Introduction of bulky tert-butyl substituents on the core of N,N′-diaryl N-heterocyclic carbenes through the corresponding vicinal diamines

Article abstract of DOI:10.1016/j.tetlet.2013.06.132

Highly bulky N,N′-diaryl imidazolinium salts substituted by one or two tert-butyl groups on the heterocyclic backbone and the corresponding silver N-heterocyclic carbene complexes are obtained by the addition of tert-butyl magnesium chloride or tert-butyl lithium on symmetrical 1,2-bisimines derived from 2,6-diisopropylaniline, 2,6-diethylaniline and 2,4,6-trimethylaniline.

Full text of DOI:10.1016/j.tetlet.2013.06.132

Tetrahedron Letters 54 (2013) 4793–4795
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Tetrahedron Letters
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Introduction of bulky tert-butyl substituents on the core of
N,N0-diaryl N-heterocyclic carbenes through the corresponding
vicinal diamines
⇑
Ulrich Jacquemard, Phoebe Harpainter, Sylvain Roland
Institut Parisien de Chimie Moléculaire, UMR CNRS 7201, UPMC–Université Paris 6, 4 Place Jussieu, 75252 Paris, France
a r t i c l e i n f o
a b s t r a c t
Highly bulky N,N0-diaryl imidazolinium salts substituted by one or two tert-butyl groups on the hetero-
cyclic backbone and the corresponding silver N-heterocyclic carbene complexes are obtained by the addi-
tion of tert-butyl magnesium chloride or tert-butyl lithium on symmetrical 1,2-bisimines derived from
2,6-diisopropylaniline, 2,6-diethylaniline and 2,4,6-trimethylaniline.
Article history:
Received 23 May 2013
Revised 24 June 2013
Accepted 26 June 2013
Available online 4 July 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Carbene ligands
Silver complexes
Imidazoliniums
Vicinal diamines
Chiral ligands
N-heterocyclic carbenes (NHCs) are now recognized as an
essential family of ligands in organometallic chemistry.1 More par-
ticularly NHCs substituted by aryl groups on the nitrogen atoms
have been extensively investigated for the development of metal-
catalyzed reactions.2 The most widely used N,N0-diaryl-substituted
NHCs are characterized by the presence of substituents (Me, i-Pr)
at the ortho positions of the aryl groups providing an efficient pro-
tection of the metal and of the carbenic center, inducing steric hin-
drance around the metal and therefore, affecting the stability and/
or activity of the catalysts (Fig. 1a). NHCs or metal–NHC complexes
can readily be obtained from the corresponding imidazoli(ni)um
salts. Many efficient methods are available for the preparation of
N,N0-diaryl azolium salts from vicinal diamines, bisimines, or ami-
dines.3 As a consequence, chiral N,N0-diaryl NHCs possessing stere-
ogenic centers on the heterocyclic skeleton have soon been
considered as attractive analogues for the development of applica-
tions in asymmetric catalysis (Fig. 1b).4 However, the synthetic ap-
proaches are much less general than for achiral NHCs.3 The Pd-
catalyzed double N-arylation of chiral enantiopure vicinal dia-
mines was used to prepare N,N0-diaryl diamines from 1,2-diphe-
nyl-1,2-diaminoethane or 1,2-diamino-cyclohexane.5 The method
enables the introduction on the nitrogen atoms of bulky aryl
groups with substituents (e.g., i-Pr groups) at the ortho positions.
However, double arylation on both nitrogen atoms is hindered by
the presence of more bulky substituents (e.g., tert-butyl groups)
on the backbone.6 Alternatively, the reductive coupling of N-aryl
imines derived from aromatic aldehydes was shown to be efficient
for synthesizing bulky N,N0-diaryl vicinal diamines, although the
diastereoselectivity is relatively low.7 Addition of Grignard re-
agents to bisimines was used to generate bulky NHCs possessing
gem-dimethyl groups at positions 3 and 4.8 This method was
previously exploited for the preparation of chiral tert-butyl substi-
tuted vicinal diamines and NHCs.9,10 Here, good diastereoselectiv-
ities have been obtained and enantiopure diamines could be
isolated. The method was applied to the formation of N,N0-dialkyl
diamines. We considered that the addition of t-Bu-metal species
on bulky N,N0-diaryl 1,2-bisimines could be an alternative strategy
for the synthesis of the corresponding diamines and NHCs (Fig. 1b;
R2 = t-Bu, R = Me or i-Pr) which are attractive ligands for asymmet-
ric catalysis.
Preliminary experiments performed with bisimine 1a demon-
strated that the addition of t-BuMgCl under the conditions previ-
ously developed for the preparation of 1,2-di-tert-butyl-1,2-
diaminoethane (hexane, 50 °C),9a and under various other condi-
tions, led exclusively to the formation of the imino-imine 2a result-
ing from the addition of a single tert-butyl group on precursor 1a
(Scheme 1).11 Compound 2a was isolated in 94% yield and the
method, applied to the less sterically demanding bisimines 1b
and 1c affords similarly the mono-adducts 2b and 2c in 90–99%
yields. Addition of less bulky or more reactive organometallic re-
⇑
Corresponding author. Tel.: +33 (0)1 44 27 55 67; fax: +33 (0)1 44 27 55 04.
E-mail address: sylvain.roland@upmc.fr (S. Roland).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.06.132

