Highly enantioselective ruthenium/PNNP-catalyzed imine aziridination: Evidence of carbene transfer from a diazoester complex

Article abstract of DOI:10.1021/om400735p

The ruthenium/PNNP complexes [RuCl(Et₂O)(PNNP)]Y (Y = PF ₆, 4PF₆; BF₄, 4BF₄; or SbF ₆, 4SbF₆) (10 mol %) catalyze the enantioselective aziridination of imines with ethyl diazoacetate (EDA) as carbene source (PNNP = (1S,2S)-N,N′-bis[o-(diphenylphosphino)benzylidene]cyclohexane-1,2-diamine) . The highest enantioselectivity was obtained with 4SbF₆, which aziridinated N-benzylidene-1,1-diphenylmethanamine (5a) to cis-ethyl 1-benzhydryl-3-phenylaziridine-2-carboxylate (cis-6a) with 93% ee at 0 C. To the best of our knowledge, this is the highest enantioselectivity ever obtained in transition metal-catalyzed asymmetric aziridination. Aziridine yields were overall moderate to low (up to 33% isolated yield of the cis isomer) because of the competitive formation of diethyl maleate (7). The scope of the catalyst was studied with p- and m-substituted imines. NMR spectroscopic studies with ¹³C- and ¹⁵N-labeled EDA indicate that aziridine 6a is formed by carbene transfer from an EDA complex, [RuCl(EDA)(PNNP)]PF₆ (8), to the imine. The observation of a dinitrogen complex (9) gives further support to this mechanism. The EDA adduct 8 decomposes to the carbene complex [RuCl(CHCO₂Et)(PNNP)]⁺ (10), whose reaction with EDA gives diethyl maleate. This unprecedented mechanism is rationalized on the basis of the nucleophilic nature of diazoalkanes, which is enhanced by coordination to a π-back-donating metal such as ruthenium(II).

Full text of DOI:10.1021/om400735p

Article
pubs.acs.org/Organometallics
Highly Enantioselective Ruthenium/PNNP-Catalyzed Imine
Aziridination: Evidence of Carbene Transfer from a Diazoester
Complex
̈
Joel Egloff, Marco Ranocchiari, Amata Schira, Christoph Schotes, and Antonio Mezzetti*
̈ ̈
Department of Chemistry and Applied Biosciences, ETH Zurich, CH-8093 Zurich, Switzerland
*
S Supporting Information
ABSTRACT: The ruthenium/PNNP complexes [RuCl-
(
4
Et O)(PNNP)]Y (Y = PF , 4PF ; BF , 4BF ; or SbF ,
SbF ) (10 mol %) catalyze the enantioselective aziridination
6
2 6 6 4 4 6
of imines with ethyl diazoacetate (EDA) as carbene source
(
PNNP = (1S,2S)-N,N′-bis[o-(diphenylphosphino)-
benzylidene]cyclohexane-1,2-diamine). The highest enantiose-
lectivity was obtained with 4SbF , which aziridinated N-
6
benzylidene-1,1-diphenylmethanamine (5a) to cis-ethyl 1-
benzhydryl-3-phenylaziridine-2-carboxylate (cis-6a) with 93%
ee at 0 °C. To the best of our knowledge, this is the highest enantioselectivity ever obtained in transition metal-catalyzed
asymmetric aziridination. Aziridine yields were overall moderate to low (up to 33% isolated yield of the cis isomer) because of the
competitive formation of diethyl maleate (7). The scope of the catalyst was studied with p- and m-substituted imines. NMR
1
3
15
spectroscopic studies with C- and N-labeled EDA indicate that aziridine 6a is formed by carbene transfer from an EDA
complex, [RuCl(EDA)(PNNP)]PF (8), to the imine. The observation of a dinitrogen complex (9) gives further support to this
6
+
mechanism. The EDA adduct 8 decomposes to the carbene complex [RuCl(CHCO Et)(PNNP)] (10), whose reaction with
2
EDA gives diethyl maleate. This unprecedented mechanism is rationalized on the basis of the nucleophilic nature of diazoalkanes,
which is enhanced by coordination to a π-back-donating metal such as ruthenium(II).
4
INTRODUCTION
complex formed from ethyl diazoacetate (EDA) (Scheme 1a).
■
He suggested that the resulting nitrogen ylide is relatively stable
and can partially dissociate from the chiral catalyst before
collapsing to aziridine, as indicated by the formation of
pyrrolidines in the presence of dimethyl fumarate (Scheme 2).
This broadly supported mechanism explains the low
enantioselectivity typically observed both with copper catalysts
Chiral alkoxycarbonyl-substituted aziridines are valuable strain-
activated electrophilic precursors to amino acids as they1
undergo ring-opening with excellent stereo- and regiocontrol.
A straightforward approach to their synthesis is the catalytic
5
2
3
aziridination of aldimines with diazo compounds. During the
last 20 years, this transformation has been performed with
catalysts that involve an intermediate carbene complex (Scheme
Scheme 2
1a) or, alternatively, Lewis (or Brønsted) acid activation of the
imine (Scheme 1b or 1b′).
In 1995, Jacobsen reported copper bisoxazoline catalysts that
operate by nucleophilic attack of the imine onto a carbene
Scheme 1
Received: July 25, 2013
Published: August 14, 2013
©
2013 American Chemical Society
4690
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Article
6
and with rhodium(II) catalysts and has contributed to the
reputation of transition metal-catalyzed imine aziridination as a
reaction of intrinsically low enantioselectivity ever since.
Other copper catalysts that possibly involve Lewis acid
activation of the imine showed improved enantioselectivity, but
Scheme 4
7
their performance was still modest. A successful variation of
the carbene transfer approach combines a metal catalyst for
diazoester decomposition with a chiral sulfide that acts as
8
carbene shuttle to imine via a sulfur ylide intermediate, but the
source of the chiral information is not the metal in this case.
The alternative approach in metal-catalyzed aziridination, that
is, nitrene transfer to an olefin, has been pioneered by Evans
(5a) to cis-ethyl 1-benzhydryl-3-phenylaziridine-2-carboxylate
20
9
(cis-6a) with good enantioselectivity (up to 84% ee). Maleate
formation severely reduced the yield of aziridine, which was
optimized by using a temperature gradient between −78 °C
and room temperature. An NMR study gave strong evidence
that aziridine is formed by carbene transfer to the imine from a
coordinated diazoester molecule (Scheme 1c), an unprece-
dented mechanism that opens the way to highly enantiose-
lective transition metal-catalyzed imine aziridination. In the
present paper, we report further advances in terms of chemo-
and Jacobsen and further developed by Katsuki with the use of
1
0
sulfonyl azides. Following seminal work with achiral
1
1
systems,
chiral, boron-based Lewis acids have been
12
successfully used for asymmetric imine aziridination. More
recently, chiral Brønsted acids have been shown to induce the
aza-Darzens reaction of imines and diazoalkanes with high
1
3−15
enantioselectivity.
In both cases, the reaction mechanism
involves the nucleophilic attack of the diazoester onto the acid-
activated imine (Scheme 1, pathways b and b′). Driven by the
success of this approach, the mechanistic understanding of acid-
catalyzed imine aziridination has been rapidly evolving. Thus, it
has been recently shown that, in the VAPOL-catalyzed
aziridination, the imine is activated by hydrogen bonding to a
and enantioselectivity and substrate scope achieved by tuning
−
the counterion Y of the catalyst [RuCl(OEt )(PNNP)]Y (4Y;
2
Y = PF , BF , or SbF ), give a full account of the previously
6
4
6
20
communicated NMR spectroscopic studies, and suggest a
general explanation for the reactivity of carbene and diazoester
complexes with imines.
12b
chiral Brønsted acid derived from the chiral borane.
Our interest in carbene transfer to imines arises from
previous studies of asymmetric cyclopropanation with
ruthenium complexes containing chiral tetradentate PNNP
ligands such as (1S,2S)-N,N′-bis[o-(diphenylphosphino)-
benzylidene]cyclohexane-1,2-diamine, which is used through-
out this paper. The five-coordinate complex [RuCl(PNNP)]-
PF (2), formed by chloride abstraction from [RuCl (PNNP)]
RESULTS AND DISCUSSION
Counterion Optimization and Substrate Scope. As
mentioned above, the catalyst [RuCl(OEt )(PNNP)]PF
■
2
6
(4PF ) gave significant yield of cis-ethyl 1-benzhydryl-3-
6
phenylaziridine-2-carboxylate (cis-6a) only in combination
with an elaborate temperature protocol.
producing aziridine in reasonable yield and high enantiose-
lectivity under simpler experimental conditions, the catalysts
2
0,21
With the goal of
6
2
1
6,17
(1) (Scheme 3),
is a highly enantioselective catalyst for the
Scheme 3
[RuCl(OEt )(PNNP)]Y (4Y) containing other low-coordinat-
2
−
−
ing anions Y (Y = BF4 or SbF ) were screened with N-
6
benzylidene-1,1-diphenylmethanamine (5a) as standard sub-
strate (Table 1).
