A Friedel-Crafts alkylation mechanism using an aminoindanol-derived thiourea catalyst

Article abstract of DOI:10.1039/c4ob00348a

Computational calculations based on experimental results shed light on the mechanistic proposal for a Friedel-Crafts alkylation reaction between indole and nitroalkenes, catalysed by a chiral aminoindanol-derived thiourea. In our hypothesis both substrate

Full text of DOI:10.1039/c4ob00348a

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A Friedel–Crafts alkylation mechanism using an
aminoindanol-derived thiourea catalyst†
Cite this: Org. Biomol. Chem., 2014,
12, 4503
David Roca-López, Eugenia Marqués-López, Ana Alcaine, Pedro Merino and
Raquel P. Herrera*
Computational calculations based on experimental results shed light on the mechanistic proposal for a
Friedel–Crafts alkylation reaction between indole and nitroalkenes, catalysed by a chiral aminoindanol-
derived thiourea. In our hypothesis both substrates are simultaneously coordinated to the catalyst in a
bifunctional mode. This study elucidates the crucial role played by the hydroxyl group of the catalyst in
the success of the reaction. The OH group seems to be involved in the preferential attack of the indole
over the nitroalkene, affording the major enantiomer and stabilizing the resulting transition state by a con-
comitant coordination with the nitroolefin. The results obtained with other catalysts from the same family,
and other indoles, are reported and discussed. Theoretical calculations are in agreement with the experi-
mental outcomes and with our previously developed mechanism, displaying the pivotal role played by
hydrogen bond interactions.
Received 14th February 2014,
Accepted 9th April 2014
DOI: 10.1039/c4ob00348a
www.rsc.org/obc
mechanisms, the essential function performed by hydrogen
bond interactions was fundamental for the reactivity and
Introduction
In the last decade, catalysts acting through hydrogen bond enantioselectivity of the processes. In both cases, two enantio-
interactions have attracted great interest, and they represent a mers of the thiourea-aminoindanol derivative 1a were the cata-
noteworthy part of the organocatalytic field.1–3 One of the lysts of choice to efficiently promote a Friedel–Crafts reaction
main families of organocatalytic structure included in this between the indoles 2 and nitroolefins 3. Transition states
large group are the thiourea/urea derivatives, and many efforts depicted in Fig. 1 (TSI and TSII) were postulated in order to
have been devoted to the design and synthesis of new ones as explain the role of the catalyst and the major enantiomer
appropriate catalysts in a large number of interesting pro- observed.
cesses.4 In the last few years, we have focused part of our
investigation on the development of new thiourea-catalysed attractive and challenging task in order to improve the process
methods.5
and to promote further developments. Moreover, information
Understanding the mechanism of a reaction is always an
The Friedel–Crafts alkylation reaction has received the about the catalyst’s mode of action could help to understand
attention of a great number of research groups, becoming an its use in similar reactions. For this purpose, computational
efficient tool for carbon–carbon bond-formation.6 In fact, studies, reinforced with experimental results, have become an
some of us pioneered the first thiourea-catalysed Friedel– important tool in organocatalysis. In the last decade, it has
Crafts alkylation reaction between indoles and nitroalkenes allowed the proposition of interesting reaction mechanisms,
(TSI, Fig. 1).5b More recently, we have also reported some pre- and has provided remarkable insights into the origin of cata-
liminary results concerning a new concept on the cooperative lysis and the selectivity of the explored processes.7
effect between a Brønsted acid additive and a chiral thiourea
The aminoindanol skeleton has been investigated several
organocatalyst in the same process (TSII, Fig. 1).5g In these times in different interesting catalyst structures acting as a
hydrogen bond promoter, following our pioneering work.8
However, to the best of our knowledge only one work using
the catalyst (1R,2S)-1a has been focused on computational
Laboratorio de Síntesis Asimétrica, Departamento de Química Orgánica. Instituto de
calculations, in an aza-Michael addition reaction.9
Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza,
E-50009 Zaragoza, Spain. E-mail: raquelph@unizar.es; Tel: +34 976761190
†Electronic supplementary information (ESI) available: Absolute (hartrees) and
relative (kcal mol−1) electronic and free energies calculated at −24 °C, including
based on experimental results (TSI and TSII, Fig. 1).5b,g Herein
Cartesian coordinates of optimized structures at PCM(CH2Cl2)/M06-2X/6-311G-
In our previously reported works on this Friedel–Crafts reac-
tion, a reasonable bifunctional mechanism was envisioned
we want to report our most recent studies on this mechanistic
(d,p) level of theory. CCDC 976490. For ESI and crystallographic data in CIF or
hypothesis, employing theoretical calculations.10,11 Compu-
other electronic formats see DOI: 10.1039/c4ob00348a
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Scheme 1 Thiourea catalysts tested in the Friedel–Crafts alkylation
reaction.
