Synthesis of a chiral artificial receptor with catalytic activity in Michael additions and its chiral resolution by a new methodology

Article abstract of DOI:10.1039/b925367j

Xanthone derivatives were tested as organocatalysts for the Michael addition of pyrrolidine to an α,β-unsaturated lactam. The receptors combine a double H-bond donor pattern that resembles the oxyanion hole in natural enzymes, with a sulfone or sulfoxide that acts as a proton-transfer group. Since these compounds cannot be obtained enantiomerically pure from natural sources, chiral resolution was necessary to study their enantioselectivity. For the most promising receptor, this was accomplished using a new methodology that exploits its supramolecular interactions with a chiral guest and that is inspired in dynamic combinatorial chemistry. The success in the resolution of the racemic mixture indicates that this new method offers an alternative to kinetic resolution.

Full text of DOI:10.1039/b925367j

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/obc | Organic & Biomolecular Chemistry
Synthesis of a chiral artificial receptor with catalytic activity in Michael
additions and its chiral resolution by a new methodology†
a
a
a
b
c
´
Luis Simo´n,* Francisco M. Mun˜iz, Angel Fuentes de Arriba, Victoria Alca´zar, Ce´sar Raposo and
Joaqu´ın R. Mora´na
Received 2nd December 2009, Accepted 25th February 2010
First published as an Advance Article on the web 8th March 2010
DOI: 10.1039/b925367j
Xanthone derivatives were tested as organocatalysts for the
Michael addition of pyrrolidine to an a,b-unsaturated lactam.
The receptors combine a double H-bond donor pattern that
resembles the oxyanion hole in natural enzymes, with a
sulfone or sulfoxide that acts as a proton-transfer group. Since
these compounds cannot be obtained enantiomerically pure
from natural sources, chiral resolution was necessary to study
their enantioselectivity. For the most promising receptor, this
was accomplished using a new methodology that exploits its
supramolecular interactions with a chiral guest and that is
inspired in dynamic combinatorial chemistry. The success in
the resolution of the racemic mixture indicates that this new
method offers an alternative to kinetic resolution.
Introduction
The feasibility of chiral catalysis in asymmetric synthesis is con-
ditioned by the accessibility of the catalyst as a single enantiomer.
In many cases, the catalyst can be obtained enantiomerically pure
from a natural source. A good and well documented example
is the use of proline or proline derivatives in organocatalysis.1–6
Nevertheless, some synthetic catalysts cannot be derived from
natural enantio-pure sources, so their application in asymmetric
synthesis requires an effective and simple method for isolating
the required enantiomer. This can be accomplished by either
asymmetric synthesis of the catalyst or by chiral supramolecular
recognition.
In recent works,7–9 we have designed and synthesized xanthone-
derived receptors with catalytic activity in the Michael addition
of amines to the a,b unsaturated lactam 1 (Fig. 1). Like many
other organocatalysts containing double H-bond donors,10–44 these
catalysts are inspired by the oxyanion hole structure45–60 present
in many enzymes (such as hydrolases, lipases, proteases, esterases,
etc). The role of H-bond donors is to stabilize the electron density
Fig. 1 Michael addition of pyrrolidine to lactam 1 and structures of the
lactam and chiral catalysts studied in previous works and prepared from
chiral natural sources.
that is accumulated during the transition state, but recently it has
been observed that the geometry of xanthone receptors better
fits the geometric parameters in oxyanion hole enzymes.61,62 In
addition to H-bond donors, these catalysts include groups that
assist the proton transfer of the amine nucleophile to the a,b-
unsaturated lactam. When the xanthone scaffold was functional-
ized with chiral amines (derived from a-amino acids), moderate
degrees of chiral assistance were observed, but the self-aggregation
derived from the basicity of these groups is detrimental for the
association of the substrate. Moreover, Bruice63,64 has pointed out
that H-bond acceptors can act as proton transport groups in the
proton slide mechanism, where the basicity of the heteroatom is
not as important as its ability to act as a good hydrogen bond
acceptor. Accordingly, receptors with amide carbonyl oxygen and
sulfonamide oxygen atoms were prepared.8 As these receptors were
obtained from chiral natural products, it was possible to observe
moderate degrees of chiral assistance.
