Bifunctional polymeric organocatalysts and their application in the cooperative catalysis of Morita-Baylis-Hillman reactions

Article abstract of DOI:10.1002/chem.200601197

A series of soluble, noncross-linked polystyrene-supported tri-phenylphosphane and 4-dimethylaminopyridine reagents were prepared. Some of these polymeric reagents contained either alkyl alcohol or phenol groups on the polymer backbone. The use of these materials as organocatalysts in a range of Morita-Baylis-Hillman reactions indicated that hydroxyl groups could participate in the reactions and accelerate product formation. In the cases examined, phenol groups were more effective than alkyl alcohol groups for catalyzing the reactions. This article is one of the first reports of the synthesis and use of non-natural, bifunctional polymeric reagents for use in organic synthesis in which both functional groups can cooperatively participate in the catalysis of reactions.

Full text of DOI:10.1002/chem.200601197

FULL PAPER
DOI: 10.1002/chem.200601197
Bifunctional Polymeric Organocatalysts and Their Application in the
Cooperative Catalysis of Morita–Baylis–Hillman Reactions
Cathy Kar-Wing Kwong,[a] Rui Huang,[b] Minjuan Zhang,[b] Min Shi,*[b] and
Patrick H. Toy*[a]
Abstract: A series of soluble, non-
cross-linked polystyrene-supported tri-
phenylphosphane and 4-dimethylami-
nopyridine reagents were prepared.
Some of these polymeric reagents con-
tained either alkyl alcohol or phenol
groups on the polymer backbone. The
use of these materials as organocata-
lysts in a range of Morita–Baylis–Hill-
man reactions indicated that hydroxyl
groups could participate in the reac-
tions and accelerate product formation.
In the cases examined, phenol groups
were more effective than alkyl alcohol
groups for catalyzing the reactions.
This article is one of the first reports of
the synthesis and use of non-natural,
bifunctional polymeric reagents for use
in organic synthesis in which both func-
tional groups can cooperatively partici-
pate in the catalysis of reactions.
Keywords: amines · Lewis bases ·
Morita–Baylis–Hillman reactions ·
organocatalysis · phosphanes
Introduction
ture concerning multifunctional supported reagents involve
the immobilization of a visualization dye onto the polymer
in addition to the reagent group,[8] systems in which both the
substrate and the catalyst are attached to the same polymer
support,[9] or polymers containing both aza crown ethers and
a fluorescent tag.[10] The fundamental drawback of the limit-
ed reactivity of monofunctional supported reagents, and our
interest in developing organic polymer-supported reagents
and catalysts,[11] led us to design multipolymer reaction sys-
tems in which multiple supported reagents are used simulta-
neously to affect the desired reaction.[12] For example, we
have recently reported a Mitsunobu reaction system in
which the phosphane and the azo reagents are immobilized
on different polymer backbones and these supported re-
agents are used together.[13] However, in many applications
it would perhaps be preferable to use a single polymeric re-
agent rather than multiple ones.
The use of polymer-supported reagents and catalysts in or-
ganic synthesis is now commonplace and many such re-
agents are either commercially available or have been re-
ported in the literature.[1] This technology has evolved to the
stage where it is now possible to use polymer-assisted syn-
thesis for molecules as complex as epothilone C[2] and (+)-
plicamine[3] by using polymeric reagents or catalysts in every
synthetic step. However, one limitation of currently avail-
able supported reagents and catalysts is that they generally
contain only a single functional group that can actively par-
ticipate in a reaction. One exception is the recently reported
example of cooperative catalysis by using a series of general
acid and base bifunctional mesoporous silica-supported ma-
terials that were used in aldol, Henry, and cyanosilylation
reactions.[4–7] The only other successful reports in the litera-
Because, to our knowledge, only the polyfunctional meso-
porous silica-supported materials previously mentioned have
been reported, we sought to develop a simple and general
method for the preparation of analogous organic polymer-
supported materials based on radical polymerization. Specif-
ically, we wanted to prepare bifunctional polystyrene-sup-
[a] C. K.-W. Kwong, Prof. P. H. Toy
Department of Chemistry, The University of Hong Kong
Pokfulam Road, Hong Kong (P.R. China)
Fax : (+852)2857-1586
E-mail: phtoy@hku.hk
ported organocatalysts[14] for use in Morita–Baylis–Hillman
[b] R. Huang, M. Zhang, Prof. M. Shi
[15,16]
School of Chemistry and Molecular Engineering
East China University of Science and Technology
30 Meilong Road, Shanghai 200237 (P.R. China)
E-mail: mshi@mail.sioc.ac.ch
(MBH)reactions.
Recent investigations into the mecha-
nisms of MBH reactions indicated that they may be acceler-
ated by the presence of weak acids or hydrogen-bond-donat-
ing groups, such as alkyl alcohols or phenols,[17] and that al-
coholic solvents are often used to perform these reactions.[18]
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
Chem. Eur. J. 2007, 13, 2369 – 2376
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2369

Furthermore, the use of bifunctional organocatalysts to
perform MBH reactions has long been established. 3-Quinu-
clidinol was identified as a very efficient catalyst for MBH
reactions of a range of substrates (Figure 1).[19] It was pro-
Scheme 1. Synthesis of NCPS-supported PPh3 reagents 1a–e (AIBN=
azobisisobutyronitrile).
used this methodology to prepare related reagents that con-
tained hydroxyl functional groups, both alkyl (1b)and aryl
(1c), to examine if the addition of the hydroxyl groups ren-
ders these new materials more effective than 1a at catalyz-
ing various MBH reactions. The synthesis of 1b and 1c was
accomplished by using monomer 3b[31] and commercially
available 3d, respectively, in the radical polymerization re-
action of 3a with 4. It is important to note that in the prepa-
ration of these new polymer-supported reagents, we pur-
posely prepared materials with a PPh3 loading level of ap-
proximately 1.0 mmolgÀ1 and incorporated approximately
two equivalents of the hydroxyl functional group for every
phosphane group (Table 1). We limited the number of hy-
droxyl groups so that the resulting polymers would remain
hydrophobic and could be precipitated with solvents such as
methanol or diethyl ether; this was accomplished by using
the appropriate quantity of 3a to dilute the functionalized
monomers. The synthesis of 1c was accomplished by means
of the saponification of 1d. In addition to 1a–d, which con-
tain phenyl, benzyl alcohol, phenol, and phenyl acetate
groups, respectively, on the polymer backbone, we used 3e
to prepare 1e, which contains anisole groups.
