Organocatalyzed Enantioselective Aldol and Henry Reactions Starting from Benzylic Alcohols

Article abstract of DOI:10.1002/adsc.201701351

Pioneering aldol and Henry reactions starting from benzylic-type alcohols are described. The aldol reaction has been successfully performed following a one-pot strategy starting from alcohols, while the Henry reaction has been carried out following a sequential protocol for the first time. In both processes, enantiomerically enriched products were obtained with good yields and high enantioselectivities. We have also demonstrated that in reactions sensitive to small amounts of acid the use of alcohols instead of aldehydes could be a good solution for improving the results of these reactions. (Figure presented.).

Full text of DOI:10.1002/adsc.201701351

Title: Organocatalyzed enantioselective aldol and Henry reactions
starting from alcohols
Authors: Juan V. Alegre-Requena, Eugenia Marqués-López, and
Raquel Herrera
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Advanced Synthesis & Catalysis
10.1002/adsc.201701351
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Organocatalyzed enantioselective aldol and Henry reactions
starting from benzylic alcohols
a
a
a
Juan V. Alegre-Requena, Eugenia Marqués-López and Raquel P. Herrera *
a
Laboratorio de Organocatálisis Asimétrica. Departamento de Química Orgánica. Instituto de Síntesis Química y
Catálisis Homogénea (ISQCH) CSIC-Universidad de Zaragoza. C/ Pedro Cerbuna 12, 50009 Zaragoza (Spain).
E-mail: raquelph@unizar.es
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. Pioneering aldol and Henry reactions starting from We have also demonstrated that in reactions sensitive to
benzylic type alcohols are described. The aldol reaction has small amounts of acid the use of alcohols instead of
been successfully performed following a one-pot strategy aldehydes could be a good solution for improving the results
starting from alcohols, while the Henry reaction has been of these reactions.
carried out following a sequential protocol for the first time.
In both processes, enantiomerically enriched products were Keywords: alcohol; aldehyde; aldol; Henry; MnO2;
obtained with good yields and high enantioselectivities.
organocatalysis; one-pot; oxidation.
on the reactivity and the enantioselectivity of diverse
organocatalytic reactions (e.g., in aminocatalysis) has
been also explored by other authors.
Introduction
Many organic reactions that initially start from
aldehydes lead to products of biological interest.
Among the plethora of reactions that start from
Hence, this problem encouraged us to explore the
challenge of forming the aldehydes in situ by oxidizing
alcohols. In fact, there is a wider variety of alcohols
available in comparison with aldehydes, and they are
much easier to handle and work with. For this reason,
it seems evident that the use of alcohols in organic
processes instead of aldehydes would significantly
increase the versatility of the reactions, especially
when the aldehydes are unstable or difficult to
[
1]
[2]
aldehydes, the aldol and the Henry reactions are
important carbon–carbon bond–forming methods in
organic synthesis.[ These processes represent two
potent strategies for the synthesis of valuable β–
hydroxy ketones and β–nitro alcohols providing, after
further transformations, efficient access to interesting
and highly functionalized intermediates. Both
reactions have been developed under many different
conditions and using diverse catalytic systems,
3]
[8]
handle.
Therefore, the exploration of new
asymmetric catalytic methodologies of reactions
where carbonyl compounds are used as starting
materials is still important for an efficient construction
of interesting building blocks. Consequently, the
development of Henry and aldol reactions starting
from alcohols would open a new area of research in the
progress of these interesting reactions (Scheme 1).
providing
from
good–to–excellent
enantioselectivities.[
4–6]
During the development of our previous Henry
protocol,[ we realized that the presence of traces of
acid in the aldehydes used could inactivate the small
amount of catalyst employed (0.0044 mmol). It is well
known that traces of acids are generated in aldehydes
due to oxidation processes (see the supporting
information for images of this process, Figure S1).
This could be a serious problem that appears when
using diverse aldehydes. In fact, many of these
aldehydes that we used were purified before the
reactions in order to avoid the inactivation of the
catalyst. The influence of different amounts of acids
7]
1
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Advanced Synthesis & Catalysis
10.1002/adsc.201701351
Results and Discussion
Among the different oxidants analyzed in the
literature (IBX, TEMPO, Swern oxidant, MnO , etc.),
we realized that the mildest and most efficient one for
2
[12]
our aim was MnO
2
.