Continuing with this research, in the present work we explore
the possibilities of xanthone receptors containing sulfone and
sulfoxide oxygens as proton-transport groups, since both groups
are strong H-bond acceptors65–67 and can assist the proton transfer
process.8,68 Cyclic compounds were also included in the study with
the aim of reducing the flexibility of the catalysts, which could
increase the chiral assistance by reducing the conformational space
aOrganic Chemistry Department, University of Salamanca, 37008, Sala-
manca, Spain. E-mail: lsimon@usal.es; Fax: +34-923-294574
bIndustrial Chemistry and Environmental Engineering Department, Jose´
Gutie´rrez Abascal 2, Universidad Polite´cnica de Madrid, 28006, Madrid,
Spain
cMass Spectrometry Service, University of Salamanca, 37008, Salamanca,
Spain
† Electronic supplementary information (ESI) available: Preparation and
physical data for receptors. Determination of the relative stereochemistry
of receptors 7u and 7l. Complete list of authors in ref.69. Details of
computational studies and cartesian atomic coordinates for optimized
structures and TS. Kinetic experiments for receptors. Competitive titration
experiments. Determination of enantiomer ratio induced by receptor (-)7u
and absolute configuration. See DOI: 10.1039/b925367j/
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 1763–1768 | 1763
©

View Article Online
than sulfones65 (the relative stereochemistry of these receptors was
assigned comparing with the reactivity of other cyclic thioeters
described in the literature,69 modelling studies and 1H NMR
chemical shifts; see electronic supplementary information for
details†).
Table 1 Catalytic activities of the receptors studied in this work
b
Receptor
t1/2 (min)a
Krel
—
—
2
3
4
5
6
7u
7l
2385
84
17
37
34
22
6.5
8
1.00
0.11
—
0.058
1.1
The similar catalytic activity obtained for receptors 7u and
7l is a striking result considering the different geometries of
both compounds. In fact, CPK models and modelling studies
have suggested that only the 7u sulfoxide could assist the proton
transfer. Inspection of 1H NMR spectra revealed that both
receptors, 7u and 7l, were in equilibrium in benzene or chloroform
solutions in the presence of a base. Under these conditions, the
carbon stereogenic center underwent a fast epimerization as a
result of its acidity (the carbanion is stabilized by amide, sulfoxide
groups and the aromatic ring). When traces of base such as
imidazole were added to a chloroform or benzene solution of
7u and 7l, receptor 7u isomerized completely to 7l, and hence
—
—
a Half life times of the catalyzed reactions ([pyrrolidine] = 3.0 M; [lactam] =
0.80 M; [receptor] = 0.04 M; solvent: benzene; T = 298 K. b Relative
association constants referred to receptor 2.
of the catalyst (and therefore the probability that different catalyst
conformers might generate opposite enantiomers). A drawback of
the catalysts included in this work is that they cannot be obtained
enantiomerically pure starting from affordable chiral compounds.
Therefore, in order to test the chiral assistance of the new catalysts
it was necessary either to prepare or to isolate a single enantiomer.
This was accomplished by means of a new technique based on the
supramolecular properties of the catalyst and its interactions with
a chiral analogue of the transition state.
1
7u could no longer be detected in the H NMR spectra (Fig. 3).
Modelling studies using the ONIOM70–72 hybrid method with the
Gaussian 98W73 program revealed that the sulfoxide oxygen can
establish two strong H-bonds with receptor NHs that stabilize
the formation of the l epimer (Fig. 4). As the chemical shifts
were insensitive to dilution, it is very likely that the formation of
Results and discussion
The sulfone and sulfoxide-based receptors shown in Fig. 2 (see ESI
for synthetic procedures†) were prepared and their performance
as catalysts in the Michael addition of pyrrolidine to lactam 1
was evaluated. The half-life times of the reaction (catalyzed by
5% mol of the receptors) are shown in Table 1. Receptor 2 (Fig. 1)
was also included in the study, since it allows the effect of the
oxyanion hole structure alone to be established because it lacks
the proton transport group. The half-life time of sulfone derivative
3 was decreased by a factor of 5 relative to the above-mentioned
receptor 2. Even though higher rigidity is desirable to develop
more efficient catalysts, receptors 4 and 5 (which have cyclic
structures) did not improve the catalytic properties of receptor
3. This is probably because they cannot match the ideal geometry
for proton transport. Receptor 6 afforded similar results to the
acyclic receptor 3. The better catalytic activity of receptors 7u and
7l is logical because sulfoxides are better hydrogen-bond acceptors
Fig. 3 1H NMR spectra of 7u and 7l receptor equilibrium mixtures as
lactam 1 is added to the benzene solution. Proton H-10 is compared.