For all of the polymerization reactions, the observed load-
ing of the phosphane groups in the products were deter-
mined by using both elemental analysis (EA)and 1H NMR
spectroscopy, and were similar to the theoretical values cal-
culated based on monomer input. The biggest discrepancy
observed was with 1e, in which the EA loading value was
approximately 30% greater than the NMR loading value,
and the average of these two was 50% higher than the theo-
retical value (Table 1, entry 5). However, this result is not
Figure 1. Bifunctional MBH reaction catalysts.
posed that the hydroxyl group accelerated the reactions by
hydrogen bonding with either the Michael acceptor carbonyl
oxygen or the enolate intermediate of the reaction. This ob-
servation led to the use of chiral bifunctional amino alco-
hols, such as quinidine, cinchonine, N-methyl ephedrine, and
N-methyl prolinol, as chiral catalysts for asymmetric MBH
reactions.[20] Subsequently, Hatakeyama et al. reported the
use of b-isocupreidine[21] and Sasai et al. described the use
of chiral binapthol/3-dialkylaminopyridine and binapthinol/
triphenylphosphane bifunctional catalysts[22] in highly enan-
tioselective MBH reactions, and this work inspired our ef-
forts to develop chiral bifunctional catalysts for asymmetric
MBH reactions.[23] A monoprotonated Sharpless ligand,[24]
a
chiral binapthyl-derived amine/thiourea compound,[25] and
an ionic liquid bearing both an amine and an alcohol
moiety[26] have also been reported to act as bifunctional
MBH reaction catalysts. These facts, coupled with our expe-
rience in studying intermolecular,[27] intramolecular,[28] and
aza[29] variations of the MBH reaction, and the use of poly-
mer-supported catalysts to perform them,[30] led us to design
and evaluate new polymers that are functionalized with tri-
phenylphosphane (1a–e)or 4-dimethylaminopyridine
(DMAP, 2a–f)groups, and that are attached to hydroxyl-
group-bearing polystyrene supports that are reported
herein.
Table 1. Synthesis of NCPS-supported PPh3 reagents 1a–e.
Results and Discussion
Entry Reagent
Monomer mixture
[mmol]
Yield [%] P Content [%]
Loading level [mmolgÀ1
]
3x:4[c]
3x
4
3a
theor[a] obsd[b] theor[a] EA[b] NMR[c] av[d]
We previously reported the
synthesis of soluble, non-cross-
linked-polystyrene-supported
1
2
3
4
5
1a
1b
1c
1d
1e
–
5.8
5.2
–
34.6
20.8
–
61
52
77
70
53
3.3
3.1
3.2
2.8
3.1
3.9
3.8
3.7
4.1
5.1
1.1
1.1
1.1
1.0
1.0
1.3
1.2
1.2
1.3
1.7
1.1
1.1
1.1
1.1
1.3
1.2
1.2
1.0
1.2
1.5
–
10.4
2.0
1.9
1.9
1.2
[e]
[e]
[e]
–
triphenylphosphane
(NCPS–
15.3
13.9
7.6
7.0
30.5
27.8
PPh3, 1a)by means of copoly-
merization of styrene (3a)with
4-vinyltriphenylphosphane (4)
(Scheme 1).[11a] Therefore, we
[a] Theoretical P content based on monomer mixture. [b] Observed P content determined by means of EA.
[c] Determined by means of H NMR spectroscopic analysis. [d] Average EA+NMR loading values that were
used in subsequent reactions. [e] Reagent 1c was prepared from reagent 1d.
1
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Morita–Baylis–Hillman Reactions
FULL PAPER
significant because 1e does not contain hydrogen-bond-do-
nating groups and was designed as an experimental control
for comparison with 1c. Furthermore, 1e was also the only
polymer in which the observed monomer incorporation de-
viated significantly from the theoretical 3/4 ratio of 2:1,
loading levels of the polymers were again determined by
means of EA, to obtain the nitrogen content, and integra-
tion of their H NMR spectra. The only observed polymer
1
loading level that deviated significantly from the theoretical
value was that for 2a, in which the observed value was ap-
proximately 33% greater than expected. However, as the
loading values for 2a obtained by means of EA and NMR
were identical, we have confidence in the value and used it
for the MBH reactions. Furthermore, polymers 2a–f all ex-
hibited almost the theoretical 3/5 ratio of 2:1.
With the bifunctional polymer-supported reagents in
hand, we examined the use of 1a–e as catalysts for intramo-
lecular MBH reactions of Z enones 6a–f, which contain
pendant electrophilic aldehyde groups (Table 3). These sub-
strates, which contain both alkyl and aryl substituents, were
chosen because it has been previously observed that PPh3 is
1
which was also determined by means of H NMR spectros-
1
copy. Importantly, both H and 31P NMR spectroscopies in-
dicated that no oxidation of the phosphane group occurred
for any of the polymers 1a–e, and thus, the loading levels
observed represent the amount of nucleophilic triphenyl-
phosphane groups present.
For the synthesis of the polystyrene-supported DMAP or-
ganocatalysts, monomer 5 was prepared according to litera-
ture methods from 4-vinylbenzyl chloride and 4-(N-methyl-
amino)pyridine.[32] This monomer was then copolymerized
under the same conditions as those for 3a, 3b, and 3d–f to
prepare 2a, 2b, and 2d–f, respectively, in moderate to good
yields (Scheme 2, Table 2). Monomer 3 f was prepared ac-
Table 3. Intramolecular MBH reactions catalyzed by 1a–e.
Entry
Substrate
Yield [%][a]
1a
1b
1c
1d
1e
1[b]
2[b]
3[c]
4[c]
5[c]
6[c]
6a: R= Et
2
37
33
53
35
31
26
55
77
67
53
44
72
84
84
75
60
52
21
33
31
63
46
39
12
15
27
59
38
35
À
À
6b: R= Bu
À
6c: R= Ph
À
6d: R= C6H4-4-Cl
À
6e: R= C6H4-3-Me
À
6 f: R= C6H4-4-Me
Scheme 2. Synthesis of NCPS-supported DMAP reagents 2a–f (TBS=
tert-butyldimethylsilyl, TBAF= tetrabutyl ammonium fluoride).
[a] Average isolated yield from at least two experiments. [b] Reactions
were performed for 36 h. [c] Reactions were performed for 18 h.