The dichloro complex [RuCl (PNNP)] (1) was activated
2
with (OEt )Y (Y = BF or SbF , 1 equiv) overnight in
3
4
6
dichloromethane to give 4Y (Scheme 3), after which 5a and
then EDA were added to the solution cooled at 0 °C. The
Table 1. Asymmetric Aziridination of 5a (at 0 °C) with
a
Precatalyst 1 Activated with (OEt )Y
3
b
crude 6
isolated cis-6
c
d
entry
Y
EDA (equiv) yield (%) cis:trans yield (%) ee (%)
1
2
3
4
5
6
PF6
BF4
SbF6
PF6
1
1
1
4
4
4
22
32
32
35
53
58
77:23
78:22
85:15
79:21
81:19
78:22
13
24
24
30
20
40
80
78
93
e
53
BF4
78
67
asymmetric, cis-selective cyclopropanation of olefins by
SbF6
diazoesters with the intermediacy of the carbene complex
+
18
[
RuCl(CHCO Et)(PNNP)] . Therefore, on the basis of the
2
a
Reaction conditions: EDA (0.48 mmol, 1 equiv vs 5a) was added
neat) in one portion to a CH Cl solution (3 mL) containing imine
a (0.48 mmol) and 4Y (10 mol %), prepared by activation of
dominant mechanistic hypothesis, it was straightforward to test
Ru/PNNP catalysts in imine aziridination with ethyl diazo-
acetate (EDA) (Scheme 4).
(
5
[
2
2
RuCl (PNNP)] (1) (0.048 mmol) with (Et O)Y (0.048 mmol)
2 3
b
We have recently reported a preliminary screening of the
overnight. The total reaction time was 24 h at 0 °C. Sum of cis and
1
c
Ru/PNNP catalysts [RuCl(L)(PNNP)]PF (L = nil, 2; L =
6
trans isomers, based on the imine, by H NMR spectroscopy. Isolated
d e
19
OH , 3; L = Et O, 4PF ), which showed that the Et O adduct
yield. The absolute configuration of cis-6a was 2R,3R. The isolated
2
2
6
2
4
PF6 aziridinates N-benzylidene-1,1-diphenylmethanamine
aziridine was contaminated with variable amounts of diethyl maleate.
4
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reaction of 4PF at a constant temperature of 0 °C gave
Table 2. Asymmetric Aziridination of Imines 5a−5f with
6
a
aziridine cis-6a in low isolated yield (13%) and 80% ee (entry
EDA Catalyzed by 4SbF
6
1
). The tetrafluoroborate analogue 4BF gave cis-6a with higher
4
b
crude 6
yield (%)
isolated cis-6
yield (24%), but with lower enantioselectivity (78% ee, entry
c
d
entry
imine
cis:trans
yield (%)
ee (%)
2
). Finally, with the hexafluoroantimonate analogue 4SbF , cis-
6
6
a was isolated with 24% yield and 93% ee (entry 3), which is,
1
2
3
4
5
6
5a
5b
5c
5d
5e
5f
32
18
16
30
46
40
85:15
85:15
84:16
cis only
93:7
24
14
9
93
91
75
79
83
93
to the best of our knowledge, the highest enantioselectivity ever
achieved in transition metal-catalyzed imine aziridination.
Major amounts of diethyl maleate (7) were formed with all
catalysts, as usually observed in imine aziridination with
carbenoids. Furthermore, variable amounts of the trans-
aziridine (trans-6a) were detected in the crude reaction
mixture. This is in contrast with the previously reported
preliminary experiments with 4PF as catalyst, in which no
more than trace amounts of the trans isomer were formed in
24
34
4
90:10
33
a
b
Reaction conditions: See footnote a in Table 1. Sum of cis and trans
isomers, based on the imine, by H NMR spectroscopy. Isolated yield
of cis-aziridine. The absolute configuration of cis-6a was 2R,3R; those
of 6b−6f were not assigned.
2
2
c
1
d
6
20
the reaction run between −78 °C and room temperature.
1
However, even when trans-aziridine was clearly visible in the H
NMR spectrum of the crude products, pure cis-6a was readily
isolated after workup (mostly as a crystalline solid), as the trans
was not determined. Besides 5a, the catalyst 4SbF gives
6
enantioselectivity higher than 90% ee with the p-chloro- and 2-
naphthyl-substituted imines 5b and 5f (91 and 93% ee,
respectively, entries 2, 6). The 3-bromo analogue 6e is formed
with a slight erosion of enantioselectivity (83% ee), but with
the highest isolated yield (34%, entry 5). The bulky 4-
methoxycarbonyl-substituted imine 5d gave the corresponding
aziridine cis-6d with lower enantioselectivity (79% ee, entry 4),
whereas 4-fluoro-substitution reduced both yield and enantio-
selectivity (entry 3). Interestingly, all these substrates gave
higher enantioselectivity than obtained with other chiral
transition metal catalysts that operate by diazoalkane
23
isomer was eluted together with the unreacted imine 5a.
In an attempt to improve the yield of aziridine, an excess of
EDA (4 equiv) was used with catalysts 4Y (entries 4−6).
Overall, lower enantioselectivity was achieved under these
conditions, and large amounts of diethyl maleate (7) were
formed, which hindered the purification of 6a and other
selected aziridines (see Supporting Information, Table S1).
Overall, the best results were obtained with catalyst 4SbF in
6
combination with a stoichiometric amount of EDA. Therefore,
these conditions were used to screen the substrate scope (see
below).
4
activation.
1
Finally, we note that the H NMR spectra of the reaction
At this stage, we do not have an explanation for the anion
effect, in particular on the enantioselectivity. Low-temperature
crude of the catalytic runs reported in Tables 1 and 2 showed
not more than trace amounts (<3% of starting imine) of
enaminoesters (such as (Z)-ethyl 3-(benzhydrylamino)-3-
phenylacrylate for imine 5a, see Supporting Information). As
enaminoesters are common byproducts with aziridination
catalysts that operate by Lewis acid activation of the imine
(path b in Scheme 1), this observation disfavors such a
reaction mechanism as discussed later on. The extended
substrate scope and the improvement of yield and enantiose-
lectivity achieved upon changing the counterion from PF to
SbF6 show that the ruthenium/PNNP catalysts still have
potential in asymmetric imine aziridination. This motivates us
to report and discuss at full length the previously
communicated stoichiometric and catalytic reactions between
3
1
19
P and F NMR spectroscopic studies of the Et O adducts
2
[
RuCl(OEt )(PNNP)]Y (4Y, Y = PF , BF , or SbF ) in
2 6 4 6
CD Cl aimed at detecting possible cation/anion interactions
2
2
showed that the dissociation of the Et O adduct 4 into the five-
coordinate complex 2 and Et O is the main dynamic process in
2
11
2
solution and failed to give conclusive evidence of the cation/
anion interactions evoked by the counterion effect observed in
catalysis (see Supporting Information). However, an interesting
observation that will be discussed in the context of the genera−l
−
6
−
mechanism is that the yield of aziridine is higher with the SbF6
−
and BF counterions, which are more coordinating than
PF .
4
−
24
19
6
The substituted benzaldimines 5b−5f (Chart 1) were used to
precatalyst 4PF , EDA, and imine 5a by NMR spectroscopy,
6
screen the scope of the reaction with complex 4SbF as catalyst
because they are the key to the understanding and improve-
ment of the chemoselectivity, which is the major issue at this
juncture.
6
Chart 1
Attempted Carbene Transfer from [RuCl(CHCO Et)-
PNNP)] (10). As the literature precedents pointed to a
2
+
(
carbene-mediated reaction, we studied first the reaction of
1
8a,c
imine 5a with the previously reported
carbene complex
+
[
RuCl(CHCO Et)(PNNP)] (10), which was prepared by
2
adding EDA (1 equiv) to [RuCl(OEt )(PNNP)]PF (4PF ) in
2
6
6
CD Cl at −78 °C. Complex 10 was obtained as the main
2
2
3
1
product (71%) (Scheme 5a), as indicated by the P NMR
spectrum of the reaction solution recorded at −78 °C just
thereafter, along with a small amount (15%) of a dinitrogen
(
10 mol %) under the conditions used above for 5a (1 equiv of
EDA, CH Cl 0 °C) (Table 2). The 4-(2-propyl)- and 4-
complex that we tentatively formulate as trans-[RuCl(N
2
)-
2
2,
+
methylphenyl analogues of 5a gave lower chemo- and/or
enantioselectivity and are not discussed further (see Supporting
Information). Pure cis-aziridines 6b−6f were obtained after
workup as discussed above, and their absolute configuration
(PNNP)] (9) (as suggested by the analogous reaction with
15
25
NNCHCO Et, see below). When imine 5a (1 equiv) was
2
added to this solution at −78 °C, no spectral changes were
observed. Therefore, the sample was slowly warmed to room
4
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Scheme 5
A New Mechanism for Carbene Transfer to Imine. The
reactions discussed in the former two paragraphs rule out the
classical mechanisms that have been proposed for carbene
transfer to imines. The failure of carbene complex 10 to react
with the imine (Scheme 5) and the ylide trapping test with
fumarate rules out path a in Scheme 1. Lewis acid activation of
the imine (path b) is excluded because we found no evidence of
imine coordination by NMR spectroscopy, the presence of
imine 5a has no influence on the course of the reaction
between 4PF and EDA, and catalyst 4PF produces only traces
4
6
of enamino esters such as (Z)-ethyl 3-(benzhydrylamino)-3-
phenylacrylate, which are typically formed in substantial
11
amounts in Lewis acid catalyzed imine aziridination. To
overcome the impasse, we decided to study the aziridination
reaction by NMR spectroscopy under conditions as close as
possible to those of the catalytic reaction. To this goal, the
reaction between EDA and imine 5a in the presence of complex
1
3
1
4PF was repeated with an excess of EDA. The experiments
temperature in 20 °C steps. A ( C, H)-HMQC experiment
showed that no aziridine was formed (Scheme 5b).
6
13
2
13
were carried out with isotope-labeled N CHCO Et ( C-
2
EDA) and with 15NNCHCO Et ( N-EDA) to enhance the
15
After 4 h at room temperature, the reaction solution
contained the alkyl complex trans-[RuCl(CH CO Et)-
PNNP)] (11) (43%) (Scheme 5c), along with the dinitrogen
complex 9 (57%, see below). The alkyl complex 11 features
two diagnostic doublets at δ 3.79 and 3.36 ( J
2
sensitivity.
