Solvent-free direct enantioselective aldol reaction using polystyrene-supported N-sulfonyl-(Ra)-binam-d-prolinamide as a catalyst

Article abstract of DOI:10.1039/c002967j

The immobilization of N-sulfonyl-(R_a)-binam-d-prolinamide using polystyrene as a support allows the recovery of an efficient catalytic system for the enantioselective direct aldol reaction between different ketones and aldehydes under solvent-f

Full text of DOI:10.1039/c002967j

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Solvent-free direct enantioselective aldol reaction using
polystyrene-supported N-sulfonyl-(Ra)-binam-D-prolinamide as a catalyst†
Abraham Ban˜o´n-Caballero, Gabriela Guillena* and Carmen Na´jera*
Received 12th February 2010, Accepted 1st July 2010
DOI: 10.1039/c002967j
The immobilization of N-sulfonyl-(Ra)-binam-D-prolinamide using polystyrene as a support
allows the recovery of an efficient catalytic system for the enantioselective direct aldol reaction
between different ketones and aldehydes under solvent-free or aqueous conditions. The
polystyrene-supported N-sulfonyl-(Ra)-binam-D-prolinamide catalyst in combination with
benzoic acid showed similar results to those obtained with unsupported N-tosyl-binam-derived
prolinamide under similar reaction conditions. The aldol products were obtained at room
temperature and using only 2 equivalents of the ketone with high yields, regio-, diastereo- and
enantioselectivities. The aldol reaction between aldehydes can also be performed under these
reaction conditions with moderate results. The recovered catalyst can be reused up to six times
without having a detrimental effect on the achieved results.
by simple acid–base work-up, more general and efficient catalyst
1 can only be recovered by direct column chromatography from
Introduction
The direct aldol reaction1 has been extensively used in industry
the reaction media.
either in bulk or in fine chemical manufacture and pharmaceu-
Several immobilization strategies, such as the use of different
tical target production to prepare polyoxygenated architectures
polymers, silica, ionic liquids, or even more sophisticated
from two carbonyl compounds. The application of enantiose-
materials such as dendrimers, nanoparticles or DNA as supports
lective organocatalytic methods2 to perform this aldol reaction3
have already been applied to proline and proline-derivatives
and other C–C or C–heteroatom4 processes implies advantages
in order to allow their recyclability as organocatalysts for
over other asymmetric methods. However, in order to obtain
different organocatalytic processes.10 Several proline and proline
high yields, the use of excess of one of the reactants, normally
derivatives have been incorporated in insoluble polymeric mate-
the nucleophile, long reaction times, high catalyst loading and
rial and used in the aldol reaction under different conditions.
polar solvents are usually needed, with these requirements
For instance, proline has been directly immobilised through
being a serious drawback for the general application of this
its carboxylic function in a 4-methylbenzhydrylamine resin
procedure. Therefore, more efficient and greener conditions5
(MBHA)11 or in a modified Merrifield resin.12
such as the use of solvent-free reaction conditions6 in asymmetric
In a similar way, several small peptides have been immobilised
organocatalytic processes7 are of great interest.
in different amine-terminated resins such as PEG-polystyrene
N-Tosyl-(Sa)-binam-L-prolinamide 18 and bisprolinamides 29
resins13 or Tentagel.14 Moreover 4-trans-aminoproline has been
derived from 1,1¢-binaphthyl-2,2¢-diamine (binam) (Fig. 1), have
been used efficiently as organocatalysts in the aldol reaction
using different reaction media, including solvent-free reaction
conditions.8,9j,k While catalyst2 is easily recoverable and reusable
incorporated in different functionalized polystyrene supports,15
and 4-trans-hydroxyproline has been supported through the
hydroxy group in poly(ethylene glycol),16 Merrifield resins17
and mercaptomethylpolystyrene resins.18 Generally, for all these
polymeric catalysts a high excess of reacting ketone was needed
in order to obtain the corresponding aldol products in good
yields; sometimes the nucleophilic ketone being the solvent of
choice to perform the reaction. The use of such excess of one
of the reagents diminished the atom efficiency of the reaction19
and hampered the use of valuable ketones as starting materials
to perform this reaction.
In this paper we describe the immobilization of compound
ent-1 in polystyrene and its use as a recoverable catalyst under
solvent-free or aqueous conditions for the aldol reaction.
Fig. 1
Results and discussion
Dpto. Qu´ımica Orga´nica and Instituto de S´ıntesis Orga´nica, Universidad
de Alicante, Apdo. 99, E-03080 Alicante, Spain.
E-mail: gabriela.guillena@ua.es, cnajera@ua.es; Fax: +34 965903549;
Tel: +34 965903549
Synthesis of the grafted polymeric organocatalyst
The use of solvent-free conditions with catalyst 1 permitted
† This paper is dedicated to the memory of Prof. Jose´ M. Concello´n.
the reduction of the excess of the required ketone to only 2
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equivalents.8 Therefore, pursuing a greener process, we were
interested in the immobilization of a catalytic system of similar
structure and its use in the aldol reaction under solvent-free
conditions. Since the functionalization of a polymer via a free-
radical addition has recently been used as a convenient strategy
for grafting chiral subunits to insoluble supports,18,20 we decided
to apply this method to incorporate our catalyst in an insoluble
polymeric support. Two synthetic steps were needed for this
purpose: (a) the synthesis of a styrylsulfonyl derivative of
binam-prolinamide 3 and (b) the thiol-ene coupling (TEC)21
reaction between a commercially available mercaptomethyl
functionalized polystyrene polymer 4 and binam-derivative 3.
In order to prepare the styryl binam-derivative 3, commer-
cially available sodium 4-vinylbenzenesulfonate was reacted
with thionyl chloride to give the expected sulfonyl chloride
derivative,20 which was trapped with (Ra)-1,1¢-binaphthyl-2,2¢-
diamine (binam, Scheme 1) under a similar procedure to that
used for the synthesis of catalyst 1.8 The described procedure20
to perform this reaction used benzene as a solvent, but we
decided to use less harmful toluene as the solvent, although
the achieved yield was slightly lower.22 The achieved binam-
sulfonyl derivative was subsequently coupled with the in situ
generated Fmoc-D-Pro chloride followed by deprotection with
piperidine affording the styryl binam-derivative 3 in 46% overall
yield. Alternatively, the binam-sulfonyl derivative could be
coupled with the in situ formed mixed anhydride of N-Boc-D-
Pro and ethyl chloroformate,23 affording after deprotection with
trifluoroacetic acid the styryl derivative 3 with similar results.
Once 3 was prepared, the grafting of the commercially avail-
able polystyrene polymer 4 (100–200 mesh, cross-linked with
1% divinylbenzene, 2.5 mmol g-1 loading) was accomplished
by a radical addition protocol (Scheme 2) giving the expected
polymer 5. After washing the obtained polymer thoroughly
several times with methanol and diethyl ether, an incorporation
of about 55% of the chiral subunit was achieved (determined by
the microanalysis data).
