Enantioselective arylations catalyzed by carbohydrate-based chiral amino alcohols

Article abstract of DOI:10.1002/ejoc.201000113

The application of carbohydrate-derived amino alcohols in the asymmetric arylation of aldehydes by using arylboronic acids as the source of transferable aryl groups is described. The best ligand is derived from the readily available sugar D-xylose and it mediates the addition of a range of arylboronic acids to various aromatic aldehydes in excellent yields and high enantiomeric excesses.

Full text of DOI:10.1002/ejoc.201000113

FULL PAPER
DOI: 10.1002/ejoc.201000113
Enantioselective Arylations Catalyzed by Carbohydrate-Based Chiral Amino
Alcohols
Ana Dionéia Wouters,[a] Gustavo H. G. Trossini,[a] Hélio A. Stefani,[a] and
Diogo S. Lüdtke*[a]
Keywords: Arylation / Boron / Zinc / Carbohydrates / Asymmetric catalysis
The application of carbohydrate-derived amino alcohols in
D-xylose and it mediates the addition of a range of aryl-
the asymmetric arylation of aldehydes by using arylboronic boronic acids to various aromatic aldehydes in excellent
acids as the source of transferable aryl groups is described. yields and high enantiomeric excesses.
The best ligand is derived from the readily available sugar
cetirizine,[7] which display antihistaminic and anticholiner-
Introduction
gic activity. In addition to their direct applications, the chi-
The boron-to-zinc exchange reaction has recently re-
ral diarymethanol nucleus can serve as a precursor for di-
ceived much attention as a tool for the generation of reac-
arylmethane derivatives by SN2 substitution at the C–O
tive arylzinc species.[1] It stands out as one of the most
interesting methods for the generation of transferable aryl
groups, as a number of arylboron compounds are commer-
cially available or easily prepared. Among the various or-
ganoboron compounds, arylboronic acids have received
special attention; their reaction with Et2Zn produces an
[ArZnEt] intermediate, which, in the presence of a chiral
ligand, can selectively transfer the aryl group to a range
of aryl aldehydes, allowing the synthesis of a number of
substituted diarylmethanols.[2] The use of arylboron rea-
gents as precursors for the reactive organozinc intermedi-
ates overcomes a number of difficulties encountered in the
reaction with the expensive and very reactive Ph2Zn[3] or
the more convenient mixture of Ph2Zn/Et2Zn. The latter
method produces the mixed PhZnEt, which is less reactive
than diphenylzinc itself, accounting for a more selective aryl
transfer process.[4] These two protocols, however, have a
serious drawback. The scope of the aryl group to be trans-
ferred is limited to the phenyl ring, because only di-
phenylzinc is a commercially available diarylzinc reagent.
Another important feature of this methodology is that both
enantiomers of a given product can be prepared by using
the same chiral ligand simply by appropriate choice of the
arylboronic acid and the aldehyde reaction partners.
bond, without loss of enantiomeric purity.[8] Compounds
possessing a chiral diarylmethane nucleus are found to be-
have as antimuscarinics,[9] antidepressants,[10] and endo-
thelin antagonists.[11]
Figure 1. Structures of bioactive diarylmethanol derivatives.
Within the classes of compounds studied to catalyze the
aryl transfer reaction to aldehydes, chiral amino alcohols
and amino-alcohol-type ligands are among the most widely
studied.[12] Other ligands with different scaffolds such as
amino thiols and thioacetates,[13] sulfonamides,[14] and binol
derivatives[15] have also found application in such transfor-
mations.