Table 2. Synthesis of NCPS-supported DMAP reagents 2a–f.
a good catalyst for the cycliza-
Entry Reagent
Monomer mixture
[mmol]
Yield [%] N Content [%]
Loading level [mmolgÀ1
]
3x:5[c]
tion of these starting materi-
als,[18t,28] and we already had
these materials and authentic
product samples in hand. Par-
allel reactions were performed
in which all five catalysts were
used individually for the same
substrates. The reactions were
performed at room tempera-
ture and allowed to proceed
until one reaction was almost
complete, as determined by
3x
5
3a
theor[a] obsd [b] theor[a] EA[b] NMR[c] av[d]
1
2
3
4
5
6
2a
2b
2c
2d
2e
2 f
–
10.7
–
12.9
17.8
17.8
16.6
5.4
–
6.5
8.9
8.9
99.8
53.5
–
25.9
35.7
35.7
45
50
80
31
40
33
2.8
1.8
3.2
2.9
3.1
4.5
2.7
2.8
2.6
3.0
1.2
0.7
1.1
1.0
1.0
0.9
1.6
1.0
1.0
0.9
1.1
1.6
1.1
1.2
1.1
1.0
0.9
1.6
–
1.0 1.8
1.1 1.9
1.0 2.0
1.1 2.2
–
[e]
[e]
[e]
[f]
[f]
[f]
[f]
–
–
–
2.0
[a] Theoretical N content based on monomer mixture. [b] Observed N content determined by means of EA.
1
[c] Determined by means of H NMR spectroscopic analysis. [d] Average EA+NMR loading values that were
used in subsequent reactions. [e] Reagent 2c was prepared from reagent 2 f. [f] Not determined.
cording to literature methods from 4-hydroxybenzalde-
hyde,[33] and 2 f was converted into 2c by treatment with
fluoride. Deprotection of silyl ether groups was chosen for
the synthesis of 2c, rather than saponification, to ensure
that the amine groups remained unprotonated, and thus, re-
tained their nucleophilicity.
As before, the DMAP loading levels of these polymers
were calculated to be approximately 1.0 mmolgÀ1, and they
contained approximately two equivalents of the functional
monomer group per DMAP group (Table 2). The actual
means of TLC analysis. At this time, all of the reactions
were stopped and the isolated yields of pure product were
determined. It should be noted that the reactions gave only
the desired product, and that products 7a–f were identical
to authentic samples (see the Supporting Information).[28]
Table 3 shows that the best catalyst for all six substrates in
the parallel reactions was phenol-substituted 1c, which led
to isolated yields of the product ranging from 52–84%. The
second best catalyst was methanol-substituted 1b, which af-
forded slightly to significantly lower yields (26–77%)for the
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M. Shi, P. H. Toy et al.
Table 5. MBH reactions of 2-cyclopenten-1-one catalyzed by 2a-e.
same substrates. The other three catalysts, 1a, 1d, and 1e,
were comparable in performance, and all afforded lower
yields than 1b and 1c. The most dramatic difference in
product yields between hydroxylated catalysts 1b and 1c,
and the non-hydroxylated ones can be seen with phenyl-sub-
stituted substrate 6c (Table 3, entry 3). The smallest differ-
ence in product yields was observed with the most electron
poor, and therefore, most activated substrate 6d, which af-
forded good yields with all catalysts (Table 3, entry 4). Less-
reactive alkyl-substituted substrates 6a and 6b also exhibit-
ed substantially higher yields with the hydroxylated catalysts
than with the non-hydroxylated ones (Table 3, entries 1 and
2).
Entry
Aldehyde
Yield [%][a]
2a
2b
2c
2d
2e
À
1
2
3
4
5
8 f: R= C6H4-3-NO2
7
30
4
36
8
27
69
27
61
29
32
81
33
87
66
17
31
8
43
10
8
56
10
44
8
À
8g: R= C6H4-4-NO2
À
8i: R= C6H4-2-NO2
À
8j: R= C6H3-2,4-(NO2)2
À
8k: R= C6H4-4-CN
[a] Average isolated yield from at least two experiments.
Subsequently, we examined the use of 2a–e as catalysts
for intermolecular MBH reactions between aryl aldehydes
8a–h and methyl vinyl ketone (9)(Table 4.) The reactions
Table 6. MBH reactions of 2-cyclohexen-1-one catalyzed by 2a–e.
Table 4. MBH reactions of methyl vinyl ketone catalyzed by 2a–e.
Entry
Aldehyde
Yield [%][a]
2a
2b
2c
2d
2e
À
1
2
3
4
5
8 f: R= C6H4-3-NO2
2
6
2
42
3
9
14
4
52
13
49
72
27
79
67
7
10
4
36
3
0
7
2
36
3
Entry
Aldehyde
Yield [%][a]
À
8g: R= C6H4-4-NO2
2a
2b
2c
2d
2e
À
8i: R= C6H4-2-NO2
À
1
2
3
4
5
6
7
8
8a: R=ÀPh
trace
24
12
31
47
37
42
33
19
36
27
42
67
55
62
49
28
41
35
50
74
64
71
56
trace
28
17
35
53
44
45
41
trace
32
19
38
57
47
51
45
8j: R= C6H3-2,4-(NO2)2
À
À
8b: R= C6H4-4-Br
8k: R= C6H4-4-CN
À
8c: R= C6H4-2-Cl
[a] Average isolated yield from at least two experiments.
À
8d: R= C6H4-4-Cl
À
8e: R= C6H4-4-F
À
8 f: R= C6H4-3-NO2
À
8g: R= C6H4-4-NO2
À
8h: R= C6H3-2,4-Cl2
highest yields in reactions with all substrates (32–87%)
amongst all of the catalysts screened. Methanol-functional-
ized catalyst 2b was again the second best catalyst for all re-
actions; 2a, 2d, and 2e all performed similarly. Interestingly,
reactions of Michael acceptor 13 afforded some of the larg-
est differences in catalytic efficiency between 2a–e observed
in this study. For reactions of 13 with aldehydes 8 f, 8g, 8i,
and 8k, catalyst 2c afforded approximately 5-fold more
product than 2b, and 10- to 20-fold more product than non-
hydroxylated catalysts 2a, 2d, and 2e.
[a] Average isolated yield from at least two experiments.
were performed in parallel as before, except that it was nec-
essary to use electron-deficient aldehydes for these reactions
to achieve good to moderate yields after 3 d at 608C in
THF. When benzaldehyde (8a)was used as the electrophile,
significant amounts of product 10a were only observed by
using hydroxylated catalysts 2b and 2c, with the latter af-
fording a higher yield (Table 4, entry 1). In fact, 2c afforded
the highest yields (28–74%)of all the catalysts for the reac-
tions of the aldehyde electrophiles with Michael acceptor 9,
and 2b afforded the second highest yields (19–67%). As
before, non-hydroxylated catalysts 2a, 2d, and 2e per-
formed similarly, and were less efficient than the hydroxylat-
ed ones, to afford at most a 57% yield of the desired prod-
uct (Table 4, entry 5).