Scheme 2 Synthesis of the grafted polymer 5.
When using the described procedure for grafting 4-trans-
hydroxyproline derivative on to mercaptomethyl polystyrene
resins,18 with binam N-Boc-protected-D-proline styryl deriva-
tive, only 46% monomer incorporation was achieved (deter-
mined by microanalysis data).
Catalysis and recycling
The aldol reaction between cyclohexanone and p-
nitrobenzaldehyde was chosen as a model process to test
the catalytic activity of the polymer 5 (Scheme 3 and Table 1).
All reactions were carried out in the presence of 20 mol% of
polymeric catalyst 5 and 5 mol% of benzoic acid as cocatalyst.
Different solvents and temperatures were tested in order to find
the best reaction conditions. The reaction failed using polar
aprotic solvents even at room temperature and after several days
of reaction (Table 1, entries 1–3). However, when the reaction
was carried out using a 1/1 mixture of DMF–H2O, the aldol
product 8aa was obtained after 3 d in high yield, diastereo- and
enantioselectivity (Table 1, entry 4). In this case, the formation
of a small amount of a,b-unsaturated aldol derivative (less
than 4%) was observed.24 Polar protic solvents such as MeOH
and H2O were then tested as reaction media. Whereas the
reaction did not proceed in MeOH, a low conversion was
Scheme 1 Synthesis of styryl derivative 3.
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Scheme 3 Direct asymmetric aldol reaction between ketones and aldehydes under solvent free conditions catalyzed by polymer 5
Table 1 Optimization of reaction conditions between cyclohexanone
and p-nitrobenzaldehydea
equivalents (Table 1, entries 13 and 14) led to a slower reaction
rate although the yields and selectivities were almost maintained.
Recently, the role of water in organocatalyzed aldol reactions has
been kinetically studied. While the addition of water increases
the catalyst concentration by suppression of the formation of
parasitic species, it decreases the relative concentration of some
intermediates such as oxazolidinones. Thus, the neat effect in the
reaction rate is the sum of these opposing roles, which depends
on the different substrates used.26d
Entry Solvent
T◦/◦C t (d) Conv.b Yield (%)c anti/synd ee (%)e
1
2
3
4
5
6
7
8
CH2Cl2
THF
25
25
25
4
4
3
3
5
5
3
1
4
4
9
3
2
3
NR
NR
NR
96
NR
32
98
97
97
NR
96
—
—
—
88
—
30
81
83
90
—
81
77
75
85
—
—
—
96/4
—
96/4
87/13
95/5
98/2
—
93/7
95/5
96/4
91/9
—
—
—
78
—
86
68
90
82
—
92
90
90
86
DMF
DMF–H2Of 25
MeOH
H2O
25
25
25
Noneg
Under the optimal reaction conditions (Table 1, entry 8),
the scope of the reaction was studied varying the ketone and
aldehyde (Scheme 3 and Table 2). Different aldehydes were used
in the reaction with cyclohexanone giving the expected products
in good yields, diastereo- and enantioselectivities. In order to
increase the reaction rates, the addition of water (aqueous
conditions) was compulsory in all these reactions (Table 2,
entries 1–5), with longer reaction times being required for non-
activated aldehydes such as benzaldehyde (Table 2, entry 3).
Then, several cyclic ketones were used as nucleophiles in the
reaction with p-nitrobenzaldehyde. As expected cyclopentanone
(6b) gave the syn-8ba product as the major isomer (Table 2,
entries 6 and 7), the best result being achieved when the
reaction was carried out under aqueous conditions at 0 ◦C
(Table 2, entry 6). Surprisingly, 4-tetrahydropyranone (6c) gave
a better yield in shorter reaction times under solvent-free
conditions, with the diastereo- and enantioselectivities achieved
being similar for both reactions (Table 2, entries 8 and 9).
With other alkyl ketones such as acetone (6d) or butanone
(6e), again the use of aqueous conditions gave high yields
(Table 2, entries 10–13). The iso-9ea product was the major
isomer for the case of butanone (Table 2, entry 12). Conversely,
the use of functionalizated ketones such as a-methoxyacetone
(6f) and a-(methylsulfanyl)acetone (6g) required the use of dry
solvent-free conditions to give the best results. Thus, for a-
methoxyacetone, product anti-8fa was obtained in good yields
with lower selectivity (Table 2, entries 14 and 15). In the case
of the less reactive a-(methylsulfanyl)acetone, product iso-9ga
was the main isomer but was obtained in low yields (Table 2,
entries 16 and 17). Unfortunately, when these conditions were
applied to the reaction between less reactive aliphatic aldehydes
such as isobutyraldehyde or cinnamaldehyde with acetone or
cyclohexanone, the reaction failed. The obtained results were
slightly lower in terms of yields, selectivity and optical purity to
those obtained under similar reactions conditions with catalyst
1,8a probably due to the longer reaction time required using
catalyst 5, which possibly competes with the background non-
catalyzed process.
none/H2Oh 25
none/H2Oh 10
9
10
11
12
13
14
none/H2Oh
0
none/H2Ohi 25
none/H2Oj 25
none/H2Ok 25
none/H2Ol 25
90
90
99
a Reaction conditions: 6a (2 equiv.), 7a (0.1 mmol), benzoic acid
(5 mol%) catalyst 5 (20 mol%) and solvent (0.6 mL). b Conversion
based on the unreacted aldehyde. c After purification by column
1
chromatography. d Determined by the H NMR of the crude product.
e Determined by chiral-phase HPLC analysis for the anti isomer. f 1/1
mixture of DMF–H2O. g Solvent-free conditions. h 100 mL of H2O were
added to the reaction mixture. i Catalyst 5 (10 mol%) and benzoic acid
j
(5 mol%). 200 mL of H2O were added to the reaction mixture. k 50mL
of H2O were added to the reaction mixture. l 25 mL of H2O were added
to the reaction mixture.
obtained in H2O giving the aldol product in high diastereo- and
enantioselectivity (Table 1, entries 5 and 6).
