Modular Urea-Based Catalytic Platforms Bearing Flexible Pyridylmethylamine and Rigid Pyridyl-Imidazolidine Fragments

Article abstract of DOI:10.1002/ejoc.201601271

The selective and concise synthesis of new urea-based catalytic platforms is described. Each platform incorporates a urea or thiourea motif with a pyridylmethylamine or pyridyl-imidazolidine fragment. These modular catalytic platforms efficiently promote

Full text of DOI:10.1002/ejoc.201601271

A Journal of
Accepted Article
Title: Modular urea-based catalytic platforms bearing flexible
pyridylmethylamine and rigid pyridyl-imidazolidine fragments
Authors: Damien Prim, Olivier Colin, Hamza Boufroura, Christine
Thomassigny, Serge Perato, Anne Gaucher, and Jerome
Marrot
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of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
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to this Accepted Article as a result of editing. Readers should obtain
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201601271
Link to VoR: http://dx.doi.org/10.1002/ejoc.201601271
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European Journal of Organic Chemistry
10.1002/ejoc.201601271
FULL PAPER
Modular urea-based catalytic platforms bearing flexible
pyridylmethylamine and rigid pyridyl-imidazolidine fragments
Olivier Colin, Hamza Boufroura, Christine Thomassigny, Serge Perato, Anne Gaucher, Jérôme Marrot,
[a]
and Damien Prim *
Abstract: The selective and concise synthesis of new urea-based
catalytic platforms is described. Each platform associates an urea or
thiourea motif to a pyridylmethylamine or a pyridyl-imidazolidine
fragment. These modular catalytic platforms efficiently organo-
promote Michael additions. Moreover, the corresponding Cu
complexes successfully catalyze Henry-type reactions.
diphenylethylenediamine,
binaphtylamine
and
cinchona
derivatives. Such catalytic platforms revealed performant in a
wide range of asymmetric organocatalysed transformations
including (hetero)-Michael additions, Huisgen cycloadditions,
reduction of ketones, alkylation of heterocycles, Horner-
Wadsworth-Emmons, aza-Henry, Mannich or Conia-ene
[
14,15]
reactions and kinetic resolutions for examples.
As part of a research program devoted to the development of
pyridylmethylamine(pma)-based catalytic systems, we found that
the pma fragment was not only able to accommodate various
Introduction
Since its artificial synthesis in 1828 by German chemist Friedrich
[16]
metallic species in metallo-catalysed reactions, but also to act
[1]
Wöhler, urea is an ubiquitous pattern in modern organic
chemistry. The H-bonding properties as well as the unique
templating or organization abilities of urea and their derivatives
have inspired the scientific community towards thriving
developments in various domains. As examples, urea-based
[17]
as a base or a H-bond acceptor in organocatalysis. In the
context of this work, these results prompted us to investigate the
preparation new urea derivatives bearing
a
chiral
diaminocyclohexyl scaffold decorated with an H-bond acceptor
pma unit (family 1). During the course of our study, attempts to
switch from a cyclic to an acyclic chiral scaffold led to the
preparation of a second family of platform comprising the urea
motif associated to a rigid pyridyl-imidazolidine system (family 2).
[
2]
materials have been successfully used as polymerization or
[
3]
[4]
[5]
corrosion
process inhibitors, gel propellants,
antibacterial agents,
gelators,
graphene exfoliation
[
[
6]
8]
[7]
adhesives,
[9]
promoters, nanoparticle stabilization agents, supramolecular
[
10]
[11]
[12]
recognition agents anion sensors or transporters.
As one of these advances, urea-based homogeneous catalysis
is a rapidly expanding area of research. Within this context, H-
bonding properties of urea derivatives and flexibility vs rigidity of
the catalytic platform play a central role in selective activation
processes. The modulation of the strength of H-bonds can be
achieved by several ways including the switch from urea to
thiourea, the modification of the substitution pattern of urea
nitrogen atoms and the installation of specific fluorinated
[13]
fragments at various sites of the platform. The control of chiral
information transfer in urea-promoted catalytic transformations is
mostly obtained from the installation of chiral substituents at
[13]
nitrogen neighbouring positions.
Combination of urea H-bond donor fragments with a chiral
scaffold and secondary or tertiary amines distributed at a single
catalytic platform recently emerged as a pillar in organic
[14]
synthesis.
In the main catalytic platforms developed to date
(
figure 1) urea is associated with cyclohexyldiamine,
[a]
O. Colin, H. Boufroura, C. thomassigny, S. Perato, A. Gaucher, J.
Marrot and D. Prim
Figure 1. Design of new catalytic platforms.
University of Versailles St-Quentin-en-Yvelines, Institut Lavoisier de
Versailles UMR CNRS 8180, 45, avenue des Etats-Unis, 78035
Versailles, France.
Fax: int-33 1 39 25 4452; Tel: int-33 1 39 25 4454;
E-mail: damien.prim@uvsq.fr
In this paper, we describe the preparation of both families of
catalytic platforms 1 and 2 using the same strategy and the
evaluation of their catalytic properties in Michael addition and
nitroaldol reactions.
Supporting information for this article is given via a link at the end of
the document.
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European Journal of Organic Chemistry
10.1002/ejoc.201601271
FULL PAPER
Results and Discussion
unequivocally confirmed, evidencing the joint presence of both
the vicinal pyridylmethylamine fragment and urea motif. We
further took advantage of the one-pot sequence to prepare thio
analogues 1b and 1c in yields ranging from 57 to 63% by using
We first focused on the preparation of platform 1a from ethylene
diamine, pyridylcarboxaldehyde and phenylisocyanate. Our
objective was to avoid the formation of bisimine adduct and
imidazolidine intermediates originated from the condensation of
ethylene diamine and pyridylcarboxaldehyde. Gratifyingly, we
found that pyridylcarboxaldehyde cleanly reacted with 2 eq. of
ethylenediamine at room temperature in the presence of
crushed 4Å molecular sieve without any solvent (scheme 1).
3 2
PhNCS and 3,5-(CF ) -PhNCS respectively instead of
phenylisocyanate.
[
18]
Chiral non racemic cyclohexyldiamine was next successfully
installed at the parent pyridine. Indeed, compounds 1d-1g were
isolated using the same one pot procedure, albeit in modest
[
20]
yields. Attempts to install diphenylethylenediamine instead of
ethylenediamine or cyclohexyldiamine led to a different issue.
Within
5 min., pyridylcarboxaldehyde was fully consumed.