Similar reactivity patterns were observed by using these
same catalysts to perform MBH reactions of both 2-cyclo-
penten-1-one (11)and 2-cyclohexen-1-one ( 13), and various
electron-deficient aldehydes (Tables 5 and 6, respectively).
In these reactions, aldehyde 8j, functionalized with two elec-
tron-withdrawing nitro groups, afforded the highest yields of
all those examined (entry 4 in both Tables 5 and 6), and cat-
alyst 2c functionalized with a phenol group afforded the
It should be noted that for all of the reactions performed
with catalysts 2a–e, products 10a–h, 12a–c, and 14a–c have
all been reported previously,[17f,18h,p,34] or were characterized
by means of H and 13C NMR spectroscopy and high-resolu-
1
tion mass spectral analysis (see the Supporting Information).
Only compounds 12d–e and 14d–e have not been previously
described in the literature.
Taken as a whole, the data clearly indicate that the hy-
droxylated catalysts are better than the non-hydroxylated
ones, and that of the former, phenol-substituted 1c and 2c
are more efficient than methanol-substituted 1b and 2b.
The methoxy- and acetoxy-functionalized catalysts per-
formed similarly to the unfunctionalized polystyrene-sup-
ported catalysts. Thus, the reactivity pattern for both sets of
catalysts were similar: 1c and 2c>1b and 2b>1a and 2aꢀ
1d and 2dꢀ1e and 2e.
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Morita–Baylis–Hillman Reactions
FULL PAPER
400 MHz for 1H analysis and 75 or 100 MHz for 13C analysis. 31P NMR
spectra were recorded in CDCl3 by using a Bruker DRX-400 spectrome-
ter operating at 162 MHz for 31P analysis. Chemical shift data is ex-
pressed in ppm with reference to TMS and the residual solvent peak(s).
HRMS (EI)data was recorded by using a Finnigan MAT 96 mass spec-
trometer.
Conclusion
In summary, we have prepared two series of bifunctional
polymeric nucleophilic organocatalysts that contain either
PPh3 (1a–e)or DMAP ( 2a–e)groups. It was found that of
these materials, those functionalized with hydroxyl groups
(1b, 1c, 2b, and 2c)are more efficient at catalyzing both
intra- and intermolecular MBH reactions than those that
are unfunctionalized (1a and 2a)or functionalized with me-
thoxy (1d and 2d)or acetoxy groups ( 1e and 2e). It is pro-
posed that these hydroxylated materials are able to coopera-
tively catalyze the reactions studied either by hydrogen-
bond activation of the Michael acceptor (Figure 2, A)or by
stabilization of the enolate intermediate that is formed in
the reactions (Figure 2, B). This hypothesis is supported by
the results of many previous examples of bifunctional small-
molecule organocatalysts, especially chiral ones, and the fact
that the more acidic phenol-functionalized reagents 1c and
2c afforded higher product yields in all reactions than meth-
anol-functionalized reagents 1b and 2b.
These results represent a new design paradigm for poly-
styrene-supported reagents and demonstrate that the poly-
mer backbone can be functionalized in such a way as to si-
multaneously incorporate multiple different catalytic or re-
agent groups. Owing to the facile synthesis of many styrene
derivatives, it is anticipated that this strategy will be applica-
ble to the generation of many other polyfunctional polysty-
rene-supported reagents and catalysts, and will simplify
product isolation from reactions that require numerous dif-
ferent reagents and catalysts. Efforts to determine the limits
of this strategy are currently underway.[35]
4-Vinylbenzyl alcohol (3b):[31]
A solution of 4-vinylbenzyl chloride
(32.0 g, 213 mmol), sodium acetate (23.0 g, 280 mmol), and Bu4NI (7.9 g,
21.3 mmol)in dry THF (300 mL)was heated to reflux for 48 h. After
cooling to room temperature, the resulting mixture was diluted with
water (200 mL), and extracted with CHCl3 (3”300 mL). The organic
layers were dried over Na2SO4, filtered, and concentrated in vacuo to
afford 4-vinylbenzyl acetate as an orange oil (37.1 g, 99%). 1H NMR
(400 MHz, CDCl3): d=2.10 (s, 3H), 5.09 (s, 2H), 5.26 (d, J=10.9 Hz,
1H), 5.76 (d, J=17.6 Hz, 1H), 6.71 (dd, J=17.6, 10.9 Hz, 1H), 7.32 (d,
J=8.1 Hz, 2H), 7.40 ppm (d, J=8.1 Hz, 2H); 13C NMR (75 MHz,
CDCl3): d=20.9, 66.0, 114.3, 126.3, 128.5, 135.4, 136.3, 137.6, 170.8 ppm;
HRMS (EI): m/z calcd for C11H12O2: 176.0837; found: 176.0833.
An aqueous 6n NaOH (50 mL)solution was added to a solution of 4-vi-
nylbenzyl acetate (37.1 g, 211 mmol)in EtOH (150 mL.) The reaction
mixture was left at reflux for 3 h. After cooling to room temperature, the
resulting mixture was diluted with water (200 mL)and extracted with
CHCl3 (3”300 mL). The dried and concentrated organic layers were pu-
rified by means of distillation (1008C, 20 mm Hg)to afford 3b as a color-
less liquid (17.0 g, 60%). 1H NMR (400 MHz, CDCl3): d=4.64 (s, 2H),
5.24 (d, J=10.9 Hz, 1H), 5.75 (d, J=17.6 Hz, 1H), 6.71 (dd, J=17.6,
10.9 Hz, 1H), 7.29 (d, J=8.1 Hz, 2H), 7.39 ppm (d, J=8.1 Hz, 2H);
13C NMR (75 MHz, CDCl3): d=65.0, 113.9, 126.4, 127.2, 136.5, 137.0,
140.4 ppm; HRMS (EI): m/z calcd for C9H10O: 134.0732; found:
134.0728.