skeleton in the cis configuration, playing a crucial role in the
enantioselectivity and the reactivity of the process. Therefore,
even though the presence of the hydroxyl group in the struc-
ture is important, it must be also placed in the appropriate
position, in order to efficiently drive the attack of the external
nucleophile through hydrogen bond coordination, as shown in
Fig. 1.5b,e,g
Fig. 1 Transition states proposed to explain the Friedel–Crafts alkyl-
ation reaction.
tational and experimental results underline the important role
played by the hydroxyl group present in the aminoindanol
structure, and the activation through hydrogen bonding of all
species involved in the mechanism. This has been found to be
crucial for the success of both reactions in terms of the reactiv-
ity and enantioselectivity (TSIII, Fig. 1).
In our mechanistic proposals (Fig. 1), we hypothesised that
the hydroxyl group would drive the attack of the indole over a
preferential face of the nitroalkene to afford the desired
product, with the corresponding configuration depending on
the enantiomer of catalyst 1a employed.5b,g The importance of
the NH group in the indole molecule seems to be in concor-
dance with a plausible hydrogen bond interaction between it
and the OH group of the catalyst (H–O⋯H–N), which would
help in the orientation of the attack of the nucleophile.
Remarkably, using catalysts 1b and 1c (Table 1, entries 3–7),5b,g
the results are very poor in terms of both reactivity and selectivity.
TSI and TSII could explain the selectivity of this process; in
the absence of a hydroxyl group the reaction affords a racemic
mixture, since the indole can attack over both faces of the
activated nitroolefin. However, they cannot explain the lack of
reactivity, which makes us think that maybe the hydroxyl
group is involved in another crucial interaction, performing
dual modes of action (TSIII, Fig. 1). On the one hand, it would
drive the attack of the indole over the nitroalkene as a conduc-
tor; and on the other hand, it should be also involved in the
activation of the nitroalkene. In this sense, the OH could
govern the reactivity of the process, explaining the lack of reac-
tivity in its absence. These experimental observations encour-
aged us to study in depth, for the first time, the proposed dual
role of the hydroxyl group in the transition state, and to
Results and discussion
It has been accepted that the nucleophilic attack of the aro-
matic ring on the electrophile is the rate-determining step in
the Friedel–Crafts reaction, causing the subsequent proton
transfer to be a faster process.12 To evaluate our proposed
mechanistic hypothesis, we started the investigation by com-
putationally studying the C–C bond formation pathway,
founded on experimental results (some of those experiments
are compiled in Scheme 1 and Table 1). Although we have
already observed the importance of the hydroxyl group in the
structure of catalyst 1a for the Friedel–Crafts alkylation reac-
tion,5b,e,g we have recently realised the importance of having
the hydroxyl group in the correct position in the catalyst skel-
eton. For example, we did not observe either reactivity or
enantioselectivity with catalyst (1R,2R)-1c,5g with the hydroxyl
group in the trans position (Table 1, entries 6 and 7). This evi-
dence supports the idea that the hydroxyl group must be in the
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Table 1 Thiourea-catalysed Friedel–Crafts alkylation reactionsa
Entry
Catalyst
Indole
T (°C)
Time (h)
Yieldb (%)
eec (%)
1d
2
(1R,2S)-1a
(1S,2R)-1a
(S)-1b
(R)-1b
(R)-1b
(1R,2R)-1c
(1R,2R)-1c
(1S,2R)-1d
(1R,2S)-1a
(1S,2R)-1a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
−24
−25
−24
r.t
−25
r.t.
−25
−25
−45
r.t.