2
2
An excess of 13C-EDA (10 equiv) was added to [RuCl-
+
(
+
(
OEt )(PNNP)] (4PF ) and imine 5a (1:1 ratio) in CD Cl
2
6
2
2
29
13
1
2
at −78 °C. The ( C, H)-HMQC spectrum at this temper-
= 11.2 Hz) in
H,H′
13
1
ature showed that no aziridine had formed. The major C-
30
the H NMR spectrum, which were assigned to the
13
13
labeled compound was unreacted C-EDA, whose C NMR
carbenoid signal is split because of slow interconversion
between the s-cis and s-trans isomers (in ca. 1:1 ratio) (Scheme
diastereotopic H atoms of the Ru−CH CO Et moiety by
2
2
31
1
13
1
means of ( P, H)-HMQC and ( C, H)-HMQC experiments.
31
The P NMR spectrum of 11 is a tight AB pattern at δ 47.9 (d,
J = 28.2 Hz) and 47.8 (d, J = 28.2 Hz) (202 MHz, CD Cl , 298
31
6
, Figure 1), which has been observed previously both for free
2
2
K, Figure S6 in the Supporting Information). Carbene
complexes of Rh(III) and Co(III) porphyrins, formed by
reaction with EDA, are known to give hydride abstraction from
undefined sources, possibly EDA itself or the solvent, to give
Scheme 6
26
the corresponding alkyl complex.
As the carbene complex 10 fails to transfer the carbene to
imine 5a and to give aziridine 6a, we rule out that the
aziridination reaction occurs according to path a in Scheme 1.
To double-check the possible involvement of a carbene
intermediate in catalytic aziridination, we used a standard
3
2
and for metal-bound ethyl diazoacetate. It should be noted
4
1
13
trapping test for azomethine ylides. In a catalytic run
that the low-temperature splitting affects all the H, C, and
N NMR signals of the NNCH−CO Et moiety, either
15
performed with 4PF6 as catalyst (10 mol %) and the
temperature gradient described above in the presence of
dimethyl fumarate (10 equiv vs 5a), the aziridine yield was only
slightly reduced from 26 to 23%, and no pyrrolidine was
observed, which strongly disfavors the intermediacy of an
2
free or metal-bound.
4
azomethine ylide and, more in general, of a carbene complex
27
(
path a in Scheme 1).
Attempted Coordination of the Imine. In an experiment
designed to test the alternative pathway involving Lewis acid
activation of the imine (Scheme 1b), imine 5a (1 equiv) was
+
added to [RuCl(OEt )(PNNP)] (4PF ) in CD Cl . As
2
6
2
2
3
1
indicated by the P NMR spectra of the reaction solution at
5 and −78 °C, the main species present in solution is the
unreacted complex 4PF , and no signals were detected that may
be assigned to an imine ruthenium complex (Scheme 5b).
Also, ( P, H)-HMQC and ( H, H)-NOESY experiments at
78 °C showed that there is no significant contact between the
H atoms of the PNNP ligand and those of imine 6a, which
further rules out the formation of an imine complex, at least in
detectable amounts. The addition of EDA (1 equiv) to this
2
6
28
31
1
1
1
−
solution at −78 °C converted 4PF to the carbene complex 10,
6
Figure 1. 13C NMR CHCO Et signals of complex 13C-8 and of free
which decomposed after several hours at room temperature
without producing aziridine.
2
EDA (marked with “*”) (126 MHz, CD Cl ).
2
2
4
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As no aziridine was observed at −78 °C, the sample was
slowly warmed to −20 °C, at which temperature a small
1
3
amount (10%) of C-labeled aziridine was detected by means
13
1
of a ( C, H)-HMQC experiment. After the sample was cooled
1
3
1
31
to −60 °C to slow down the reaction, the C, H, P (and
1
5
N, see below) NMR spectra revealed that the major species
present in the reaction solution was the ethyl diazoester
1
3
+
13
complex trans-[RuCl( C-EDA)(PNNP)] ( C-8) (Scheme
7
3
3
).
Scheme 7
Figure 3. 31P NMR spectrum (202 MHz, CD Cl , −60 °C) of the
2
2
13
reaction solution of 4PF6 with C-EDA (10 equiv) showing the
13
+
13
signals (8a and 8b) of [RuCl( C-EDA)(PNNP)] ( C-8) (62%),
dinitrogen complex 9 (29%), and of an unknown impurity (marked
with an asterisk) (9%).
In the 13C NMR spectrum, the carbenoid N CHCO Et
2
2
1
3
carbon atom of C-8 resonates at δ 58.0 and 58.1, which is
34
diagnostic of an approximately linear N−N−C moiety and
close to that of the free diazoalkane at δ 47.5 and 46.5 (s-cis and
31a
13
1
s-trans, respectively) (Figure 2). The C (and H) NMR
Figure 4. 31P NMR signals of 13C-8 (202 MHz, CD Cl ) at different
2
2
temperatures showing the decoalescence of the signals of the s-cis and
s-trans isomers (8a and 8b) (the asterisk marks the unknown impurity
2
5,28
deriving from 4PF6).
.
13
1
Figure 2. ( C, H)-HMQC NMR spectrum of the reaction solution of
13
31
4
PF , imine 5a, and C-EDA (1:1:10) (500 MHz, CD Cl , −60 °C).
confirmed by a selective irradiation experiment of the P NMR
signal at δ 42.1 at −40 °C, which saturated and suppressed the
signal of the other isomer at δ 41.1. Accordingly, upon raising
the temperature to −20 °C, the signals coalesce and then
resolve into a single AX system at 20 °C (Figure 4). Finally, a
6
2
2
13
The CHCO Et signals of C-8 are labeled “*”.
2
signals of 13C-8 exhibit the typical dynamic behavior discussed
1
3
above for C-EDA (Figure 1), but the decoalescence
temperature is much lower than for free EDA, which will be
discussed below.
31
1
( P, H)-HMQC NMR spectrum at −60 °C (Figure S9 in the
Supporting Information) revealed the signals of the N C-H
proton of the C-EDA ligand, which does not exhibit NOESY
1
3
2
The 31P NMR spectrum of the reaction solution at −60 °C
13
(
Figure 3) shows that the major P-containing species in
contacts to any other signal.
13
13
solution is the C-EDA complex C-8 (62%), whose signals
appear as two resolved AX systems (8a and 8b) in a 1:1 ratio
owing to the freezing out of the s-cis/s-trans isomerism. Besides
We formulate the EDA complex trans-[RuCl(EDA)-
(PNNP)]PF as an end-on diazoalkane complex of type Ia or
Ib (Chart 2) on the basis of the C NMR shifts and of
chemical analogy, as transition metals of the d configuration
6
13
13
6
the signals of the s-cis and s-trans isomers of EDA complex C-
3
5
8
,
a slightly broadened signal at ca. δ 49 (31% of total
tend to form linear or singly bent end-on diazoalkane
3
4a,36,37
intensity) is assigned to the dinitrogen complex 9 (Scheme 7).
The AX patterns marked with asterisks in Figures 3 and 4
belong to the already observed noncarbenoid impurity (see
footnote 28).
The assignment of signals 8a and 8b to the s-cis and s-trans
rotamers of 8 in slow mutual exchange at this temperature was
complexes.
For instance, [RuCl (L)(PNP)] (L =
2
diazofluorene, PNP = 2,6-bis(di-tert-butylphosphinomethylpyr-
idine)) features Ru−N−N and N−N−C angles of 158.3(2)°
3
4g
and 170.1(3)°, respectively.
Linear end-on diazoalkane
8
complexes are well-known with d metals as well, and in
34d−f
particular of rhodium(I) and iridium(I).
4
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Chart 2
indicates that the two phosphorus atoms occupy cis positions to
38b
the dinitrogen ligand. A signal at δ −40.2, which is diagnostic
15
of a Ru−N N moiety, suggests an equilibrium between the
1
5
15
Ru− N−N and the Ru−N− N regioisomers and rules out the
38b,40
bridged end-on/end-on coordination.
This equilibrium
possibly involves N -dissociation from 9, as the signal of free
2
1
3
5
1
41
NN in solution is visible at δ −71.0. The low-temperature
P signal of 9 is a singlet (Figure 3) that broadens at higher
temperatures, possibly because of the Ru− N−N/Ru−N− N
exchange. This multiplicity is apparently inconsistent with the
15
15
+
suggested formulation trans-[RuCl(N )(PNNP)] , but the two
2
Conclusive evidence of the formation of the EDA (8) and
dinitrogen (9) complexes was obtained by repeating the above
phosphines might be fortuitously isochronous, as the
inequivalent P atoms of C -symmetric trans Ru/PNNP
1
5
1
reaction, ceteris paribus, with terminally N-labeled
19
complexes generally exhibit similar chemical shifts.
1
5
15
NNCHCCOEt ( N-EDA, see Supporting Information).
In sum, the above experiments show that, when a CD Cl
The 3 P NMR spectrum of the reaction solution at −80 °C
1
2
2
solution of [RuCl(OEt )(PNNP)]PF (4PF ) and imine 5a (1
2
2
6
6
shows a J coupling constant of about 2 Hz in the high-
13
15
P,N
equiv) is treated with C-EDA (or N-EDA) in excess (10
frequency 31P NMR signals of the cis-P−Ru− NNCHCCOEt
15
equiv) at −78 °C, the EDA complex trans-[RuCl(EDA)-
1
5
+
15
moiety of trans-[RuCl( N-EDA)(PNNP)] ( N-8) (Figure
+
3
8
15
(PNNP)] (8) is the major species in solution below −20 °C.