Finally, solvent-free conditions were used at room tempera-
ture. Under these conditions the reaction took place in a similar
yield to that achieved in DMF–H2O but with lower diastereo-
and enantioselectivity (Table 1, compare entries 4 and 7). In
order to accelerate the reaction, water (55 equiv.) was added
to the reaction mixture,25 achieving the aldol product in only 1
d, in comparable yields to those previously obtained and with
the highest enantioselectivity (Table 1, compare entries 4, 7 and
8). Lowering the temperature to 10 ◦C increased the reaction
time to 4 d but decreased the enantioselectivity probably due
to competition with the non-catalyzed reaction (Table 1, entry
◦
9), with the reaction failing at 0 C (Table 1, entry 10). Under
aqueous conditions, the amount of catalyst and co-catalyst were
reduced (10 mol% of 5 and 5 mol% benzoic acid) performing
the reaction at room temperature. As expected, the reaction time
suffered an increase from 1 d to 9 d, but with product 8aa being
achieved with similar yields, diastereo- and enantioselectivities
(Table 1, compare entries 8 and 11). Finally, the amount of added
water26 was optimized under the general reaction conditions
outlined in entry 8 of Table 1. For the obtained results it
could be concluded that increasing the amount of water to 110
equivalents (Table 1, entries 12) or decreasing it to 28 or 14
Polymer 5 was also able to catalyse the aldol reaction between
aldehydes 7a and 7f, although high catalyst loading (40 mol%)
and longer reaction times (10 d) were needed to reach a moderate
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Table 2 Reaction between ketones and aldehydes under solvent-free or
aqueous conditions catalyzed by polymer 5a
Table 2 (Contd.)
Yield
ee
Yield
ee
Entry Product
t (d) (%)b 8/9c anti/sync (%)d
Entry Product
1e
t (d) (%)b 8/9c anti/sync (%)d
15
3
10
82
20
89/11 83 : 17
20/80 —
88
84
1
3
8
3
3
83
78
69
81
79
—
—
—
—
—
95 : 5
94 : 6
94 : 6
93 : 7
94 : 6
88
76
86
88
84
16e
2e
3e
4e
5e
17
8
22
17/83 —
82
a Reaction conditions: 6 (2 equiv.), 7 (0.25 mmol), benzoic acid (5 mol%)
catalyst (20 mol%), rt. b After purification by column chromatography.
c Determined by the H NMR of the crude product. d Determined by
1
chiral-phase HPLC analysis for the anti isomer. e 200 mL of H2O were
added to the reaction mixture. f The reaction was carried out at 0 ◦C.
yield for product 10 (Scheme 4). The use of the polymer under
different reaction conditions for the direct aldol intramolecular
reaction of 1,5-diketones8 failed, unfortunately.
6ef
4
77
—
37 : 63
74
Scheme 4 Aldol reaction between p-nitrobenzaldehyde and propanal
using polymeric catalyst 5.
Finally, recycling studies were carried out using the model
reaction between cyclohexanone and p-nitrobenzaldehyde under
aqueous conditions (Table 3, Scheme 3). After each cycle the
reaction was quenched by filtration and the resin was washed
with a 0.5 M solution of NaOH, to remove the benzoic acid
occluded in the polymeric matrix. Then, the resin was washed
several times either with ethyl acetate, ethanol or acetone and
dried under vacuum. The obtained results were consistently high
in terms of yields, diastereo- and enantioselectivities even after
six reaction cycles.
7
3
5
78
52
—
—
37 : 63
95 : 5
56
86
8e
9
3
3
75
76
—
—
94 : 6
—
82
73
10e
Table 3 Recycling studies for compound 8aaa
11
5
3
72
69
—
—
73
86
12e
43/57 —
Entry
Cycle
t (d)
Yield (%)b
anti/sync
ee (%)d
1
2
3
4
5
6
1
2
3
4
5
6
1
1
1
1
1
1
83
80
79
70
69
75
94 : 6
95 : 5
95 : 5
94 : 6
94 : 6
93 : 7
84
88
88
90
88
84
13
5
5
30
20
37/63 —
88/12 80 : 20
84
80
14e
a Reaction conditions: 6a (2 equiv.), 7a (0.2 mmol), benzoic acid (5 mol%)
catalyst (20 mol%), 200 mL of H2O, rt. b After purification by column
1
chromatography. c Determined by the H NMR of the crude product.
d Determined by chiral-phase HPLC analysis for the anti isomer.
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ethyl acetate) to give the (R)-N-(2¢-amino-1,1¢-binaphthyl-2-
Conclusions
yl)-4-vinylbenzenesulfonamide in 65% yield. Fmoc-D-proline
chloride was prepared by slow addition of SOCl2 (1.7 mL, 22
mmol) to a solution of Fmoc-D-proline (0.763 g, 2.2 mmol)
dissolved in dry CH2Cl2 (15 mL), and subsequent reflux for 1 h
and removal of the solvent and excess of the reactants.
Polystyrene-supported binam-prolinamide was easily prepared
by standard procedures in two steps starting from commercially
available mercaptomethyl polystyrene and synthetic styrylsul-
fonyl binam-derivative using TEC coupling. This polymer
has been used in the aldol reaction between several ketones
and aldehydes in the presence of benzoic acid under solvent-
free or aqueous conditions affording the corresponding aldol
product in high yields, regio-, diastereo-, and enantioselectiv-
ities. These results are comparable to those obtained under
homogeneous conditions using soluble catalyst N-tosyl-(Sa)-
binam-L-prolinamide 1. This polymer was also able to catalyse
the reaction between aldehydes with moderate results. The
recyclability of the polymeric material was confirmed by its
recovery by filtration and reused up to six times without
detrimental results. Currently, the use of this polymeric material
for other organocatalytic processes is under investigation.