Moreover, the use of the other
oxidants mentioned would lead to the generation of
acids during the oxidation reactions, which could
inhibit the successive catalytic reactions in this
investigation. In order to demonstrate our hypothesis,
we first explored the aldol reaction depicted in Table
[13]
1.
This example represents the first one–pot aldol
Scheme 1. The goal of this research: developing aldol and
Henry reactions starting from alcohols.
reaction starting from benzylic alcohols and catalyzed
by a cinchona–derived primary amine.
[14]
The oxidation of alcohols to aldehydes or ketones is
an important process in organic synthesis and several
methods have been successfully developed to
accomplish this transformation, like for example,
using organocatalytic procedures.[10] However, it is
much rarer to find examples where the carbonyl group
generated in the oxidation is involved in a subsequent
asymmetric catalytic process. In fact, there are only a
few studies on this and in all of them, the second
As reported in Table 1, it was possible to
successfully oxidize alcohols in different solvents.
Interestingly, the final product 5a was produced with
consistently better results when alcohol 1a was used
instead of aldehyde 2a. In the original study starting
from aldehydes, the authors noticed that when the
amount of acid was higher than 15%, the yield of the
reactions dropped. Therefore, the decrease observed
in the yield when 2a is used could be mostly caused by
the residual amounts of acid that this aldehyde
generates through its oxidation over time. It is
remarkable that, in all examples, the in situ generated
aldehyde was used without having been purified,
following a one–pot procedure.
[9]
[13]
reactions were carried out using proline–derived
catalysts.[
11]
Therefore, the development of new
oxidative processes of alcohols to generate aldehydes
involved in subsequent organocatalytic protocols is
highly desirable.
Table 1. Screening of the one–pot cinchona–catalyzed aldol reaction starting from alcohol 1a or aldehyde 2a in different
solvents.[
a]
Entry Solvent
Oxidation Time (min/h)
T (°C)
Time (h) Yield 5a d.r. 5a[b,d] ee 5a
Yield 5a d.r. 5a[f,d] ee 5a
oxidation of 1a catalysis (%)[b,c]
anti:syn
(%)[b,e]
(%)
[f,c]
anti:syn
(%)[f,e]
using 2a
98
using 1a using 1a
using 1a using 2a using 2a
1
2
3
4
5
6
THF
DMF
DMSO
60
3 h
23
45
45
23
12
22
73
75
77
85
39
32
95:5
91:9
86:14
95:5
94:6
90:10
99
98
98
99
96
94
58
44
70
61
32
30
95:5
100
100
15 min
15 min
15 min
15 h
88:12
84:16
>95:5
94:6
95
97
99
99
Toluene 100
CH
2
Cl
2
30
55
CHCl
3
3 h
89:11
93
[
a]
2
Experimental conditions: to a suspension of MnO (2.5 mmol) in the solvent (0.5 mL) and at the temperature indicated in
the table, alcohol 1a (0.5 mmol) was added. After the oxidation time, the reaction was cooled down to room temperature
and a mixture of catalyst 3 (0.05 mmol), TfOH (0.075 mmol) and 4 (1 mL) in 1.5 mL of the corresponding solvent was added
in one portion. After the reaction time, the process was quenched with a saturated NH
4
Cl aqueous solution (20 mL) and
extracted with AcOEt (3 x 30 mL). The organic phases were dried with MgSO and the solvent was evaporated. Adduct 5a
4
[c]
[
b]
was isolated by column chromatography. Results starting from alcohol 1a. After isolation by column chromatography.
[
d]
1
[e]
The diastereoisomeric ratio was determined by H–NMR spectroscopy of the crude reaction mixture. Determined by
chiral HPLC analysis for the major diastereoisomer. Results starting from commercially available aldehyde 2a.