4-tert-Butyldimethylsilyloxybenzaldehyde:[33] A solution of tert-butyldi-
methylsilylchloride (6.8 g. 45.0 mmol)in dry CH 2Cl2 (50 mL)was added
dropwise to a solution of 4-hydroxybenzaldehyde (3.7 g, 30.0 mmol)and
triethylamine (6.3 mL, 45.0 mmol)in dry CH 2Cl2 (50 mL). The reaction
mixture was stirred at room temperature for 2 h and then quenched with
water (100 mL). The organic layer was separated and the aqueous layer
was extracted with CH2Cl2 (3”100 mL). The combined organic layers
were washed with water (150 mL)and brine (150 mL,) dried over
MgSO4, filtered, and concentrated in vacuo. The crude product was puri-
fied by means of flash column chromatography by using 10% EtOAc/
hexane as the eluent to afford 4-tert-butyldimethylsilyloxybenzaldehyde
as a yellow oil (6.9 g, 98%). 1H NMR (400 MHz, CDCl3): d=0.15 (s,
6H), 0.89 (s, 9H), 6.84 (d, J=8.5 Hz, 2H), 7.69 (d, J=8.5 Hz, 2H),
9.79 ppm (s, 1H); 13C NMR (75 MHz, CDCl3): d=À4.4, 18.2, 25.7, 120.5,
130.4, 131.9, 161.5, 190.9 ppm; HRMS (EI): m/z calcd for C13H20O2Si:
236.1233; found: 236.1230.
Experimental Section
General methods: All reactions were carried out under a nitrogen or an
argon atmosphere in oven- or flame-dried glassware. Tetrahydrofuran
was purified by using a Solv-Tek purification system that employs activat-
ed Al2O3. Dichloromethane (DCM)and 1,2-dichloroethane (DCE)were
distilled from CaH2 under an argon atmosphere. Commercially available
reagents were used as received. All reactions were monitored by TLC
analysis by using GF254 silica gel coated plates. Column chromatography
was carried out by using silica gel (300–400 mesh)at increased pressure.
1H and 13C NMR spectra were recorded in CDCl3 or DMSO by using
either a Bruker DRX-300 or 400 spectrometer operating at 300 or
4-tert-Butyldimethylsilyloxystyrene (3 f):[33] nBuLi (2.5m solution in
hexane, 18 mL, 45.0 mmol)was added dropwise to a solution of methyl-
triphenylphosphonium bromide (16.1 g, 45.0 mmol)in dry THF (50 mL)
at 08C. After stirring for 15 min, a solution of 4-tert-butyldimethylsilylox-
ybenzaldehyde (6.9 g, 30.0 mmol)in dry THF (50 mL)was added by
using a dropping funnel. Upon complete addition, the reaction mixture
Figure 2. Catalysis of MBH reactions by bifunctional polymer-supported PPh3 reagent 1c.
Chem. Eur. J. 2007, 13, 2369 – 2376
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2373

M. Shi, P. H. Toy et al.
was allowed to warm to room temperature. The yellow suspension was
stirred for 4 h and then quenched with an aqueous saturated NH4Cl solu-
tion (100 mL). The organic layer was separated, and the aqueous layer
was extracted with hexane (3”100 mL). The combined organic layers
were washed with water (3”150 mL)and brine (3”150 mL,) dried over
MgSO4, filtered, and concentrated in vacuo. The crude product was puri-
fied by means of flash column chromatography by using hexane as the
eluent to afford 3 f as a colorless oil (5.3 g, 75%). 1H NMR (400 MHz,
CDCl3): d=0.19 (s, 6H), 0.98 (s, 9H), 5.12 (d, J=10.9 Hz, 1H), 5.60 (d,
J=17.6 Hz, 1H), 6.65 (dd, J=17.6, 10.9 Hz, 1H), 6.79 (d, J=8.5 Hz, 2H),
7.28 ppm (d, J=8.5 Hz, 2H); 13C NMR (75 MHz, CDCl3): d=À4.4, 18.3,
25.7, 111.7, 120.2, 127.4, 131.0, 136.4, 155.6 ppm; HRMS (EI): m/z calcd
for C14H22OSi: 234.1440; found: 234.1441.
water (100 mL). The organic layer was separated, and the aqueous layer
was extracted with EtOAc (3”50 mL). The combined organic layers
were washed with brine (200 mL), dried over MgSO4, filtered, and con-
centrated in vacuo. The residue was taken up in THF (5 mL)and the so-
lution was added slowly to vigorously stirred cold MeOH (200 mL)at
08C. The white precipitate was filtered and dried in vacuo to afford 1c as
a white powder (3.5 g, 77%). 1H NMR (300 MHz, CDCl3): d=0.88–1.83
(brm, 16H), 6.19–7.84 ppm (brm, 41H); 31P NMR (162 MHz, CDCl3):
d=À6.33 ppm. The ratio of monomer incorporation into 1c was deter-
1
mined by means of H NMR spectroscopy to be 3.2:1.9:1.0 (styrene/4-hy-
droxystyrene/4). This ratio corresponds to
a PPh3 loading level of
1.2 mmolgÀ1 for 1c. EA indicated that 1c contained 3.7% P, which corre-
sponds to a PPh3 loading level of 1.2 mmolgÀ1 for 1c.
4-(N-Methyl-N-vinylbenzylamino)pyridine (5):[32] NaH (60% in mineral
oil, 1.2 g, 52.0 mmol)was added to a solution of 4-( N-methylamino)pyri-
dine (4.2 g, 39.0 mmol)in dry THF (30 mL)at 0 8C. The reaction mixture
was stirred at 08C for 30 min and then at room temperature for 30 min.
The reaction mixture was then cooled to 08C again before 4-vinylbenzyl
chloride (4 mL, 26.0 mmol)was added dropwise. Upon complete addi-
tion, the reaction was stirred at room temperature for 18 h. The reaction
mixture was filtered and the filtrate was concentrated in vacuo. The re-
sulting oil was dissolved in CH2Cl2 (150 mL), washed with water (3”
150 mL)and brine (3”150 mL), dried over MgSO 4, filtered, and concen-
trated in vacuo. The crude product was purified by means of flash
column chromatography by using 1% MeOH/CH2Cl2 as the eluent to
Poly[styrene-co-(4-acetoxystyrene)-co-(4-styryldiphenylphosphane)]
(1d): Procedure A was followed by using styrene (3.2 g, 30.5 mmol), 3d
(2.5 g, 15.3 mmol), 4 (2.2 g, 7.6 mmol), and AIBN (0.1 g, 0.5 mmol) in tol-
uene (40 mL). The residue was redissolved in THF (8 mL) and cold
MeOH (500 mL)was used for precipitation to afford 1d as a white
powder (5.5 g, 70%). 1H NMR (300 MHz, CDCl3): d=0.94–1.78 (brm,
19H), 2.24 (brs, 6H), 6.53–7.39 ppm (brm, 36H); 31P NMR (162 MHz,
CDCl3): d=À6.26 ppm; after oxidation: 31P NMR (162 MHz, CDCl3,
TMS): d=29.98 ppm. The ratio of monomer incorporation into 1d was
determined by means of 1H NMR spectroscopy of oxidized 1d to be
3.3:1.9:1.0 (styrene/3d/4). This ratio corresponds to a PPh3 loading level
of 1.1 mmolgÀ1 for 1d. EA indicated that 1d contained 4.1% P, which
corresponds to a PPh3 loading level of 1.3 mmolgÀ1 for 1d.