5
). The N NMR spectrum of the reaction solution at −60
We have recently reinvestigated the behavior of [RuCl(OEt )-
2
(
PNNP)]PF (4PF ) in CD Cl solution and found that it
6 6 2 2
dissociates to give the five-coordinate complex 2 and Et O even
2
below room temperature, whereas the aqua complex 3 is
19
considerably more stable and less labile (Scheme 3). As the
Et O adduct 4PF reacts with a stoichiometric amount of EDA
2
6
to give 8 quantitatively even at −78 °C, we conclude that end-
on-bound EDA is a better ligand than Et O and is in agreement
2
with the weak binding of Et O. The reactivity of the EDA
2
complex 8 is discussed in the next paragraph.
Reaction of EDA Complex 8 with Imine 5a. Upon
slowly raising the temperature of solutions containing the
13
diazoester complex 8, imine 5a, and an excess of C-EDA from
−78 °C, the imine is fully converted to aziridine 6a, and the
signals of free EDA disappear (see Supporting Information,
experiment 3). After reaching room temperature, the diazoester
Figure 5. 31P NMR signals of [RuCl( N-EDA)(PNNP)] ( N-8)
13
+
15
(
(
202 MHz, CD Cl , −80 °C) showing the P,N-coupling of 2 Hz
signals marked “*” belong to an unknown impurity).
2
2
25,28
.
1
3
complex 8 begins to decay to the carbene complex C-10 just
after free N213CHCO Et is consumed completely (Figure S11
2
°
C shows, along with the signals of the s-trans and s-cis isomers
1
3
1
5
31b
in the Supporting Information). The formation of C-10 is
quantitative within 15 min. After 4 h, the trans-carbene complex
C-10 is decomposed to the alkyl derivative [RuCl-
of free, unreacted NNCHCO Et at δ −7.6 and −1.3, two
2
broad signals at δ −24.8 and −25.3 that we assign to the
1
3
1
5
+
15
rotamers of trans-[RuCl( N-EDA)(PNNP)] ( N-8) (Figure
3
9
13
13
42
6
).
A broad triplet at δ −89.9 is assigned to the Ru− NN
isomer of the above-mentioned dinitrogen complex trans-
( CH
complex 4PF
2 2
CO Et)(PNNP)] ( C-11). The reaction between
15
13
, imine 5a, and C-EDA (1:1:10 ratio) in CD Cl
2 2
6
was repeated three times in the temperature range between
−78 and 25 °C with essentially the same results.
+
2
31 15
[
RuCl(N )(PNNP)] (9). The J ( P, N) value of 2.3 Hz
2
The above experiment was slightly modified to test whether
aziridine 6a is formed in the presence of EDA complex 8 after
quantitative EDA consumption (see experiment 5 in the
Supporting Information). Thus, a CD Cl solution of the EDA
2
2
complex 13C-8 (prepared as describe above) was warmed to 0
°
C in the NMR spectrometer until free N213CHCO Et was
2
consumed. Then, the sample was cooled to −78 °C, imine 5a
(
1 equiv) was added thereto, and the sample temperature was
13
1
increased in 20 °C steps. At −20 °C, a ( C, H)-HMQC
experiment showed the signals of 13C-labeled aziridine 6a
(
22%), along with those of unreacted EDA complex 8 (74%)
and a small amount (4%) of carbene complex 10 (Scheme 8).
The facts that no free EDA is present in the solution under
these conditions and that the dissociation of EDA complex 8 is
43
slow on the NMR time scale below 0 °C are a strong
indication that the carbene is transferred to the imine from the
EDA complex 8.
Figure 6. 15N{ H} NMR spectrum of the reaction solution of 4PF , 5a
1
6
(
1 equiv), and 15N-EDA (10 equiv) at −60 °C (50.7 MHz, CD Cl ).
2
2
4
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4
6
Scheme 8
place. This has been originally proposed by Kodadek and
47 48
recently supported both by experiment and by theory.
44
Calculations on Rh(I)/PCP complexes have suggested that
the I−V coordination modes of phenyldiazomethane may be
close in energy. According to Milstein, the end-on complex I is
not a true intermediate in the decomposition of the diazoalkane
to carbene, but rather a resting state, and the diazoalkane
49
dissociates and reattacks the metal with the carbenoid C atom
to give a σ-C complex of type V, which then undergoes fast N
extrusion.
2
3
4g,44,50
An important consequence for the present discussion is that,
to form the carbene complex 10, the diazoester must dissociate
from complex 8 and reattack the coordinatively unsaturated
As the EDA complex 8 is competent for aziridine formation,
the rate of its decay to the carbene complex 10 must affect the
yield of aziridine, and hence the chemoselectivity of the
reaction. The possible mechanism of the formation of carbene
complex 10 and its involvement in the formation of diethyl
maleate are discussed in the next paragraphs.
[
RuCl(PNNP)]+ (2) with a different coordination mode.
During this process, any donor present in solution (such as
Et O or even the anion, see below) can intercept the 16-
2
electron species 2 to form a coordinatively saturated complex
that cannot react with EDA. The relevance of this point to the
chemoselectivity of aziridine formation will be discussed below.
The Formation of Maleate. To prove its involvement in
The Decay of EDA Complex 8. A key feature of the above
results is that the outcome of the reaction of [RuCl(OEt )-
2
+
(
PNNP)] (4PF ) with EDA depends on the amount of EDA
6
used. In fact, 4PF reacts with a stoichiometric amount of EDA
6
the formation of diethyl maleate, the nonlabeled carbene
to give the carbene complex 10 at −78 °C, whereas an excess of
EDA (10 equiv) gives the diazoester complex 8 as the most
abundant species in solution. At −78 °C, only about 5% of
EDA is converted to diethyl maleate (7) after 8 h, whereas
substantial amounts of 7 (about 50%) are formed at −20 °C
during few minutes. However, the carbene complex 10 is
formed in detectable amounts only after depletion of free EDA.
We explain the above observations on the basis of the
reactions in Scheme 9. The Et O adduct 4PF , in which the
+
complex [RuCl(CHCO Et)(PNNP)] (10), prepared from
2
[
RuCl(PNNP)]PF (2) and EDA in CD Cl at room
6
2
2
18a,51
13
temperature,
was treated with1 C-EDA (2 equiv) at −78
13
1
°
C. The ( C, H)-HMQC and H NMR spectra recorded
immediately after reinserting the sample into the spectrometer
1
3
at −78 °C showed the presence of the diazoester complex C-
8
(
maleate, which were quantified by integration of the H NMR
spectrum (41% mono- C-labeled 7b, 52% doubly labeled 7c,
and 7% unlabeled 7a) (Scheme 10).
1
3
, of traces of the carbene complex [RuCl( CHCO Et)-
2
13
PNNP)]PF ( C-10), and of different isotopomers of diethyl
6
2
6
1
13
Scheme 9
Scheme 10
The formation of the monolabeled 7b (41%) is diagnostic of
1
9
13
the reaction of N2 CHCO Et with unlabeled [RuCl-
Et O ligand is weakly bound, possibly reacts with EDA with
2
2
+
13
(
CHCO Et)(PNNP)] (10), whereas 2,3-bis( C)-ethyl mal-
the intermediacy of the 16-electron complex 3a (equilibrium a)
to give either the end-on EDA complex 8 in a reversible fashion
path b) or irreversible N extrusion to the carbene complex 10
2
eate (7c, 52%) is formed by successive carbene formation from
C-EDA. Accordingly, upon increasing the temperature, the
C-10:10 ratio gradually increased as the nonlabeled carbene
1
1
3
3
(
2
(
path c). When present in excess, EDA reacts with the carbene
complex 10 to give diethyl maleate (7) (path d), and a further
equivalent of EDA re-forms the diazoester complex 8. This
reaction sequence explains why the EDA complex 8 is the main
species in solution in the presence of EDA in excess and why
large amounts of carbene complex 10 are formed only after
quantitative EDA consumption.
complex was consumed. Finally, we attribute the small amount
12
13
of nonlabeled 7a (7%) to residual C in N CHCO Et, whose
2
2
isotopic purity was 97%.
We conclude that the carbene complex 10, besides being
nonproductive in aziridination, is competent for the formation
of diethyl maleate by reaction with the diazoalkane.
+
Overall, diazoalkane complexes are assumed to form the
corresponding carbene complexes by dinitrogen extrusion, but
the mechanistic details of this process are still not completely
Analogously, the carbene complex [Rh(CHPh)(PCP)] (PCP
is the tridentate pincer ligand 1,3-bis[(diisopropylphosphanyl)-
methyl]benzene) reacts with PhCHN to give stilbene at −50
2
3
4g,44,45
understood.
A crucial point for the decomposition to
°C, a temperature at which the decomposition of the
carbene is that an end-on diazalkane complex of type I must
diazoalkane complex to the corresponding carbene species is
44
isomerize to structure V (Chart 2) before N extrusion can take
very slow. Also Co(II) porphyrin carbene complexes react
2
4
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2
6c
+
with EDA to give diethyl maleate. The selective formation of
adduct [RuCl(OEt )(PNNP)] (4) and the 16-electron
2
+
the cis-olefin (that is, maleate rather than fumarate) with the
complex [RuCl(PNNP)] (2) (Scheme 11c) is fast on the
Ru/PNNP catalyst 4PF is consistent with the previously
NMR time scale at room temperature and is frozen out at −40
6
19
suggested mechanisms for the nucleophilic attack of aryldiazo-
°C. Therefore, we suggest that diethyl ether competes with
EDA for coordination to the 16-electron complex 2 at the
reaction temperature (0 °C) and hence slows down the
formation of the carbene complex 10 because the latter reaction
52
methanes onto metal carbene complexes of Rh(II) and Cu(I).