Filtration of the reaction mixture over Celite followed by quick
removal of the excess of ethylenediamine in vacuo and further
addition of PhNCO in AcOEt for an additional 5 min. gave the
imine-urea intermediate. The latter was not isolated and further
Under
the
aforementioned
reaction
conditions,
diphenylethylenediamine cleanly did not afford the expected
platform 1 but urea-pyridine-imidazolidine platform 2 (scheme 2).
It is worthy to note that the presence of the pyridine ring induces
the selective formation of the imidazolidine ring as evidenced by
crude product H NMR study (ESI-1). Neither the bis imine nor
the mono imine adduct could be observed. Further addition of
isocyanate derivatives led to platforms 2a-g in yields ranging
4
reduced through addition of MeOH and NaBH (2eq.) into the
1
[18]
expected platform 1a in an overall 50% yield for three steps.
[
21]
from 65 to 85%.
In this sequence, the addition of NaBH
4
allowed reducing the unreacted residual isocyanates and
revealed essential to avoid the formation of bisurea adducts.
Ph
Ph
(
NH2
2 eq.),
X
.
1
) H N
NHAr
Ph
2
mol sieve 4A
min., r.t.
N
N
5
N
HN
Ph
Ph
X
N
HN
2
) ArNCX (1 eq.)
O
AcOEt, 5 min., r.t.
) NaBH4 (2 eq.)
MeOH, r. t., 20 min.
Ph
a-g
ArHN
N
3
H
2
not observed
1a
Scheme 1. Strategy towards the one-pot preparation of platforms 1.
Our pseudo-sequential one-pot methodology requires one
filtration during the process and selectively afforded 1a in ca. 30
minutes. Single crystals suitable for X-ray analysis were
obtained by slow evaporation of DCM solution of 1a (scheme
Scheme 2. One-pot access to platforms 2.
[
19]
1).
As shown, the molecular structure of 1a has been
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European Journal of Organic Chemistry
10.1002/ejoc.201601271
FULL PAPER
Relative as well as absolute configurations have been
fact, best catalytic compromise was obtained using 0.1 eq. of
platform 1g, 1 eq. of isobutyraldehyde at 85°C in DCE for 28h.
Under condition B, adduct 3 was isolated in 91% yield and 58%
ee (compare entry 3 with entries 1, 2 and 4). As expected the
decrease of platform loading to 0.05 eq. even after prolonged
reaction time showed erosion of both yield and ee (entry 5). In
the case of platform 1d, conditions B were again found superior
to condition A (compare entries 6 and 7) affording the best
results within this series of platforms. Indeed, 1e and 1f were
both less effective under identical reaction conditions.
[22]
unequivocally assigned by X-ray analysis
of the platform 2b
(
scheme 2) and the corresponding Pd complex (ESI-2). X-ray
analysis confirmed the selective installation of urea motives in
full agreement with recent Arai’s observations in the mono N-
[23]
alkylated pyridyl-imidazolidine series.
Our next objective was to evaluate the catalytic properties of
platforms 1 and 2 on two model reactions: the organo-catalysed
Michael addition of isobutyraldehyde to N-phenylmaleimide and
Cu-promoted nitroaldol reaction.
We first started to evaluate platforms 1 and 2 as the catalyst for
Michael addition of isobutyraldehyde to N-phenymaleimide
The further step was to compare the efficiency of ligand 1d and
cyclic analogues 2a-2g. Under the aforementioned conditions,
2a-2g (0.2 eq.) revealed highly selective and Michael adduct 3
was obtained in high ees ranging from 72 to 98% (compare
entries10-16). Decrease of catalytic loading to 0.1 eq. revealed
detrimental to conversion albeit without erosion of selectivity.
(
table 1).
89% yield and 97% ee were obtained using ligand 2f (entry 15),
which represented the best results within the pyridyl imidazoline
series. Interestingly, R and S adducts can be independently
obtained from platforms 2a and 2f to 2b and 2g respectively. In
fact, we have two reliable catalytic platforms: (i) a flexible acyclic
platform 1d, composed by a pyridylmethyl, a cyclohexyldiamine
and a H-bonding donor phenylurea leading to the Michael
adduct in 91% yield and 74% ee for a 0.1 eq. of catalytic loading.
Table 1. Michael addition pormoted by platforms 1 and 2
[
a]
Entry
Platform (eq.)
Conditions
Yield (%)
e.e.(%)
[
c]
1
2
3
4
5
6
7
8
9
1g (0.1)
1g (0.05)
A
A
B
C
D
B
A
B
B
B
B
B
B
B
B
B
72
30
91
74
59
91
72
70
80
49
49
46
50
68
89
56
57 (R)
62 (R)
58 (R)
42 (R)
52 (R)
74 (R)
32 (R)
48 (R)
72 (R)
94 (R)
93 (S)
96 (R)
96 (R)
98 (R)
97 (R)
72 (S)
(
ii) a rigid cyclic platform 2f, composed by a pyridyl-imidazoline
core decorated by a strong H-bonding donor thiourea motif
leading to the Michael adduct in 89% yield and 97% ee for a 0.2
eq. of catalytic loading.
1g (0.1)
Platform 2a-(2R,4S,5S) (0.2 eq.) was next used under
1g (0.2)
conditions
phenylmaleimide
B
(table 1) for the Michael addition of N-
to phenylacetaldehyde and
1g (0.05)
cyclohexylcarboxaldehyde. If adduct 4b could be isolated in 78%
ee under these conditions, 4a could not be obtained even after
prolonged reaction course (96h).
1d (0.1)
1d (0.1)
1e (0.1)
1f (0.1)
10
11
12
13
14
15
16
2a-(2R,4S,5S) (0.2)
2b-(2S,4R,5R) (0.2)
2c (0.2)
Figure
2.
Michael
adducts
using
phenylacetaldehyde
and
2d (0.2)
cyclohexylcarboxaldehyde as substrates.
2e (0.2)
2f-(2S,4R,5R) (0.2)
2g-(2R,4S,5S) (0.2)
We next focused on metal-catalysed transformations, to
evidence that the present platforms are not only able to organo-
promoted but also metal-promoted reactions. In this context, Cu-
promoted nitroaldol reaction is a benchmarck reaction of current
[
a] Condition A : DCM, 40°C, 72h. Condition B : DCE, 85°C, 28h. Condition C :
[24]
interest.