1
afford 5 as a viscous brown oil (4.8 g, 85%). H NMR (400 MHz, CDCl3):
d=3.06 (s, 3H), 4.56 (s, 2H), 5.23 (d, J=10.9 Hz, 1H), 5.73 (d, J=
17.6 Hz, 1H), 6.54 (d, J=6.0 Hz, 2H), 6.69 (dd, J=17.6, 10.9 Hz, 1H),
7.12 (d, J=8.0 Hz, 2H), 7.37 (d, J=8.0 Hz, 2H), 8.21 ppm (d, J=5.8 Hz,
2H); 13C NMR (75 MHz, CDCl3): d=37.7, 54.7, 106.7, 113.9, 126.6, 129.2,
136.3, 136.7, 136.78, 149.9, 153.8 ppm; HRMS (EI): m/z calcd for
C15H16N2: 224.1313; found: 224.1309.
Poly[styrene-co-(4-methoxystyrene)-co-(4-styryldiphenylphosphane)]
(1e): Procedure A was followed by using styrene (2.9 g, 27.8 mmol), 3e
(1.9 g, 13.9 mmol), 4 (4.0 g, 7.0 mmol), and AIBN (0.1 g, 0.5 mmol) in tol-
uene (34 mL). The residue was redissolved in THF (10 mL) and cold
MeOH (600 mL)was used for precipitation to afford 1e as a white
powder (4.7 g, 53%). 1H NMR (300 MHz, CDCl3): d=1.39–1.78 (brm,
20H), 3.70 (brs, 6H), 6.55–7.33 ppm (brm, 49H); 31P NMR (162 MHz,
CDCl3): d=À6.26 ppm; after oxidation: 31P NMR (162 MHz, CDCl3):
d=30.10 ppm. The ratio of monomer incorporation into 1e was deter-
mined by means of 1H NMR spectroscopy of oxidized 1e to be
2.5:1.2:1.0 (styrene/3e/4). This ratio corresponds to a PPh3 loading level
of 1.3 mmolgÀ1 for c. EA indicated that 1e contained 5.1% P, which cor-
responds to a PPh3 loading level of 1.7 mmolgÀ1 for 1e.
General procedure for non-cross-linked polystyrene-supported PPh3 re-
agent synthesis (procedure A): AIBN was added to a solution of styrene,
polar styrene monomer 3b or 3d–e and 4 in toluene. The mixture was
purged with N2 for 30 min and the solution was then stirred at 858C for
24 h. The solution was concentrated in vacuo and then the residue was
redissolved in THF. This solution was added slowly to vigorously stirred
MeOH at 08C. The white precipitate was filtered and dried in vacuo. EA
was used to determine the phosphorous content, and thus the PPh3 load-
ing level.
General procedure for non-cross-linked polystyrene-supported DMAP
reagent synthesis (procedure B): AIBN was added to a solution of sty-
rene, polar styrene monomer 3b or 3d–f and 5 in toluene. The mixture
was purged with N2 for 30 min and the solution was stirred at 858C for
24 h. The solution was concentrated in vacuo and then the residue was
redissolved in THF. This solution was added slowly to vigorously stirred
cold MeOH at 08C. The precipitate was filtered and dried in vacuo. EA
was used to determine nitrogen content, and thus the DMAP loading
level.
Poly[styrene-co-(4-styryldiphenylphosphane)] (1a): Procedure A was fol-
lowed by using styrene (3.6 g, 34.6 mmol), 4 (1.7 g, 5.8 mmol), and AIBN
(0.1 g, 0.4 mmol)in toluene (26 mL). The residue was redissolved in THF
(5 mL)and cold MeOH (300 mL)was used for precipitation to afford 1a
as a white powder (3.2 g, 61%). 1H NMR (400 MHz, CDCl3): d=0.88–
1.85 (brm, 18H), 6.45–7.38 ppm (brm, 44H); 31P NMR (162 MHz,
CDCl3): d=À6.18 ppm. The ratio of monomer incorporation into 1a was
determined by means of 1H NMR spectroscopy to be 5.5:1.0 (styrene/4).
This ratio corresponds to a PPh3 loading level of 1.1 mmolgÀ1 for 1a. EA
indicated that 1a contained 3.9% P, which corresponds to a PPh3 loading
level of 1.3 mmolgÀ1 for 1a.
Poly{styrene-co-[4-(N-methyl-N-vinylbenzylamino)pyridine]} (2a): Proce-
dure
B was followed by using styrene (6.9 g, 99.8 mmol), 5 (3.7 g,
16.6 mmol), and AIBN (0.2 g, 1.2 mmol) in toluene (70 mL). The residue
was redissolved in THF (10 mL)and cold MeOH (600 mL)was used for
precipitation to afford 2a as a yellow powder (4.8 g, 45%). 1H NMR
(400 MHz, CDCl3): d=0.88–2.18 (brm, 16H), 3.00 (brs, 3H), 4.41 (brs,
2H), 6.49–7.26 (brm, 25H), 8.21 ppm (brs, 2H). The ratio of monomer
Poly[styrene-co-(4-vinylbenzyl alcohol)-co-(4-styryldiphenylphosphane)]
(1b): Procedure A was followed by using styrene (2.2 g, 20.8 mmol), 3b
(1.4 g, 10.4 mmol), 4 (1.4 g, 5.2 mmol), and AIBN (0.1 g, 0.4 mmol) in tol-
uene (28 mL). The residue was redissolved in THF (5 mL) and cold
MeOH (300 mL)was used for precipitation to afford 1b as a white
powder (2.6 g, 52%). 1H NMR (300 MHz, CDCl3): d=0.92–2.17 (brm,
19H), 4.52 (brs, 4H), 6.54–7.60 ppm (brm, 42H); 31P NMR (162 MHz,
CDCl3): d=À16.64 ppm. The ratio of monomer incorporation into 1b
1
incorporation into 2a was determined by means of H NMR spectroscopy
to be 4.0:1.0 (styrene/5). This ratio corresponds to a DMAP loading level
of 1.6 mmolgÀ1 for 2a. EA indicated that 2a contained 4.5% N, which
corresponds to a DMAP loading level of 1.6 mmolgÀ1 for 2a.