Fig. 4 Optimized geometry (ONIOM B3LYP/3-21G**::PM3MM) of
the model of receptor 7l establishing intramolecular H-bonds between the
NH groups and the sulfoxide oxygen atom.
Fig. 2 Structures of the catalysts studied in this work.
1764 | Org. Biomol. Chem., 2010, 8, 1763–1768
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
intermolecular complexes is not relevant, so the only interaction is
the intermolecular H-bonds in the l form. The additional stability
of these H-bonds shifts the position of the equilibrium to this
diastereoisomer.
resembles a possible transition state for the reaction of lactam
1 and pyrrolidine. Considering the good catalytic activity of the
receptor 7u, this structural similarity might involve an H-bond
interaction between the hydroxyl group in the urea and the sul-
foxide in the catalysts. Additionally, this compound was obtained
from asparagine (see ESI†), and therefore can readily be prepared
enantiomerically pure. Competitive titration in chloroform (see
ESI†) revealed that urea 8 was associated with one of the u
sulfoxide stereoisomers 7.14 times more strongly than with the
other u stereoisomer, and more than 264 times more strongly than
with either of the two l stereoisomers.
Under conditions that facilitate the equilibrium, the intramolec-
ular H-bonds favored the 7l form, but when an excess of urea 8
was added, the thermodynamic advantage of the 7l form was
lost since the complex formation broke the intramolecular H-
bonds. Since any of the 7u receptor enantiomers can make stronger
complexes than the 7l receptors, it was indeed expected that the
epimerization equilibrium would be displaced to the u form. When
only 0.5 equivalents of chiral urea 8 were added, the amount of
guest was insufficient to make the complex with the receptor,
and accordingly only one enantiomer of the receptor (the one
involved in the stronger diastereomeric complex) would interact
with the guest under thermodynamic control. Since the formation
of the strongest complex exhausts the guest added, the other
enantiomer would remain in the l form, because in this way
the stabilization of the intramolecular H-bonds can be exploited.
When equilibrium was reached, the racemic mixture of receptor
7l was transformed into a mixture of two diastereoisomers. One
of them was involved in the formation of the strongest complex
with the chiral guest 8 (and therefore corresponded to the u form).
The other was present in the equilibrium in the most stable form
when no guest was present, the l form, since this geometry is
compatible with the intramolecular H-bonds. It is important to
note that this methodology does not correspond either to kinetic
resolution80–82 or to dynamic kinetic resolution,80,81,83–87 since in this
case the resolution was performed under thermodynamic control
(and therefore time-independent) conditions.
The mixture of diastereoisomers obtained by this thermody-
namic control was resolved by column chromatography using silica
gel impregnated with L-tartaric acid (TLC analysis revealed two
spots corresponding to the diastereoisomers, but in the preparative
scale the acid in the stationary phase was needed to prevent further
epimerization, as it freezes the equilibrium for the mixture of
receptors). The complex with the urea was broken, and owing to
the intramolecular H-bonds the l sulfoxide was more easily eluted
than the u form (see ESI†). This procedure afforded two fractions
corresponding to 70% e.e. and 66% e.e. of each enantiomer, but it
could be repeated on the enriched mixtures to obtain a product
with e.e. >95%. An advantage of this procedure is that unlike other
methods based on supramolecular recognition that use differential
elution on TLC plates impregnated with a chiral guest88 it can be
scaled up to several grams of product.
This hypothesis was confirmed after the addition of increasing
amounts of a guest to the receptors, such as the lactam 1 used
as substrate in the reaction. The guests are able to compensate
the effect of the intramolecular H-bonds, since the formation
of the complex competes with the intramolecular interactions.