Carbohydrates are widespread in nature as enantiomer-
ically pure compounds, which have interesting stereochemi-
cal diversity and have served as a chiral pool for the prepa-
ration of chiral auxiliaries, ligands, and catalysts.[16] In the
context of our research program towards the use of readily
available carbohydrates as the starting material in organic
synthesis,[17] we describe herein the application of amino
Enantioenriched diarylmethanols are present in
a
number of biologically and pharmacologically active com-
pounds (Figure 1).[5] For example it can be found in the
structure of (R)-orphenadrine, (R)-neobenodine,[6] and (S)-
[a] Faculdade de Ciências Farmacêuticas, Universidade de São
Paulo, USP,
CEP 05508-900, São Paulo, São Paulo, Brazil
Fax: +55-11-3815-4418
E-mail: dsludtke@usp.br
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A. D. Wouters, G. H. G. Trossini, H. A. Stefani, D. S. Lüdtke
FULL PAPER
alcohols derived from -xylose and -glucosamine as chiral and again the enantioselectivity of the arylation reaction
ligands for the asymmetric arylation of aldehydes was low, and the corresponding diarylmethanols were iso-
(Scheme 1). Precedent for the ability of carbohydrate-de- lated with ee values of 30–35% (Table 1, Entries 4–6).
rived amino alcohols to mediate organozinc additions was
found in the literature in the work of Cho[18] and Davis[19]
who, respectively, developed xylose- and glucosamine-based
Table 1. Glucosamine-derived ligands in the arylation of aldehydes.
ligands for the enantioselective addition of Et2Zn to alde-
hydes. To the best of our knowledge, this is the first time
that sugar-based compounds were employed as chiral li-
gands in the asymmetric aryl transfer reaction.
Entry
R
Ligand
Temp [°C] Yield [%]
ee [%][a]
1
2
3
4
5
6
p-Me
p-Me
p-Me
p-OMe
o-Cl
2a
2b
2c
2c
2c
2c
0
0
0
0
0
0
75
73
78
92
87
89
Ͻ20
Ͻ20
36
31
30
o-Br
35
[a] Enantiomeric excess values determined by HPLC with a chiral
stationary phase. Absolute configuration determined by compari-
son with literature data.
Scheme 1. Carbohydrate-derived ligands for the enantioselective
arylation of aldehydes.
Disappointed by the results obtained in the arylations
mediated by the ligands from the glucosamine series, we
turned our attention to amino alcohols 4a–c based on the
xylose scaffold (Scheme 3). These ligands were readily pre-
pared in a simple procedure, by reaction of tosylate 3 with
an appropriate secondary amine and isopropanol as the sol-
vent.
Results and Discussion
First, we focused our efforts on the application of -glu-
cosamine-derived ligands, as an amino group is already
found in the starting sugar. Thus, the required amino
alcohols were straightforwardly prepared by deprotection
of the N-Ac group in 1, followed by reaction with a di-
iodoalkane in the presence of K2CO3 in boiling acetonitrile
to afford the corresponding aza-ring derivatives 2a–c in
good yields (Scheme 2).
Scheme 3. Synthesis of -xylose-derived ligands.
With these γ-amino alcohols in hands, we screened their
behavior as chiral ligands in the phenylation of p-tolylalde-
Scheme 2. Synthesis of -glucosamine-derived ligands.
These chiral carbohydrate derivatives were then tested as hyde. The screening reactions were carried out at 0 °C, with
ligands in the asymmetric phenyl transfer reaction to p-tol- a catalytic loading of 20 mol-%, and by using toluene as the
ylaldehyde by using phenylboronic acid as the phenyl solvent. Analysis of the results depicted in Table 2 reveals
source. Unfortunately, disappointing results were achieved that all ligands afforded the desired product in high yields,
with the use of 20 mol-% of ligands 2a–c (Table 1). Pyrrol- and the best result in terms of enantioselectivity was ob-
idine and piperidine derivatives 2a and 2b afforded the tained with morpholine ligand 4c, which delivered (R)-
phenyl(p-tolyl)methanol in good yields, however, with very phenyl(p-tolyl)methanol in 93% yield and an excellent ee of
low ee values (Ͻ20%ee; Table 1, Entries 1 and 2). Ligand 96% (Table 2, Entry 3). Further studies were carried out
2c, which possesses a morpholine ring, afforded slightly bet- with this ligand. The temperature has an important influ-
ter, albeit still unsatisfactory, enantiomeric excess values ence on the selectivity of the arylation reaction, because
(36%ee; Table 1, Entry 3). In view of the poor results ob- when the reaction was conducted at room temperature, a
tained in the phenyl transfer reaction to p-tolylaldehyde, we sharp decrease in the ee values was observed (Table 2, com-
also tested the reaction with three other aromatic aldehydes, pare Entries 3 and 6). The use of DiMPEG (dimethoxypo-
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Enantioselective Arylations Catalyzed by Carbohydrate-Based Amino Alcohols
lyethylene glycol), a commonly used additive for the im- chlorophenylboronic acid and excellent yields and good en-
provement of selectivity in asymmetric organozinc ad- antiomeric excesses were obtained (Table 3, Entries 10 and
ditions, also proved to be detrimental to the reaction out- 11).