[
f]
2
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Advanced Synthesis & Catalysis
10.1002/adsc.201701351
We then explored the efficiency of the one–pot
the process depends on the electronic effects of the
aromatic rings, as better yields are obtained with
electron–withdrawing substituents in shorter reaction
times. However, these electronic effects are not
correlated with the enantioselectivity of the process.
protocol using a variety of benzylic alcohols (Table 2
and Scheme S1) under the best reaction conditions
found during the screening (Table 1, entry 4). As
depicted in Table 2, the aldol reaction led to the desired
β–hydroxy ketones 5 in good yields and excellent
enantioselectivities (up to 99% ee). The reactivity of
Table 2 Scope of the one–pot cinchona–catalyzed aldol reaction starting from alcohols 1a–g.[a]
Entry
Ar (1a–h)
Time (h)
catalysis
17
17
18
63
64
100
101
Yield 5 (%)[b]
d.r. 5[c]
anti:syn
93:7
92:8
91:9
ee 5 (%)[d]
1
2
3
4
5
6
7
4–NO
3–NO
2
Ph (1a)
Ph (1b)
83
71
75
76
70
53
71
99
99
98
97
97
>99
93
2
4–CNPh (1c)
4–ClPh (1d)
4–BrPh (1e)
Ph (1f)
92:8
90:10
90:10
75:25
2–furyl (1g)
[
a]
2
Experimental conditions: to a suspension of MnO (2.5 mmol) in toluene (0.5 mL) at 80 ºC, alcohol 1 (0.5 mmol) was
added. After the oxidation time, the reaction was cooled down to room temperature and a mixture of catalyst 3 (0.05
mmol), TfOH (0.075 mmol) and 4 (1.5 mL) was added in one portion. After the reaction time, the process was quenched
with a saturated NH
4
Cl aqueous solution (20 mL) and extracted with AcOEt (3 x 30 mL). The organic phases were dried
[
b]
with MgSO and the solvent was evaporated. Adduct 5 was isolated by column chromatography. After isolation by
4
[
c]
1
column chromatography. The diastereoisomeric ratio was determined by H–NMR spectroscopy of the crude reaction
mixture. [ Determined by chiral HPLC analysis for the anti diastereoisomer.
d]
Recently, we have developed
a
trifunctional
squaramide catalyst that promotes the Henry reaction
[7]
through a multidentate activation. Encouraged by the
results obtained for the aldol reaction, we envisioned
to apply this idea (Scheme 1) also to that reaction.
Initially, the screening of the oxidation reaction
using benzylic alcohol 1f (reported in Table S1) was
conducted in CH
Henry step was successfully performed in mixtures of
this solvent with MeNO . Compound 1f reacted
completely in the oxidative process using 5
3
CN, since the following catalytic
2
equivalents of MnO at 80 °C (Table S1, entry 6).
2
Interestingly, traces of acid or other by–products from
1
alcohol 1f were not detected by H–NMR during the
process even after long reaction times, supporting our
initial aim.
Then, the time necessary for the total conversion of
each alcohol 1 in its corresponding aldehyde 2 was
analyzed (Scheme 2). We observed that alcohols with
aromatic rings that bear electron–withdrawing groups
(
alcohols 1a–e,j) required longer oxidation times in
comparison with alcohols 1f–i.
Scheme 2. Oxidation of alcohols 1. Reaction conditions: 1
mmol of 1 and 5 mmol of MnO in 1 mL of CH CN at 80
ºC.
2
3
With the optimal reaction conditions in hand for the
oxidation step (Scheme 2), we firstly analyzed the
catalytic Henry system following a one–pot protocol
as shown in Scheme 3.
3
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Advanced Synthesis & Catalysis
10.1002/adsc.201701351
during this step was filtered and the catalytic reaction
was performed in a sequential manner. Then, 100 μL
of the filtered solution, without purification of the in
situ generated aldehyde, were added over a mixture of
catalyst 7 and MeNO
terms of enantioselectivity (83% ee) and reactivity
53% yield) (Table 3, entry 6) and, again, better yields
were found when alcohol 1f was employed in
comparison with the outcomes observed when using
aldehyde 2f (35% yield).
The efficiency of this protocol was further studied
for a range of different benzylic alcohols (1a–j) and
the results were compared to those obtained when the
initial reagents were the corresponding commercially
available aldehydes (2a–j) (Table 3).
2
. The process worked well in
(
Scheme 3. One-pot Henry reaction.
Unfortunately, product 6f was not observed after 4
days of reaction. This fact made us think that some of
the reagents or by–products that come from the
oxidation step were inactivating the subsequent Henry
process. To avoid these impurities, the solid generated
Table 3. Scope of the squaramide–catalyzed Henry reaction starting from alcohols 1a–j and from aldehydes 2a–j under the
[
a]
same reaction conditions.