To a solution of (R)-N-(2¢-amino-1,1¢-binaphthyl-2-yl)-4-
vinylbenzenesulfonamide (1.03 g, 2.29 mmol) dissolved in dry
CH2Cl2 (15 mL) was added a solution of Fmoc-D-proline
chloride (1.21 g, 3.4 mmol) in dry CH2Cl2 (15 mL) and
triethylamine (0.95 mL, 6.8 mmol) at 0 ◦C. The ice-bath was
removed and the reaction was stirred for 24 h at rt. The solvents
were removed under reduced pressure (15 Torr) and the resulting
solid residue was dissolved in ethyl acetate and washed with
brine (3 ¥ 10 mL). The organic layer was dried over Na2SO4,
filtered and the solvents were removed under reduced pressure
(15 Torr). The resulting crude product ◦was dissolved in dry
DMF (10 mL) and to this solution at 0 C, piperidine (7 mL,
70 mmol) was added drop wise. After removal of the ice-bath,
the reaction was stirred for 1 h at rt. 20 ml of ethyl acetate were
added to the mixture and the resulting solution was washed
alternatively with brine and water (5 ¥ 5 mL). The organic layer
was dried over Na2SO4, filtered and the solvents were removed
under reduced pressure (15 Torr). The resulting crude product
was purified by column chromatography (hexane–ethyl acetate)
to give product 3 (0.876 g, 70%) as a white solid (Found: C, 71.6;
H, 5.4; N 7.1; S 5.0. C33H29N3O3S, requires C, 72.4; H, 5.3; N
7.7; S 5.8). Mp 210–212 ◦C (EtOAc); HPLC (HPLC Chiralpak
AD-H, n-hexane/i-PrOH: 80/20, 1.0 mL min-1), Rt = 51.29; Rf
0.28 (EtOAc); [a]D +111.7 (c 1.0 in CHCl3); IR nmax/cm-1 (KBr)
3828, 3369, 3289, 3167, 2965, 2855, 1682, 1592, 1501, 1402,
1313, 1160; dH (300 MHz; CDCl3, Me4Si) 0.66 (1H, m, CH2),
1.17 (2H, m, CH2), 1.58 (1H, m, CH2), 1.73 (1H, m, CH2), 2.18
(1H, m, CH2), 3.27 (1H, dd, J 4.1, 9.6, CH), 5.42 (1H, d, J 10.8,
CH2 ), 5.48 (1H, d, J 17.6, CH2 ), 6.67 (1H, dd, J 10.8, 17.6,
CH), 6.84 (1H, d, J 8.4, ArH), 6.92 (1H, d, J 8.4, ArH), 7.17
(2H, m, ArH), 7.31 (2H, d, J 8.2, ArH), 7.39 (2H, m, ArH),
7.50 (2H, d, J 8.6, ArH), 7.86 (1H, d, J 8.2, ArH), 7.93 (1H,
d, J 8.2, ArH), 8.00 (1H, d, J 9.0, ArH), 8.06 (1H, d, J 9.2,
ArH), 8.21 (1H, d, J 9.2, ArH), 8.83 (1H, d, J = 9.0, ArH), 9.26
(1H, s, NHCO); dC (75 MHz; CDCl3, Me4Si) 25.2 (CH2), 30.5
(CH2), 46.0 (CH2NH), 60.4 (CH), 116.8 (ArC), 117.9 (CH2 ),
119.1 (ArC), 119.2 (ArC), 120.6 (ArC), 124.0, 125.1, 125.6, 126.4
(ArCH), 127.4 (ArC), 127.45, 127.6, 127.7, 128.1, 128.6, 130.1,
130.5 (ArCH), 130.7, 131.1, 132.1, 133.5 (ArC), 135.0 (CH ),
138.0, 142.0 (ArC), 173.4 (CO).
Experimental
General
All reactions for the catalyst preparation were carried out
under argon. Dry DMF, dry toluene, dry CH2Cl2, piperidine
and triethylamine and all others reagents were commercially
available and used without further purification. Propanal and
benzaldehyde were distilled prior to use. Only the structurally
most important peaks of the IR spectra (recorded on a Nicolet
1
Impact 400D) are listed. H NMR (300 MHz, 400 MHz) and
13C NMR (75 MHz) spectra were obtained on a Bruker AC-300
using CDCl3 as solvent and TMS as internal standard, unless
otherwise stated. Optical rotations were measured on a Perkin
Elmer 341 polarimeter. HPLC analyses were performed on an
Agilent 1100 series equipped with a chiral column (detailed for
each compound below), using mixtures of n-hexane/isopropyl
alcohol (IPA) as mobile phase, at 25 ◦C. Analytical TLC was
performed on Schleicher & Schuell F1400/LS silica gel plates
and the spots were visualised under UV light (l = 254 nm). For
flash chromatography we employed Merck silica gel 60 (0.063–
0.2 mm). Elemental analysis was carried out in the Research
Technical Services of the University of Alicante.
Synthesis of supported polymeric organocatalyst
Synthesis of (R)-N-[(R)-2¢-(4-vinylphenylsulfonamido)-1,1¢-
binaphthyl-2-yl]pyrrolidine-2-carboxamide 3. To a solution of
4-vinylbenzenesulfonate (1.1 g, 5.3 mmol) in dry toluene (30 mL)
were added SOCl2 (2 mL, 27.6 mmol) and a few drops of dry
DMF. The resulting solution was refluxed for 15 h and all the
volatiles were removed under reduced pressure (0.1 Torr) to yield
the corresponding sulfonylchloride derivative. This compound
was dissolved in dry CH2Cl2 (20 mL) under inert atmosphere and
added to a solution of (Ra)-1,1¢-binaphthyl-2,2¢-diamine (1 g,
3.5 mmol) in 20 mL of dry CH2Cl2 and dry pyridine (3.5 mL,
43.44 mmol). The resulting mixture was stirred for 12 h at rt,
and then treated with a HCl 5% solution (3 ¥ 15 mL). The
organic layer was dried over Na2SO4, filtered off and the solvents
were removed under reduced pressure (15 Torr). The resulting
crude product was purified by column chromatography (hexane–
Alternative synthesis of (R)-N-[(R)-2¢-(4-vinylphenylsul-
fonamido)-1,1¢-binaphthyl-2-yl]pyrrolidine-2-carboxamide
3.
To a solution of Boc-D-proline (0.215 g, 1 mmol) and
triethylamine (0.14 mL, 1.0 mmol) in dry THF (7.5 mL) at
0
◦C was drop wise added ethyl chloroformate (0.102 mL,
1 mmol). After stirring the resulting solution for 30 min at
0
◦C, a solution of (R)-N-(2¢-amino-1,1¢-binaphthyl-2-yl)-
4-vinylbenzenesulfonamide (0.45 g, 1.0 mmol) dissolved in
dry THF (7.5 mL) was added over 15 min. The ice-bath was
removed and the reaction was refluxed for 48 h at rt. The
solvents were removed under reduced pressure (15 Torr) and
the resulting solid residue was dissolved in dichloromethane
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(7.5 mL) and trifluoroacetic acid (2 mL) was added. The
resulting mixture was stirred for 1 h. NaOH (3 M) was added to
the reaction mixture until pH 7 and the resulting solution was
washed with water (3 ¥ 7 mL). The organic layer was dried over
MgSO4, filtered and the solvents were removed under reduced
pressure (15 Torr). The resulting crude product was purified by
column chromatography (hexane–ethyl acetate) to give product
3 (0.380 g, 70%) as a white solid
(75 MHz; CDCl3, Me4Si) 24.7, 27.8, 30.8, 42.6, 57.4, 74.7, 127.0,
127.9, 128.3, 140.8, 215.5; HPLC (Chiralcel ODH, n-hexane/i-
PrOH: 95/5, 0.50 mL min-1), anti: Rt 25.358 (minor), Rt 39.835
(major), syn Rt 19.262 (major), Rt 21.677 (minor).
(R)-2-[(S)-Hydroxy(2-nitrophenyl)methyl]cyclohexanone anti-
8ad28. dH (300 MHz; CDCl3, Me4Si) 1.55–1.87 (m, 5H), 2.04–
2.17 (m, 1H), 2.28–2.49 (m, 2H), 2.71–2.80 (m, 1H), 4.19 (br s,
1H), 5.45 (d, J 7.2, 1H), 7.40–7.46 (m, 1H), 7.61–7.66 (m,
1H), 7.75–7.86 (m, 2H); dC (75 MHz; CDCl3, Me4Si) 24.9,
27.7, 31.0, 42.8, 57.2, 69.7, 124.0, 128.3, 128.9, 133.0, 136.5,
148.6, 214.9; HPLC (Chiralcel AD-H, n-hexane/i-PrOH: 95/5,
0.7 mL min-1), anti: Rt 48.851 (minor), Rt 51.491 (major), syn:
Rt 32.517 (minor), Rt 35.193 (major).