Taking into account the aforementioned catalytic
DCE, 85°C, 15h. Condition D: DCE, 85°C, 72h.
results, platforms 1d and 2f were first tested (Table 2). To this
end, Cu salt and the ligand were mixed for 24h in order to
generate the corresponding Cu complexes prior to the addition
of nitroaldol reagents. The formation of adduct 4, was strongly
depending on the nature of the Cu salt. Indeed, reactants
1
g, combining a 3,5-bis(trifluoromethyl)phenyl thiourea group
and a cyclohexyldiamine chiral unit, was chosen as the model
platform to set best conditions to promote Michael addition. In
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European Journal of Organic Chemistry
10.1002/ejoc.201601271
FULL PAPER
remained unchanged by using a combination of ligand 2f- Conclusions
(
2S,4R,5R) with CuCl
2
(entry 1). In contrast, switch of the Cu
resulted in the formation of the expected
source to Cu(OAc)
2
The preparation of two new families of urea-based catalytic
platforms has been described. Pyridylmethylamine fragments
completed the urea and thiourea core of the acyclic flexible
familly 1. We were also able to prepare (thio)urea decorated by
rigid pyridyl-imidazolidines motives as well. Both families can be
easily obtained through one pot sequences within minutes.
In a second part of our paper, we have shown that catalytic
nitro adduct in fair 40% yield and 44% ee (entry 2). As shown in
entries 3-5, no conversion was observed when the control
reaction was realized without the catalytic system, without the
ligand or the copper salt clearly indicating that the Cu(OAc) -
2
ligand combination is mandatory to catalyze the Henry reaction.
Attempts to improve both yields and selectivities using ligands
1
(
d or even 1g were next realized but led to disappointing results
entries 6, 7) such as 7 and 15% yields of the corresponding
nitroaldol adduct respectively. The use of Et N as an additive to
Cu(OAc) -1g catalytic system led to an impressive increase of
platforms designed from a pyridylmethylamine or pyridyl-
imidazolidine core in association with urea fragments are able to
independently promote both Michael-type addition and nitroaldol
reaction under organo- and metallo-assisted conditions
respectively. Micheal-type adducts were obtained in high yields
and ee’s up to 91 and 98% respectively. In combination with Cu
salt, pyridyl-imidazolidine-Cu complexes successfully catalyzed
Henry-type additions.
3
2
yield to 80% but a poor 15% ee (entry 8). A clear improvement
was observed when pyridyl-imidazoline 2e was used leading to
54% yield and 44% ee (entry 9) by comparison with analogue 2f.
Tridentate (O,N,N) 2c based on a quinoline core afforded
modest yields and ee (24 and 44% respectively). Finally, 2a
incorporating an urea motive voided of CF
the best compromise, leading to 60% yield and 61% ee (entry
1). As already observed by us, the use of Et N as an additive
was shown beneficial to the yield but detrimental to the ee (entry
2).
3
groups, represented
Experimental Section
1
3
General remarks:
1
Solvents and reagents were purchased and used without further
purification except for DCM who was freshly distilled from calcium
hydride and stored under Ar. Reaction progress was carried out using
silica gel 60 F245 precoated aluminum plates (0.25 mm), which were
visualized by UV fluorescence quenching or vanillin staining. Silica gel 60
1
(
40-63 μm) was used for flash chromatography. H NMR spectra were
recorded at 300 MHz and 298 K, referenced to TMS signal and were
6
calibrated using residual CHCl
3
(δ = 7.26 ppm), DMSO-d (δ = 2.50 ppm)
19
or MeOD (δ = 3.31 ppm). F NMR spectra were recorded at 300 MHz
and 298 K, and were calibrated using CFCl (δ = 0.00 ppm). C NMR
3
Table 2. Cu-promoted Nitroaldol reaction
13
spectra were recorded at 75 MHz and 298 K, and were calibrated using
Entry
Platform
Cu(II)/additive
Yield
e.e.(R,%)
6
[
c]
CDCl3 (δ = 77.16 ppm) DMSO-d (δ = 39.52 ppm) or MeOD (δ = 49.00
(%)
1
ppm). H NMR spectroscopic data are reported as follow: chemical shift δ
[
ppm] (multiplicity, coupling constant [Hz], integration). Multiplicities are
1
2
3
4
5
6
7
8
9
2f-(2S,4R,5R)
CuCl
2
0
reported as follow: s = singlet, d = doublet, t = triplet, q = quadruplet, sext
= sextuplet, hept = heptuplet, dd = doublet of doublet, td = triplet of
doublet, tt = triplet of triplet, ddd = doublet of doublet of doublet, m =
multiplet. C NMR spectroscopic data are reported in terms of chemical
shifts δ [ppm] and when it was necessary, multiplicity and coupling
constant [Hz]. IR spectra are reported in wavenumbers (cm ). High-
resolution mass spectra (HRMS) were obtained with a QTOF instrument
with an electrospray ionization source (ESI ), using enkephaline leucine
as internal calibrant. UPLC/ESI analyses were performed on a QTOF
instrument with ESI detector and the achiral stationary-phase UPLC C18
2f-(2S,4R,5R)
Cu(OAc)
2
40
0
44
13
-
-
-1
2f-(2S,4R,5R)
-
0
-
Cu(OAc)
Cu(OAc)
Cu(OAc)
2
2
2
0
+
+
[
[
a]
a]
1d
7
+
.
The eluent is: solvent A - H
HCOOH, A/B 95/5 during 0.5 min then gradient A/B 95/5 to 0/100 during
2
O + 0.1 % HCOOH, solvent B - ACN + 0.1 %
1g
15
80
54
25
60
87
-1
4
.5 min, 0.450 mL.min . Optical rotations were measured by using
sodium D radiation (589 nm) or mercury radiation (578 nm) at 25 °C and
are reported as follow [α] (c in g/100 mL, solvent). HPLC analyses were
1g
2e
Cu(OAc)
2
/ Et
3
N
15
44
24
61
23
λ
Cu(OAc)
Cu(OAc)
Cu(OAc)
2
2
2
performed with a UV detector and a chiral stationary-phase column and
reported as follow (column, solvent, flow, temperature, λ UV detector).
10
11
12
2e
2a-(2S,4R,5R)
2a-(2S,4R,5R)
General procedure for the preparation of platforms 1 and 2. The
-1
diamine (1 equiv., 0.3 mol.L ) was dissolved in AcOEt in a round bottom
flask with molecular sieves 4 Å crush. The aldehyde (1 equiv.) was
added, and the reaction mixture was stirred at room temperature for 5
minutes. Further aromatic(thio)isocyanate (1 equiv.) was added. The
reaction mixture was stirred at room temperature for 5 minutes, then was
2 3
Cu(OAc) / Et N
[
a] e.e were not determined.
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European Journal of Organic Chemistry
10.1002/ejoc.201601271
FULL PAPER
-
1
transferred to a NaBH
4
/MeOH suspension (2 equiv., 0,2 mol.L ). The
1-phenyl-3-((1R,2R)-2-((pyridin-2-ylmethyl)amino)cyclohexyl)urea 1d.