Poly{styrene-co-(4-vinylbenzyl alcohol)-co-[4-(N-methyl-N-vinylbenzyl-
1
was determined by means of H NMR spectroscopy to be 3.7:2.0:1.0 (sty-
A
rene/3b/4). This ratio corresponds to a PPh3 loading level of 1.1 mmolgÀ1
for 1b. EA indicated that 1b contained 3.8% P, which corresponds to a
PPh3 loading level of 1.2 mmolgÀ1 for 1b.
53.5 mmol), 3b (1.4 g, 10.7 mmol), 5 (1.2 g, 5.4 mmol), and AIBN (0.1 g,
0.7 mmol)in toluene (35 mL.) The residue was redissolved in THF
(10 mL)and cold MeOH (400 mL)was used for precipitation to afford
2b as a white powder (3.5 g, 50%). 1H NMR (300 MHz, CDCl3): d=
0.88–1.65 (brm, 27H), 2.98 (brs, 3H), 4.11–4.58 (brm, 5H), 6.49–7.06
(brm, 37H), 8.16 ppm (brs, 2H). The ratio of monomer incorporation
into 2b was determined by means of 1H NMR spectroscopy to be
Poly[styrene-co-(4-hydroxystyrene-)co-(4-styryldiphenylphosphane)]
(1c): Compound 1d (5.0 g, 10.5 mmol)was added to a solution of NaOH
(4.2 g, 105.8 mmol)in 1:1:3 MeOH/H 2O/THF (50 mL). The reaction mix-
ture was stirred at room temperature for 24 h and then quenched with
2374
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ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 2369 – 2376

Morita–Baylis–Hillman Reactions
FULL PAPER
5.7:1.8:1.0 (styrene/3b/5). This ratio corresponds to a DMAP loading
level of 1.0 mmolgÀ1 for 2b. EA indicated that 2b contained 2.7% N,
which corresponds to a DMAP loading level of 1.1 mmolgÀ1 for 2b.
General procedure for intermolecular MBH reactions between aldehydes
8 f–g and 8i–k and 2-cyclopenten-1-one (11): Compound 11 (42 mL,
0.5 mmol)was added to a solution of aldehydes 8 f–g or 8i–k (0.5 mmol)
and 2a–e (0.5 mmol)in CH 2Cl2 (0.5 mL)under a nitrogen atmosphere.
The reaction mixture was stirred at room temperature for 5 d and then
concentrated in vacuo. The crude product was purified by means of flash
column chromatography to afford the desired product 12a–e.
Poly{styrene-co-(4-hydroxystyrene)-co-[4-(N-methyl-N-vinylbenzylami-
no)pyridine]} (2c): Compound 2 f (2.7 g, 4.9 mmol)was added to a solu-
tion of 1m TBAF (24.3 mL, 24.3 mmol)in THF (10 mL.) The reaction
mixture was stirred at room temperature for 24 h and then concentrated
in vacuo. The residue was redissolved in THF (4 mL)and the solution
was added slowly to vigorously stirred cold MeOH (200 mL)at 0 8C. The
white precipitate was filtered and dried in vacuo to afford 2c as a white
powder (1.7 g, 80%). 1H NMR (300 MHz, DMSO): d=1.23–2.15 (brm,
19H), 3.09 (brs, 4H), 4.57 (brs, 2H), 6.67–7.14 (brm, 29H), 8.18 ppm
(brs, 2H). The ratio of monomer incorporation into 2c was determined
General procedure for intermolecular MBH reactions between aldehydes
8 f–g and 8i–k and 2-cyclohexen-1-one (13): 2-Cyclohexen-1-one (13)
(48 mL, 0.5 mmol)was added to a solution of aldehydes 8 f–g or 8i–k
(0.5 mmol)and 2a–e (0.5 mmol)in CH Cl2 (0.5 mL)under a nitrogen at-
2
mosphere. The reaction mixture was stirred at room temperature for 5 d
and then concentrated in vacuo. The crude product was purified by
means of flash column chromatography to afford the desired product
14a–e.
1
by means of H NMR spectroscopy to be 3.2:2.0:1.0 (styrene/4-hydroxys-
tyrene/5). This ratio corresponds to
a DMAP loading level of
1.2 mmolgÀ1 for 2c. EA indicated that 2c contained 2.8% N, which cor-
responds to a DMAP loading level of 1.0 mmolgÀ1 for 2c.
Poly{styrene-co-(4-acetoxystyrene)-co-[4-(N-methyl-N-vinylbenzylami-
no)pyridine]} (2d): Procedure B was followed by using styrene (2.7 g,
25.9 mmol), 3d (2.1 g, 12.9 mmol), 5 (1.5 g, 6.5 mmol), and AIBN (0.1 g,
0.5 mmol)in toluene (30 mL.) The residue was redissolved in THF
(5 mL)and cold MeOH (300 mL)was used for precipitation to afford 2d
as a yellow powder (1.9 g, 31%). 1H NMR (300 MHz, CDCl3): d=0.93–
1.78 (brm, 20H), 2.16 (brs, 6H), 3.01 (brs, 2H), 4.42 (brs, 2H), 6.51–7.26
(brm, 31H), 8.21 ppm (brs, 2H). The ratio of monomer incorporation
into 2d was determined by means of 1H NMR spectroscopy to be
3.5:2.0:1.0 (styrene/3d/5). This ratio corresponds to a DMAP loading
level of 1.1 mmolgÀ1 for 2d. EA indicated that 2d contained 2.6% N,
which corresponds to a DMAP loading level of 0.9 mmolgÀ1 for 2d.
Acknowledgements
This research was financially supported by the University of Hong Kong,
the South China University of Science and Technology, the Research
Grants Council of the Hong Kong Special Administrative Region, P.R. of
China (project no. HKU 7027/03P), the Shanghai Municipal Committee
of Science and Technology (04JC14083 and 06XD14005), the Chinese
Academy of Sciences (KGCX2-210-01), and the National Natural Sci-
ence Foundation of China (20472096, 203900502, and 20272069).
Poly{styrene-co-(4-methoxystyrene)-co-[4-(N-methyl-N-vinylbenzylami-
no)pyridine]} (2e): Procedure B was followed by using styrene (3.7 g,
35.7 mmol), 3e (2.4 g, 17.8 mmol), 5 (2.0 g, 8.9 mmol), and AIBN (0.1 g,
0.6 mmol)in toluene (30 mL.) The residue was redissolved in THF
(7 mL)and cold MeOH (600 mL)was used for precipitation to afford 2e
as a yellow powder (3.3 g, 40%). 1H NMR (300 MHz, CDCl3): d=0.93–
2.17 (brm, 23H), 2.95 (brs, 3H), 3.73 (brs, 7H), 4.41 (brs, 2H), 6.50–7.26
(brm, 37H), 8.20 ppm (brs, 2H). The ratio of monomer incorporation
into 2e was determined by means of 1H NMR spectroscopy to be
4.4:2.2:1.0 (styrene/3e/5). This ratio corresponds to a DMAP loading
level of 1.0 mmolgÀ1 for 2e. EA indicated that 2e contained 3.0% N,
which corresponds to a DMAP loading level of 1.1 mmolgÀ1 for 2e.