Synthesis of polystyrene-supported organocatalyst 5. To a
suspension of styryl binam-derivative 3 (0.3 g, 0.55 mmol) and
mercaptomethyl polystyrene 4 (0.275 g, 0.55 mmol) in dry THF
(15 mL) was added AIBN (0.054 g, 0.3 mmol) and the mixture
was refluxed for 48 h. After cooling at room temperature, the
resin was filtered and washed with MeOH and diethyl ether.
The resin was dried under a high vacuum to give 0.350 g
of polymer 5, which corresponds to approximately 55% of
monomer incorporation calculated on the basis of elemental
analysis and weight difference (Found: C, 78.64; H, 6.74; N,
2.65; C61H57N3O3S2 corresponding to 100% of polymer requires
C, 77.6; H, 6.1; N, 4.5), IR nmax/cm1 (KBr) 3079, 3053, 3022,
2970, 2918, 2845, 1687, 1598, 1510, 1494, 1312, 1151.
(R)-2-[(S)-Hydroxy(3-nitrophenyl)methyl]cyclohexanone anti-
8ae28. dH (300 MHz; CDCl3, Me4Si) 1.37–1.43 (m, 1H), 1.52–
1.61 (m, 3H), 1.65–1.70 (m, 1H), 1.81–1.85 (m, 1H), 2.09–2.15
(m, 1H), 2.33–2.41 (m, 1H), 2.48–2.65 (m, 1H), 4.12 (s, 1H), 4.89
(d, J = 8.4 Hz, 1H), 7.51–7.55 (m, 1H), 7.67 (d, J 7.6, 1H), 8.15–
8.21 (m, 2H); dC (100 MHz; CDCl3, Me4Si) 24.6, 27.6, 30.7, 42.6,
57.1, 74.0, 122.0, 122.8, 129.2, 133.1, 143.2, 148.2, 214.8; HPLC
(Chiralcel AD-H, n-hexane/i-PrOH: 95/5, 0.7 mL min-1), anti:
Rt 52.412 (minor), Rt 67.849 (major). syn: Rt 40.715 (minor),
Rt 46.446 (major).
General procedure for the aldol reaction catalysed by polymer
5 under aqueous conditions. To a mixture of the corresponding
aromatic aldehyde (0.1 mmol), catalyst 5 (0.02 mmol, 27 mg)
and benzoic acid (0.005 mmol, 0.6 mg) at 25 ◦C was added
the corresponding ketone (0.2 mmol) and H2O (100 mL). The
reactionwas stirreduntilthe aldehyde was consumed (monitored
by TLC). Then, the mixture was filtered and washed with
either EtOAc, EtOH or acetone (3 ¥ 2 mL). The solvents were
removed under reduced pressure and the residue was purified by
flash chromatography (hexanes/AcOEt) to yield the pure aldol
product.
(R) - 2 - [(S) - Hydroxy(4 - nitrophenyl)methyl]cyclopentanone
8ba27. dH (300 MHz; CDCl3, Me4Si) 1.72–1.75 (m, 2H), 1.96–
2.09 (m, 1H), 2.30–2.74 (m, 2H), 2.74 (d, J 4.8, 1H, syn), 4.77
(br s, 1H, anti), 4.84 (d, J 9.1, 1H, anti), 5.42 (s, 1H, syn),
7.52 (d, J 8.4, 2H), 8.21 (d, J 8.7, 2H); dC (75 MHz; CDCl3,
Me4Si) syn 20.2, 22.2, 38.8, 56.0, 70.3, 123.6, 126.3, 147.0,
150.2, 219.6; anti 20.2, 26.7, 38.5, 55.0, 74.3, 123.5, 127.3, 147.2,
148.5, 219.7; HPLC (Chiralcel AD-H, n-hexane/i-PrOH: 95/5,
1.0 mL min-1), syn: Rt 25.282 (minor), Rt 35.441 (mayor), anti:
Rt 43.471 (mayor), Rt 45.885 (minor).
(R) - 2 - [(S) - Hydroxy(4 - nitrophenyl)methyl]cyclohexanone
8aa27. dH (300 MHz; CDCl3, Me4Si) 1.28–1.49 (m, 1H), 1.52–
1.73 (m, 3H), 1.79–1.83 (m, 1H), 2.06–2.14 (m, 1H), 2.21–2.31
(m, 1H), 2.33–2.50 (m, 1H), 2.54–2.63 (m, 1H), 3.12 (br s, 1H
syn), 4.02 (brs, 1H anti), 4.88 (d, J 8.4, 1H anti), 5.46 (s, 1H syn),
7.49 (d, J 8.7, 2H), 8.19 (d, J 8.7, 2H); dC (75 MHz; CDCl3,
Me4Si) anti 24.6, 27.5, 30.6, 42.6, 57.1, 73.9, 123.5, 127.8, 147.4,
148.3, 214.6; syn 24.7, 25.8, 27.7, 42.5, 56.7, 70.0, 123.4, 126.5,
147.5, 149.2, 213.9; HPLC (Chiralcel AD, n-hexane/i-PrOH:
90/10, 0.7 mL min-1), anti: Rt 37.104 (major), Rt 49.183 (minor),
syn: Rt 27.271 (minor), Rt 33.833 (major).
(R)-3-[(S)-Hydroxy(4-nitrophenyl)methyl]dihydro-2H-pyran-
4(3H)-one 8ca29. dH (300 MHz; CDCl3, Me4Si) 2.50–2.57 (m,
1H), 2.63–2.73 (m, 1H), 2.85–2.93 (m, 1H), 3.46 (t, J 9.8, 1H),
3.73–3.81 (m, 2H), 4.16–4.27 (m, 1H), 5.00 (d, J 9.8, 1H, anti),
5.54 (d, J 2.9, 1H, syn), 7.52 (d, J 8.7, 2H), 8.23 (d, J 8.8, 1H),.
dC (75 MHz; CDCl3, Me4Si) 42.7, 57.5, 68.2, 69.7, 71.2, 123.8,
127.4, 147.4, 147.7, 209.1; HPLC (Chiralcel AD-H, n-hexane/i-
PrOH: 80/20, 1.0 mL min-1), anti: Rt 18.906 (mayor), Rt 22.258
(minor), syn: Rt 13.447 (minor), Rt 15.795 (mayor).