Following general procedure for the preparation of platforms, the
reaction mixture was stirred at room temperature for 20 minutes, and
then was filtered through a pad of Celite, and the solvent was removed in
vacuo. The residue was purified by flash chromatography
compound 1d was obtained as a yellow oil with a yield of 45 %. R
f
= 0.27
(30 % in water) 100/10/2). H NMR (300 MHz, CDCl ) δ
= 8.84 (s, 1H), 8.54 (d, J = 4.7 Hz, 1H), 7.62 (td, J = 7.7 and 1.7 Hz, 1H),
.33-7.18 (m, 6H), 7.00 (t, J = 7.1 Hz, 1H), 5.53 (s, 1H), 4.09 (d, J = 14.2
1
(DCM/MeOH/NH
3
3
(DCM/MeOH/NH
3
(30 % in water) 100/0.1/2) to give the expected product.
7
Hz, 1H), 3.96 (d, J = 14.2 Hz, 1H), 3.49 (s, 1H), 2.98 (s, 1H), 2.38 (td, J =
10.3 and 4.0 Hz, 1H), 2.09 (t, J = 11.8 Hz, 2H), 1.73 (t, J = 1.73 Hz, 2H),
General procedure for the Michael addition. Isobutyraldehyde (1
-1
equiv., 0.2 mol.L ), N-phenylmaleimide (1 equiv.) and the catalyst (20
mol %) in DCE were mixed in a screw-capped tube. The mixture was
kept for 17 h at 85 °C, and then the solvent was removed in vacuo. The
residue was purified by flash chromatography (pentane/AcOEt 4/1) to
give the expected product.
13
1
1
1
3
.34-1.11 (m, 4H). C NMR (75 MHz, CDCl
49.1 (CH), 139.7 (C), 136.9 (CH), 128.9 (CH), 122.9 (CH), 122.4 (CH),
22.3 (CH), 119.5 (CH), 62.2 (CH), 56.0 (CH), 52.7 (CH ), 33.2 (CH ),
2.1 (CH ), 24.9 (CH ). IR: 3307, 3051, 2927, 2854, 1650, 1594, 1546,
498, 1438, 1314, 1224, 749, 729, 693, 631 cm . HRMS (ESI ) m/z
3
) δ = 159.1 (C), 157.1 (C),
2
2
2
2
-1
+
1
+
ꢁꢂ
calcd. for C19
H
25
4
N O [M + H] : 325.2028; found: 325.2029. [α]ꢀ -7.4 (c
General procedure for the Henry reaction. To
Cu(OAc) .H O (5 mol %) dissolved in dry DCM (1.10 mol.L ) was the
2 2
a solution of
ꢁꢂ
-2
-1
1.0, CHCl ); [α]ꢂꢃꢄ -7.9 (c 1.0, CHCl ).
3 3
added ligand (5 mol %). The solution was stirred under argon at room
temperature for 17 h. The solvent was removed under reduced pressure.
Next, the residue was dissolved in EtOH (2.5x10 mol.L ). To the
mixture was added nitromethane (40 equiv.) and benzaldehyde (1 equiv.)
under argon. After stirring for 24 h at room temperature, the solvent was
removed in vacuo. The residue was purified by flash chromatography
1
-phenyl-3-((1R,2R)-2-((pyridin-2-ylmethyl)amino)cyclohexyl)-
-2
-1
thiourea 1e. Following general procedure for the preparation of platforms,
the compound 1e was obtained as a yellow oil with a yield of 25 % yield
under multiple rotamers form. R
f
= 0.53 (DCM/MeOH/NH
3
(30 % in water)
1
1
7
2
2
00/10/2). H NMR (300 MHz, CDCl ) δ = 8.52-8.32 (m, 2H), 7.55 (td, J =
.7,and 1.6 Hz, 1H), 7.26-7.16 (m, 6H), 6.51 (s, 1H), 4.03-3.91 (m, 2H),
.61 (s, 1H), 2.38 (s, 1H), 2.03 (d, J = 11.7 Hz, 1H), 1.70 (d, J = 10.6 Hz,
3
H), 1.27-1.13 (m, 4H). C NMR (75 MHz, CDCl ) δ = 183.2 (C), 159.9
3
(pentane/AcOEt 9/1) to give the expected product.
13
1
-phenyl-3-(2-((pyridin-2-ylmethyl)amino)ethyl)urea 1a. Following
general procedure for the preparation of platforms, the compound 1a was
obtained as yellow oil with yield of 50 %. 0.46
DCM/MeOH/NH (30 % in water) 100/10/2). H NMR (300 MHz, CDCl ) δ
8.50 (d, J = 4.8 Hz, 1H), 8.05 (s, 1H), 7.59 (td, J = 7.7 and 1.8 Hz, 1H),
.28-7.13 (m, 6H), 6.97 (t, J = 7.1 Hz, 1H), 6.02 (d, J = 5.0 Hz, 1H), 3.87
(
(
C), 158.9 (C), 157.1 (C), 149.1 (CH), 139.8 (CH), 136.9 (CH), 128.9
CH), 122.9 (CH), 122.3 (CH), 119.4 (CH), 63.9 (CH), 55.7 (CH), 52.3
a
R
f
=
1
(CH
2
), 33.1 (CH
2 2 2
), 31.7 (CH ), 25.0 (CH ). IR: 3208, 3045, 2926, 2854,
(
=
7
3
3
-1
+
1526, 1496, 1317, 1258, 750, 716, 692 cm . HRMS (ESI ) m/z calcd. for
+
ꢁꢂ
C
CHCl
19 25 4
ꢀ
H N S [M + H] : 341.1800; found: 341.1797. [α] +47.5 (c 1.0,
ꢁꢂ
1
3
3 3
); [α]ꢂꢃꢄ +48.6 (c 1.0, CHCl ).
(s, 2H), 3.32 (q, J = 5.4 Hz, 2H), 2.78 (t, J = 5.5 Hz, 2H), 2.28 (s, 1H).
C
3
NMR (75 MHz, CDCl ) δ = 159.1 (C), 156.8 (C), 149.4 (CH), 139.4 (C),
1
-(3,5-bis(trifluoromethyl)phenyl)-3-((1R,2R)-2-((pyridin-2-
1
1
2
39.5 (CH), 136.8 (CH), 129.1 (CH), 122.8 (CH), 122.6 (CH), 122.3 (CH),
20.0 (CH), 54.7 (CH ), 49.4 (CH ), 40.4 (CH ). IR: 3306, 3051, 2929,
839, 1656, 1593, 1547, 1497, 1435, 1309, 1231, 751, 693 cm . HRMS
ylmethyl)amino)cyclohexyl)-urea 1f. Following general procedure for
the preparation of platforms, the compound 1f was obtained as a yellow
2
2
2
-1
+
+
oil with a yield of 50 % under multiple rotamers form. R
f
= 0.39
(30 % in water) 100/10/2). H NMR (300 MHz, CDCl
δ = 8.47 (d, J = 4.1 Hz, 1H), 7.66 (s, 2H), 7.54 (t, J = 7.5 Hz, 1H), 7.31 (s,
(ESI ) m/z calcd. for C15
19 4
H N O [M + H] : 271.1559; found: 271.1562.