4794
U. Jacquemard et al. / Tetrahedron Letters 54 (2013) 4793–4795
R2
R2
a)
b)
R
R
R
R
N
N
N
N
R1
R1
R1
R
R
R1
R
R
Figure 1. (a) Commonly used N,N0-diaryl NHCs (R = i-Pr, Me) and (b) backbone
substituted (chiral) analogues.
t-Bu
t-Bu
LiAlH4
t-BuMgCl
THF, 0 °C
90–99%
Ar
N
N Ar
THF, 70 °C
Ar
Ar NH HN Ar
Ar NH
N
1a-c
2a (94%)
2b (90%)
2c (99%)
3a (76%)
3b (58%)
3c (43%)
Figure 2. ORTEP diagram of diamine 6. Selected torsion angles: N2–C11–C10–
N1 = 87.78°; C21–C10–C11–C25 = 144.14°.
Cl–
t-Bu
t-Bu
HC(OEt)3
HCl 4 M in dioxane
Ag2O
CH2Cl2, 20 °C
N
N
N
N
5a (6 mol %)
Ar
Ar
Ar
130 °C
Ar
OH
[Pd(allyl)Cl]2 (2.5 mol %)
AgCl
OAc
4a (85%)
4b (71%)
4c (68%)
PhCHO
+
Ph
Et2Zn (3.5 equiv)
THF, 20 °C
78%
5a (88%)
5b (98%)
Et
i-Pr
i-Pr
Scheme 3. Example of Pd-catalyzed allylation with 5a as the NHC transfer agent.
(a) Ar =
(b) Ar =
(c) Ar =
2,6-(Et)2C6H3
Et
2,6-(i-Pr)2C6H3
2,4,6-(Me)3C6H2 (Mes)
The molecular structure of 6 was confirmed by X-ray analysis of
single crystals obtained by slow evaporation in acetonitrile. The
ORTEP view is depicted in Figure 2.
Scheme 1. Synthetic pathway for the preparation of N,N0-diaryl 3-tert-butyl-
substituted NHCs.
Attempts to resolve the racemic diamine 6 by crystallization of
diastereomeric salts with camphorsulfonic acid or tartaric acid
derivatives under reported conditions remained inconclusive.15
This is in accordance with previous observations on the resolution
of N,N0-diaryl vicinal diamines substituted by aromatic groups on
the carbon chain (i.e. on the stereogenic centers), that could be re-
solved by chiral HPLC.7 Resolution of monosubstituted diamines 3
and imino-amines 2 was also unsuccessful.
agents such as i-PrMgCl, MeMgCl, allylMgBr, t-BuLi, n-BuLi or MeLi
to isolated 2a or to the intermediate magnesium amide was unsuc-
cessful. Reduction of imines 2a–c was not observed with NaBH4
and requires the use of LiAlH4 to produce the corresponding dia-
mines 3a–c in 43–76% yield after purification. The diamines were
then cyclized with triethylorthoformate in the presence of HCl by
using standard conditions,3 to give the mono-substituted imidazo-
linium chlorides 4a–c in 68–85% yields.12 Finally, treatment of 4a
and 4b with Ag2O leads to the silver–NHC complexes 5a and 5b.
These complexes are characterized by the presence of two doublets
in the 13C NMR spectrum which are centered at 211.9 ppm for 5a
and 210.6 ppm for 5b and correspond to the signal of the carbenic
carbon associated with Ag–C coupling constants of 257 and 223 Hz
in both cases.13
In contrast to mono-subsituted diamines 3, the cyclization of
the more hindered diamine 6 to produce the imidazolinium salt
could be achieved neither under the standard conditions described
previously for 3 (Scheme 1), nor under less acidic conditions (NH4-
Cl, cat. HCOOH).16 In all cases, the starting material was recovered
unchanged. Finally, with the aim of forming the aminal, diamine 6
was treated with formaldehyde. Surprisingly, we found that the
imidazolinium salt 7 is formed in a reproducible manner, although
in moderate yields (29%), by heating the mixture at 100 °C
(Scheme 2). The salt 7 is presumably formed by O2-mediated oxi-
dation of the intermediate aminal. Oxidation of aminals by various
oxidizing agents has been reported in the literature.3,17 However,
examples of direct oxidation with molecular O2 or air are scarce.18