(S)-4-Hydroxy-4-(4-nitrophenyl)-butan-2-one
8da27. dH
(R) - 2 - [(S) - Hydrox4 - (4 - cyanophenyl)methyl]cyclohexanone
anti-8ab28. dH (300 MHz; CDCl3, Me4Si). 1.28–1.49 (m, 1H),
1.52–1.84 (m, 4H), 2.04–2.17 (m, 1H), 2.30–2.47 (m, 1H), 2.50–
2.61 (m, 2H), 4.07 (s, 1H), 4.84 (d, 8.4 J = Hz, 1H), 7.45 (d,
J = 8.3 Hz, 2H), 7.65 (d, J 8.3, 2H); dC (75 MHz, CDCl3,
Me4Si) 24.6, 27.5, 30.6, 42.6, 57.0, 74.1, 111.6, 118.6, 127.7,
132.2, 146.3, 214.8; HPLC (Chiralcel AD-H, n-hexane/i-PrOH:
95/05, 1.0 ml min-1), anti: Rt 39.774 (major), Rt 50.913 (minor),
syn: Rt 26.595 (major), Rt 33.786 (minor).
(300 MHz; CDCl3, Me4Si). 2.22 (s, 3H), 2.85 (d, J 2.9, 2H),
3.59 (d, J 3.3, 1H), 5.27 (dd, J 2.9, 3.3, 1H), 7.54 (d, J 8.8, 2H),
8.21 (d, J 8.8, 2H); dC (75 MHz, CDCl3, Me4Si) 30.6, 51.4,
68.8, 123.7, 126.3, 147.3, 149.9, 208.2; HPLC Chiralcel AS-H
n-hexane/i-PrOH: 85/15, 1.0 ml min-1: Rt 45.236 (major), Rt
32.386 (minor).
(S)-1-Hydroxy-1-(4-nitrophenyl)pentan-3-one
9ea27. dH
(300 MHz; CDCl3, Me4Si). 1.09 (t, J 7.3, 3H), 2.48 (q, 2H), 2.82
(d, J 4.2, 2H), 3.64 (s, 1H), 5.27 (dt, J 3.5, 7.7, 1H), 7.53 (d, J
8.6, 2H), 8.21 (d, J 9.8, 2H); dC (75 MHz, CDCl3, Me4Si) 7.4,
29.7, 36.8, 50.2, 69.1, 123.7, 126.4, 147.3, 150.1, 211.4. HPLC
(Chiralcel AS n-hexane/i-PrOH: 95/05, 0.7 ml min-1), anti: Rt
(R)-2-[(S)-Hydroxy(phenyl)methyl]cyclohexanone anti-8ac28.
dH (300 MHz; CDCl3, Me4Si) 1.27–1.36 (m, 1H), 1.50–1.80
(m, 4H), 2.04–2.12 (m, 1H), 2.30–2.50 (m, 2H), 2.58–2.67 (m,
1H), 4.05 (br s, 1H), 4.78 (d, J 8.9, 1H), 7.29–7.37 (m, 5H); dC
1604 | Green Chem., 2010, 12, 1599–1606
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169.781 (major), Rt 110.287 (minor), iso: Rt 219.421 (major),
Rt 98.961 (minor)
Biomimetic Concepts to Applications in Asymmetric Synthesis, Wiley-
VCH, Weinheim, 2005; (c) P. Kocˇovsky´, A. V. Malkov, Issue ed.;
Tetrahedron, 2006, 62, 255 (thematic issue on Organocatalysis in
Organic Synthesis, no. 2–3); (d) H. Pellissier, Tetrahedron, 2007, 63,
9267–9331; (e) Enantioselective Organocatalysis, P. I. Dalko, Ed.;
Wiley-VCH, Weinheim, 2007; (f) B. List, Chem. Rev., 2007, 107,
5413(Special Issue in Organocatalysis); (g) D. Enders, C. Grondal
and M. R. M. Hu¨ttl, Angew. Chem., Int. Ed., 2007, 46, 1570–1581;
(h) G. Guillena, D. J. Ramo´n and M. Yus, Tetrahedron: Asymmetry,
2007, 18, 693–700; (i) R. M. de Figueiredo, R. Marcia and M.
Christmann, Eur. J. Org. Chem., 2007, 2575–2600; (j) H. Kotsuki, H.
Ikishima and A. Okuyama, Heterocycles, 2008, 75, 493–529; (k) H.
Kotsuki, H. Ikishima and A. Okuyama, Heterocycles, 2008, 75, 757–
797; (l) D. W. C. MacMillan, Nature, 2008, 455, 304–308; (m) S.
Bertelsen and K. A. Jørgensen, Chem. Soc. Rev., 2009, 38, 2178–
2189.
(3R,4R)-4-Hydroxy-3-methoxy-4-(4-nitrophenyl)butan-2-one
anti-8fa30. dH (300 MHz; CDCl3, Me4Si) 2.16 (s, 3H), 3.20 (s,
1H), 3.32 (s, 3H), 3.70 (d, J 6.2, 1H), 5.02 (d, J 6.2, 1H), 7.56
(d, J 8.8, 2H), 8.22 (d, J 8.8, 2H). dC (75 MHz; CDCl3, Me4Si)
27.5, 59.6, 73.3, 89.6, 123.4, 127.7, 146.7, 147.7, 209.9. HPLC
(Chiralpak ODH, n-hexane/i-PrOH: 90/10, 0.8 mL min-1), anti:
Rt 16.274 (minor), Rt 19.208 (mayor); syn: Rt 20.222 (mayor),
Rt 25.535 (minor).
(S)-4-Hydroxy-1-(methylthio)-4-(4-nitrophenyl)butan-2-one
iso-9ga30.
dH (300 MHz; CDCl3, Me4Si) 2.06 (s, 3H), 3.04–3.07
3 (a) G. Guillena, C. Na´jera and D. J. Ramo´n, Tetrahedron: Asymmetry,
2007, 18, 2249–2293; (b) L. M. Geary and P. G. Hultin, Tetrahedron:
Asymmetry, 2009, 20, 131–173; (c) S. G. Zlotin, A. S. Kucherenko
and I. P. Beletskaya, Russ. Chem. Rev., 2009, 78, 737–784.
4 (a) M. Marigo and K. A. Jørgensen, Chem. Commun., 2006, 2001–
2011; (b) G. Guillena and D. J. Ramo´n, Tetrahedron: Asymmetry,
2006, 17, 1465–1492.
(m, 2H), 3.19 (s, 2H), 3.50 (d, J 3.6, 1H), 5.26–5.31 (m, 1H), 7.57
(d, J 8.5, 1H), 8.22 (d, J 8.8, 1H). dC (75 MHz; CDCl3, Me4Si)
15.6, 43.3, 48.0, 69.3, 123.7, 126.7, 147.4, 149.8, 204.7. HPLC
(Chiralpak ODH, n-hexane/i-PrOH: 88/12, 1.0 mL min-1), Rt
16.006 (mayor), Rt 17.103 (minor).
5 (a) P. T. Anastas, J. C. Warner, Green Chemistry, Theory and
Practice, Oxford University Press, Oxford, 1998; (b) R. Noyori,
Chem. Commun., 2005, 1807–1811.
