Imidazolin-2-ylidenaminophosphines as Highly Electron-Rich Ligands for Transition-Metal Catalysts

Article abstract of DOI:10.1002/anie.201504993

A variety of chemical transformations benefit from the use of strong electron-donating ancillary ligands, such as alkylphosphines or N-heterocyclic carbenes when electron-rich metal centers are required. Herein, we describe a facile and highly modular access to monodentate and bidentate imidazolin-2-ylidenamino-substituted phosphines. Evaluation of the phosphine's electronic properties substantiate that the formal replacement of alkyl or aryl groups by imidazolin-2-ylidenamino groups dramatically enhance their donor ability beyond that of alkylphosphines and even N-heterocyclic carbenes. The new phosphines have been coordinated onto palladium(II) centers, and the beneficial effect of the novel substitution patterns has been explored by using the corresponding complexes in the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction of non-activated aryl chloride substrates. Upgrading phosphines: A conceptually new approach to a family of extremely electron-rich phosphines is based on the use of imidazolin-2-ylidenamino groups directly attached to the phosphorus atom. The steric and electronic properties of the new ligands can be easily varied owing to the general and modular synthesis, which provides new prospects for phosphine ligands in catalysis.

Full text of DOI:10.1002/anie.201504993

Angewandte
Chemie
International Edition: DOI: 10.1002/anie.201504993
German Edition: DOI: 10.1002/ange.201504993
Ligand Design
Imidazolin-2-ylidenaminophosphines as Highly Electron-Rich Ligands
for Transition-Metal Catalysts
Marius A. Wünsche, Paul Mehlmann, Tim Witteler, Florenz Buß, Patrick Rathmann, and
Fabian Dielmann*
Dedicated to Professor Manfred Scheer on the occasion of his 60th birthday
Abstract: A variety of chemical transformations benefit from
the use of strong electron-donating ancillary ligands, such as
alkylphosphines or N-heterocyclic carbenes when electron-rich
metal centers are required. Herein, we describe a facile and
highly modular access to monodentate and bidentate imida-
zolin-2-ylidenamino-substituted phosphines. Evaluation of the
phosphineꢀs electronic properties substantiate that the formal
replacement of alkyl or aryl groups by imidazolin-2-yliden-
amino groups dramatically enhance their donor ability beyond
that of alkylphosphines and even N-heterocyclic carbenes. The
new phosphines have been coordinated onto palladium(II)
centers, and the beneficial effect of the novel substitution
patterns has been explored by using the corresponding
complexes in the palladium-catalyzed Suzuki–Miyaura cross-
coupling reaction of non-activated aryl chloride substrates.
heterocyclic carbenes (NHCs), have gained considerable
significance as ancillary ligands in transition-metal catalysis,
in particular because of their stronger s-donor character
compared to tertiary phosphines.[7] Consequently, the recent
isolation of the very basic cyclic (alkyl)(amino)carbenes
(CAACs)[8] and imidazolin-5-ylidenes (also termed abnormal
NHCs)[9] were major breakthroughs. In contrast, concerning
the donor properties of phosphines, tri-tert-butylphosphine is
still regarded as the benchmark electron-rich ligand.[10]
A
successful approach to electron-rich phosphines was reported
by Moloy and Petersen, who showed that despite the
electron-withdrawing effect of the amino substituents,
tris(N-pyrrolidinyl)phosphines has equal donor properties to
tris(n-butyl)phosphine.[11] They attributed this effect to the
potent N-to-P lone pair donation. Further investigation by
Woollins revealed that for the third dialkylamino substituent
this effect is offset by the electron-withdrawing character of
the nitrogen atoms, and they showed that phosphines
comprising two pyrrolidinyl groups and one alkyl substituent
can be equally strong donors as tri-tert-butylphosphine.[12]
We reasoned that a promising strategy to increase the
electron-donating ability of phosphines would be to decorate
them with strong p-donating substituents such as the imida-
zolin-2-ylidenamino groups. The ability of the anionic imida-
zolin-2-iminato ligands to efficiently act as imido-type 2s,4p-
electron donors towards metal atoms has been extensively
explored by Tamm and co-workers.[13] Recent success in
stabilizing electron-deficient species, such as a phosphinoni-
trene[14] and iminophosphenium salts[15] by using two phos-
phorus-bound imidazolidin-2-ylidenamino groups inspired us
to exploit their strong p-donating character for the design of
extremely electron-rich phosphines with potential applica-
tions in catalysis.
