, J. Am. Chem. Soc., 121, 9471 (1999). b) Y. Pan and
W. T. Ford, Macromolecules, 33, 3731 (2000).
S
96
98
94
98
6
7
CHO
8
CHO
5CHO
8
9
9
4
3
>99
>99
>99
96
98
96c
Ph
Ph
a) P. Bhyrappa, J. K. Young, J. S. Moore, and K. S. Suslick, J. Am.
Chem. Soc., 118, 5708 (1996). b) G. E. Oosterom, R. J. Haaren,
J. N. H. Reek, P. C. J. Kamer, and P. W. N. M. van Leeuwen,
Chem. Commun., 1999, 1119. c) M. Ooe, M. Murata, T. Mizugaki,
K. Ebitani, and K. Kaneda, J. Am. Chem. Soc., 126, 1604 (2004).
a) Y. Niu, L. K. Yeung, and R. M. Crooks, J. Am. Chem. Soc., 123,
6840 (2001). b) M. Ooe, M. Murata, T. Mizugaki, K. Ebitani, and
K. Kaneda, Nano Lett., 2, 999 (2002).
For recent reviews on dendritic catalysts, see: a) D. Astruc and
F. Chardac, Chem. Rev., 101, 2991 (2001). b) R. van Heerbeek,
P. C. J. Kamer, P. W. N. M. van Leeuwen, and J. N. H. Reek,
Chem. Rev., 102, 3717 (2002). c) L. J. Twyman, A. S. H. King,
and I. K. Martin, Chem. Soc. Rev., 31, 69 (2002).
‘‘Modern Aldol Reactions,’’ ed. by R. Mahrwald, Wiley-VCH,
Weinheim (2004).
CHO
10
aReaction conditions: aldehyde 0.5 mmol, silyl enolate 0.7 mmol,
Q-G3-C10(Iꢂ) 0.0036 mmol (0.05 mmol of Iꢂ), toluene 2 mL, Ar
b
c
atmosphere. Determined by GC based on aldehyde. 1,4-addi-
tion product was obtained (1,2-/1,4- = 1.9).
4
5
reaction of the trimethylsilyl enolate with various aldehydes cat-
alyzed by Q-G3-C10(Iꢂ) at 60 ꢁC. Aromatic aldehydes func-
tioned succesfully as acceptors (Entries 1–5). The heteroaromat-
ic aldehyde of 2-thiophencalbaldehyde, known to deactivate
Lewis acid catalysts,10 also afforded the corresponding aldol
product (Entry 6). Compared with the aromatic aldehydes, the
aliphatic aldehyde of n-octanal required longer reaction time
(Entry 8), which was similar to that for other Lewis base cata-
lysts.6,10 In the case of ꢁ,ꢂ-unsaturated carbonyl compound, cin-
namaldehyde gave a mixtures of 1,2- and 1,4-addition of the silyl
acetal (Entry 10).
6
7
8
9
M. T. Reetz and D. Giebel, Angew. Chem., Int. Ed., 39, 2498
(2000).
S. E. Denmark and R. A. Stavenger, Acc. Chem. Res., 33, 432
(2000).
K. Miura, T. Nakagawa, and A. Hosomi, J. Am. Chem. Soc., 124,
536 (2002).
The interaction between Q-G3-C10(Iꢂ) and 1-methoxy-
2-methyl-1-(trimethylsilyloxy)propene was examined by
13C NMR spectroscopy. Figure 2 shows the chemical shifts of
the ꢁ and ꢂ carbons of the silyl acetal at 149.2 and 90.6 ppm, re-
spectively. These signals shifted to 177.2 and 77.2 ppm, respec-
tively, in the presence of Q-G3-C10(Iꢂ).17 In contrast, treatment
of Q-G3-C10(Iꢂ) with benzaldehyde did not cause any change in
the chemical shift of the carbonyl carbon of benzaldehyde,
which indicates that benzaldehyde was not activated by Q-G3-
C10(Iꢂ). Presumably, the quaternary ammonium iodide dendri-
mer acts not as a Lewis acid but as a Lewis base catalyst to afford
the aldol products. In contrast to TBAI and THAI, the high ac-
tivity of the quaternarized dendrimers would be due to the high
polarity within the dendrimers, which might accelerate sever-
ance of the oxygen–silicon bond even in toluene solvent.13
In summary, we report the quaternary ammonium iodide
10 T. Mukaiyama, H. Fujisawa, and T. Nakagawa, Helv. Chim. Acta,
85, 4518 (2002).
11 R. Noyori, K. Yokoyama, J. Sakata, I. Kuwajima, E. Nakamura,
and M. Shimizu, J. Am. Chem. Soc., 99, 1265 (1977).
12 S. Matsukawa, N. Okano, and T. Imamoto, Tetrahedron Lett., 41,
103 (2000).
13 The aldol reaction of silyl enolates with benzaldehyde proceeds
without catalyst in polar solvents such as water and DMSO,
see: a) T.-P. Loh, L.-C. Feng, and L.-L. Wei, Tetrahedron, 56,
7309 (2000). b) Y. Genisson and L. Gorrichon, Tetrahedron Lett.,
41, 4881 (2000).
´
14 A. P. H. J. Schenning, C. Elissen-Roman, J.-W. Weener,
M. W. P. L. Baars, S. J. van der Gaast, and E. W. Meijer,
J. Am. Chem. Soc., 120, 8199 (1998).
15 a) J. L. Kreider and W. T. Ford, J. Polym. Sci., Part A: Polym.
Chem., 39, 821 (2001). b) E. Murugan, R. L. Sherman, Jr.,
H. O. Spivey, ꢂand W. T. Ford, Langmuir, 20, 8307 (2004).
ꢂ
16 BF4 and PF6 dendrimers were prepared by anion exchange of
Q-G3-C10(Iꢂ) using AgBF4 and AgPF6 in DMF. Q-G3-C16(Iꢂ);
Anal. Calcd for C358H730N30O16I14: C, 57.42; H, 9.83; N, 5.61.
Found: C, 58.12; H, 9.13; N, 5.14%. Q-G3-C10(BF4ꢂ); Anal.
Calcd for C262H538N30O16 B14F64: C, 54.89; H, 9.46; N, 7.33.
Found: C, 54.21; H, 9.85; N, 6.86%. Q-G3-C10(PF6ꢂ); Anal.
Calcd for C262H538N30O16P14F84: C, 49.21; H, 8.48; N, 6.57.
Found: C, 48.73; H, 9.02; N, 6.12%.
N+
77.2 ppm
-
90.64 ppm
I
O Si(CH3)3
O
O
Si(CH3)3
Q-G -C (I )
3
10
Cβ Cα
Cβ Cα
177.21 ppm
149.22 ppm
O
17 In 13C NMR spectrum, the chemical shifts of the ꢁ and ꢂ carbons
of the silyl enolate did not change with the parent dendrimer
Figure 2. 13C NMR shifts of the silyl acetal with quaternarized
dendrimer Q-G3-C10(Iꢂ).
G3-C10
.
Published on the web (Advance View) February 22, 2005; DOI 10.1246/cl.2005.420