6 (a) J. O. Metzger, Angew. Chem., Int. Ed., 1998, 37, 2975–2978; (b) K.
Tanaka, Solvent-free Organic Synthesis, Wiley-VCH, Weinheim,
2003; (c) G. Kaupp, Top. Curr. Chemistry, 2005, 95–184.
General procedure for the aldol reaction between aldehydes
catalysed by polymer 5 under aqueous conditions.
To a mixture of the corresponding aromatic aldehyde (0.1
mmol), catalyst 5 (0.04 mmol, 54 mg) and benzoic acid
(0.010 mmol, 1.2 mg) at 25 ◦C was added the propanal
(1.0 mmol, 0.072 mL) and H2O (100 mL). The reaction was
stirred until the aldehyde was consumed (monitored by TLC).
Then, the mixture was filtered and washed with EtOAc. The
solvents were removed under reduced pressure and the residue
was diluted with MeOH (1 mL) then NaBH4 (0.25 mmol, 0.010
g) was added at 0 ◦C, and the mixture was stirred for 1 h.
The resulting residue was purified by flash chromatography
(hexanes/AcOEt 4 : 1 to yield the pure product.
7 For some recent examples of solvent free-asymmetric organocatalytic
reactions, see: (a) A. Berkessel, K. Roland and J. M. Neudo¨rfl, Org.
Lett., 2006, 8, 4195–4198; (b) B. Rodr´ıguez, T. Rantanen and C. Bolm,
Angew. Chem., Int. Ed., 2006, 45, 6924–6926; (c) A. Carlone, M.
Marigo, C. North, A. Landa and K. A. Jørgensen, Chem. Commun.,
2006, 4928–4930; (d) Y. Hayashi, S. Aratake, T. Itoh, T. Okano,
T. Sumiya and M. Shoji, Chem. Commun., 2007, 957–959; (e) B.
Rodr´ıguez, A. Bruckmann and C. Bolm, Chem.–Eur. J., 2007, 13,
4710–4722; (f) T. Rantanen, I. Schiffers and C. Bolm, Org. Process
Res. Dev., 2007, 11, 592–597; (g) T. Ishino and T. Oriyama, Chem.
Lett., 2007, 36, 550–551; (h) P. Li, L. Wang, M. Wang and Y. Zhang,
Eur. J. Org. Chem., 2008, 1157–1160; (i) Y. Hayashi, T. Urushima,
S. Aratake, T. Okano and K. Obi, Org. Lett., 2008, 10, 21–24; (j) D.
Almas¸i, D. A. Alonso and C. Na´jera, Adv. Synth. Catal., 2008, 350,
2467–2472; (k) A. Scretti, A. Massa, L. Palombi, R. Villano and
M. R. Acocella, Tetrahedron: Asymmetry, 2008, 19, 2149–2152; (l) D.
Almas¸i, D. A. Alonso, A.-N. Balaguer and C. Na´jera, Adv. Synth.
Catal., 2009, 351, 1123–1131; (m) X. Zeng and G. Zhong, Synthesis,
2009, 1545–1550; (n) Y.-C. Teo and P. P.-F. Lee, Synth. Commun.,
2009, 39, 3081–3091; (o) S. Guizzetti, M. Benaglia, A. Puglisi and L.
Raimondi, Synth. Commun., 2009, 39, 3731–3742; (p) C. Worch and
C. Bolm, Synlett, 2009, 2425–2428.
(1R,2R)-2-Methyl-1-(4-nitrophenyl)propane-1,3-diol
H (300 MHz; CDCl3, Me4Si) anti 0.78 (d, J 7.0, 3H), 2.01–2.06
1031.
d
(m, 1H), 2.74 (br s, 1H), 3.72–3.85 (m, 3H), 4.72 (d, J 7.8, 1H
anti), 7.54 (d, J 8.7, 2H), 8.23 (d, J 8.7, 2H). (75 MHz; CDCl3,
Me4Si) anti 13.6, 41.5, 67.4, 79.3, 123.6, 127.5, 147.4, 150.5. dH
(300 MHz; CDCl3, Me4Si) syn 0.82(d, J 7.2, 3H), 2.01–2.06 (m,
1H), 3.28 (d, J 3.6, 1H), 3.67–3.84 (m, 3H), 5.14 (s, 1H), 7.54 (d,
J 8.7, 2H), 8.23 (d, J 8.7, 2H). (75 MHz; CDCl3, Me4Si) syn 9.8,
41.1, 66.6, 75.4, 123.3, 128.3, 147.6, 150.6. HPLC (Chiralpak
AD-H, n-hexane/i-PrOH: 96/4, 0.9 mL min-1), anti: Rt 70.698
(minor), Rt 75.298 (mayor); syn: Rt 63.017 (minor), Rt 67.671
(mayor).
8 (a) G. Guillena, C. Na´jera and S. F. Vio´zquez, Synlett, 2008,
3031–3035; (b) B. Bradshaw, G. Etxebarr´ıa-Jardi, J. Bonjoch, S. F.
Vio´zquez, G. Guillena and C. Na´jera, Adv. Synth. Catal., 2009, 351,
2482–2490.
9 (a) G. Guillena, M. C. Hita and C. Na´jera, Tetrahedron: Asymmetry,
2006, 17, 729–733; (b) D. Gryko, B. Kowalczyk and L. Zawadzki,
Synlett, 2006, 1059–1062; (c) G. Guillena, M. C. Hita and C.
Na´jera, Tetrahedron: Asymmetry, 2006, 17, 1493–1497(corrigendum:
Tetrahedron: Asymmetry 2007, 18, 1031); (d) G. Guillena, M. C.
Hita and C. Na´jera, Tetrahedron: Asymmetry, 2006, 17, 1027–
1031(corrigendum: Tetrahedron: Asymmetry 2007, 18, 1030); (e) S.
Guizzetti, M. Benaglia, L. Pignataro and A. Puglisi, Tetrahedron:
Asymmetry, 2006, 17, 2754–2770; (f) G. Guillena, M. C. Hita and C.
Na´jera, Tetrahedron: Asymmetry, 2007, 18, 1272–1277; (g) G.-N. Ma,
Y.-P. Zhang and M. Shi, Synthesis, 2007, 197–208; (h) S. Guizzetti, M.
Benaglia, L. Raimondi and G. Celentano, Org. Lett., 2007, 9, 1247–
1250; (i) G. Guillena, M. C. Hita and C. Na´jera, ARKIVOC, 2007, iv,
260–269 (corrigendum: ARKIVOC 2007, i, 146–147); (j) G. Guillena,
M. C. Hita, C. Na´jera and S. F. Vio´zquez, Tetrahedron: Asymmetry,
2007, 18, 2300–2304; (k) G. Guillena, M. C. Hita, C. Na´jera and S. F.