T
he success of homogeneous catalysis is linked largely to the
development of a diverse range of ancillary ligands with
tunable steric and electronic properties. Such tailoring of the
ligand architecture is crucial to ensure optimum steric
protection and stereoelectronic control of the catalytic
species and very often allows a remarkable degree of control
over the outcome of transition-metal-promoted reactions. In
this context, phosphine ligands (PR3) are arguably the most
versatile ancillary ligands because their donor ability and
steric requirements can be easily adjusted in a predictable
manner by variation of the R substituents.[1] Specifically, when
electron-rich metal centers are required strong electron-
releasing alkylphosphines are the ligands of choice over
arylphosphines.[2] Their application in catalysis has led to
major breakthroughs in many fields of academic and indus-
trial research, as exemplified by olefin metathesis,[3] hydro-
formylation,[4] catalytic C H bond activation, and palla-
[5]
À
dium-catalyzed cross-coupling reactions.[6]
Herein, we describe a general procedure for the synthesis
of imidazolin-2-ylidenaminophosphines (IAPs) (Figure 1).
The successive replacement of the R substituents in phos-
phines PR3 by strong p-donating imidazolin-2-ylidenamino
The synthesis of new strong-donor ligands has therefore
become an important challenge of chemical research. During
the past two decades, another class of ligands, namely N-
[*] M. A. Wünsche, P. Mehlmann, T. Witteler, F. Buß, P. Rathmann,
Dr. F. Dielmann
Institut für Anorganische und Analytische Chemie
Westfälische Wilhelms-Universität Münster
Corrensstrasse 30, 48149 Münster (Germany)
E-mail: dielmann@uni-muenster.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201504993.
Figure 1. Structural features of IAPs and their influence on the donor
properties of IAPs.
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Table 1: TEP values and Huynh’s parameter of IAPs 3–7, 11, and 12. The
values of commonly used phosphines and NHCs are included for
comparison.
groups makes IAPs more electron rich than alkylphosphines
and even abnormal N-heterocyclic carbenes. Moreover,
owing to the NHC-nature of the backbone, steric and
electronic fine-tuning of IAPs is easily achieved by drawing
on the versatile class of NHCs as exemplified by using 1,3-
diisopropylbenzimidazolin-2-ylidenamino (NBiPr) and 1,3-
dimesityl-4,5-dimethylimidazolin-2-ylidenamino
(NIMes)
substituents in our studies. We also demonstrate the beneficial
effect of the imidazolin-2-ylidenamino substitution in a series
of IAPs in Suzuki–Miyaura reactions using non-activated aryl
chlorides as challenging substrates.
For the synthesis of IAPs two straightforward procedures
were developed (see Scheme 1 and the Supporting Informa-
[b]
Entry
Ligand L
TEP[a]
[Ni(CO)3L]
dCcarbene
[PdBr2(BiPr)L]
1
2
3
4
5
6
7
8
P(NBiPr)Ph2 (3)
P(NBiPr)2Ph (4)
P(NBiPr)iPr2 (5)
P(NBiPr)2iPr (6)
P(NBiPr)3 (7)
P(NIMes)iPr2 (11)
P(NIMes)2iPr (12)
PPh3
2060.8
2051.0
2053.6
2049.2
2044.3
2047.8
2038.6
(2068.9)
(2059.2)
(2056.1)
(2051.5)
178.0
183.0
181.5
184.5
186.1
183.7
[d]
–
(173.1)
175.9
–
9
10
11
PiPr3
PtBu3
IPr[c]
(177.5)
[a] Values in cmÀ1; measured in CH2Cl2, (literature values[1,19]). [b] Values
in ppm; measured in CDCl3 and internally referenced to the solvent
residual signal at d=77.7 ppm relative to TMS, (literature values[18]).
[c] 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene. [d] trans-[PdBr2-
(BiPr)(12)] not formed.
analysis of the A1 CO stretching frequency of [Ni(CO)3L]
complexes.[1] The observed TEP values indicate that the
donor power of the IAPs is higher than that of the electron-
rich alkylphosphines (Table 1) with the exception of 3 having
a TEP value with the same order of magnitude as PnBu3
(2060.3 cmÀ1). Remarkably, IAPs 6, 7, 11, and 12 are even
better donor ligands than classical NHCs. By analyzing the X-
ray molecular structures of free triaminophosphines and
those of their transition-metal complexes, Woollins et al.
concluded that only two nitrogen lone pairs donate electron
density towards phosphorus, while the third nitrogen lone pair
is oriented such that the nitrogen atom simply acts as an
electron-withdrawing substituent.[12] In contrast to this obser-
vation, the TEP value of NBiPr-substituted phosphines 3–7
increases almost unvaryingly with a higher degree of sub-
stitution (Ph substitution: av. 8.2 cmÀ1, iPr substitution: av.