1
Therefore, the preference for the l epimer disappears and the H
NMR spectrum reveals a 1/1 mixture of u and l forms when
enough guest has been added. Interestingly, under the reaction
conditions, the amount of active u form should have been less than
50%, regardless of which isomer was initially used. This explains
the similar catalytic activity of both receptors and indicates that
the catalytic activity of the active u form can be calculated to be
at least (2385/6.5) ¥ (1/0.05) ꢀ 7300, considering that only 5% of
mol of catalyst is used. Moreover, if the l form is not as effective
catalyzing the reaction and only one half of the catalyst is in the
u form, the real catalytic activity could be as high as 7300 ¥ 2 =
14600.
Receptor 7u (or 7l) is a good candidate for study of its
asymmetric induction, since the chiral sulfoxide should support
proton transfer through a single face of the lactam. Instead
of designing its asymmetric synthesis, we considered that the
epimerization equilibrium between the u and l forms would offer a
possibility to resolve the racemic mixture using a strategy similar to
dynamic combinatorial chemistry, by means of the supramolecular
properties of the receptor and its interaction with a template
analogue to the transition state of the reaction.
Dynamic combinatorial chemistry74–79 is based on the reversible
formation of covalent or non-covalent bonds in the presence of a
template, such that when equilibrium is reached, a prevalence of
the compound(s) that can establish supramolecular interactions
with the template is favored. The driving force that displaces the
equilibrium is the formation of the supramolecular complex with
this template. In the case of receptors 7u and 7l, traces of a base
made the equilibrium possible. This epimerization changes the
geometry of the receptor dramatically, which affects its ability to
interact with the template. Thus, although no additional bonds are
formed, the methodology of dynamic combinatorial chemistry can
be used to select a particular enantiomer of the receptors, provided
that the appropriate chiral template is used.
Based on the above ideas, we designed chiral urea 8 (Scheme 1)
as a good candidate to assist in this resolution. This structure
The absolute configuration of chiral centers was studied in this
l form since intramolecular H-bonds allow easier interpretation
of the circular dichroism spectrum. This spectrum was simulated
with theoretical methods (time dependent-DFT), following the
procedures described in the literature89,90 (see ESI†). After com-
paring the theoretical and experimental CD spectra (Fig. 5), it
was observed that the l isomer obtained as indicated above when
Scheme 1 Chiral resolution of receptor 7 using urea 8.
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 1763–1768 | 1765
©

View Article Online
Conclusions
As in previous studies,8 this work confirms that non basic groups
can assist proton transfer mechanisms if they are able to act as
H-bond acceptors. This was not only confirmed by the increase in
the catalytic activities, but also by the enantioselectivity observed
in the reaction when the chiral catalyst was used. Nevertheless the
chiral enrichment should be improved to consider the synthetic
usefulness of the catalysts, although the confirmation of the
catalytic role of sulfones and sulfoxides might inspire the design
of new catalysts able to improve the e.e. and reaction rates.
In a precedent work,91 we have observed that xanthone receptors
containing amino groups showed kcat/kuncat values up to 104 for
this reaction, but the half-life time was not reduced accordingly
since self aggregation of these receptors precludes the association
of the substrate. With these new receptors, which include groups
different than amines for assisting the proton transfer, the catalytic
activity is not improved significantly. Nevertheless, the increase of
the association constant implies a considerable reduction in the
half-life time of the reaction.
More interestingly, we have employed a new method used for
the chiral resolution of the catalysts that offers an alternative
to kinetic resolution. The method described is based on the
supramolecular interactions of the catalyst with a chiral guest
and on the reversible epimerization of the catalysts, in full
agreement with the principles and ideas underlying dynamic
combinatorial chemistry. This is not limited to the separation of
catalyst enantiomers, but a similar methodology might be useful
in the resolution of other compounds of interest with at least two
stereogenic centers, provided that: i) an epimerization equilibrium
is possible and ii) that the diastereoisomers are involved in the
formation of supramolecular complexes with a chiral receptor
such that the receptor shows a preference for association with one
of the four possible diastereoisomers. The first condition is similar
to the racemization required in dynamic kinetic resolution, and
important advances have been obtained through the use of metal
catalysts92–98 or enzymes.93,96 The second condition replaces the
need for a selective chiral catalyst that will preferentially react with
one enantiomer.99–101 Considering the advances in supramolecular
chemistry and chiral recognition, fulfilling this second condition
might be possible in cases where no chiral catalyst exists, offering
a new possibility for resolution.