1
(DCM/MeOH/NH
3
3
)
1-phenyl-3-(2-((pyridin-2-ylmethyl)amino)ethyl)thiourea 1b. Following
1H), 7.16-7.11 (m, 2H), 4.10 (d, J = 14.0 Hz, 1H), 3.95 (d, J = 14.9 Hz,
general procedure for the preparation of platforms, the compound 1b was
obtained as white needles with yield of 57 %. 0.53
(30 % in water) 100/10/2). Mp = 85- 86 °C. H NMR
) δ = 8.67 (s, 1H), 8.38 (d, J = 4.0 Hz, 1H), 7.53 (t, J =
.7 Hz, 1H), 7.28-7.04 (m, 8H), 3.79 (s, 2H), 3.66 (s, 2H), 2.81 (t, J = 5.2
1H), 3.68-3.28 (m, 2H), 2.52-2.42 (m, 1H), 2.20-1.96 (m, 2H), 1.82-1.60
a
R
f
=
13
1
(m, 2H), 1.39-1.03 (m, 4H). C NMR (75 MHz, CDCl
3
) δ = 157.5 (C),
49.2 (CH), 141.6 (C), 137.0 (CH), 131.7 (q, J = 33 Hz, C), 123.3 (q, J =
73 Hz, C),122.8 (CH), 118.2 (CH), 114.9 (CH), 63.1 (CH), 56.5 (CH),
(
(
DCM/MeOH/NH
300 MHz, CDCl
3
1
2
3
7
19
1
3
55.0 (CH
2
), 33.2 (CH
2 2 2
), 32.0 (CH ), 24.9 (CH ). F NMR (188 MHz,
Hz, 2H), 2.16 (s, 1H). C NMR (75 MHz, CDCl
3
) δ = 180.1 (C), 159.2 (C),
49.2 (CH), 139.7 (C), 136.5 (CH), 129.7 (CH), 126.4 (CH), 125.5 (CH),
24.6 (CH), 122.2 (CH), 54.2 (CH ), 47.4 (CH ), 44.8 (CH ). IR: 3158,
012, 2942, 2844, 1594, 1514, 1424, 1310, 1300, 1240, 1168, 1041, 845,
54, 729, 690, 609 cm . HRMS (ESI ) m/z calcd. for C15H N S [M + H] :
19 4
87.1330; found: 287.1336.
CDCl
386, 1274, 1169, 1122, 1027, 999, 879, 755, 730, 702, 681 cm . HRMS
3 3
/CHF ) δ = -63.44. IR: 3296, 2934, 2859, 1663, 1560, 1473, 1436,
1
1
3
7
2
-1
1
2
2
2
+
+
(ESI ) m/z calcd. for C21
H
23
F
6
ꢁꢂ
N
4
O [M + H] : 461.1776; found: 461.1776.
ꢁ
ꢂ
-
1
+
+
[α]
ꢀ
+7.9 (c 1.0, CHCl
3
); [α]ꢂꢃꢄ +7.1 (c 1.0, CHCl ).
3
1-(3,5-bis(trifluoromethyl)phenyl)-3-((1R,2R)-2-((pyridin-2-
ylmethyl)amino)cyclohexyl)-thiourea 1g. Following general procedure
for the preparation of platforms, the compound 1g was obtained as a
1
-(3,5-bis(trifluoromethyl)phenyl)-3-(2-((pyridin-2-ylmethyl)amino)-
ethyl)thiourea 1c. Following general procedure for the preparation of
platforms, the compound 1c was obtained as a brown oil with a yield of
white powder with a yield of 42 % under multiple rotamers form. R
f
= 0.79
(30 % in water) 100/10/2). Mp = 64.2 °C. H NMR (300
) δ = 8.55 (s, 1H), 7.68 (s, 2H), 7.58 (t, J = 7.6 Hz, 1H), 7.44
s, 1H), 7.21-7.15 (m, 2H), 6.40 (s, 1H), 4.12-4.01 (m, 2H), 3.50 (s, 1H),
1
(
DCM/MeOH/NH
MHz, CDCl
3
6
3 % under multiple rotamers form. R
f
= 0.49 (DCM/MeOH/NH
water) 100/10/2). H NMR (300 MHz, CDCl ) δ = 8.40 (m, 2H), 8.12-7.74
m, 3H), 7.58 (t, J = 7.6 Hz, 1H), 7.45 (s, 1H), 7.13 (d, J = 7.4 Hz, 2H),
3
(30 % in
1
3
3
(
(
1
3
13
2.42 (s, 1H), 2.10 (s, 2H), 1.80 (s, 2H), 1.37-1.22 (m, 4H). C NMR (75
MHz, CDCl ) δ = 183.3 (C), 156.9 (C), 149.9 (CH), 137.0 (CH), 131.3 (q,
J = 35 Hz, C), 123.0 (CH), 123.1 (q, J = 272 Hz, C), 122.6 (CH), 122.4
(CH), 121.4 (C), 64.7 (CH), 62.6 (CH), 54.4 (CH ), 32.6 (CH ), 24.9 (CH ),
) δ = -63.32. IR: 3219, 3013,
2933, 2858, 1594, 1542, 1473, 1383, 1274, 1169, 1122, 881, 755, 730,
3
.93 (s, 2H), 3.82 (m, 1H), 3.41 (m, 1H), 2.97 (s, 2H). C NMR (75 MHz,
) δ = 182.9 (C), 181.2 (C), 157.5 (C),156.5 (C),149.3 (CH), 141.8
C),140.4 (C),136.9 (CH), 131.4 (q, J = 34 Hz, C), 123.1 (q, J = 273 Hz,
3
CDCl
(
3
19
2
2
2
C), 54.1 (CH
CDCl /CHF ) δ = -63.42. IR: 3236, 3045, 2929, 2847, 1594, 1544, 1472,
381, 1273, 1168, 1121, 1106, 882, 847, 755, 727, 699, 680 cm . HRMS
2 2 2 2
), 51.0 (CH ), 48.0 (CH ), 45.8 (CH ). F NMR (188 MHz,
19
2
2 3 3
4.7 (CH ). F NMR (188 MHz, CDCl /CHF
3
3
-1
1
-
1
+
+
+
+
700, 680, 645 cm . HRMS (ESI ) m/z calcd. for C21
H
23
F
6
ꢁꢂ
N
4
S [M + H] :
17 6 4
(ESI ) m/z calcd. for C17H F N S [M + H] : 423.1078; found: 423.1082.
