Structure and Reactivity of Half-Sandwich Rh(+3) and Ir(+3) Carbene Complexes. Catalytic Metathesis of Azobenzene Derivatives

Article abstract of DOI:10.1021/jacs.7b12673

Traditional rhodium carbene chemistry relies on the controlled decomposition of diazo derivatives with [Rh₂(OAc)₄] or related dinuclear Rh(+2) complexes, whereas the use of other rhodium sources is much less developed. It is now shown that half-sandwich carbene species derived from [Cp?MX₂]₂ (M = Rh, Ir; X = Cl, Br, I, Cp? = pentamethylcyclopentadienyl) also exhibit favorable application profiles. Interestingly, the anionic ligand X proved to be a critical determinant of reactivity in the case of cyclopropanation, epoxide formation and the previously unknown catalytic metathesis of azobenzene derivatives, whereas the nature of X does not play any significant role in 'OH insertion reactions. This perplexing disparity can be explained on the basis of spectral and crystallographic data of a representative set of carbene complexes of this type, which could be isolated despite their pronounced electrophilicity. Specifically, the donor/acceptor carbene 10a derived from ArC( - N₂)COOMe and [Cp?RhCl₂]₂ undergoes spontaneous 1,2-migratory insertion of the emerging carbene unit into the Rh-Cl bond with formation of the C-metalated rhodium enolate 11. In contrast, the analogous complexes 10b,c derived from [Cp?RhX₂]₂ (X = Br, I) as well as the iridium species 13 and 14 derived from [Cp?IrCl₂]₂ are sufficiently stable and allow true carbene reactivity to be harnessed. These complexes are competent intermediates for the catalytic metathesis of azobenzene derivatives, which provides access to α-imino esters that would be difficult to make otherwise. Rather than involving metal nitrenes, the reaction proceeds via aza-ylides that evolve into diaziridines; a metastable compound of this type has been fully characterized.