72
72
72
120
72
96
120
96
72
78
40
15
24
85 (ref. 5b) (R)-4aa
82 (ref. 5g) (S)-4aa
Rac. f (ref. 5b)
Rac. f (ref. 5g)
Rac. f (ref. 5g)
Rac. f (ref. 5g)
10 (S)-4aa
54 (S)-4aa
74 4ba (ref. 5b)
20 4ba (ref. 5g)
3d
4e
5
n.d.g
n.d.g
n.d.g
26
6
7
8
9d
10e
82
94
72
a Experimental conditions: to a mixture of catalyst 1a–d (20 mol%) and nitroalkene 3a (0.1 mmol) in CH2Cl2 (0.25 mL), indole 2a,b (0.15 mmol)
was further added, in a test tube at the corresponding temperature. After the reaction was complete, products 4aa and 4ba were isolated by flash
chromatography. b Isolated yield. c Determined by chiral HPLC. d 0.1 mL CH2Cl2. e 0.5 mL CH2Cl2. f Racemic mixture. g Not determined.
elucidate the mechanism of this Friedel–Crafts alkylation reac- both reagents. Additionally, in Fig. 2 some relevant distances
tion using catalyst 1a.13
have been marked on the transition states, indicating the for-
mation of a C–C bond and all plausible hydrogen bond inter-
actions involved in the activation of the process. These values
Theoretical calculations based on the real catalytic system
All the calculations were carried out at the PCM(CH2Cl2)/M06- are related to the interactions between the NH of the thiourea
2X/6-311G(d,p) level,14 including minima, transition states,
1 and the nitroalkene 3, the C–C bond formation between the
structure optimisations and frequencies analyses. The thermal indole 2 and the nitroalkene 3, the coordination between the
and entropic contributions to the free energies were also OH of the catalyst 1 and the NH of indole 2, and, even more
interestingly, the interaction found between the hydroxyl
obtained from the vibrational frequencies analyses, performed
at −24 °C, which is the temperature at which the highest group and one of the oxygen atoms of the nitroalkene 3
experimental enantiomeric excess was obtained. Although the (O–H⋯O–NvO) (TS1, TS2, TS5 and TS6). Furthermore, an
additional relevant interaction has been found between the
mechanism of our reaction was initially studied in a simplified
system, for more clarity we report here only the complete H atom of the hydroxyl group and the S atom of the thiourea
system with catalyst (1R,2S)-1a, indole (2a) and nitrostyrene (O–H⋯S), which is acting as a hydrogen acceptor (TS3 and
TS4).
(3a). This allows us to obtain a more accurate approach of our
active system in the rate determining step.
We have also examined the energetic cost for the uncata-
To prove the robustness of our mechanism, different para- lysed reaction represented in Scheme 1, between indole (2a)
and nitrostyrene (3a), and found that it is 28 kcal mol−1, in
meters were widely analysed. As such, the conformations of
the catalysts, the attack through both faces of the nitroalkene, contrast to 11 kcal mol−1 for ΔG‡ in the case of TS1, the most
the possibility of bidentate or monodentate coordination stable state for the catalysed reaction (Fig. 2). This outcome is
consistent with the stabilizing effect promoted by the presence
through directional hydrogen bonding between the nitro-
alkene and the thiourea, the coordination of the hydroxyl of the catalyst, and the subsequent acceleration of the reaction.
group to the indole, and the approaching face of the indole Free energy values for the calculated transition states are given
relative to the most stable, TS1, to which was assigned an
test the accuracy of our proposed mechanism, we analysed energy value of 0.
were some key aspects of the comprehensive study. In order to
different transition states for the C–C bond formation step –
that is, the attack of indole 2 over the nitroalkene 3 activated
Some interesting conclusions could be extracted from these
outcomes (Fig. 2). In all cases, the oxygen atom in the hydroxyl
with the thiourea catalyst (1R,2S)-1a through hydrogen bond group of the catalyst 1a prefers to interact with the NH group
interactions – using the complete catalytic system. The analysis of the indole (2a) through H–O⋯H–N, leading to the attack of
the nucleophile over the nitroalkene 3, as we previously pre-
the nitroalkene 3 and the active catalytic complex were also dicted (Fig. 1).5b,g The small differences in activation barrier
of the global reactivity in terms of Fukui’s indices for indole 2,
calculated at the ground state (see ESI†).
for the attack of the indole (2a) over the Si face of the nitro-
styrene (3a) (TS1, 0.0 kcal mol−1) and the Re face (TS2, 2.1 kcal
In this respect, we focused this computational work on the
study of all possible hydrogen bond interactions between all mol−1) could explain why the higher enantiomeric excess
involved species, which are expected to stabilize the catalytic achieved was around 85% (Table 1, entries 1 and 2). According
to the experiments, the most stable transition state TS1 would
system in the transition state. Based on an extensive confor-
mational search, we were able to find several transition states. afford the R enantiomer of the final product (R)-4aa obtained
Among all of the possibilities studied, only the most stable with (1R,2S)-1a (Table 1, entry 1).5b The opposite is true for the
catalyst (1S,2R)-1a, which would afford the S enantiomer of 4aa
transition states calculated are shown in Fig. 2. In these states,
the reaction occurs through a concomitant coordination of (Table 1, entry 2). To unambiguously establish the absolute
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Fig. 2 Transition states for the Friedel–Crafts alkylation reaction using catalyst (1R,2S)-1a. Relative free energies are expressed in kcal mol−1; distances are in Å.