come, as it led to sluggish reactions and to erosion in both
the yields and ee values (Table 2, Entries 4 and 5). To fur-
ther examine the effect of the temperature, we lowered the
temperature even more to –20 °C. Under these conditions,
unfortunately, no further improvement was achieved, and
the product was obtained in a decreased yield and ee
(Table 2, Entry 7). Finally, we confirmed that 20 mol-% of
the ligand was necessary to achieve high enantioselectivity,
and lowering the ligand loading to 10 and 15 mol-% re-
sulted in lower ee values (Table 2, Entries 8 and 9).
Table 3. Asymmetric arylation of aldehydes.
Entry
Ar1
Ar2
Yield [%] ee [%][a]
1
2
3
4
5
6
7
8
phenyl
phenyl
phenyl
phenyl
phenyl
phenyl
phenyl
phenyl
phenyl
4-methylphenyl
2-methylphenyl
4-methoxyphenyl
2-methoxyphenyl
4-chlorophenyl
2-chlorophenyl
4-bromophenyl
2-bromophenyl
cyclohexyl
97
96
94
96
96
91
95
91
84
95
94
91
92
92
96
90
80
78
83
87
88
87
67
84
82
83
88
86
Table 2. Asymmetric arylation of p-tolualdehyde in the presence of
xylose-derived ligands 4a–c.
9
10
11
12
13
14
4-methylphenyl
4-chlorophenyl
4-methylphenyl 4-chlorophenyl
4-chlorophenyl 4-methylphenyl
phenyl
phenyl
4-biphenyl
4-methylphenyl
Entry
Ligand (mol-%) Temp [°C]
Yield [%]
ee [%][a]
[a] Enantiomeric excess values determined by HPLC with a chiral
stationary phase. Absolute configuration determined by compari-
son with literature data.
1
2
3
4a (20)
4b (20)
4c (20)
4c (20)
4c (20)
4c (20)
4c (20)
4c (10)
4c (15)
0
0
0
25
25
25
–20
0
92
94
93
75
51
96
90
80
78
60
79
96
53
35
78
86
66
72
4[b]
5[c]
6
Moreover, the synthesis of diarylmethanols substituted
at both aromatic rings with high enantioselectivity is also
possible by varying the substitution pattern of the aryl-
boronic acid and the aldehyde at the same time. For exam-
ple, the reaction between p-tolylboronic acid with 4-chloro-
benzaldehyde smoothly produced the corresponding (R)-di-
arylmethanol in excellent yield and 84%ee. The opposite
combination of substituents, that is, 4-chlorobenzaldehyde
and p-tolylaldehyde, resulted in the opposite (S) enantiomer
of the above-mentioned diarylmethanol, with a similar level
of enantioselection (Table 3, compare Entries 12 and 13).
7
8
9
0
[a] Enantiomeric excess values determined by HPLC with a chiral
stationary phase, Chiralcel OD-H column, λ = 254 nm, hexanes/
iPrOH (90:10), 0.5 mLmin–1. Absolute configuration determined
by comparison with literature data. [b] DiMPEG (20 mol-%) MW
2000 was used as an additive. [c] DiMPEG (10 mol-%) MW 2000
was used as an additive.