Entry
R
Time (h)
Yield 6 (%)
ee 6 (%)
using 1
79
93
81
83
84
83
92
Yield 6 (%)
using 2
>95
>95
>95
73
ee 6 (%)
using 2
80
93
80
85
85
85
[
b,c]
[b,d]
[c,e]
[d,e]
using 1
>95
>95
76
89
86
53
69
37
66
1
2
3
4
5
6
7
8
9
4–NO
3–NO
4–CNPh (1c)
4–ClPh (1d)
4–BrPh (1e)
Ph (1f)
2–furyl (1g)
4–MePh (1h)
1–Naphthyl (1i)
3–ClPh (1j)
2
2
Ph (1a)
Ph (1b)
23
23
23
96
96
69
93
93
93
96
33
35
26
n.r.
n.r.
n.r.
90
f
n.d.g
86
80
83
f
g
n.d.
f
n.d.g
1
0
87
[
a]
2 3
Experimental conditions: to a suspension of MnO (5 mmol) in CH CN (1 mL) at 80 °C, alcohol 1 (1 mmol) was added.
After the oxidation time (Scheme 2), the reaction was cooled down to room temperature and the suspension was filtered
using a HPLC filter of 0.22 μm. Then, 0.1 mL of the solution filtrated were collected and added to a solution of catalyst 7
[
b]
(
0.005 mmol) in MeNO
2
(0.4 mL) at –24 °C. After the reaction time, adduct 6 was isolated by column chromatography.
[
c]
[d]
[e]
Results starting from alcohols 1. After isolation by column chromatography. Determined by chiral HPLC analysis.
Results starting from commercially available aldehydes 2. No reaction observed after 3 days. Not determined.
[
f]
[g]
As shown in Table 3, the Henry reaction took place
rendering the desired β–nitro alcohols 6 in good to
excellent yields (up to >95%) and high
enantioselectivities (up to 93% ee) with very clean
reaction crudes. The enantioselectivity did not depend
on the electronic effects of the alcohols. However, the
reactivity is probably correlated with the electronic
effects of the aromatic rings since the reagents with an
electron–withdrawing group in the aromatic ring
exhibited more reactivity (Table 3, entries 1–5 and 10).
presence of traces of acid in these aldehydes
inactivates the small amount of catalyst used in the
[7a]
process. In fact, in our previous research, many of
the aldehydes required a preliminary treatment in order
to remove the acids and avoid such inactivation. In
some cases, a few minutes after purifying the
aldehydes, the generation of acid was observed in the
aldehydes.
Although the enantiomeric excesses observed when Conclusion
using alcohols are practically identical compared with
those obtained when aldehydes are employed, the
reactivity is better in almost all the cases (see 1d–j). It
is remarkable that in the reactions using commercially
available aldehydes 2h–j without previous purification
no products were formed. This occurs because the
In summary, we have successfully developed the first
asymmetric catalytic aldol and Henry reactions
starting from benzylic type alcohols 1. The
combination of an oxidation and a successive aldol or
Henry protocol produced β–hydroxy ketones 5 and β–
4
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Advanced Synthesis & Catalysis
10.1002/adsc.201701351
nitro alcohols 6, respectively, with very good results. References
It was found that, in some cases, the same Henry
reactions using commercially available aldehydes 2
did not work after four days. Moreover, we have
proven that the oxidation step can be carried out for
diverse substituted aromatic alcohols using different
solvents without impairing in the results of the reaction.
Our protocol demonstrates that using alcohols leads in
general, to better results than using aldehydes,
especially in cases where aldehydes oxidized easily or
are difficult to handle. The procedure described herein
could open new opportunities and could be applied to
other reactions which start from aldehydes. Further
research on the efficacy of this organocatalytic
approach in other asymmetric reactions is ongoing in
our lab in order to extend this idea.
[1] a) C. A. Wurtz, Bull. Soc. Chim. Fr. 1872, 17, 436-442;
b) C. A. Wurtz, J. Prakt. Chem. 1872, 5, 457-464.
[
2] L. Henry, C. R. Hebd. Séances Acad. Sci. 1895, 120,
265-1268.