A New Imine Aziridination Mechanism. The available
evidence suggests that the Ru/PNNP-catalyzed imine aziridi-
nation follows the unprecedented path c of Scheme 1, whose
key feature is the intermediacy of the end-on diazoester complex
2
requires the η -N,N-coordination of EDA, which should be less
44
favored than end-on coordination as in 8. In agreement with
+
trans-[RuCl(EDA)(PNNP)] (8) (Scheme 11). In fact, the
the above interpretation, aziridine is formed also at room
temperature with the aqua complex [RuCl(OH )(PNNP)]PF
2
6
Scheme 11
20
(
3), because water binds to ruthenium more strongly than
Et O and its dissociation is less favorable both thermodynami-
2
19
cally and kinetically.
The above line of reasoning would also explain the anion
effect on the chemoselectivity (Table 1). Although the low-
temperature studies were inconclusive (see above and
Supporting Information), there is literature precedent for the
ranking of the coordinating ability of so-called “noncoordinat-
−
−
−
ing” anions such as PF , BF , and SbF , which shows that
6
4
6
BF4 and SbF6− are more coordinating than PF . In the case
−
−
24
6
of 4Y, we suggest that SbF6 and BF4− intercept the 16-electron
−
+
−
complex [RuCl(PNNP)] (2) more efficiently than PF , thus
6
53
preventing the decay of EDA to carbene. Overall, the above
results suggest that any coordinating species present in solution
(
either neutral molecule or anion) improves the chemo-
selectivity toward aziridination, which opens the space for
further improvement.
Why Are Ruthenium Carbenes Weak Electrophiles?
We have discussed above the role played by the EDA complex
8
and by the carbene complex 10 in the formation of aziridine.
The question to be answered in this paragraph is why imine 5a
reacts with the EDA complex 8 but not with carbene complex
10. The lack of reactivity of carbene complex 10 toward imines
reactions discussed above show that complex 8, formed from
finds an interesting precedent in Che’s report of ruthenium
27
the labile Et O adduct 4 or with the intermediacy of the 16-
porphyrin-catalyzed imine aziridination. Also in that case, the
carbene complex formed in situ from [Ru(CO)(F -TPP)]
2
19
electron complex 2, (i) is the resting species of the catalyst
during aziridination in the presence of an excess of EDA, (ii)
reacts with the imine to give aziridine 6a and the dinitrogen
complex 9 (reaction b), and (iii) decays to the carbene complex
2
0
(H (F -TPP) = meso-tetrakis(pentafluorophenyl)porphyrin)
2
20
failed to react with imines. In contrast, imine aziridination
4
6
with copper(I) and rhodium(II) catalysts is thought to
involve nucleophilic attack of the imine onto a carbene complex
1
0 after quantitive EDA consumption (reaction e). The latter
reaction probably involves EDA dissociation from 8 and
reattack of EDA to give the carbene complex 8 (reactions d,
e). Literature precedents suggest that the latter reaction may
involve an undetected intermediate, possibly an EDA adduct
with a different binding mode as discussed above (Chart
(
Scheme 1a). Late transition metals are known to form carbene
54
complexes that are particularly electrophilic. An extremely
1
8a
simplified, but useful, explanation of the high electrophilicity of
55
mononuclear transition metal complexes is given in Figure 7,
which sketches the π bond between the metal and the carbene
ligand.
3
4g,44,46,47
2).
In the reactions on the left of Scheme 11, the EDA adduct 8
produces aziridine (reactions a and b), whereas the right branch
leads to the formation of diethyl maleate (7) by the reaction of
the carbene complex 10 with of EDA (reaction f). This reaction
has been observed even at −78 °C (see above) and is thus
faster than carbene transfer from the EDA complex 8 to the
imine. Therefore, the chemoselectivity toward aziridine is
controlled by the rate of formation of carbene 10.
The coordinatively unsaturated complex 2 is the most
reactive species in solution and most probably the common
intermediate in the formation either of the EDA adduct 8 or of
the carbene complex 10. Therefore, all factors that influence its
concentration and reactivity in solution are expected to play a
pivotal role in determining the chemoselectivity. We have
Figure 7. Qualitative sketch of form and energy of the π-M−C orbital
in carbene complexes.
previously reported that the equilibrium between the Et O
2
4
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The energy of the metal d orbital sinks significantly below
that of the p orbital of the carbenoid C atom upon changing the
metal from ruthenium (case A) to a late transition metal such
as copper (case B). Therefore, going on from A to B, the π-
bonding MO increases its localization on the metal, whereas the
empty π* orbital shifts toward the carbene. As the latter orbital
is the LUMO involved in a nucleophilic attack, carbene
complexes of late transition metals tend to be more
electrophilic than those of the elements to their left in the
periodic table. Therefore, we suggest that the electrophilicity of
ruthenium carbenes may be too low for azomethine ylide
formation with imines, which are weak nucleophiles (Schemes
contribution to the resonance hybrid than in free EDA, thus
accounting for the increased nucleophilicity of the former.
A qualitative MO-LCAO analysis of the π-back-donation
from the d metal ion reinforces this line of reasoning. The
HOMO of free diazomethane is a nonbonding orbital of π-
6
symmetry that is substantially localized on the carbon atom
56
(Figure 8, left). In the linear diazoalkane complexes (B and
1
a and 2). In the next paragraph, we discuss electronic
Figure 8. Qualitative sketch of the HOMO of free (left) and metal-
arguments that support the alternative pathway c, in which the
metal-bound diazoalkane acts as nucleophile toward the imine.
Reactivity of Diazoalkane Complexes. In linear (Ia) or
singly bent (Ib) end-on diazoalkane complexes (Chart 2), the
bound (right) CH N .
2
2
57
B′, Chart 3), the 4-electron π−π repulsion with the fully
6
occupied d orbitals of π-symmetry of the octahedral d metal
−
diazoalkane acts as a 2e σ-donor, but the bonding interaction
ion destabilizes the HOMO of the CH N2 ligand and
2
is complemented, at least in principle, by a π-back-bonding
contribution with late transition metals. Accordingly, the
structure of end-on bound diazoesters is very sensitive to the
electronic properties of the metal and to the substitution
pattern of the carbenoid C atom. Complexes of type Ia contain
a neutral diazoalkane ligand whose carbenoid atom has some
sp character, which increases its carbanion character and
hence its nucleophilicity. To understand this, it is useful to
consider the total valence bond representation of non-
coordinated EDA to which both structures A and B contribute.
This is depicted in Chart 3, which shows the relevant canonical
structures for free and coordinated EDA.
rehybridizes it toward the carbenoid C atom (Figure 8,
58
right), thus increasing its nucleophilic character. In agreement
with the suggestion that the coordination to an electron-rich
late-transition metal enhances the nucleophilicity of diazo-
akanes, Lebel has claimed that the [RhCl(PPh ) ]-catalyzed
3
3
methylenation of aldehydes with trimethylsilyldiazomethane
3
34a
5
9
involves an end-on linear TMSCHN2 complex whose
carbenoid C atom undergoes protonation by 2-propanol and
60
other alcohols.
Also, diazoalkanes are believed to behave as nucleophiles
1
2e
toward imines in acid-catalyzed aziridination
and in 1,3-
61
dipolar cycloaddition reactions. The frontier orbital (FO)
energies calculated for ethyl diazoacetate (HOMO: −9.75
62
63
Chart 3
eV) and N-methylbenzaldimine (LUMO 3.0 eV), which can
be taken as model for 5a, show a FO gap of 12.75 eV (Figure
9
). Both in the Brønsted acid-catalyzed aza-Darzens reac-
Figure 9. Effect of coordination on the energies of the frontier orbitals
involved in carbene transfer from EDA to imine.
13−15
11,12
tion
and with Lewis acidic catalysts,
this gap is reduced
because the acid stabilizes the LUMO of the imine. In the case
of the ruthenium-catalyzed aziridination, we suggest that the
FO gap is reduced because the coordination to a metal with
filled π-orbitals destabilizes the HOMO of the diazoester (as
discussed above), which promotes the nucleophilic attack of the
carbenoid C atom of EDA to the free, nonactivated imine.
As the HOMO of the diazoester and the LUMO of the imine
are mainly localized on the respective C atoms, the formation
of the C−C bond should play a major role in both cases.
Accordingly, it is broadly accepted that the first step of acid-
catalyzed imine aziridination is the attack of the diazoalkane
onto the C−N π-bond to give a α-diazononium-β-amino ester
We recall that the chemical shift of the carbenoid C atom and
the dynamic NMR spectroscopic behavior suggest a linear, end-
on structure for the EDA complex 8, which implies that the
canonical structures B1 and B2 prevail over A1. The low
rotation barrier around the EtO C−CHN bond in 8 as
2
2
compared to free EDA (Figure 1) indicates that the
contribution of the canonical structures of type B to resonance
increases upon coordination at the cost of structures of types A
and B′. We conclude that, in coordinated EDA, the canonical
structures B1 and B2, in which the carbenoid C atom is mostly
3
sp and bears a formal negative charge, give a larger
4
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Organometallics
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that collapses to the aziridine by intramolecular, S 2-like attack
of the azomethine nitrogen onto the carbenoid C atom. In
were carried out by the Laboratory of Microelemental Analysis (ETH
N
15a
̈
Zurich). Enantiomeric excesses were determined by chiral HPLC (IB
column, 3 μm) equipped with a DAD detector to check peak purity.
Standard Catalytic Run with 4Y. In the optimized protocol (see
Supporting Information, Table S1), the catalyst was prepared by
stirring a CH Cl solution (3 mL) of [RuCl (PNNP)] (1) (0.0482
the case of the EDA adduct 8, the elimination of N is assisted
2
by the formation of the dinitrogen complex trans-[RuCl(N )-
2
+
64
(
PNNP)] (9) (Scheme 11).