Fig. 3 X-ray crystal structure of (S)-4ab.
Fig. 4 Transition states for the Friedel–Crafts alkylation reaction using
catalyst (S)-1b. Relative free energies are expressed in kcal mol−1; dis-
tances are in Å.
configuration of the final Friedel–Crafts adducts 4 using cata-
lyst (1S,2R)-1a, single crystals were grown from adduct 4ab. As
TS1 could be attributed to a less hindered packaging, since the
indole (2a) is farther from the aromatic ring of the amino-
indanol part of the catalyst than in TS2, which would cause
stronger repulsions. In this sense, the indole–nitroalkene
relative orientation plays a crucial role in determining the
selectivity observed in the final products (4).
Having identified the most stable transition state TS1, we
proceeded to vary the structure firstly of the catalyst 1 and then
of the indole 2. Centred on our experiments, we examined the
expected, the stereochemical outcome was determined to be S
for the final product 4 (Fig. 3).15
Moreover, it is interesting to note that except in TS2, the
nitroalkene 3 prefers to be coordinated through a bidentate
coordination, as first observed by Etter and co-workers.16 This
bidentate coordination provides a more rigid TS among the
three species, although previous works have also postulated a
plausible monodentate coordination between a thiourea and a
nitroalkene.17 The stability of the more stable transition state
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Fig. 5 Transition states for the Friedel–Crafts alkylation reaction using
Fig. 6 Transition states for the Friedel–Crafts alkylation reaction using
catalyst (1R,2R)-1c. Relative free energies are expressed in kcal mol−1
;
catalyst (1R,2S)-1d. Relative free energies are expressed in kcal mol−1
;
distances are in Å.
distances are in Å.
TS for catalyst (S)-1b (Fig. 4). The outcome of replacing the OH
in the catalyst with H was interesting. First of all, the energetic
differences among the different conformations of the catalytic
system which afford enantiomers (R)-4 and (S)-4 are reduced.
This trend supports the observation of a racemic mixture
being formed when catalyst 1b is used (Table 1, entries 3–5).
The ΔG‡ for TS7 was found to be 17 kcal mol−1, 6 kcal
mol−1 more energetic than in the case of TS1. This demon-
strates that the hydroxyl group not only has a driving effect in
this process, orientating the attack of the indole 2, but also
has a stabilising effect. This is also in concordance with the
experimental outcomes reached, since the reaction proceeds
poorly and in a racemic way (Table 1, entries 3–5).
Fig. 7 Transition states for the Friedel–Crafts alkylation reaction of 2b
using catalyst (1R,2S)-1a. Relative energies are expressed in kcal mol−1
;
distances are in Å.
A similar effect is observed when catalyst (1R,2R)-1c, which
has a trans configuration, is employed (Fig. 5). Interestingly, in
this case a preferred hydrogen bond interaction between the
hydroxyl group and the S atom of the thiourea is found
(O–H⋯S). This coordination does not stabilise the TS more
than in the absence of the hydroxyl group, since the ΔG‡ for
TS9 was found to be 18 kcal mol−1, the same order of energy
as that obtained in TS7 (17 kcal mol−1). In both reactions, the
high ΔG‡ values fit with the almost complete lack of reactivity
observed (Table 1, entries 6 and 7).
In this case, the obtainment of the same enantiomer
(R)-4aa would be expected, since the configuration of the
carbon bearing the NH group in the aminoindanol structure of
the catalyst (1R,2R)-1c is the same as in catalyst (1R,2S)-1a
(Table 1, entry 1). Remarkably, a variation in the final enantiomer
is computationally predicted, because the attack of the indole 2
occurs preferentially by the Re face of the nitroalkene 3,
affording an S configuration in the final product 4. This result
is in accordance with the experimental outcome (Table 1,
entry 7). Although the energetic difference between the two
transition states (TS9 and TS10) is small, the preferred S con-
figuration could be due to a more congestive conformation in
TS10 between the indole 2 and the aminoindanole ring of the
catalyst. In this case, we found preferential monodentate
coordination between the nitrostyrene (3a) and the thiourea
(1R,2R)-1c (TS9).