1
[3] F. A. Luzzio, Tetrahedron 2001, 57, 915-945.
[
4] a) R. Mahrwald (Ed.) Modern aldol reaction. Wiley-
VCH: Weinheim, 2004; b) C. Palomo, M. Oiarbide, J.
M. García, Chem. Eur. J. 2002, 8, 36-44; c) B. M. Trost,
C. S. Brindle, Chem. Soc. Rev. 2010, 39, 1600-1632; d)
M. Bhanushali, C.-G. Zhao, Synthesis 2011, 1815-1830;
e) V. Bisai, A. Bisai, V. K. Singh, Tetrahedron 2012, 68,
4
541-4580; f) M. M. Heravi, S. Asadi, Tetrahedron:
Asymmetry 2012, 23, 1431-1465; g) M. M. Heravi, V.
Zadsirjan, M. Dehghani, N. Hosseintash, Tetrahedron:
Asymmetry 2017, 28, 587-707.
Experimental Section
[
5] J. Boruwa, N. Gogoi, P. P. Saikia, N. C. Barua,
General experimental methods. Purification of reaction
products was carried out by column chromatography using
silica-gel (0.063-0.200 mm). Analytical thin layer
chromatography was performed on 0.25 mm silica gel 60-F
Tetrahedron: Asymmetry 2006, 17, 3315-3326.
[6] a) C. Palomo, M. Oiarbide, A. Mielgo, Angew. Chem.
Int. Ed. 2004, 43, 5442-5444; b) C. Palomo, M. Oiarbide,
A. Laso, Eur. J. Org. Chem. 2007, 2561-2576; c) Y.
Alvarez-Casao, E. Marqués-López, R. P. Herrera,
Symmetry 2011, 3, 220-245.
1
13
plates. H-NMR spectra were recorded at 300 MHz; C-
APT-NMR spectra were recorded at 75 MHz; CDCl was
used as the deuterated solvents. Chemical shifts were
3
3
reported in the δ scale relative to residual CHCl (7.28 ppm)
1
for H-NMR and to the central line of CDCl
3
(77 ppm) for
[
7] a) J. V. Alegre-Requena, E. Marqués-López, R. P.
Herrera, Adv. Synth. Catal. 2016, 358, 1801-1809.
Highlighted in Synfacts 2016, 12, 743; b) J. V. Alegre-
Requena, E. Marqués-López, R. P. Herrera, ACS Catal.
13
C-APT-NMR.
[
13]
[15]
6b,[16] 6c,[17]
Materials. Spectral data for 5a-g,
6a,
[
15]
[17]
[17]
[17]
[18]
[18]
[18]
6
d,
6e,
6f,
6g,
6h,
6i,
and 6j
are
2
017, 7, 6430-6439; c) J. V. Alegre-Requena, E.
consistent with values previously reported in the literature.
See supporting information for all spectra and HPLC
chromatograms.
Marqués-López, R. P. Herrera, Chem. Eur. J. 2017 DOI:
10.1002/chem.201702841.
[
[
[
8] a) R. J. K. Taylor, M. Reid, J. Foot, S. A. Raw, Acc.
Chem. Res. 2005, 38, 851-869; b) K. Ekoue-Kovi, C.
Wolf, Chem. Eur. J. 2008, 14, 6302-6315.
Representative procedure for the organocatalyzed aldol
reaction starting from alcohols.
2
To a suspension of MnO (2.5 mmol) in toluene (0.5 mL) at
8
0 ºC, alcohol 1a-g (0.5 mmol) was added. After the
9] G. Tojo, M. Fernandez (Eds.) Oxidation of alcohols to
aldehydes and ketones. Springer Science: New York,
oxidation time, the reaction was cooled down to room
temperature and a mixture of catalyst 3 (0.05 mmol), TfOH
2
006.
(
0.075 mmol) and 4 (1.5 mL) was added in one portion.
After the reaction time (Table 2), the process was quenched
with a saturated NH Cl aqueous solution (20 mL) and
extracted with AcOEt (3 x 30 mL). The organic phases were
dried with MgSO and the solvent was evaporated. Adduct
was isolated by column chromatography.
10] For a few examples, see: a) C. B. Tripathi, S.
Mukherjee, J. Org. Chem. 2012, 77, 1592-1598; b) M.