The observation of the dinitrogen complex 9 is enlightening
for a further reason. As N is weaker both as σ-donor and as π-
acceptor than the isoelectronic CO ligand, only a few
ruthenium complexes meet the requirements for the formation
of dinitrogen complexes, which are the presence of a ligand
with low trans influence (Cl or N) in the trans position (to
2
2
2
mmol, 0.1 equiv) and (Et O)Y (0.0482 mmol, 0.1 equiv) at room
3
2
temperature overnight, upon which the color changed from red to
brown. Then, the imine (0.49 mmol, 1 equiv) was added, and the
resulting solution was cooled down to 0 °C. Ethyl 2-diazoacetate
(EDA) (0.48 mmol, 1 equiv, or 1.92 mmol, 4 equiv, neat) was added
in one portion, and the reaction solution was stirred for 24 h at 0 °C.
Then, a known amount of 2,4,6-trimethoxybenzene was added as
internal standard to the crude mixture, and the conversion of the imine
65
avoid competition with N ) and of strong σ-donors (aryl,
2
alkynyl, or alkyl phosphines) to enhance the electron density at
(
5) and the yield of crude cis- and trans- aziridines (6) were
the metal and hence π-back-bonding to N . Both conditions are
1
2
determined by H NMR spectroscopy. The oily residue was subjected
to flash chromatography on silica (hexane/ethyl acetate 95:5) to give a
white crystalline solid, which consisted exclusively of cis-aziridine. The
enantiomeric excess of cis-6 was determined by chiral HPLC analysis
(see Supporting Information).
fulfilled for some recently reported dinitrogen complexes of
6
6
67
68
69
70
ruthenium(II) with a PCP, PNP, POP, P N , or P4
2
2
+
donor set. In trans-[RuCl(N )(PNNP)] (9), N is trans to the
2
2
chloro ligand, which has a small trans influence. On the other
hand, the formation of 9 suggests that, despite the positive
charge of the complex and the presence of aryl (rather than
ASSOCIATED CONTENT
Supporting Information
■
alkyl) phosphines, the π-back-donating ability of the [RuCl-
*
S
+
(
PNNP)] fragment is significant, which plays a key role in the
Details of NMR spectroscopic studies, experimental details of
catalytic reactions, and product characterization data. This
material is available free of charge via the Internet at http://
pubs.acs.org.
activation of EDA as discussed above.
Conclusion and Outlook. Ruthenium/PNNP catalysts
give the highest enantioselectivity ever observed in the
transition metal-catalyzed aziridination of imine with diazo-
esters. We suggest that the reaction mechanism implies carbene
transfer from an intermediate diazoalkane complex rather than
from a carbene complex. The fundamental difference with Cu-
and Rh-based catalysts is that no azomethine ylide is formed,
whose dissociation from the chiral catalyst has been held
responsible for the low enantioselectivity observed with late
transition metal catalysts. The disclosure of this unprecedented
mechanism generates new hope in the endeavor of developing
highly enantioselective imine aziridination catalysts based on
transition metals that may complement those based on chiral
acids. Our next goal is to produce further evidence for the
suggested mechanism and to gather fundamental understanding
of the factors that govern the decay of the diazoalkane adduct
to the carbene complex and the mechanism of enantioselection,
which is necessary to improve the chemoselectivity toward
aziridine formation.
AUTHOR INFORMATION
Corresponding Author
E-mail: mezzetti@inorg.chem-ethz.ch.
■
*
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors are grateful to the Swiss National Science
Foundation for financial support (Grant No. 2-77767-10).
REFERENCES
■
(
3
1) (a) Michaux, J.; Niel, G.; Campagne, J. M. Chem. Soc. Rev. 2009,
8, 2093. (b) Sweeney, J. B. Chem. Soc. Rev. 2002, 31, 247.
(
c) McCoull, W.; Davis, F. A. Synthesis 2000, 1347. (d) Hu, X. E.
Tetrahedron 2004, 60, 2701.
2) Moessner, C.; Bolm, C. Catalyzed Asymmetric Aziridinations. In
(
EXPERIMENTAL SECTION
■
Transition Metals for Organic Synthesis, 2nd ed.; Beller, M., Bolm, C.,
Eds.; Wiley-VCH: Weinheim, DE, 2004; Vol. 2, pp 389−402.
(3) (a) Pellissier, H. Tetrahedron 2010, 66, 1509. (b) Friestad, G. K.;
General. Reactions with air- or moisture-sensitive materials were
carried out under an argon atmosphere using Schlenk techniques. All
solvents were distilled from an appropriate drying agent under argon
prior to use (CH Cl and CD Cl from CaH , hexane from Na/
Mathies, A. K. Tetrahedron 2007, 63, 2541. (c) Mu
Chem. Rev. 2003, 103, 2905.
̈
ller, P.; Fruit, C.
2
2
2
2
2
benzophenone, diethyl ether from Na/phthalic acid ethyl ester).
(4) Hansen, K. B.; Finney, N. S.; Jacobsen, E. N. Angew. Chem., Int.
Ed. 1995, 34, 676.
(5) Bartnik, R.; Mloston, G. Tetrahedron 1984, 40, 2569.
[
(
RuCl (PPh ) ] and [RuCl (PNNP)] (1) (PNNP = N,N′-bis{o-
2
3
3
2
diphenylphosphino)benzylidene}-(1S,2S)-diaminocyclohexane) were
7
1,72
prepared as reported.
bromobenzylidene)cyclohexane-1,2-diamine, (Et O)PF , and (Et O)-
Commercial (1S,2S)-N,N′-bis(2-
(6) Moran, M.; Bernardinelli, G.; Mu
78, 2048.
̈
ller, P. Helv. Chim. Acta 1995,
3
6
3
BF (stabilized with 3−5% diethyl ether) were used without further
(7) (a) Juhl, K.; Hazell, R. G.; Jorgensen, K. A. J. Chem. Soc., Perkin
Trans. 1 1999, 2293. See also: (b) Redlich, M.; Hossain, M. M.
Tetrahedron Lett. 2004, 45, 8987.
(8) (a) Aggarwal, V. K.; Thompson, A.; Jones, R. V. H; Standen, M.
C. H. J. Org. Chem. 1996, 61, 8368. (b) Aggarwal, V. K.; Vasse, J. L.
Org. Lett. 2003, 5, 3987. (c) Aggarwal, V. K.; Winn, C. L. Acc. Chem.
Res. 2004, 37, 611.
(9) (a) Evans, D. A.; Faul, M. M.; Bilodeau, M. T.; Anderson, B. A.;
Barnes, D. M. J. Am. Chem. Soc. 1993, 115, 5328. (b) Li, Z.; Quan, R.
W.; Jacobsen, E. N. J. Am. Chem. Soc. 1995, 117, 5889.
(10) Kawabata, H.; Omura, K.; Uchida, T.; Katsuki, T. Chem. Asian J.
2007, 2, 248.
4
purification. Triethyloxonium hexafluoroantimonate was prepared by a
literature procedure by using silver hexafluoroantimonate instead of
7
3
13
silver tetrafluoroborate. Isotopically labeled N2 CHCO Et and
2
1
5
NNCHCO Et were prepared according to a published procedure
see Supporting Information). Imines were obtained from the
2
74
(
corresponding amines by condensation reactions. For NMR spectra,
1
13
H and C positive chemical shifts δ (in ppm) are downfield from
tetramethylsilane, and are referenced to the residual solvent signal.
Mass spectra were measured by the MS service of the Laboratorium
fu
̈ ̈
r Organische Chemie (ETH Zurich). Optical rotations were
measured in a thermostated 1 dm cell (20 °C). Elemental analyses
4
699
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Organometallics
Article
(
11) Casarrubios, L.; Perez, J. A.; Brookhart, M.; Templeton, J. L. J.
Org. Chem. 1996, 61, 8358.
12) Account article: (a) Zhang, Y.; Lu, Z.; Wulff, W. D. Synlett 2009,
715. Selected papers: (b) Hu, G.; Huang, L.; Huang, R. H.; Wulff,
(28) The only other significant signal is the already observed
2
unknown impurity featuring an AX pattern at δ 42.3 and 36.3 ( J
=
P,P′
(
2
24.8 Hz) (Figure S7 in the Supporting Information) of an unknown
product (13%), which cannot be either the imine complex [RuCl(5a)
+
W. D. J. Am. Chem. Soc. 2009, 131, 15615. (c) Hu, G.; Gupta, A. K.;
Huang, R. H.; Mukherjee, M.; Wulff, W. D. J. Am. Chem. Soc. 2010,
(PNNP)] , as it is formed also in the reaction of the ether complex
4PF with EDA, in which no imine is present (see Supporting
6
1
1
2
32, 14669. (d) Desai, A. A.; Wulff, W. D. J. Am. Chem. Soc. 2010, 132,
3100. (e) Vetticatt, M. J.; Desai, A. A.; Wulff, W. D. J. Am. Chem. Soc.
010, 132, 13104. (f) Gupta, A. K.; Mukhejee, M.; Wulff, W. D. Org.
Information, experiment 2, and footnote 25), or a carbenoid of any
kind or a different isomer of the carbene complex 10, as the present
reaction does not involve the addition of EDA.
(
29) The 31P NMR spectrum of the reaction mixture at −78 °C
Lett. 2011, 13, 5866. Seminal paper: (g) Antilla, J. C.; Wulff, W. D. J.
Am. Chem. Soc. 1999, 121, 5099.
(
showed that complex 4PF was quantitatively converted to a mixture
6
of products that encompass the dinitrogen complex 9 (13%) and
several unknown species.