With ligand 4c identified as the most effective, we exam- Finally, a diarylmethanol containing halogen groups at
ined the scope of the arylation reaction with a varied set of both rings and a biphenyl derivative were also prepared in
aldehydes containing diverse steric and electronic properties high yields with good ee values. In addition to the reaction
(Table 3). The reaction tolerates a broad range of substitu- with aryl aldehydes, the arylation of cyclohexanecarboxal-
ents, and as a general trend, the reactions performed with dehyde was also performed and the arylated product was
aldehydes possessing electron-withdrawing groups gave achieved in 84% yield with moderate enantioselectivity
higher yields and ee values relative to the values obtained (67%ee; Table 3, Entry 9).
with the strong electron-donating methoxy group. For ex-
The mechanism of the reaction is believed to proceed as
ample, the product of phenylation of 4-bromobenzaldehyde depicted in Scheme 4. First, reaction of amino alcohol 4c
was formed in 95% yield with 88%ee, whereas the same with the PhZnEt reagent results in the formation of zinc
reaction with 4-anisaldehyde resulted in the corresponding complex A, which is the actual catalyst for the enantioselec-
product in comparative yields, but with a decreased ee value tive aryl transfer reaction. Formation of ethyl-substituted
of 80%. Particularly relevant is that the arylation reaction chiral zinc complex A is favored over phenyl-substituted
tolerates ortho substitution, as the level of enantioselectivity complex B, as proposed by Pericàs.[4c,12i,20] Following this,
obtained was similar to that obtained with para-substituted the aldehyde reacts with the catalyst, resulting in a tricyclic
derivatives. For instance, high ee values were obtained with transition state (TS), as originally proposed by Noyori.[21]
ortho-tolylaldehyde (90%ee; Table 3, Entry 2) and 2-chloro- Transition-state structure C, with an anti–trans conforma-
and 2-bromobenzaldehyde (87%ee; Table 3, Entries 6 and tion is preferred over anti–cis structure D, because it avoids
8). As regards the tolerance of our catalytic system to varia- axial positioning of the aldehyde Ar group, thus minimizing
tions at the boronic acid counterpart, we first examined the any steric interactions with the ethyl group attached to the
arylation of benzaldehyde with p-tolylboronic acid and 4- zinc atom. Accordingly, aryl transfer to the Re face of the
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A. D. Wouters, G. H. G. Trossini, H. A. Stefani, D. S. Lüdtke
FULL PAPER
Scheme 4. Proposed reaction pathway.
aldehyde results in the formation of the (R)-diarylmethanol
as the major product. This is in agreement with the results
observed experimentally.
To obtain more evidence of the validity of the proposed
mechanism, some theoretical calculations were performed
by using a semiempirical PM3 method. Due to the large
size of the structures involved, the PM3 method was chosen
instead of the more time-consuming methods (DFT, MP2).
Results for transition-state calculation with the use of the
PM3 method usually predict efficiently the reaction out-
come in enantioselective processes.[22] Transition-state
structures were calculated by using ligand 4c for the phenyl-
transfer reaction to 4-tolylaldehyde. The most important
diastereomeric TSs according to the pioneering work or
Noyori,[23] namely, anti–trans, anti–cis, syn–cis, and syn–
trans, were considered, and the four most stable TSs were
located with their relative energies and are depicted in Fig-
ure 2. The anti–trans and syn–trans structures would lead
to the (R) product, whereas the anti–cis and syn–cis systems
would lead to the (S) enantiomer. Among these, the anti–
trans structure was found to be the most stable TS structure,
followed by the anti–cis. The syn–trans and syn–cis TSs are
higher in energy and should not contribute substantially to
product formation. Thus, in this case, the selectivity of the
reaction should be mainly determined by the energy gap
between the two anti arrangements. To our delight, the cal-
culated TSs are in accordance with our proposed model,
and the energy difference for the anti–trans/anti–cis TS was
found to be 6.3 kcalmol–1, leading to the prediction of (R)-
(4-tolyl)phenylmethanol as the main product. In addition,
the distance between the aryl group in the aldehyde and the
spectator ethyl group was found to be 4.24 and 3.93 Å for
Figure 2. PM3 transition-state structures of ligand 4c.