[1] a)S. V. Ley, I. R. Baxendale, R. N. Bream, P. S. Jackson, A. G.
Leach, D. A. Longbottom, M. Nesi, J. S. Scott, R. I. Storer, S. J.
Taylor, J. Chem. Soc., Perkin Trans. 1 2000, 3815–4195; b)A.
Kirschning, H. Monenschein, R. Wittenberg, Angew. Chem. 2001,
113, 670–701; Angew. Chem. Int. Ed. 2001, 40, 650–679; c)B. Clap-
ham, T. S. Reger, K. D. Janda, Tetrahedron 2001, 57, 4637–4662;
d)N. E. Leadbeater, M. Marco, Chem. Rev. 2002, 102, 3217–3274;
e)C. A. McNamara, M. J. Dixon, M. Bradley, Chem. Rev. 2002, 102,
3275–3300; f)Q.-H. Fan, Y.-M. Li, A. S. C. Chan, Chem. Rev. 2002,
102, 3385–3466; g)S. Brꢁse, F. Lauterwasser, R. E. Ziegert, Adv.
Synth. Catal. 2003, 345, 869–929; h)S. Bhattacharyya, Curr. Opin.
Drug Discovery Dev. 2004, 7, 752–764; i)P. H. Toy, M. Shi, Tetrahe-
dron 2005, 61, 12025.
[2] a)R. I. Storer, T. Takemoto, P. S. Jackson, S. V. Ley, Angew. Chem.
2003, 115, 2625–2629; Angew. Chem. Int. Ed. 2003, 42, 2521–2525;
b)R. I. Storer, T. Takemoto, P. S. Jackson, D. S. Brown, I. R. Baxen-
dale, S. V. Ley, Chem. Eur. J. 2004, 10, 2529–2547.
[3] I. R. Baxendale, S. V. Ley, C. Piutti, Angew. Chem. 2002, 114, 2298–
2301; Angew. Chem. Int. Ed. 2002, 41, 2194–2197.
[4] a)S. Huh, H.-T. Chen, J. W. Wiench, M. Pruski, V. S.-Y. Lin, J. Am.
Chem. Soc. 2004, 126, 1010–1011; b)S. Huh, H.-T. Chen, J. W.
Wiench, M. Pruski, V. S.-Y. Lin, Angew. Chem. 2005, 117, 1860–
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Solovyov, A. J. Pascall, A. Katz, J. Am. Chem. Soc. 2006, 128, 3737–
3747.
[5] We have reported the synthesis of a bifunctional polymeric trifli-
mide/amine reagent, which unfortunately did not function efficiently
as a triflating reagent: C. W. Y. Chung, P. H. Toy, Tetrahedron 2005,
61, 709–715.
Poly{styrene-co-(4-tert-butyldimethylsilyloxystyrene)-co-[4-(N-methyl-N-
vinylbenzylamino)pyridine]} (2 f): Procedure B was followed by using sty-
rene (3.7 g, 35.7 mmol), 3 f (4.2 g, 17.8 mmol), 5 (2.0 g, 8.9 mmol), and
AIBN (0.1 g, 0.6 mmol)in toluene (50 mL). The residue was redissolved
in THF (8 mL)and cold MeOH (600 mL)was used for precipitation to
afford 2 f as a yellow powder (3.3 g, 33%). 1H NMR (300 MHz, CDCl3):
d=0.07 (brs, 12H), 0.97 (brs, 18H), 1.39–1.77 (brm, 22H), 2.93 (brs,
3H), 4.40 (brs, 2H), 6.50–7.24 (brm, 35H), 8.20 ppm (brs, 2H). The ratio
1
of monomer incorporation into 2 f was determined by means of H NMR
spectroscopy to be 4.2:2.0:1.0 (styrene/3 f/5). This ratio corresponds to a
DMAP loading level of 0.9 mmolgÀ1 for 2 f.
General procedure for intramolecular MBH reactions catalyzed by re-
agents 1a–e: Compounds 1a–e (0.125 mmol)were added to a solution of
6a–f (0.5 mmol)in DCE (3 mL)under an argon atmosphere. The reac-
tion mixture was stirred at room temperature until TLC indicated that
the starting material had almost completely disappeared in one reaction
by using 1a–e. The reaction mixture was then diluted with EtOAc,
washed with water, dried over Na2SO4, filtered, and concentrated in
vacuo. The crude product was purified by means of flash column chroma-
tography to afford the desired product 7a–f.
[6] A poly(4-vinylpyridine)-supported DMAP reagent has been report-
ed, see: A. Deratani, G. D. Darling, D. Horak, J. M. J. Frꢂchet, Mac-
romolecules 1987, 20, 767–772.
General procedure for intermolecular MBH reactions between aldehydes
8a–h and methyl vinyl ketone (9) catalyzed by reagents 2a–e: Aldehydes
8a–h (0.5 mmol)and 9 (126 mL, 1.5 mmol)were added to solutions of
2a–e (0.05 mmol)in THF (2 mL)under an argon atmosphere. The reac-
tion mixture was stirred at 608C for 3 d and then concentrated in vacuo.
The crude product was purified by means of flash column chromatogra-
phy to afford the desired product 10a–h.
[7] For interesting reports of polymeric 1,1’-bi-2-naphthol (BINOL)and
bis-BINOL ligands in which multiple BINOL groups coordinate to
metal centers to form active catalysts, see: a)T. Sekiguti, Y. Iizuka,
S. Takizawa, D. Jayaprakash, T. Arai, H. Sasai, Org. Lett. 2003, 5,
2647–2650; b)T. Arai, T. Sekiguti, K. Otsuki, S. Takizawa, H. Sasai,
Angew. Chem. 2003, 115, 2194–2197; Angew. Chem. Int. Ed. 2003,
42, 2144–2147; c)S. Takizawa, H. Somei, D. Jayaprakash, H. Sasai,
Chem. Eur. J. 2007, 13, 2369 – 2376
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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M. Shi, P. H. Toy et al.
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Received: August 17, 2006
Published online: December 15, 2006
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