ꢂ
4
77.1548; found: 477.1552; [α]ꢁ +31.8 (c 1.0, CHCl
3
); [α] +32.2 (c 1.0,
ꢀ
ꢂꢃꢄ
3
CHCl ).
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201601271
FULL PAPER
(
2R,4S,5S)-N’,4,5-triphenyl-2-(pyridin-2-yl)imidazolidine-1-
155.5 (C), 149.6 (CH), 139.9 (C), 139.4 (C), 138.8 (CH), 138.1 (C), 137.3
(C), 129.0 (CH), 128.9 (CH), 128.5 (CH), 127.9 (CH), 127.4 (CH), 126.9
(CH), 124.2 (CH), 122.7 (CH), 121.6 (CH), 121.1 (CH), 119.3 (CH), 76.9
(CH), 70.9 (CH), 69.8 (CH). IR: 3288, 3240, 3056, 3029, 2892, 1665,
1596, 1581, 1536, 1498, 1442, 1428, 1318, 1245, 1146, 1072, 992, 903,
carboxamide 2a-(2R,4S,5S). Following general procedure for the
preparation of platforms, the compound 2a-(2R,4S,5S) was obtained as a
1
white powder with a yield of 77 %. R
NMR (300 MHz, CDCl
7
3
8
f
= 0.75 (AcOEt). Mp = 103 °C. H
3
) δ = 9.83 (s, 1H), 8.74 (d, J = 4.8 Hz, 1H), 7.90-
.85 (m, 2H), 7.39-7.32 (m, 8H), 7.25 (t, J = 7.6 Hz, 2H), 7.19-7.13 (m,
H), 7.02-6.93 (m, 3H), 6.22 (s, 1H), 5.07 (d, J = 8.6 Hz, 1H), 4.38 (d, J =
-1
+
748, 695, 632, 618, 554, 532, 506 cm . HRMS (ESI ) m/z calcd. for
+
32 28 5
C H N O [M + H] : 498.2294; found: 498.2291.
13
3
.6 Hz, 1H), 3.30 (s, 1H). C NMR (75 MHz, CDCl ) δ = 160.7 (C), 155.7
(C), 149.0 (CH), 140.1 (C), 139.9 (C), 137.9 (CH), 137.9 (C), 128.9 (CH),
(2S,4R,5R)-N’-(3,5-bis(trifluoromethyl)phenyl)-4,5-diphenyl-2-
1
1
3
1
28.7 (CH), 128.5 (CH), 127.6 (CH), 127.4 (CH), 126.8 (CH), 123.3 (CH),
22.4 (CH), 120.8 (CH), 119.1 (CH), 76.8 (CH), 70.7 (CH), 69.7 (CH). IR:
294, 3059, 3021, 2898, 1666, 1593, 1553, 1498, 1444, 1321, 1254,
(
pyridin-2-yl)imidazolidine-1-carboxamide 2e. Following general
procedure for the preparation of platforms, the compound 2e was
obtained as a white powder with 65 % yield. R
1
f
= 0.44 (AcOEt/pentane
) δ = 11.49 (s, 1H), 8.80 (d,
-1
+
135, 1002, 904, 748, 695, 618, 533, 506 cm . HRMS (ESI ) m/z calcd.
1
/4). Mp = 112 °C. H NMR (300 MHz, CDCl
3
+
for C27
H
25
N
4
O [M + H] : 421.2028; found: 421.2022. [α]
).
D
-181 (c 0.9,
J = 3.4 Hz, 1H), 7.96-7.89 (m, 4H), 7.45 (s, 2H), 7.38-7.33 (m, 5H), 7.13
CHCl ). [α]578 -186 (c 0.9, CHCl
3
3
(d, J = 3.0 Hz, 3H), 6.86 (s, 2H), 6.24 (s, 1H), 5.11 (d, J = 9.0 Hz, 1H),
13
4
3
.32 (d, J = 8.4 Hz, 1H), 3.22 (s, 1H). C NMR (75 MHz, CDCl ) δ =
(2S,4R,5R)-N’,4,5-triphenyl-2-(pyridin-2-yl)imidazolidine-1-
160.4 (C), 155.4 (C), 149.0 (CH), 141.7 (C), 139.7 (C), 138.5 (CH), 137.1
carboxamide 2b-(2S,4R,5R). Following general procedure for the
(C), 132.1 (q, J = 33 Hz, C), 129.1 (CH), 128.8 (CH), 128.7 (CH), 127.6
preparation of platforms, the compound 2b-(2S,4R,5R) was obtained as
(CH), 127.4 (CH), 126.4 (CH), 123.7 (CH), 123.5 (q, J = 271 Hz, C),
1
19
a white powder with a yield of 85 %. R
NMR (300 MHz, CDCl
f
= 0.75 (AcOEt). Mp = 103 °C. H
120.3 (CH), 118.9 (CH), 115.3 (CH), 76.9 (CH), 70.8 (CH), 69.6 (CH).
NMR (188 MHz, CDCl /CHF
1676, 1588, 1473, 1447, 1337, 1318, 1275, 1170, 1124, 946, 879, 843,
F
3
) δ = 9.94 (s, 1H), 8.75 (d, J = 4.6 Hz, 1H), 7.90-
.85 (m, 2H), 7.44-7.33 (m, 8H), 7.25 (t, J = 6.1 Hz, 2H), 7.17-7.13 (m,
H), 7.00-6.97 (m, 3H), 6.21 (s, 1H), 5.07 (d, J = 8.7 Hz, 1H), 4.38 (d, J =
3
3
) δ = -63.45. IR: 3304, 3064, 3032, 2905,
7
3
8
1
1
7
-
1
+
754, 697, 681, 619 cm . HRMS (ESI ) m/z calcd. for C29
H
23
F
6
N
4
O [M +
1
6
+
.4 Hz, 1H), 3.31 (s, 1H). H NMR (300 MHz, DMSO-d ) δ = 10.67 (s,
H), 8.88 (d, J = 4.5 Hz, 1H), 8.00 (t, J = 7.7 Hz, 1H), 7.89 (d, J = 7.8 Hz,
H), 7.52-7.48 (m, 3H), 7.40-7.36 (m, 5H), 7.30 (t, J = 7.6 Hz, 2H), 7.12-
.10 (m, 3H), 6.95 (t, J = 7.3 Hz, 1H), 6.80-6.83 (m, 2H), 6.16 (d, J = 7.4
H] : 557.1776; found: 557.1774. [α]
1.0, CHCl ).