These calculations are in agreement with the experimen-
tally observed selectivity. Thus, it was shown that the theo-
retical calculations performed in the PM3 model correctly
predict the stereochemical outcome observed for the aryl-
ation of aromatic aldehydes with the use of xylose-derived
ligand 4c.
Conclusions
In summary we have described the application of chiral
the anti–trans and anti–cis TS, respectively. The calculated amino alcohols with a sugar backbone as ligands in the
distances indicate that the axial positioning of the 4-tolyl asymmetric arylation of aldehydes by using arylboronic ac-
group indeed results in a more severe steric interaction with ids as the source of the transferable aryl group. The most
the ethyl group, accounting for the higher energy of the TS. efficient ligand identified by the present study was a deriva-
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Enantioselective Arylations Catalyzed by Carbohydrate-Based Amino Alcohols
127.9, 128.4, 131.9, 143.2, 156.5 ppm. HPLC (Chiralcel OD-H, 2%
tive from -xylose, which possesses a furanoside backbone
and a morpholino group. Yields of the arylation reaction
in the presence of ligand 4c were generally high, and the
iPrOH/hexane, 0.5 mLmin–1): tR = 60.7 (R), 73.7 (S) min.
(4-Methoxyphenyl)phenylmethanol: Yield: 101 mg (94%). 1H NMR
diarylmethanol products were obtained with ee values of (300 MHz, CDCl3): δ = 2.3 (s, 1 H, OH), 3.7 (s, 3 H, OCH3), 5.7
(s, 1 H, CH), 6.8 (m, 2 H, Ar), 7.2–7.3 (m, 7 H, Ar) ppm. 13C
up to 96%.
NMR (75 MHz, CDCl3): δ = 55.2, 75.7, 113.8, 126.3, 127.3, 127.8,
128.3, 136.1, 144, 158.9 ppm. HPLC (Chiralcel OD-H, 10% iP-
rOH/hexane, 0.5 mLmin–1): tR = 20.2 (S), 21.1 (R) min.
Experimental Section
(2-Chlorophenyl)phenylmethanol: Yield: 99 mg (91%). 1H NMR
General Considerations: All reactions were performed under an ar-
(300 MHz, CDCl3): δ = 6.2 (s, 1 H, CH), 7.1–7.3 (m, 8 H, Ar), 7.5
gon atmosphere with dried glassware. The solvents used for reac-
(d, J = 7.2 Hz, 1 H, Ar) ppm. 13C NMR (75 MHz, CDCl3): δ =
tions under inert atmosphere were dried, and the reagents were
72.6, 126.8, 127, 127.3, 128, 128.4, 128.6, 129.4, 132.4, 140.9,
purified according to standard procedures,[24] unless otherwise
142.2 ppm. HPLC (Chiralcel OD-H, 10% iPrOH/hexane,
noted. The progress of the reactions was monitored by thin-layer
0.5 mLmin–1): tR = 14.7 (R), 16.5 (S) min.
chromatography (TLC) by using silica gel GF254 (0.25 mm thick-
(4-Chlorophenyl)phenylmethanol: Yield: (R)-product, 105 mg
(96%); (S)-product, 103 mg (94%). H NMR (300 MHz, CDCl3):
δ = 2.4 (s, 1 H, OH), 5.74 (s, 1 H, CH), 7.22–7.33 (m, 9 H, Ar) ppm.