Furthermore, we analysed the effect of the catalyst in the
absence of an aromatic ring in the aminoindanol skeleton,
that is, using (1R,2S)-1d (Fig. 6). The most stable transition
states (TS11 and TS12) are similar to TS1 and TS2, with the
same differences in energy and the same favoured coordi-
nation by the hydroxyl group to the NH in the indole 2
(H–O⋯H–N) and to the O atom in the nitro group of the
alkene 3 (O–H⋯O–NvO). The ΔG‡ for TS11 was found to be
12.5 kcal mol−1, 1.5 kcal mol−1 more energetic than in the
case of TS1. Although the absence of the aromatic ring seems
not to have a great effect on the calculated energies, the experi-
mental results are very different to those reached with catalyst
1a (Table 1, entries 1, 2 and 8). In this case, the influence of
the aromatic ring seems to be really important in the origin of
the selectivity of the process. We can envision a strong steric
effect of the aromatic ring in catalyst 1a, avoiding an attack of
the indole 2 by the other side, that does not exist in the case of
catalyst 1d.
After analysing the catalyst structure, we further considered
varying the indole skeleton (Fig. 7). When we explored
2-methylindole (2b) as the nucleophile, the central core of the
most stable transition states and all the hydrogen bonds
remained unaltered compared with TS1 and TS2 (Fig. 2).
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However, the difference in energy between TS13 and TS14 is
very small. The ΔG is in agreement with the less enantio-
selective process observed (Table 1, entries 9 and 10). The ΔG‡
Experimental section
Materials
for TS13 was found to be 9.0 kcal mol−1. The energy barrier is All commercially available solvents and reagents were used as
much lower (2.1 kcal mol−1) than in the case of TS1, indicating received. CH2Cl2 was filtered through basic alumina prior to
a much higher reactivity. This behaviour agrees well with the use, to avoid the presence of trace amounts of acid. The 1H
higher reaction rate observed in this process. This is due to and 13C NMR spectra for the catalysts (1R,2S)-1a,5b (1S,2R)-
the inductive effect provided by the methyl group, which 1a,5g (S)-1b,18 (R)-1b,5g (1R,2R)-1c,5g and (1S,2R)-1d,5e and the
favours an attack through the third position of the indole 2b.
final products 4aa,5g 4ab5g and 4ba5g are consistent with
It is worth noting that we found a preferred monodentate values previously reported in the literature.
coordination between the thiourea and the nitroalkene 3
(TS13). The coordination of the hydroxyl group to the nitro
group through O–H⋯O–NvO was also found in both tran-
Friedel–Crafts alkylation reaction of indoles with nitroalkenes
sition states (TS13 and TS14, Fig. 7).
With all these outcomes in mind, we have modified our pre-
vious two transition states TSI and TSII (Fig. 1), which were
(0.15 mmol) was further added, in a test tube at low tempera-
not far from the possible mechanistic activation. In order to
better understand the experimental results, we have now
the residue was purified by flash chromatography (SiO2;
included the crucial interaction between the OH group of the
catalyst and an oxygen atom of the nitroalkene (O–H⋯
O–NvO) (Fig. 1, TSIII). These theoretical calculations have
Representative procedure for a thiourea organocatalysed
To a mixture of catalyst 1a–d (20 mol%) and nitroalkene 3a or
b (0.1 mmol) in CH2Cl2 (0.1, 0.25 or 0.5 mL), indole 2a or b
ture. After the appropriate reaction time (see Table 1),
hexane–EtOAc, 8 : 2) to afford the final adducts (4). Yields and
enantioselectivities are reported in Table 1. Spectral and
analytical data for compounds 4aa, 4ab and 4ba are in agree-
underlined the essential role of hydrogen bonding in the
ment with those previously reported in the literature.5g
success of the process.