13) (a) Hashimoto, T.; Uchiyama, N.; Maruoka, K. J. Am. Chem. Soc.
2
008, 130, 14380. (b) Hashimoto, T.; Nakatsu, H.; Yamamoto, K.;
1
(
30) The H NMR CHCO Et signal of free EDA is split by the
Maruoka, K. J. Am. Chem. Soc. 2011, 133, 9730. (c) Hashimoto, T.;
Nakatsu, H.; Yamamoto, K.; Watanabe, S.; Maruoka, K. Chem. Asian J.
2
13
1
coupling to C ( J
experiment 3, Figure S8). The signals of the carbene complex C-9,
C-maleate, and of an unknown C-containing species were present
= 205 Hz) (see Supporting Information,
C,H
1
3
2
011, 6, 607.
14) Selected aza-Darzens reactions catalyzed by chiral phosphoric
acids: (a) Akiyama, T.; Suzuki, T.; Mori, K. Org. Lett. 2009, 11, 2445.
b) Zeng, X.; Zeng, X.; Xu, Z.; Lu, M.; Zhong, G. Org. Lett. 2009, 11,
036.
15) (a) Review article: Johnston, J. N.; Muchalski, H.; Troyer, T. L.
1
3
13
(
13
in traces (2−3% of C-EDA). The latter species must be closely
related to EDA because of its J value, which is comparable to the
(
3
(
C,H
13
ones of N2 CHCO Et (Figure S8 in the Supporting Information).
2
This signal disappeared upon heating to −20 °C and was never
observed at higher temperatures.
Angew. Chem., Int. Ed. 2010, 49, 2290. (b) Mechanistic studies:
Troyer, T. L.; Muchalski, H.; Hong, K. B.; Johnston, J. N. Org. Lett.
(
31) (a) Kaplan, F.; Meloy, G. K. J. Am. Chem. Soc. 1966, 88, 950.
b) Lichter, R. L.; Srinivasan, P. R.; Smith, A. B.; Dieter, R. K.; Denny,
C. T.; Schulman, J. M. J. Chem. Soc., Chem. Commun. 1977, 366.
32) Gao, Y.; Jennings, M. C.; Puddephatt, R. J.; Jenkins, H. A.
Organometallics 2001, 20, 3500.
33) The trans configuration is indicated by a ( P, H)-HMQC
(
2
011, 13, 1790.
16) For the first synthesis of 2a, see: Gao, J. X.; Ikariya, T.; Noyori,
R. Organometallics 1996, 15, 1087.
17) Account articles on Ru/PNNP catalysts: (a) Mezzetti, A. Dalton
Trans. 2010, 7851. (b) Bonaccorsi, C.; Mezzetti, A. Curr. Org. Chem.
006, 10, 225.
18) (a) Bachmann, S.; Furler, M.; Mezzetti, A. Organometallics 2001,
0, 2102. (b) Bonaccorsi, C.; Bachmann, S.; Mezzetti, A. Tetrahedron:
(
(
(
31
1
(
spectrum of 8 at −60 °C (Figure S10 in the Supporting Information)
2
(
2
4
that shows a J coupling constant of about 18 Hz for both imine H
P,H
atoms (despite their signals being overlapped with those of the other
Ru/PNNP complexes in solution). This is diagnostic of two trans-P−
Ru−N moieties and hence of the trans configuration (see ref 19 for a
discussion).
Asymmetry 2003, 14, 845. (c) Bonaccorsi, C.; Mezzetti, A. Organo-
metallics 2005, 24, 4953.
(
3
(
19) Schotes, C.; Ranocchiari, M.; Mezzetti, A. Organometallics 2011,
0, 3596.
20) Ranocchiari, M.; Mezzetti, A. Organometallics 2009, 28, 3611.
(34) (a) Dartiguenave, M.; Menu, M. J.; Deydier, M.; Dartiguenave,
Y.; Siebald, H. Coord. Chem. Rev. 1998, 178, 623. See also:
(b) Mizobe, Y.; Ishii, Y.; Hidai, M. Coord. Chem. Rev. 1995, 139, 281.
Selected examples: (c) Brandt, L-; Wolf, J.; Werner, H. J. Organomet.
Chem. 1993, 444, 235. (d) Werner, H.; Schneider, M. E.; Bosch, M.;
Wolf, J.; Teuben, J. H.; Meetsma, A.; Troyanov, S. I. Chem.Eur. J.
20
(
21) In the previously reported procedure, EDA (1 or 4 equiv vs
4
PF ) was added (neat) in one portion to a cooled (−78 °C) CH Cl
6
2
2
solution (3 mL) containing 5a (0.48 mmol) and the catalyst 4PF (10
6
mol%) (prepared by activation of [RuCl (PNNP)] (1) (0.048 mmol)
with (Et O)PF (1 equiv) overnight), followed by rapid heating to
2
2
̈
000, 6, 3052. (e) Ortmann, D. A.; Weberndorfer, B.; Ilg, K.;
3
6
Laubender, M.; Werner, H. Organometallics 2002, 21, 2369. (f) Werner,
H.; Mahr, N.; Wolf, J.; Fries, A.; Laubender, M.; Bleuel, E.; Garde, R.;
Lahuerta, P. Organometallics 2003, 22, 3566. (g) Zhang, J.;
Gandelman, M.; Shimon, L. J. W.; Milstein, D. Organometallics
room temperature.
22) The yield of crude aziridine is given as the sum of the cis and
(
1
trans isomers as obtained by integration of the H NMR spectrum of
the crude reaction mixture after addition of 1,3,5-trimethoxybenzene
as internal standard.
2
008, 27, 3526. (h) Dias, E. L.; Brookhart, M.; White, P. S. J. Am.
Chem. Soc. 2001, 123, 2442.
35) We did not assign signals 8a and 8b to a particular isomer,
(
23) The fate of the small amounts of trans-6a was assessed by
performing a catalytic run under the conditions of Table S1, entry 4
see Supporting Information), but with a 2-fold amount of catalyst,
(
31
whereas the assignment of the P NMR signal at δ 49.2 (at −60 °C)
to a dinitrogen complex such as 9 is supported by the results of
reaction with NNCHCO Et (see below).
(
imine, EDA, and solvent. Under the standard workup conditions (flash
chromatography over silica with hexane/ethyl acetate in 95:5 ratio),
trans-6a was detected in the fractions containing the unreacted imine
15
2
(
36) The bending of N−N−C angle is diagnostic of some extent of
36a,b
π-back-bonding from the metal to the diazoalkane ligand.
5
(
a.
24) (a) Although there is no general consensus concerning the
(
(
a) Schramm, K. D.; Ibers, J. A. Inorg. Chem. 1980, 19, 1231.
b) Herrmann, W. A.; Kriechbaum, G.; Ziegler, M. L.; Wulknitz, P.
−
−
−
−
relative coordinating ability of PF , BF , and SbF , PF is
6
4
6
6
Chem. Ber. 1981, 114, 276. For further examples of linear or singly
6
considered to be the least coordinating anion in these series, see:
b) Beck, W.; Sunkel, K. Chem. Rev. 1998, 88, 1405. (c) Honeychuck,
R. V.; Hersh, W. H. Inorg. Chem. 1989, 28, 2869.
25) A further byproduct is an unknown species (14%) that features
bent N−N−C diazoalkane complexes of d metal ions, see refs 34c−f
(
̈
and: (c) Schramm, K. D.; Ibers, J. A. Inorg. Chem. 1977, 16, 3287.
(d) Menu, M. J.; Crocco, G.; Dartiguenave, M.; Dartiguenave, Y.;
Bertrand, G. J. Chem. Soc., Chem. Commun. 1988, 1598. (e) Bart, S. C.;
Bowman, A. C.; Lobkovsky, E.; Chirik, P. J. J. Am. Chem. Soc. 2007,
129, 7212. (f) Albertin, G.; Antoniutti, S.; Baldan, D.; Castro, J.;
Comparin, G. Organometallics 2013, 32 (11), 3157−3160.
(
2
an AX pattern at δ 42.3 and 36.3 ( JP,P′ = 24.8 Hz) (see Supporting
Information, experiment 1, Figure S5, and footnote 28).
(
26) (a) Zhang, L. R.; Chan, K. S. Organometallics 2007, 26, 679.
(37) (a) Additionally, both neutral and cationic d6 diazoester
complexes of osmium(II) are known, but have not been characterized
3
7b
37c
(
b) Lu, H. J.; Dzik, W. I.; Xu, X.; Wojtas, L.; de Bruin, B.; Zhang, X. P.
J. Am. Chem. Soc. 2011, 133, 8518. See also: (c) Penoni, Wanke, R.;
Tollari, S.; Gallo, E.; Musella, D.; Ragaini, F.; Demartin, F.; Cenini, S.
Eur. J. Inorg. Chem. 2003, 1452.
structurally: (b) Werner, H.; Stu
̈
er, W.; Wolf, J.; Laubender, M.;
Weberndorfer, B.; Herbst-Irmer, R.; Lehmann, C. Eur. J. Inorg. Chem.
̈
(
27) Li, Y.; Chan, P. W. H.; Zhu, N. Y.; Che, C. M.; Kwong, H. L.
1999, 1889. (c) Albertin, G.; Antoniutti, S.; Bordignon, E.; Carrera, B.
Inorg. Chem. 2000, 39, 4646.
Organometallics 2004, 23, 54.
4
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Organometallics
Article
15
(
38) (a) The 31P, N coupling was not resolved at −60°C, probably
(56) (a) Fleming, I. Molecular Orbitals and Organic Chemical
Reactions, reference ed.; Wiley-VCH: Weinheim, 2010; p 325.