Fig. 5 Comparison between the experimental (De (265 nm)= -25.36;
De (215 nm)= +29.26) and TD-DFT simulated CD spectra (in red:
B3LYP/3-21G**; in green: MPW1PW91/3-21G**).
L-asparagine derived urea was used had an R absolute config-
uration on the sulfur and R on the carbon atom. Thus, the u
stereoisomer with the strongest association constant with urea 8
derived from L-asparagine has an absolute configuration of S on
the sulfur and R on the carbon atom.
The asymmetric induction obtained with this receptor was in-
vestigated under the same conditions as in previous experiments,7–9
but the nucleophile concentration was reduced to 0.80 M. To
determine the degree of chiral assistance, a xanthone-based chiral
shift reagent was used, which splits a pyrrolidine 1H NMR
signals of enantiomeric amino lactams. Integration of these signals
afforded a 5 : 1 enantiomeric ratio at the half-life time. The R
absolute configuration of the major product was established by
circular dichroism.8 CPK models and modelling studies confirmed
that this was indeed the expected configuration when the sulfoxide
oxygen was involved in the proton transfer. In the case of
modelling studies, two diastereomeric transition state structures
were obtained, the one yielding the R compound being 6.14 kcal
mol-1 more stable (Fig. 6). The energy difference obtained is large
compared with the observed enantioselectivities, but it should be
noted that the size of the system precludes to use of a higher level
of theory, which would allow more reliable results to be obtained.
Acknowledgements
This research was supported by a Marie Curie European Reinte-
gration Grant (ERG) within the 7th Framework Program (FP7-
PEPLE-ERG-2008-239244) and by a grant from the Spanish
Direccio´n General de Investigacio´n, Ciencia y Tecnolog´ıa (CTQ-
2005-074007BQU). A. F. A. is grateful for his fellowship to the
Ministerio de Educacio´n y Ciencia (MEC). We also thank Anna
Lithgow for recording the 400-MHz spectra.
Notes and references
1 M. Movassaghi and E. N. Jacobsen, Science, 2002, 298, 1904–1905.
Fig.
6
Optimized transition state structures (ONIOM B3LYP/
2 P. I. Dalko and L. Moisan, Angew. Chem., Int. Ed., 2004, 43, 5138–
3-21G**:PM3MM, further details in ESI†) leading to R (left) and S (right)
enantiomers for the addition of pyrrolidine to lactam 1 catalyzed by (-)
receptor 7l (model).
5175.
3 A. Dondoni and A. Massi, Angew. Chem., Int. Ed., 2008, 47, 4638–
4660.
1766 | Org. Biomol. Chem., 2010, 8, 1763–1768
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
4 S. Mukherjee, J. W. Yang, S. Hoffmann and B. List, Chem. Rev.
(Washington, DC, U. S.), 2007, 107, 5471–5569.
5 B. List, Chem. Commun., 2006, 819–824.
6 P. I. Dalko and L. Moisan, Angew. Chem., Int. Ed., 2001, 40, 3726–
3748.
7 L. Simo´n, F. M. Mun˜iz, S. Sa´ez, C. Raposo, F. Sanz and J. R. Mora´n,
Helv. Chim. Acta, 2005, 88, 1682–1701.
8 L. Simo´n, F. M. Mun˜iz, S. Sa´ez, C. Raposo and J. R. Mora´n,
Eur. J. Org. Chem., 2008, 2397–2403.
46 J. D. Robertus, J. Kraut, R. A. Alden and J. J. Birktoft, Biochemistry,
1972, 11, 4293–4303.
47 M. Marquart, J. Walter, J. Deisenhofer, W. Bode and R. Huber, Acta
Crystallogr., Sect. B: Struct. Sci., 1983, 39, 480–490.
48 J. Kraut, Annu. Rev. Biochem., 1977, 46, 331–358.
49 P. Bryan, M. W. Pantoliano, S. G. Quill, H.-Y. Hsiao and T. Poulos,
Proc. Natl. Acad. Sci. U. S. A., 1986, 83, 3743–3745.