+161 (c 1.0, CHCl ). [α]578 +169 (c
D 3
3
(2S,4R,5R)-N’-(3,5-bis(trifluoromethyl)phenyl)-4,5-diphenyl-2-
Hz, 1H), 4.91 (d, J = 8.9 Hz, 1H), 4.61 (dd, J = 12.5 and 7.5 Hz, 1H), 4.18
(
pyridin-2-yl)imidazolidine-1-carbothioamide 2f-(2S,4R,5R). Following
13
(dd, J = 12.3 and 9.1 Hz, 1H). C NMR (75 MHz, CDCl
3
) δ = 160.7 (C),
general procedure for the preparation of platforms, the compound 2f-
(
0
1
7
1
155.7 (C), 149.0 (CH), 140.1 (C), 139.9 (C), 137.9 (CH), 137.8 (C), 128.9
2S,4R,5R) was obtained as a white powder with a yield of 84 %. R
f
=
1
(
(
(
CH), 128.7 (CH), 128.5 (CH), 127.6 (CH), 127.4 (CH), 126.7 (CH), 123.3
.50 (AcOEt/pentane 1/4). Mp = 143 °C. H NMR (300 MHz, CDCl
3
) δ =
CH), 122.4 (CH), 120.7 (CH), 119.1 (CH), 76.7 (CH), 70.7 (CH), 69.6
2.91 (s, 1H), 8.82 (d, J = 4.5 Hz, 1H), 8.23 (s, 2H), 7.99-7.94 (m, 2H),
.55 (s, 1H), 7.49 (t, J = 5.8 Hz, 1H), 7.41 (s, 5H), 7.13 (s, 1H), 7.12 (s,
13
6
CH). C NMR (75 MHz, DMSO-d ) δ = 160.8 (C), 154.9 (C), 149.0 (CH),
1
1
1
2
1
41.0 (C), 140.2 (C), 138.3 (CH), 137.9 (C), 128.7 (CH), 128.5 (CH),
28.0 (CH), 127.6 (CH), 126.8 (CH), 126.2 (CH), 123.3 (CH), 121.7 (CH),
20.0 (CH), 118.4 (CH), 76.8 (CH), 70.6 (CH), 69.0 (CH). IR: 3307, 3022,
908, 2844, 2806, 1670, 1622, 1593, 1561, 1498, 1446, 1364, 1330,
H), 7.11 (s, 1H), 6.77 (s, 1H), 6.76 (s, 1H), 6.56 (d, J = 6.7 Hz, 1H), 5.63
13
(d, J = 9.1 Hz, 1H), 4.44 (t, J = 9.6 Hz, 1H), 3.42 (t, J = 7.7 Hz, 1H).
C
NMR (75 MHz, CDCl
3
) δ = 181.1 (C), 159.3 (C), 148.6 (CH), 142.0 (C),
1
1
1
7
3
39.6 (CH), 138.9 (CH), 136.8 (C), 131.4 (q, J = 33 Hz, C), 129.1 (CH),
28.8 (CH), 128.4 (CH), 127.5 (CH), 127.1 (CH), 126.7 (CH), 123.9 (CH),
-1
+
257, 1133, 1005, 911, 748, 690, 556, 507 cm . HRMS (ESI ) m/z calcd.
+
for C27
H
25
N
4
O [M + H] : 421.2028; found: 421.2024. [α]
).
D
+178 (c 1.1,
23.4 (q, J = 275 Hz, C), 122.4 (CH), 121.0 (CH), 116.8 (CH), 80.4 (CH),
19
CHCl ). [α]578 +186 (c 1.1, CHCl
3
3
2.7 (CH), 70.9 (CH). F NMR (188 MHz, CDCl
3 3
/CHF ) δ = -63.41. IR:
270, 3247, 3034, 2914, 1588, 1471, 1456, 1369, 1339, 1273, 1173,
-1
(2S,4R,5R)-2-(8-hydroxyquinolin-2-yl)-N,4,5-triphenylimidazolidine-1-
1128, 1008, 977, 899, 882, 759, 740, 697, 680, 629, 529 cm . HRMS
(ESI ) m/z calcd. for C29
[α] +326 (c 1.0, CHCl ). [α]578 +342 (c 1.0, CHCl
+
+
carboxamide 2c. Following general procedure for the preparation of
H
23
F
6
N
4
S [M + H] : 573.1548; found: 573.1542.
).
platforms,the compound 2c was obtained as a white powder with a yield
D
3
3
1
of 66 %. R
f
= 0.71 (AcOEt). Mp = 92 °C. H NMR (300 MHz, CDCl
3
) δ =
8
6
1
1
.13 (d, J = 8.5 Hz, 1H), 7.86 (d, J = 8.5 Hz, 1H), 7.36-6.37 (m, 20H),
(
(
2R,4S,5S)-N’-(3,5-bis(trifluoromethyl)phenyl)-4,5-diphenyl-2-
pyridin-2-yl)imidazolidine-1-carbothioamide 2g-(2R,4S,5S).
.55 (s, 1H), 6.37 (s, 1H), 4.81 (d, J = 7.4 Hz, 1H), 4.43 (d, J = 7.4 Hz,
13
H). C NMR (75 MHz, CDCl
3
) δ = 158.8 (C), 155.0 (C), 152.1 (C),
Following general procedure for the preparation of platforms, the
compound 2g-(2R,4S,5S) was obtained as a white powder with a yield of
38.7 (C), 138.5 (C), 138.2 (C), 137.7 (CH), 137.4 (C), 129.5 (CH), 128.9
1
(
(
CH), 127.3 (CH), 127.1 (CH), 119.5 (CH), 118.2 (CH), 111.0 (CH), 76.3
CH), 71.2 (CH),70.1 (CH) ppm. IR: 3395, 3291, 3053, 3028, 2892, 1651,
6
5 %. R
CDCl
f
= 0.50 (AcOEt/pentane 1/4). Mp = 149 °C. H NMR (300 MHz,
3
) δ = 12.85 (s, 1H), 8.82 (d, J = 4.7 Hz, 1H), 8.21 (s, 2H), 7.98-7.94
m, 2H), 7.55 (s, 1H), 7.49 (t, J = 5.5 Hz, 1H), 7.40 (s, 5H), 7.12 (s, 1H),
1
6
4
596, 1529, 1498, 1441, 1318, 1237, 1156, 1084, 1028, 896, 837, 748,
(
-1
+
+
91, 533, 502 cm . HRMS (ESI ) m/z calcd. for C31
87.2134; found: 487.2139. [α] +185 (c 1.5, CHCl ). [α]578 +190 (c 1.5,
).