5.0 cmÀ1). Phosphines 11 and 12, decorated with the NIMes
backbone, show an even more prominent gain in donor
power. Monosubstitution shifts the TEP value (PiPr3:
2059.2 cmÀ1) by 11.4 cmÀ1 (11: 2047.8 cmÀ1) below that of
classical NHCs, and the second substitution by another
9.2 cmÀ1 (12: 2038.6 cmÀ1) below that of abnormal NHCs.
These values support the notion that the NIMes substituent is
a much better p donor than the NBiPr group, and also
indicates that if appropriately substituted, IAPs can surpass
the donor abilities of CAACs or abnormal NHCs.
Scheme 1. Synthesis of IAPs. Reagents and conditions (yields):
a) BrCN, toluene, 1108C, and then KOH (90%); b) nBuLi, THF,
À788C, and then chlorophosphine, room temperature; 3 (94%), 4
(89%), 5 (84%), 6 (86%), 7 (94%); c) nBuLi, THF, À788C, and then
[Fe(C5H4PCl2)2] (81%); d) KOtBu, toluene, À788C, and then TMSN3,
1108C (49%); e) 11: PiPr2Cl, THF, (99%); 12: PCl3, THF, À788C, and
then iPrMgCl, THF, À788C, (87%).
tion). NBiPr-substituted phosphines 3–8 were prepared in
excellent yields through a two-step sequence. The reaction of
diamine 1[16] with cyanogen bromide and subsequent basic
workup afforded imine 2 in 90% yield. Deprotonation of 2
and treatment with the respective chlorophosphine afforded
the IAPs 3–8 as white (3–7) or orange (8) solids in very good
yields. An alternative route to IAPs is based on readily
available imidazolium salts (Scheme 1). Following a synthetic
approach reported by Tamm,[17] deprotonation of the imida-
zolium salt 9 at À788C gives the free NHC, which reacts with
trimethylsilyl azide to afford imine 10 upon N2 elimination in
fair yield. Treatment of 10 with chlorodiisopropylphosphine
afforded IAP 11 upon elimination of trimethylsilyl chloride in
a clean reaction as an off-white solid. The sterically demand-
ing phosphine 12 was prepared by reacting imine 10 with PCl3
and subsequent treatment of the phosphenium chloride salt
with isopropylmagnesium chloride to afford IAP 12 as a white
solid in very good yield.
To demonstrate the reliability of the TEP analysis for the
IAPs, we decided to examine their donor ability by means of
a second method, which is not based on the CO stretching
frequency. Huynh et al. recently reported a parameter that
utilizes the 13C NMR chemical shift of the carbene carbon
atom in trans-[PdBr2(BiPr)L] complexes as a probe for the
measurement of the donor strength of the ligand L.[18] The
To evaluate the donor endowment of the new phosphines,
we determined the Tolman electronic parameter (TEP) by
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analysis of the 13C carbene signal of these complexes
containing IAPs revealed the same qualitative trend as the
TEP analysis (Table 1). However, Huynhꢀs method rates the
donor strength of the IAPs as higher. Accordingly, IAP 3
exhibits a donor ability comparable to NHCs and is already
more electron-rich than alkylphosphines, while phosphines 4,
6, 7, and 11 exceed the donor ability of abnormal NHCs.[18]
Numerous catalytic processes that require electron-rich
ligands at the metal center should benefit from the electronic
and steric properties of IAPs. As an example of such a process,
we decided to test the viability of IAPs in palladium-catalyzed
Suzuki–Miyaura cross-coupling reactions of non-activated
aryl chlorides. Previously, high reactions rates were observed
with sterically hindered electron-rich alkyl phosphine and
NHC ligands,[6,7a–c] in some cases even at room temper-
ature,[20] while triphenylphosphine does not promote the
coupling reaction.[21] Thus, we were curious to see what
influence the NBiPr-substitution pattern for IAPs 3, 4, and 7
has on the catalytic performance. We adopted the reaction
conditions from a previous study by Nolan et al. who showed
that the catalytic system involving [PdCl(allyl)(NHC)] as the
catalyst and NaOtBu as the base is highly active for the
Suzuki–Miyaura cross-coupling of aryl chlorides.[22] The
[PdCl(allyl)L] complexes 13–16 (Scheme 2) were readily
buried volume from the X-ray data of the [PdCl(allyl)L]
complexes. A higher degree of NBiPr-substitution increases
the buried volume[24] for PPh3 (29.6%), 3 (39.7%), and 7
(43.4%). The steric demand of IAP 11 (45.9%) resembles
that of Buchwald-type phosphines,[6c] and nicely illustrates
how effectively the steric bulk of IAPs can be modulated.