Vio´zquez, J. Org. Chem., 2008, 73, 5933–5943; (l) A. S. Kucherenko,
D. E. Syutkin and S. G. Zlotin, Russ. Chem. Bull., 2008, 57, 591–594.
10 (a) M. Gruttadauria, F. Giacalone and R. Noto, Chem. Soc. Rev.,
2008, 37, 1666–1688; (b) The Power of Functional Resins in Organic
Acknowledgements
This research was supported by the Ministerio de Ciencia e Inno-
vacio´n (Projects CTQ2007-62771/BQU and Consolider Ingenio
2010 CSD2007-00006), the Generalitat Valenciana (Project
PROMETEO/2009/039) and the University of Alicante.
References
1 Modern Aldol Reactions, R. Marhrwald, Ed.; Wiley-VCH, Wein-
heim, 2004, Vols 1 and 2.
2 For selected comprehensive books and selected reviews, see: (a) P. I.
Dalko and L. Moisan, Angew. Chem., Int. Ed., 2004, 43, 5138–
5175; (b) A. Berkessel, H. Gro¨ger, Asymmetric Organocatalysis: From
This journal is
The Royal Society of Chemistry 2010
Green Chem., 2010, 12, 1599–1606 | 1605
©

View Article Online
Synthesis, J. Tulla-Puche, F. Albericio, Ed. Wiley-VCH, Weinheim,
2008.
11 G. Szo¨llo˝si, G. London, L. Bala´spiri, C. Somlai and M. Barto´k,
Chirality, 2003, 15, S90–S96.
12 J. Yan and L. Wang, Synthesis, 2008, 2065–2072.
13 (a) K. Akagawa, S. Sakamoto and K. Kudo, Tetrahedron Lett., 2005,
46, 8185–8187; (b) M. R. M: Andreae and A. P. Davis, Tetrahedron:
Asymmetry, 2005, 16, 2487–2492.
14 (a) P. Krattiger, R. Kovasy, J. D. Revell, S. Ivan and H. Wennemers,
Org. Lett., 2005, 7, 1101–1103; (b) J. D. Revell, D. Gantenbein, P.
Krattiger and H. Wennemers, Biopolymers, 2006, 84, 105–113.
15 (a) Y.-X. Liu, Y.-N. Sun, H.-H. Tan, W. Liu and J.-C. Tao,
Tetrahedron: Asymmetry, 2005, 16, 2487–2492; (b) Y.-X. Liu, Y.-N.
Sun, H.-H. Tan and J. C. Tao, Catal. Lett., 2008, 120, 281–287.
16 (a) M. Benaglia, G. Celentano and F. Cozzi, Adv. Synth. Catal., 2001,
343, 171–173; (b) M. Benaglia, M. Cinquini, F. Cozzi, A. Puglisi and
G. Celentano, Adv. Synth. Catal., 2002, 344, 533–542.
17 (a) K. Kondo, T. Yamano and K. Takemoto, Makromol. Chem.,
1985, 186, 1781–1785; (b) D. Font, C. Jimeno and M. A. Perica`s,
Org. Lett., 2006, 8, 4653–4655; (c) D. Font, S. Sayalero, A. Bastero,
C. Jimeno and M. A. Perica`s, Org. Lett., 2008, 10, 337–340.
18 (a) F. Giacolone, M. Gruttaduria, A. M. Marculescu and R.
Noto, Tetrahedron Lett., 2007, 48, 255–259; (b) M. Gruttaduria,
F. Giacolone, A. M. Marculescu, P. Lo Meo, S. Riela and R. Noto,
Eur. J. Org. Chem., 2007, 4688–4698; (c) M. Gruttaduria, A. M: P.
Salo, F. Giacolone, P. Agrigento and R. Noto, Eur. J. Org. Chem.,
2009, 5437–5444.
20 V. J. Forrat, D. J. Ramo´n and M. Yus, Tetrahedron: Asymmetry, 2009,
20, 65–67.
21 A. Dondoni, Angew. Chem., Int. Ed., 2008, 47, 8995–
8997.
22 If fact when the reaction of 4-vinylbenzenesulfonyl chloride and (Ra)-
1,1¢-binaphthyl-2,2¢-diamine was carried out in benzene as solvent,
75% yield of the sulfonyl derivative was achieved instead of the 65%
yield obtained by performing the reaction in toluene.
23 Y. Wen, Y. Xiong, L. Chang, J. Huam, X. Liu and X. Feng, J. Org.
Chem., 2007, 72, 7715–7719.
24 In some cases, during the optimization experiments, the presence of
1
a,b-unsaturated aldol derivative (less than 2%) was detected by H
NMR.
25 (a) A. I. Nyberg, A. Usano and P. M. Pinko, Synlett, 2004, 1891–
1896; (b) M. Gruttdauria, F. Giacalone and R. Noto, Adv. Synth.
Catal., 2009, 351, 33–57.
26 For further discussion and studies about the role of water in the aldol
reaction see: (a) A. P. Brogan, T. J. Dickerson and K. D. Janda, Angew.
Chem., Int. Ed., 2006, 45, 8100–8102; (b) Y. Hayashi, Angew. Chem.,
Int. Ed., 2006, 45, 8103–8104; (c) D. G. Blackmond, A. Armstrong,
V. Coombe and A. Wells, Angew. Chem., Int. Ed., 2007, 46, 3798–
3800; (d) N. Zotova, A. Franze, A. Armstrong and D. G. Blackmond,
J. Am. Chem. Soc., 2007, 129, 15100–15101.
27 K. Sakthivel, W. Notz, T. Bui and C. F. III Barbas, J. Am. Chem.
Soc., 2001, 123, 5260–5267.
28 N. Mase, Y. Nakai, N. Ohara, H. Yoda, K. Takabe, F. Tanaka and
C. F. III Barbas, J. Am. Chem. Soc., 2006, 128, 734–735.
29 P. Diner and M. Amedjkouh, Org. Biomol. Chem., 2006, 4, 2091–
2096.
19 (a) B. M. Trost, Science, 1991, 254, 1471–1477; (b) R. A. Sheldon,
Pure Appl. Chem., 2000, 72, 1233–1246; (c) B. M. Trost, Acc. Chem.
Res., 2002, 35, 695–705; (d) B. M. Trost, M. U. Frederiksen, U.
Mathias and M. T. Rudd, Angew. Chem., Int. Ed., 2005, 44, 6630–
6666; (e) G. Guillena, D. J. Ramo´n and M. Yus, Angew. Chem., Int.
Ed., 2007, 46, 2358–2364.
30 C. Baker-Glenn, R. Ancliff and V. Gouverneur, Tetrahedron, 2004,
60, 7607–7619.
31 S. Zhang, W. Duan and W. Wang, Adv. Synth. Catal., 2006, 348,
1228–1234.
1606 | Green Chem., 2010, 12, 1599–1606
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