Computational methods
Conclusions
All calculations were performed using the Gaussian09
program.14 Molecular geometries were optimized with the
We have reported an unprecedented theoretical study of the
M06-2X functional19 in conjunction with the 6-311G(d,p) basis
mechanism of a thiourea-catalysed Friedel–Crafts alkylation
set.20 Analytical second derivatives of the energy were calcu-
reaction for the addition of indoles 2 to nitroalkenes 3. The
lated to classify the nature of every stationary point, to deter-
catalyst at the centre of the study was the aminoindanol
mine the harmonic vibrational frequencies, and to provide
derived thiourea (1R,2S)-1a and its enantiomer (1S,2R)-1a.
zero-point vibrational energy corrections. The thermal and
Some other catalysts derived from this crucial structure have
entropic contributions to the free energies were also obtained
been also considered. Our work sheds light on the experi-
from the vibrational frequency calculations, using the
unscaled frequencies, and a value of −24 °C for the tempera-
ture (as this is the temperature at which the highest experi-
mental enantiomeric excess was obtained). Full optimization
mental results obtained in this process and provides further
support for them. The computational results are in accordance
with our previously disclosed mechanisms (Fig. 1).
It is revealed that indole 2 is coordinated to the crucial
hydroxyl group of the catalyst through a hydrogen bond
(HO⋯H–N) and that the nitroalkene 3 is preferentially co-
calculations have been carried out considering solvent effects
(CH2Cl2) with the PCM model.21
ordinated via bidentate hydrogen bonds with the thiourea 1.
Additionally, we have found an interesting interaction between
the hydroxyl group of the catalyst 1 and an oxygen atom of the
nitro group of the nitroalkene 3 (O–H⋯O–NvO), supporting
Acknowledgements
the lack of reactivity when the OH function is not present in the We thank the Spanish Ministry of Economía y Competitividad
catalyst structure or it is not placed in the correct position. (MICINN. Madrid. Spain, Project CTQ2010-19606) and the Gov-
Based on extensive computational studies, we can elucidate a ernment of Aragón (Zaragoza. Spain. Research Group E-10) for
preference in the attack of the indole 2 over the appropriate face financial support of our research. D. R.-L. thanks the Spanish
of the nitroalkene 3, affording the observed major enantiomer Ministry of Education (MEC) for a pre-doctoral grant (FPU
in each case. This clarifies the origin of the enantioselectivity in program). We thank Dr Pablo J. Sanz Miguel (ISQCH) for X-ray
this Friedel–Crafts alkylation reaction for different catalyst struc- structure analysis. We acknowledge the Institute of Biocompu-
tures and indoles. We think that our work could be an impor- tation and Physics of Complex Systems (BIFI) at the University
tant theoretical study to explain the role of the aminoindanol of Zaragoza for computer time at clusters Terminus and
skeleton in organocatalysts, especially the role of the hydroxyl Memento. Molecular graphics have been performed with
group, and it could help to understand future mechanisms in CYLview 1.0 software (C. Y. Legault, University of Sherbrooke,
which an aminoindanol structure is involved.
Canada).
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VCH, Weinheim, 2012, pp. 175–199; (i) A. Alcaine,
E. Marqués-López and R. P. Herrera, RSC Adv., 2014, 4,
9856.
6 For reviews on Friedel–Crafts organocatalyzed alkylation
reactions, see: (a) E. Marqués-López, A. Diez-Martinez,
P. Merino and R. P. Herrera, Curr. Org. Chem., 2009, 13,
1585; (b) S.-L. You, Q. Cai and M. Zeng, Chem. Soc. Rev.,
2009, 38, 2190; (c) V. Terrasson, R. M. de Figueiredo and
J. M. Campagne, Eur. J. Org. Chem., 2010, 2635; (d) M. Zeng
and S.-L. You, Synlett, 2010, 1289.
Notes and references
1 (a) A. Berkessel, in Organocatalysis by Hydrogen Bonding Net-
works in Organocatalysis, ed. M. T. Reetz, B. List, H. Jaroch
and H. Weinmann, Springer-Verlag, Berlin, Heidelberg,
2008, vol. 2, pp. 281–297; (b) Hydrogen Bonding in Organic
Synthesis, ed. P. M. Pihko, Wiley-VCH, Weinheim, 2009;
(c) E.-E. Kerstin and A. Berkessel, Top. Curr. Chem., 2010,
291, 1–27.
2 For selected reviews on organocatalysis, see for instance:
(a) Asymmetric Organocatalysis, ed. A. Berkessel and H. Gröger,
Wiley-VCH, Weinheim, 2004; (b) Acc. Chem. Res, 2004, 37(8),
special issue on organocatalysis; (c) Enantioselective Organo-
catalysis, ed. P. I. Dalko, Wiley-VCH, Weinheim, 2007; (d) Chem.
Rev., 2007, 107(12), special issue on organocatalysis; (e) Recent
Developments in Asymmetric Organocatalysis, ed. H. Pellissier,
RSC Publishing, Cambridge, 2010; (f) Asymmetric Organo-
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