(b) Jorgensen, W. L.; Salem, L. The Organic Chemist’s Book of
Orbitals; Academic Press: New York, 1973; p 127.
owing to the s-cis/s-trans equilibration process (Scheme 6) (see
2
31 15
Supporting Information, experiment 4). The J( P, N) value of ca. 2
Hz is diagnostic of a cis arrangement of the phosphine and EDA
38b
31
1
ligands.
The ( P, H)-HMQC spectrum shows a cross peak
(57) Caulton, K. G. New J. Chem. 1994, 18, 25.
1
between the H NMR signal (2 H) of the imine protons of the
PNNP ligand and the phosphines, which is diagnostic of a trans
(58) As the binding to a Lewis acidic cationic complex is expected to
decrease the electrophilicity of the ligand, the overall effect of the
coordination of a diazoalkane to a transition metal complex discussed
here is counterintuitive. However, it should be noticed that
diazoalkanes use an energetically low-lying orbital for the σ-bond to
the metal, whereas the HOMO has π-character with respect to the
metal−diazoalkane bond and its energy primarily responds to π-effects.
stereochemistry for the N complex 9, as discussed above for the EDA
2
complex 13C-8. (b) Donovan-Mtunzi, S.; Richards, R. L.; Mason, J. J.
Chem. Soc., Dalton Trans. 1984, 469.
33
(
39) The signals of 8 are broadened because of the lower barrier to
rotation in the complex as compared to free EDA, see Results and
5
7
Discussion.
(
2
(
Also, the presence of a π-donating chloro ligand trans to EDA in
complex 8 enhances the π-back-bonding from ruthenium to the EDA
ligand and hence increases its nucleophilicity.
40) Field, L. D.; Hazary, N.; Li, H. L.; Luck, I. J. Magn. Reson. Chem.
003, 41, 709.
41) In previous experiments,
NMR signal at δ ca. 49 of the dinitrogen complex 9, but we incorrectly
assigned it to trans-[RuCl (PNNP)] (1), which resonates at δ 48.0 in
1
8a,c
we have observed the broad 31
P
(59) For the preparation and X-ray study of a similar complex, see ref
3
(
4h.
60) (a) Lebel, H.; Paquet, V. J. Am. Chem. Soc. 2004, 126, 320.
Interestingly, Wilkinson’s catalyst [RhCl(PPh ) ] was found to be
2
16
15
CDCl3. Clearly, the use of NNCHCO Et was pivotal to assess the
3 3
2
more active in this reaction than the isoelectronic Ru(0) analogue
RuCl(NO)(PPh ) ]. A possible explanation based on the above
identity of 9.
(
42) After 10 h at 20 °C, the 31P NMR spectrum of the reaction
mixture shows the signals of the dinitrogen complex 9 (55%) and of
the alkyl complex [RuCl( CH CO Et)(PNNP)] ( C-11) (45%).
The latter signal is the AB part of an ABX system, where X is
Figure S12 in the Supporting Information). The alkyl complex C-11
is the main species in solution after 3 days at room temperature.
43) In a separate experiment in which the C NMR signal at δ 58.0
of the C-EDA ligand of 8 was irradiated in the presence of free C-
EDA at 0 °C, no effect on the intensity of the latter signal was
observed, which indicates that the exchange between free and
coordinated EDA is slow at 0 °C.
44) Cohen, R.; Rybtchinski, B.; Gandelman, M.; Rozenberg, H.;
Martin, J. M. L.; Milstein, D. J. Am. Chem. Soc. 2003, 125, 6532.
45) (a) Werner, H.; Schwab, P.; Bleuel, E.; Mahr, N.; Steinert, P.;
3 2
[
+
arguments is that NO , a very strong π-accepting ligand, competes for
the electron density on ruthenium and reduces the π-back-donation to
the diazoalkane and, thus, its nucleophilic character. (b) Lebel, H.;
13
13
2
2
6
0b
13
C
13
Paquet, V. Organometallics 2004, 23, 1187.
(
(61) Review article: (a) Huisgen, R. J. Org. Chem. 1976, 41, 403.
13
(b) Bastide, J.; Henri-Rousseau, O.; Aspart-Paccot, L. Tetrahedron
1974, 30, 3355.
(
13
13
(
2
(
62) Cheung, K. W. J.; Reynisson, J.; McDonald, E. Tetrahedron Lett.
010, 51, 5915.
63) (a) This value is more in keeping with the LUMO energy of
6
3b
6
3c
4
.2 eV calculated for methyleneimine than an alternative suggestion
(
63d
(
−0.21 eV). (b) Dal Colle, M.; Distefano, G.; Jones, D.; Guerrino,
A.; Seconi, G.; Modelli, A. J. Chem. Soc., Perkin Trans. 194, 789. (c)
See ref 56b, p 83. (d) Lerestif, J. M.; Perrocheau, J.; Tonnard, F.;
Bazureau, J. P.; Hamelin, J. Tetrahedron 1995, 51, 6757.
(
Wolf, J. Chem.Eur. J. 1997, 3, 1375. (b) Wolf, J.; Brandt, L.; Fries,
A.; Werner, H. Angew. Chem., Int. Ed. Engl. 1990, 29, 510.
(64) Further studies will be directed to assess the stereochemistry of
(
46) (a) Maxwell, J. L.; Brown, K. C.; Bartley, D. W.; Kodadek, T.
Science 1992, 256, 1544.
47) Wong, F. M.; Wang, J.; Hengge, A. C.; Wu, W. Org. Lett. 2007,
, 1663 and references therein.
48) (a) Nowlan, D. T.; Gregg, T. M.; Davies, H. M. L.; Singleton, D.
A. J. Am. Chem. Soc. 2003, 125, 15902. (b) Dzik, W. I.; Xu, X.; Zhang,
X. P.; Reek, J. N. H.; de Bruin, B. J. Am. Chem. Soc. 2010, 132, 10891.
49) Accordingly, an excess of EDA inhibits the formation of carbene
the approach between imine and diazoester, which can occur either in
12e
a transoid, antiperiplanar or in a cisoid, quasi [2 + 3] fashion.
65) Que, L.; Tolman, W. B. Comprehensive Coordination Chemistry
II; Pergamon: Oxford, 2003; Vol. 8.
66) Zhang, J.; Barakat, K. A.; Cundari, T. R.; Gunnoe, T. B.; Boyle,
P. D.; Petersen, J. L; Day, C. S. Inorg.Chem. 2005, 44, 8379.
67) (a) Zhang, J.; Gandelman, M.; Shimon, L. J. W.; Rozenberg, H.;
(
9
(
(
(
(
(
Milstein, D. Organometallics 2004, 23, 4026. (b) Amoroso, D.; Jabri,
A.; Yap, G. P. A.; Gusev, D. G.; dos Santos, E. N.; Fogg, D. E.
Organometallics 2004, 23, 4047.
complex 10, as it prevents the dissociation of 8 (besides scavenging the
carbene complex 9 to give diethyl maleate (7). In the experiments with
the Et O adduct 4PF , we did not observe any signal that may be
2
6
(
68) Major, Q.; Lough, A. J.; Gusev, D. D. Organometallics 2005, 24,
492.
69) Adams, C. J.; Bowen, L. E.; Humphrey, M. G.; Morrall, J. P. L.;
Samoc, M.; Yellowlees, L. J. Dalton Trans. 2004, 4130.
70) (a) Field, L. D.; Guest, R. W.; Vuong, K. Q.; Dalgarno, S. J.;
assigned to EDA coordination of type V.
50) These calculations have also shown that bulky ligands hinder
intramolecular isomerization along the pathway I → II → III → IV
or I → II → IV → V), hence hindering diazoalkane decomposition to
carbene.
2
(
(
(
(
51) The low-temperature 31P and H NMR spectra of the reaction
1
Jensen, P. Inorg. Chem. 2009, 48, 2246. (b) Takei, I.; Nishibayashi, Y.;
Ishii, Y.; Mizobe, Y.; Uemura, S.; Hidai, M. J. Organomet. Chem. 2003,
679, 32.
(
solution indicate the formation of the carbene species [RuCl(CH-
CO Et)(PNNP)] (10) (84%) and of the dinitrogen complex 9 (16%)
Figure S15 in the Supporting Information).
52) (a) Oshima, T.; Nagai, T. Tetrahedron Lett. 1980, 21, 1251.
b) Ravi Shankar, B. K.; Shechter, H. Tetrahedron Lett. 1982, 23, 2277.
53) At this stage, we have no rationale for the effect of the anion on
+
2
(
1
(
1
71) Hallman, P. S.; Stephenson, T. A.; Wilkinson, G. Inorg. Synth.
970, 12, 237.
72) Gao, J. X.; Ikariya, T.; Noyori, R. Organometallics 1996, 15,
087.
(
(
(
(
(73) Hederich, V.; Wunderlich, K. Arch. Pharm. 1958, 291, 541.
the enantioselectivity. However, we have previously observed a
beneficial effect of SbF6 on the enantioselectivity of the asymmetric
(74) Searle, N. E. Org. Synth. 1963, Collect. Vol. 4, 424.
−
cyclopropanation of olefins catalyzed by [RuCl (PNNP)] after
2
18c
activation with AgSbF6.
54) Nugent, W. A.; Mayer, J. M. In Metal-Ligand Multiple Bonds;
Wiley: New York, USA, 1988; pp 28−29.
55) A different explanation must be considered for dimeric Rh(II)
(
(
complexes, which form superelectrophilic carbene complexes via a 3-
center/4-electron M−M−C bond: Berry, J. F. Dalton Trans. 2012, 41,
700.
4
701
dx.doi.org/10.1021/om400735p | Organometallics 2013, 32, 4690−4701