Our model system reveals a clear correlation between the
catalytic performance of the [PdCl(allyl)(IAP)] catalyst with
the degree of NBiPr-substitution of the corresponding IAP
ligands (Table 2). While PPh3 does not promote the catalytic
Table 2: Suzuki–Miyaura cross-coupling of aryl chlorides with phenyl-
boronic acid.
entry
aryl chloride
product
ligand
yield [%][a]
1
2
3
4
PPh3
0
9
62
94
j
j
j
j
3
4
7
10
83
99
5
6
7
3
4
7
8
56
99
j
j
j
7
70
99
8
9
10
3
4
7
7
26
42
j
j
j
8
61
77
11
12
13
3
4
7
69
97
97
j
j
j
84
98
99
14
15
16
3
4
7
4
13
19
j
j
j
4
18
23
[a] Yields as determined by NMR spectroscopy (average of two runs)
using the palladium dimers [{PdCl(allyl)}2]j[{PdCl(cinnamyl)}2].
process (entry 1),[21] the use of the mono-substituted IAP 3
provides low catalytic activity. The increasing donor strength
and steric demand of IAPs 4 and 7 gives superior catalytic
performances for all the aryl chloride substrates tested. The
same trend was observed for 3, 4, and 7 when [{PdCl-
(cinnamyl)}2] was used as palladium source (Table 2). The
higher yields compared to the allyl-system are in agreement
with the reported more facile activation of [PdCl(cinnamyl)-
(NHC)] complexes.[20a] This example beautifully demon-
strates the ability of IAPs to increase the electron density at
Pd centers and reveals the vast potential of IAPs in the
development and improvement of transition-metal-catalyzed
reactions.
Scheme 2. Synthesis of the [PdCl(allyl)(IAP)] complexes 13–16
a) [{PdCl(allyl)}2]. Molecular structures of 13, 15, and 16. Hydrogen
atoms are omitted for clarity; thermal ellipsoids are set at 50%
probability. Selected bond lengths [Š]: 13: Pd–Cl 2.3651(4), Pd–P
2.2872(4), P–N1 1.6395(12). 15: Pd–Cl 2.3568(8), Pd–P 2.2829(7), P–
N1 1.646(3), P–N4 1.653(3), P–N7 1.637(3). 16: Pd–Cl 2.3792(6), Pd–
P 2.2967(6), P–N1 1.624(2).
prepared in quantitative yields by addition of IAPs 3, 4, 7,
and 11 to [{PdCl(allyl)}2], and isolated as air stable off-white
solids.[23] X-ray diffraction studies confirmed the expected
connectivity. The steric influence of the phosphine units on
the palladium atom was analyzed by determination of their
In summary, our studies provide a conceptually new
approach to the design of extremely electron-rich phosphines
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based on the use of imidazolin-2-ylidenamino groups directly
attached to the phosphorus atom. The IAPs are readily
obtained through a short and highly modular synthesis, which
also allows for the design of multi-dentate variants as
exemplified by the preparation of IAP 8. When used as
a ligand, IAPs show excellent donor abilities, which can even
exceed those of CAACs or abnormal NHCs. The beneficial
effect of this property in the field of homogeneous catalysis
has been explored in Pd-catalyzed Suzuki reactions using
non-activated aryl chlorides as challenging substrates. Con-
sidering the convenient access to IAPs with diverse ligand
architectures, in addition to the variety of chemical trans-
formations that benefit from the use of strong electron-
donating ligands, we anticipate that IAPs are likely to find
widespread use as ancillary ligands in transition-metal-
catalyzed reactions.
Acknowledgements
We gratefully acknowledge financial support from the
Alexander von Humboldt Foundation (Feodor Lynen
Return Fellowship for F.D.), from the DFG (IRTG 2027)
and from the FCI (Liebig Fellowship for F.D.). Thanks are
due to Prof. F. E. Hahn for his generous support.
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Keywords: cross-coupling · ligand design · ligand effects ·
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Received: June 2, 2015
Published online: August 10, 2015
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