13C NMR (75 MHz, CDCl3): δ = 75.5, 126.4, 127.7, 127.8, 128.51,
128.55, 133.1, 142.1, 143.3 ppm. HPLC (Chiralpak AD-H, 10%
iPrOH/hexane, 1.0 mLmin–1): tR = 8.4 (R), 9.1 (S) min.
ness). For visualization, TLC plates were either placed under ultra-
violet light or stained with phosphomolybdic acid, followed by
heating. Column chromatography was performed by using silica gel
1
(230–400 mesh) by following the methods described by Still.[25] 1
H
and 13C NMR spectra were obtained with a Bruker spectrometer
at 300 and 75 MHz, respectively. Chemical shifts are reported in
ppm referenced to the solvent peak of residual CHCl3 or tetrameth-
ylsilane (TMS) as reference. Analysis of enantiomeric excess was
performed by using HPLC equipped with columns with a chiral
stationary phase. All measurements were performed at a column
temperature of 20 °C by using a UV detector at 254 nm, except
where noted otherwise. Theoretical calculations were performed in
Gaussian 03W v.6 software. Optimization of the bond angles and
distances was made by molecular mechanics. Transition-state calcu-
lations were performed by using the semiempirical PM3 method,
and the results were visualized in GaussView 3.09 software.
(2-Bromophenyl)phenylmethanol: Yield: 120 mg (91%). 1H NMR
(300 MHz, CDCl3): δ = 2.8 (s, 1 H, OH), 6.1 (s, 1 H, CH), 7.0–7.5
(m, 9 H, Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 74.6, 122.7,
126.9, 127.6, 128.3, 128.4, 129, 130.1, 132.7, 142.1, 142.4 ppm.
HPLC (Chiralcel OD-H, 10% iPrOH/hexane, 0.8 mLmin–1): tR
10.4 (R), 11.9 (S) min.
=
(4-Bromophenyl)phenylmethanol: Yield: 125 mg (95%). 1H NMR
(300 MHz, CDCl3): δ = 2.4 (s, 1 H, OH), 5.7 (s, 1 H, CH), 7.2–7.4
(m, 9 H, Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 75.6, 121.3,
126.4, 127.8, 128.1, 128.6, 131.4, 142.7, 143.3 ppm. HPLC (Chi-
ralcel OB-H, 10% iPrOH/hexane, 0.5 mLmin–1): tR = 22.6 (R), 30.2
(S) min.
Typical Experimental Procedure for the Enantioselective Arylation:
To a solution of arylboronic acid (1.2 mmol) in toluene (2 mL) was
added diethylzinc (1  in toluene, 3.5 mL, 3.5 mmol) at room tem-
perature. The reaction was stirred at 60 °C for 1 h and then cooled
to room temperature. A solution of the ligand (20 mol-%) in tolu-
ene (1 mL) was added to the reaction, and the system was stirred
for 20 min at this temperature. The reaction was then cooled to
0 °C, and the aldehyde (0.5 mmol) was added. The reaction mixture
was stirred, and it was kept at this temperature for 6 h. The reaction
was quenched by the addition of water and extracted with CH2Cl2
(3ϫ20 mL). The organic layers were combined and dried with
magnesium sulfate. Evaporation of the solvent under reduced pres-
sure and purification with flash chromatography (hexane/ethyl ace-
tate, 4:1) gave the desired diarylmethanol. Enantiomeric excess
were determined by HPLC analysis with a chiral stationary phase.
(4-Chlorophenyl)-4-methylphenylmethanol: (R)-product, 105 mg
1
(91%); (S)-product, 107 mg (92%). H NMR (300 MHz, CDCl3):
δ = 2.3 (s, 3 H, CH3), 5.7 (s, 1 H, CH), 7.1–7.3 (m, 8 H, Ar) ppm.
13C NMR (75 MHz, CDCl3): δ = 21, 75.3, 126.4, 127.7, 128.4,
129.2, 133, 137.5, 140.5, 142.3 ppm. HPLC (Chiralcel OD-H, 10%
iPrOH/hexane, 0.2 mLmin–1): tR = 40.1 (R), 42.1 (S) min.