50 K. H. G. Verschueren, F. Selje´e, H. J. Rozeboom, K. H. Kalk and
B. W. Dijkstra, Nature, 1993, 363, 693–698.
9 L. Simo´n, F. M. Mun˜iz, S. Sa´ez, C. Raposo and J. R. Mora´n,
Eur. J. Org. Chem., 2007, 4821–4830.
10 M. S. Taylor and E. N. Jacobsen, Angew. Chem., Int. Ed., 2006, 45,
1520–1543.
51 W. W. Cleland and M. M. Kreevoy, Science, 1994, 264, 1887–1890.
52 P. A. Frey, S. A. Whitt and J. B. Tobin, Science, 1994, 264, 1927–
1930.
53 P. Grochulski, F. Bouthillier, R. J. Kazlauskas, A. N. Serreqi, J. D.
Schrag, E. Ziomek and M. Cygler, Biochemistry, 1994, 33, 3494–3500.
54 M. Harel, D. M. Quinn, H. K. Nair, I. Silman and J. L. Sussman,
J. Am. Chem. Soc., 1996, 118, 2340–2346.
11 A. G. Doyle and E. N. Jacobsen, Chem. Rev. (Washington, DC, U. S.),
2007, 107, 5713–5743.
12 M. T. Robak, M. Trincado and J. A. Ellman, J. Am. Chem. Soc., 2007,
129, 15110–15111.
55 M. Nardini and B. W. Dijkstra, Curr. Opin. Struct. Biol., 1999, 9,
13 Y.-L. Shi and M. Shi, Adv. Synth. Catal., 2007, 349, 2129–2135.
14 Y. Yamaoka, H. Miyabe and Y. Takemoto, J. Am. Chem. Soc., 2007,
129, 6686–6687.
732–737.
56 B. J. Bahnson, V. E. Anderson and G. A. Petsko, Biochemistry, 2002,
41, 2621–2629.
15 S. J. Zuend and E. N. Jacobsen, J. Am. Chem. Soc., 2007, 129, 15872–
57 J. Pawlak, B. J. Bahnson and V. E. Anderson, Nukleonika (Suppl.1),
2002, 47, 115–155.
15883.
16 Y.-Q. Fang and E. N. Jacobsen, J. Am. Chem. Soc., 2008, 130, 5660–
5661.
58 K. Line, M. N. Isupov and J. A. Littlechild, J. Mol. Biol., 2004, 338,
519–532.
17 G. Gasparini, L. J. Prins and P. Scrimin, Angew. Chem., Int. Ed., 2008,
59 A. L. B. Valina, D. Mazumder-Shivakumar and T. C. Bruice,
Biochemistry, 2004, 43, 15657–15672.
47, 2475–2479.
18 P. Li, Y. Wang, X. Liang and J. Ye, Chem. Commun., 2008, 3302–3304.
19 X. Li, H. Deng, S. Luo and J.-P. Cheng, Eur. J. Org. Chem., 2008,
4350–4356.
60 D. A. Kraut, P. A. Sigala, B. Pybus, C. W. Liu, D. Ringe, G. A. Petsko
and D. Herschlag, PLoS Biol., 2006, 4, e99.
61 L. Simo´n and J. M. Goodman, J. Org,. Chem., 2009, ASAP article.
10.1021/jo901503d.
62 F. M. Mun˜iz, V. A. Montero, A. L. Fuentes de Arriba, L. Simo´n, C.
Raposo and J. R. Mora´n, Tetrahedron Lett., 2008, 49, 5050–5052.
63 P. Y. Bruice and T. C. Bruice, J. Am. Chem. Soc., 1974, 96, 5523–5532.
64 P. Y. Bruice and T. C. Bruice, J. Am. Chem. Soc., 1974, 96, 5533–5542.
65 M. H. Abraham and J. A. Platts, J. Org. Chem., 2001, 66, 3484–3491.
66 O. Lamarche and J. A. Platts, Chem.–Eur. J., 2002, 8, 457–466.
67 J. A. Platts, Phys. Chem. Chem. Phys., 2000, 2, 3115–3120.
68 D. Balcells, G. Ujaque, I. Fernandez, N. Khiar and F. Maseras, J. Org.
Chem., 2006, 71, 6388–6396.