Note that the aminal could not be formed or isolated by the treat-
ment of 6 with formaldehyde, regardless of the conditions.
The treatment of 7 with Ag2O at 20 °C led to the symmetrical di-
substituted silver complex 8 in 94% yield. Similarly to 5a and 5b,
the 13C NMR spectrum of 8 exhibits two doublets for the carbenic
Next, we focussed on the synthesis of N,N0-diaryl diamines
substituted by two tert-butyl groups. We assumed that the use of
more reactive lithium reagents would favor the expected double
addition of tert-butyl carbanions onto the bisimines.14 The treat-
ment of bisimine 1a with t-BuLi yields a mixture of non-identified
compounds along with 2a and therefore is not suitable for the syn-
thesis of the di-substituted diamine. A marked difference is ob-
served with the mesityl-substituted bisimine 1b that leads to the
expected diamine 6, isolated in 80% yield as a single d,l diastereo-
mer, after addition of t-BuLi at low temperature in THF (Scheme 2).
carbon
centered
at
213.7 ppm
(J{13C–109Ag} = 260 Hz;
J{13C–107Ag} = 225 Hz). Silver(I)–NHCs have been used as carbene
transfer agents for the in situ preparation of other metal com-
plexes.13 Complex 5a, used as the NHC transfer agent in the palla-
dium-catalyzed allylation of aldehydes in the presence of
diethylzinc,19 produces the expected homoallylic alcohol in 78%
yield (Scheme 3).
In conclusion, we demonstrate herein that either one or two
sterically demanding tert-butyl groups can be introduced on the
backbone of NHCs possessing bulky aryl substituents on the nitro-
gen atoms. The Grignard reagent (t-BuMgCl) is suitable for the
preparation of mono-substituted derivatives whereas t-BuLi is re-
quired to enable a double addition on the least substituted bis-
imine. The most bulky di-tert-butyldiamine could be cyclized to
t-Bu
t-Bu
t-BuLi 1.6 M in hexanes
Mes
N
N Mes
Mes
Mes NH HN
THF, –78 to 20 °C
80%
1b
6
t-Bu
t-Bu
N
Cl–
(HCHO)n
t-Bu t-Bu
Ag2O
HCl/dioxane
N
Mes
Mes
CH2Cl2, 20 °C
94%
100 °C
N
N
Mes
Mes
29%
AgCl
7
8
Scheme 2. Preparation of the N,N0-bis(mesityl) diamine 6 substituted by two tert-
butyl groups and of the corresponding silver–NHC 8.

U. Jacquemard et al. / Tetrahedron Letters 54 (2013) 4793–4795
4795
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Acknowledgments
Financial support from the Centre National de la Recherche Sci-
entifique (CNRS) and the Université Pierre et Marie Curie-Paris 6
are gratefully acknowledged. We thank P. Herson (IPCM) for the
X-Ray structure.
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Supplementary data
11. This protocol was previously reported to allow formation of the di-tert-butyl
diamine. However, the reaction could not be reproduced regardless of the
Preparation and characterization of 1a–c, 2a–c, 3a–c, 4a–c, 5a,
5b, 6, 7, and 8, and crystal structure information (6), this material
can be found in the online version at http://dx.doi.org/10.1016/
j.tetlet.2013.06.132. Crystallographic data (excluding structure fac-
tors) for the structure of diamine 6 have been deposited with the
Cambridge Crystallographic Data Center as supplementary publi-
cation no. CCDC 939920. Copies of the data can be obtained free
of charge, on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK.
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