Hayashi, M. Shibuya, Y. Iwabuchi, J. Org. Chem. 2012,
77, 3005-3009; c) A. Abramovich, H. Toledo, E.
Pisarevsky, A. M. Szpilman, Synlett 2012, 23, 2261-
2265; d) A. Al-Hunaiti, M. Räisänen, P. Pihko, M.
Leskelä, T. Repo, Eur. J. Org. Chem. 2014, 6141-6144;
e) X. Chen, Y. Zhang, H. Wan, W. Wang, S. Zhang,
Chem. Commun. 2016, 52, 3532-3535.
4
4
5
Representative procedure for the organocatalyzed
Henry reaction starting from alcohols.
To a suspension of MnO
2
(5 mmol) in CH
3
CN (1 mL) at
8
0 °C, alcohol 1a-j (1 mmol) was added. After the oxidation
time (Scheme 2), the reaction was cooled down to room
temperature and the suspension was filtered using a HPLC
filter of 0.22 μm. Then, 0.1 mL of the solution filtrated were
collected and added to a solution of catalyst 7 (0.005 mmol)
[
11] For the scarce examples of oxidation of alcohols in
iminium catalysis, see: a) A. Quintard, A. Alexakis, C.
Mazet, Angew. Chem. Int. Ed. 2011, 50, 2354-2358; b)
M. Rueping, H. Sundén, E. Sugiono, Chem. Eur. J. 2012,
in MeNO
2
(0.4 mL) at –24 °C. After the reaction time (Table
3
), adduct 6 was isolated by flash chromatography.
1
8, 3649-3653; c) M. Rueping, H. Sundén, L. Hubener,
E. Sugiono, Chem. Commun. 2012, 48, 2201-2203; d) C.
W. Suh, D. Y. Kim, Org. Lett. 2014, 16, 5374-5377; e)
N. K. Rana, H. Joshi, R. K. Jha, V. K. Singh, Chem. Eur.
J. 2017, 23, 2040-2043.
Acknowledgements
We thank the Government of Aragon DGA (Research Group E–
1
04) for financial support of our research. J.V.A.–R. thanks the
[
2
12] MnO could be passivated over time with moisture
DGA for a predoctoral contract. The authors thank Leah C.
Weatherman for her help during the text editing process.
from the air. Therefore, activated MnO was employed
2
5
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Advanced Synthesis & Catalysis
10.1002/adsc.201701351
in this study from different commercial sources (85-90%
[15] M. Steurer, C. Bolm, J. Org. Chem. 2010, 75, 3301-
purity).
3310.
[
[
13] B.-L. Zheng, Q.-Z. Liu, C.-S. Guo, X.-L. Wang, L. He,
[16] S. Kitagaki, T. Ueda, C. Mukai, Chem. Commun. 2013,
49, 4030-4032.
Org. Biomol. Chem. 2007, 5, 2913-2915.
14] For selected reviews concerning primary amine
[17] C. V.-L. Bray, F. Jiang, X.-F. Wu, J.-B. Sortais, C.
catalysis, see: a) F. Peng, Z. Shao, J. Mol. Catal. A 2008,
Darcel, Tetrahedron Lett. 2010, 51, 4555-4557.
2
2
85, 1-13; b) L. W. Wu, Y. Lu, Org. Biomol. Chem.
008, 6, 2047-2053; c) L.-W. Xu, J. Luo, Y. Lu, Chem.
[
18] B. Zheng, M. Wang, Z. Li, Q. Bian, J. Mao, S. Li, S.
Liu, M. Wang, J. Zhong, H. Guo, Tetrahedron:
Asymmetry 2011, 22, 1156-1160.
Commun. 2009, 1807-1821; d) Y.-C. Chen, Synlett 2008,
919-1930; e) U. V. S. Reddy, M. Chennapuram, C. Seki,
E. Kwon, Y. Okuyama, H. Nakano, Eur. J. Org. Chem.
016, 4124-4143.
1
2
6
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10.1002/adsc.201701351
FULL PAPER
Organocatalyzed enantioselective aldol and Henry
reactions starting from benzylic alcohols
Adv. Synth. Catal. Year, Volume, Page – Page
Juan V. Alegre-Requena, Eugenia Marqués-López
and R. P. Herrera*
7
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