20 J. P. Malerich, K. Hagihara and V. H. Rawal, J. Am. Chem. Soc., 2008,
130, 14416–14417.
21 A. Puglisi, M. Benaglia, R. Annunziata and D. Rossi, Tetrahedron:
Asymmetry, 2008, 19, 2258–2264.
22 C. Rabalakos and W. D. Wulff, J. Am. Chem. Soc., 2008, 130, 13524–
13525.
23 M. Shi and X.-G. Liu, Org. Lett., 2008, 10, 1043–1046.
24 Y. Sohtome, N. Takemura, R. Takagi, Y. Hashimoto and K. Naga-
sawa, Tetrahedron, 2008, 64, 9423–9429.
25 S. Tang, Y. Xu, J. He, Y. He, J. Zheng, X. Pan and X. She, Org. Lett.,
2008, 10, 1855–1858.
69 C. R. Johnson and D. McCants, J. Am. Chem. Soc., 1965, 87, 1109–
1114.
70 T. Vreven and K. Morokuma, J. Comput. Chem., 2000, 21, 1419–1432.
71 S. Dapprich, I. Koma´romi, K. S. Byun, K. Morokuma and M. J.
Frisch, J. Mol,. Str., 1999, 461–462.
26 C. Uyeda and E. N. Jacobsen, J. Am. Chem. Soc., 2008, 130, 9228–
9229.
27 B. Vakulya, S. Varga and T. Soo´s, J. Org. Chem., 2008, 73, 3475–3480.
28 C. Wang, Z. Zhou and C. Tang, Org. Lett., 2008, 10, 1707–1710.
29 C.-J. Wang, X.-Q. Dong, Z.-H. Zhang, Z.-Y. Xue and H.-L. Teng,
J. Am. Chem. Soc., 2008, 130, 8606–8607.
30 W.-M. Zhou, H. Liu and D.-M. Du, Org. Lett., 2008, 10, 2817–2820.
31 X. Company, G. Valero, L. Crovetto, A. Moyano and R. Rios, Chem.–
Eur. J., 2009, 15, 6564–6568.
32 O. Coulembier, D. P. Sanders, A. Nelson, A. N. Hollenbeck, H. W.
Horn, J. E. Rice, M. Fujiwara, P. Dubois and J. Hedrick, Angew.
Chem., Int. Ed., 2009, 48, 5170–5173.
33 X.-Q. Dong, H.-L. Teng and C.-J. Wang, Org. Lett., 2009, 11, 1265–
1268.
72 M. Svensson, S. Humbel and K. Morokuma, J. Chem. Phys., 1996,
105, 3654–3661.
73 R. A. Gaussian 98W, M. J. Frisch and et al., Gaussian, Inc., Pittsburgh
PA, 1998.
74 S. Otto, R. L. E. Furlan and J. K. M. Sanders, Curr. Opin. Chem.
Biol., 2002, 6, 321–327.
75 S. J. Rowan, S. J. Cantrill, G. R. L. Cousins, J. K. M. Sanders and J. F.
Stoddart, Angew. Chem., Int. Ed., 2002, 41, 898–952.
76 P. T. Corbett, J. Leclaire, L. Vial, K. R. West, J.-L. Wietor, J. K. M.
Sanders and S. Otto, Chem. Rev. (Washington, DC, U. S.), 2006, 106,
3652–3711.
34 X. Han, J. Kwiatkowski, F. Xue, K.-W. Huang and Y. Lu, Angew.
Chem., 2009, 121, 7740–7743.
77 C. D. Meyer, C. S. Joiner and J. F. Stoddart, Chem. Soc. Rev., 2007,
35 C. G. Kokotos and G. Kokotos, Adv. Synth. Catal., 2009, 351, 1355–
1362.
36, 1705–1723.
78 R. Vilar, Angew. Chem., Int. Ed., 2003, 42, 1460–1477.
79 M. Kruppa and B. Ko¨nig, Chem. Rev. (Washington, DC, U. S.), 2006,
106, 3520–3560.