(4-Biphenyl)-(4-tolyl)methanol: Yield: 126 mg (92%). 1H NMR
(300 MHz, CDCl3): δ = 2.3 (s, 3 H, CH3), 2.4 (s, 1 H, OH), 5.7 (s,
1 H, CH), 7.1–7.5 (m, 13 H, Ar) ppm. 13C NMR (75 MHz, CDCl3):
δ = 21, 75.8, 126.4, 126.8, 127, 127.12, 127.18, 128.6, 129.1, 137.2,
140.2, 140.7, 140.8, 142.9 ppm. HPLC (Chiralcel OD-H, 10% iP-
rOH/hexane, 0.2 mLmin–1): tR = 40.1 (R), 42.1 (S) min.
(2-Tolyl)phenylmethanol: Yield: 105 mg (96%). 1H NMR
(300 MHz, CDCl3): δ = 2.2 (s, 3 H, CH3), 5.9 (d, J = 1.8 Hz, 1 H,
CH), 7.1–7.4 (m, 9 H, Ar) ppm. 13C NMR (75 MHz, CDCl3): δ =
19.3, 73.3, 126, 126.2, 127, 127.5, 128.4, 130.5, 135.3, 141.4,
142.8 ppm. HPLC (Chiralpak AD-H, 2% iPrOH/hexane,
0.5 mLmin–1): tR = 16.8 (R), 18.6 (S) min.
Cyclohexyl(phenyl)methanol: Yield: 80 mg (84%). 1H NMR
(300 MHz, CDCl3): δ = 0.9–1.2 (m, 5 H), 1.35–1.40 (m, 1 H), 1.51–
1.65 (m, 3 H), 1.75–1.83 (m, 2 H, CH2), 1.99–2.01 (m, 1 H, CH),
4.33 (d, J = 7.0 Hz, 1 H, CH), 7.2–7.35 (m, 5 H, Ar) ppm. 13C
NMR (75 MHz, CDCl3): δ = 26.0, 26.2, 26.7, 29.0, 29.6, 45.1, 79.9,
126.7, 127.6, 128.4, 143.7 ppm. HPLC (Chiralcel OD-H, 5% iP-
rOH/hexane, 0.5 mLmin–1): tR = 14.6 (S), 18.1 (R) min.
(4-Tolyl)phenylmethanol: Yield: (R)-product, 106 mg (97%); (S)-
1
product, 104 mg (95%). H NMR (300 MHz, CDCl3): δ = 2.3 (s,
3 H, CH3), 5.7 (s, 1 H, CH), 7.1–7.3 (m, 9 H, Ar) ppm. 13C NMR
(75 MHz, CDCl3): δ = 21, 76, 126.4, 126.5, 127.3, 128.3, 129.1,
137.1, 140.9, 143.9 ppm. HPLC (Chiralcel OD-H, 10% iPrOH/hex-
ane, 0.5 mLmin–1): tR = 40.3 (S), 42.6 (R) min.
Acknowledgments
We are grateful to Fundação de Amparo à Pesquisa do Estado de
São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento
Científico e Tecnológico (CNPq) for financial support. Comissão
de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and
1
(2-Methoxyphenyl)phenylmethanol: Yield: 103 mg (96%). H NMR
(300 MHz, CDCl3): δ = 3.7 (s, 3 H, OCH3), 6.0 (d, J = 3.9 Hz, 1
H, CH), 6.8–6.9 (m, 2 H, Ar), 7.2–7.3 (m, 7 H, Ar) ppm. 13C NMR CNPq are also acknowledged for fellowships to A. D. W. and
(75 MHz, CDCl3): δ = 55.2, 71.7, 110.6, 120.6, 126.4, 126.9, 127.6,
D. S. L., respectively. Dr. Márcio W. Paixão (UFSCar) is also ac-
Eur. J. Org. Chem. 2010, 2351–2356
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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Received: January 27, 2010
Published Online: March 8, 2010
2356
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Eur. J. Org. Chem. 2010, 2351–2356