27 4 2
H N O [M + H] :
7
.11 (s, 1H), 7.10 (s, 1H), 6.75 (s, 1H), 6.74 (s, 1H), 6.55 (s, 1H), 5.62 (d,
13
D
3
J = 9.1 Hz, 1H), 4.42 (s, 1H), 3.35 (s, 1H). C NMR (75 MHz, CDCl
1
1
) δ =
81.2 (C), 159.4 (C), 148.7 (CH), 142.1 (C), 139.6 (CH), 138.9 (CH),
36.9 (C), 131.3 (q, J = 33 Hz, C), 129.1 (CH), 128.8 (CH), 128.4 (CH),
3
CHCl
3
(
2S,4R,5R)-2-([2,2'-bipyridin]-6-yl)-N’,4,5-triphenylimidazolidine-1-
127.5 (CH), 127.1 (CH), 126.8 (CH), 124.0 (CH), 123.4 (q, J = 271 Hz, C),
19
carboxamide 2d. Following general procedure for the preparation of
platforms, the compound 2d was obtained as a white powder with a yield
of 65 %. R
122.6 (CH), 121.1 (CH), 116.9 (CH), 80.4 (CH), 72.7 (CH), 71.0 (CH).
NMR (188 MHz, CDCl /CHF ) δ -63.40. IR: 3260, 3061, 3033, 2896,
1591, 1471, 1456, 1367, 1342, 1272, 1169, 1127, 1026, 1007, 977, 882,
F
3
3
1
f
= 0.72 (AcOEt). Mp = 171 °C. H NMR (300 MHz, CDCl
3
) δ =
-
1
+
8
(
.75 (s, 1H), 8.43 (d, J = 7.6 Hz, 1H), 8.34 (d, J = 8.0 Hz, 1H), 8.01-7.91
m, 2H), 7.75 (t, J = 7.8 Hz, 1H), 7.38 (s, 6H), 7.28-7.10 (m, 10H), 6.95 (t,
J = 7.1 Hz, 1H), 6.30 (s, 1H), 5.09 (d, J = 8.2 Hz, 1H), 4.46 (d, J = 8.0 Hz,
845, 758, 740, 697, 680, 641, 552, 529 cm . HRMS (ESI ) m/z calcd. for
+
29 23 6 4
C H F N S [M + H] : 573.1548; found: 573.1550.
13
1
3
H), 3.50 (s, 1H). C NMR (75 MHz, CDCl ) δ = 160.0 (C), 155.8 (C),
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201601271
FULL PAPER
2
-(2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-methylpropanal 3. Following
[13] for recent reviews see a) Z. Ju, S. Yan, D. Yuan, Chem. Mater. 2016,
28, 2000-2010. b) S. H. Kim, S. H. Hong, Org. Lett. 2016, 18, 212-215.
c) L. P. Jay, T. J. Barker, Eur. J. Org. Chem. 2016, 1829-1831. d) S.
Antunes, C. Douat, G. Guichard, Eur. J. Org. Chem. 2016, DOI:
10.1002/ejoc.201600177. d) I. Giannicchi, B. Jouvelet, B. Isare, M.
Linares, A. Dalla Cort, L. Bouteiller, Chem. Commun. 2014, 50, 611-
613. e) X. Huang, S. Xu, Q. Tan, M. Gao, M. Li, B. Xu, Chem. Commun.
2014, 50, 1465-1468. f) D. Tan, V. Strukil, C. Mottillo, T. Friscic, Chem.
Commun. 2014, 50, 5248-5250. g) D. D. M. Nickerson, V. V. Angeles, T.
J. Auvil, S. S. So, A. E. Mattson, Chem. Commun. 2013, 49, 4289-4291.
g) P. W. Siu, Z. J. Brown, O. K. Farha, J. T. Hupp, K. A. Scheidt, Chem.
Commun. 2013, 49, 10920-10922. i) G. S. Kumar, R. A. Kumar, P. S.
Kumar, N. V. Reddy, K. V. Kumar, M. L. Kantam, S. Prabhakar, K. R.
Reddy, Chem. Commun. 2013, 49, 6686-6688. j) K. M. Lippert, K. Hof,
D. Gerbig, D. Ley, H. Hausmann, S. Guenther, P. R. Schreiner , Eur. J.
Org. Chem. 2012, 5919-5927.
Michael addition procedure with isobutyraldehyde, the compound 3 was
1
obtained as a yellow oil. R
MHz, CDCl ) δ = 9.51 (s, 1H), 7.48-7.38 (m, 3H), 7.27 (dd, J = 8.3 and
.7 Hz, 2H), 3.15 (dd, J = 9.4 and 5.3 Hz, 1 H), 2.97 (dd, J = 18.0 and 9.4
f
= 0.15 (AcOEt/pentane 1/4). H NMR (200
3
1
Hz, 1H), 2.61 (dd, J = 18.0 and 5.3 Hz, 1H), 1.32 (s, 3 H), 1.28 (s, 3H).
HPLC (Venusil Chiral OD-H column, heptane/2-propanol 75/25, 0.9
mL.min , 30 °C, 230 nm) t
concordance with the literature.
-1
r r
(S) = 16.8 min, t (R) = 18.1 min. Data were in
[
25]
2-nitro-1-phenylethanol 4. Following Henry reaction procedure, the
1
compound 4 was obtained as a yellow oil. H NMR (200 MHz, CDCl
3
) δ =
.40-7.26 (m, 5H), 5.47 (dd, J = 9.0 and 3.4 Hz, 1H), 4.67-4.45 (m, 2H),
.96 (s, 1H). HPLC (Venusil Chiral OD-H column, heptane/2-propanol
7
2
8
-1
r r
5/15, 1 mL.min , 30 °C, 230 nm) t (S) = 8.2 min, t (R) = 9.2 min. Data
[
24h]
were in concordance with the literature.
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1
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1
1
[
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European Journal of Organic Chemistry
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Entry for the Table of Contents (Please choose one layout)
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FULL PAPER
The selective and concise
synthesis of new urea-
based catalytic platforms is
Urea-based catalytic platforms
Olivier Colin, Hamza Boufroura, Christine
Thomassigny, Serge Perato, Anne Gaucher,
Jérôme Marrot, and Damien Prim*
described.
These
new
catalytic systems efficiently
promote
Michael
catalyze
reactions.
enantioselective
additions and
Henry-type
Page No. – Page No.
Modular urea-based catalytic platforms
bearing flexible pyridylmethylamine and
rigid pyridyl-imidazolidine fragments
*one or two words that highlight the emphasis of the paper or the field of the study
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