36 D. Leow and C.-H. Tan, Chem.–Asian J., 2009, 4, 488–507.
37 P. G. McGarraugh and S. E. Brenner, Tetrahedron, 2009, 65, 449–
455.
80 J. M. Keith, J. F. Larrow and E. N. Jacobsen, Adv. Synth. Catal., 2001,
343, 5–26.
81 D. E. J. E. Robinson and S. D. Bull, Tetrahedron: Asymmetry, 2003,
14, 1407–1446.
82 J. R. Dehli and V. Gotor, Chem. Soc. Rev., 2002, 31, 365–370.
83 F. F. Huerta, A. B. E. Minidis and J. E. Backvall, Chem. Soc. Rev.,
2001, 30, 321–331.
84 H. Pellissier, Tetrahedron, 2003, 59, 8291–8327.
85 H. Pellissier, Tetrahedron, 2008, 64, 1563–1601.
86 R. S. Ward, Tetrahedron: Asymmetry, 1995, 6, 1475–1490.
87 E. Vedejs and M. Jure, Angew. Chem., Int. Ed., 2005, 44, 3974–4001.
88 A. Tejeda, A. I. Oliva, L. Simo´n, M. Grande, M. Cruz Caballero and
J. R. Mora´n, Tetrahedron Lett., 2000, 41, 4563–4566.
89 A. Brown, C. M. Kemp and S. F. Mason, J. Chem. Soc. A, 1971,
751–755.
38 C. R. Jones, G. D. Pantoc¸, A. J. Morrison and M. D. Smith, Angew.
Chem., Int. Ed., 2009, 48, 7391–7394.
39 M. P. Sibi and K. Itoh, J. Am. Chem. Soc., 2007, 129, 8064–8065.
40 N. J. A. Martin, L. Ozores and B. List, J. Am. Chem. Soc., 2007, 129,
8976–8977.
41 D. R. Li, A. Murugan and J. R. Falck, J. Am. Chem. Soc., 2008, 130,
46–48.
42 K. H. Jensen and M. S. Sigman, Angew. Chem., Int. Ed., 2007, 46,
4748–4750.
43 R. P. Herrera, D. Monge, E. Mart´ın-Zamora, R. Ferna´ndez and J. M.
Lassaletta, Org. Lett., 2007, 9, 3303–3306.
44 D. Leow, S. Lin, S. K. Chittimalla, X. Fu and C.-H. Tan, Angew.
Chem., 2008, 120, 5723–5727.
45 R. Henderson, J. Mol. Biol., 1970, 54, 341–354.
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 1763–1768 | 1767
©

View Article Online
90 J. Autschbach, T. Ziegler, S. J. A. van Gisbergen and E. J. Baerends,
J. Chem. Phys., 2002, 116, 6930–6940.
91 L. Simo´n, F. M. Mun˜iz, S. Sa´ez, C. Raposo and J. R. Mora´n,
ARKIVOC, 2007, 47–64.
95 O. Pa`mies and J.-E. Ba¨ckvall, Trends Biotechnol., 2004, 22, 130–135.
96 N. J. Turner, Curr. Opin. Chem. Biol., 2004, 8, 114–119.
97 B. Mart´ın-Matute and J.-E. Ba¨ckvall, Curr. Opin. Chem. Biol., 2007,
11, 226–232.
92 R. Stu¨rmer, Angew. Chem., Int. Ed. Engl., 1997, 36, 1173–1174.
93 M. T. El Gihani and J. M. J. Williams, Curr. Opin. Chem. Biol., 1999,
3, 11–15.
94 M.-J. Kim, Y. Ahn and J. Park, Curr. Opin. Biotechnol., 2002, 13,
578–587.
98 Y. Ahn, S.-B. Ko, M.-J. Kim and J. Park, Coord. Chem. Rev., 2008,
252, 647–658.
99 J.-M. Lehn, Angew. Chem., Int. Ed. Engl., 1990, 29, 1304–1319.
100 I. Stibor and P. Zlatukova´, Top Curr Chem, 2005, 255, 31–63.
101 C. Caltagirone and P. A. Gale, Chem. Soc. Rev., 2009, 38, 520–563.
1768 | Org. Biomol. Chem., 2010, 8, 1763–1768
This journal is
The Royal Society of Chemistry 2010
©