Full text of DOI:10.1021/jacs.7b12673

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Article
Structure and Reactivity of Half-Sandwich Rh(+3) and Ir(+3) Carbene
Complexes. Catalytic Metathesis of Azobenzene Derivatives
Daniel J. Tindall, Christophe Werlé, Richard Goddard, Petra Philipps, Christophe Farès, and Alois Fürstner
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b12673 • Publication Date (Web): 14 Jan 2018
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Structure and Reactivity of Half-Sandwich Rh(+3) and Ir(+3)
Carbene Complexes. Catalytic Metathesis of Azobenzene De-
rivatives
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Daniel J. Tindall, Christophe Werlé, Richard Goddard, Petra Philipps, Christophe Farès, and Alois
Fürstner*
Max-Planck-Institut für Kohlenforschung, D-45470 Mülheim/Ruhr, Germany
ABSTRACT: Traditional rhodium carbene chemistry relies on the controlled decomposition of diazo derivatives with [Rh2(OAc)4]
or related dinuclear Rh(+2) complexes, whereas the use of other rhodium sources is much less developed. It is now shown that half-
sandwich carbene species derived from [Cp*MX2]2 (M = Rh, Ir; X = Cl, Br, I, Cp* = pentamethylcyclopentadienyl) also exhibit
favorable application profiles. Interestingly, the anionic ligand X proved to be a critical determinant of reactivity in the case of
cyclopropanation, epoxide formation and the previously unknown catalytic metathesis of azobenzene derivatives, whereas the na-
ture of X does not play any significant role in -OH insertion reactions. This perplexing disparity can be explained on the basis of
spectral and crystallographic data of a representative set of carbene complexes of this type, which could be isolated despite their
pronounced electrophilicity. Specifically, the donor/acceptor carbene 10a derived from ArC(=N2)COOMe and [Cp*RhCl2]2 under-
goes spontaneous 1,2-migratory insertion of the emerging carbene unit into the Rh−Cl bond with formation of the C-metalated
rhodium enolate 11. In contrast, the analogous complexes 10b,c derived from [Cp*RhX2]2 (X = Br, I) as well as the iridium species
13 and 14 derived from [Cp*IrCl2]2 are sufficiently stable and allow true carbene reactivity to be harnessed. These complexes are
competent intermediates for the catalytic metathesis of azobenzene derivatives, which provides access to α-imino esters that would
be difficult to make otherwise. Rather than involving metal nitrenes, the reaction proceeds via aza-ylides that evolve into diaziri-
dines; a meta-stable compound of this type has been fully characterized.
INTRODUCTION
be isolated in crystalline form (for its structure in the solid
state, see Figure S1) lends credence to the proposed pathway.12
Dirhodium carbenes A formed in situ upon reaction of a diazo
derivative with a (chiral) dinuclear Rh(II) tetracarboxylate
complex are exceptionally versatile synthetic intermediates
that power a host of transformations, including (asymmetric)
cyclopropanations, C−H insertions, cycloaddition reactions
and a myriad of ylide chemistry (Scheme 1).1-7 Although the
original report on the use of [Rh2(OAc)4] had indicated that a
salt as simple as RhCl3⋅3H2O is also catalytically competent,8a
mononuclear Rh(+3) carbene complexes in general and half-
sandwich carbenes derived from [Cp*RhX2] precursors in
particular have not been studied nearly as thoroughly.8a,9 Only
recently have intermediates of this type been implicated in
directed C−H activation reactions, in which the precatalyst is
first ionized e. g. with a soluble Ag(I) salt; the resulting elec-
trophilic metal fragment [Cp*Rh]2+ then (cyclo)metalates the
(arene) substrate prior to reaction with a diazo derivative to
give a putative Rh(+3) carbene of type C which undergoes
migratory insertion to give an ortho-substituted product.10 This
sequence has become quite popular: although most applica-
tions use transient carbenes C with at least one acceptor sub-
stituents (R1 and/or R2 = electron withdrawing group),11 the
example from our laboratory shown in Scheme 1 proves that
even a donor/donor carbene is sufficiently electrophilic to give
the meta-stable metallacycle 3 (Ar = MeOC6H4-) comprising a
rare tert-alkyl rhodium unit, which could be characterized by
crystallographic means (Figure 1).12 The fact that complex 4 as
the neutral analogue of the purported intermediate 2 could also
In contrast to the popularity of this type of directed C-H acti-
vation via cyclometalated rhodium carbenes C, proper piano-
stool Cp*Rh(+3) carbene complexes of type B have been
studied much less extensively.13 This situation, however,
might be unjustified: During recent studies on structure and
bonding in late-transition metal carbene complexes,14-16 we
found such species to be competent intermediates in catalytic
cyclopropanation, alkoxyfuran formation, as well as RO−H
and R3Si−H insertion reactions.17 Moreover, crystal structures
of two reactive complexes of type B have been obtained.17 We
now follow up on these initial results and disclose a more
comprehensive investigation into half-sandwich Cp*M car-
bene complexes of Rh(+3) and Ir(+3). Most notably, a striking
correlation between the chosen counterion X and the stability
and reactivity of the corresponding carbene was noticed that
can be explained on the basis of the acquired structural data.
Moreover, we now report that the new pianostool carbene
complexes enable catalytic metathesis reactions of azo com-
pounds which seem to be unprecedented in the literature.
Scheme 1. Prototype Rhodium Carbene Complexes (top);
Example of a “Donor/Donor” Carbene Participating in
Directed CH-Activation/Carbene Insertiona
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R
cis-disposition of the ester and the aryl substituent (see Figure
S2) implies intervention of the ylide conformer E which is
X
1
O
Rh
O
R
O
O
2
3
favored over D on steric grounds as it avoids the substituent R
from clashing into the bulky ligand sphere about Rh compris-
ing the Cp* and two chloride ligands. Epoxide formation
proceeded without incident even if an electron-withdrawing
substituent on the arene ring renders the aldehyde oxygen
atom less nucleophilic and hence carbonyl ylide formation less
favorable (entry 6).23 Overall, [Cp*RhI2]2 compares favorably
with Rh2(OAc)4 previously used in the literature (compare
entries 2/3 and 7/8), whereas [Cp*RhCl2]2 is inadequate.19 As
previously communicated, [Cp*RhI2]2 also performed well in a
Si−H insertion reaction;17 once again, use of the iodide-
containing catalyst is necessary, whereas its chloride-based
analogue basically fails to react.
R2
R1
Rh
O
X
X
Rh
R2
R2
O
Rh
O
Z
O
R
R
R1
R1
4
5
6
7
8
9
A
B
C
Ar Ar
Rh
NR1
SbF6
Rh
SbF6
N
N
b)
Ph
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a)
c)
Ph
HN
R2HN
1 = Ph, R2 = H
1 = H, R2 = Ph
NH2
3
R
2
3'
R
NH
N2
1
Rh
Cl
N
Table 1. Catalyst Screening: Cyclopropanation
X
X
Ph
5a
, X = OMe
NH2
4
X
5b, X = NMe2
RO
O
O
MeO
a
Reagents and Conditions: a) (i) [Cp*Rh(MeCN)3][SbF6]2,
MeCN, reflux, see ref. 12; b) 5a, CH2Cl2; c) [Cp*RhCl2]2,
NaOAc, toluene, reflux; Ar = 4-methoxyphenyl
OR
N2
X
OMe
7
6a, X = OMe, R = Me
b
c
, X = H, R = Me
, X = COOMe, R = Et
Entry Substrate
Catalyst
Solvent
T
Yield
(1 mol%)
[Cp*RhCl2]2
[Cp*RhI2]2
[Cp*IrCl2]2
[Cp*IrI2]2
(°C)
22
22
40
22
(%)a
≤ 46
79
1
2
3
4
6a
6a
6a
6c
pentane
pentane
CH2Cl2
CH2Cl2
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58
a Yield of isolated product
Table 2. Catalyst Screening: Darzens-type Epoxide Formationa
O
X
X
O
O
O
O
X
R
O
OMe
R
OMe
6
R
[Rh]
Figure 1. Structure of the cyclometalated product 3 formed by di-
rected C−H activation followed by carbene insertion; the disordered
SbF6− counterion and solute CH2Cl2 are not shown for clarity
[Rh]
COOMe
E
8
D
R
Nr Substrate
R
Catalyst
(1 mol%)
Yield
(%)c
RESULTS AND DISCUSSION
1
2
3
4
5
6
7
8
6b
6b
6b
6b
6a
6b
6b
6b
Ph
Ph
Ph
[Cp*RhCl2]2
[Cp*RhI2]2 b
Rh2(OAc)4
[Cp*RhI2]2
[Cp*RhI2]2
[Cp*RhI2]2
[Cp*RhI2]2 b
Rh2(OAc)4
[Cp*RhI2]2
7 (GC)
61
Strong Effect of the Anionic Ligand on Reactivity. The
reaction of the diazo derivative 6a with excess 4-
methoxystyrene was chosen for an initial catalyst screening
(Table 1). [Cp*RhCl2]2 (1 mol%) afforded the expected cyclo-
propane 7, but the yield remained low (≤ 46%) despite at-
tempted optimization. Surprisingly, the result was improved
when the chloride ligands on rhodium where replaced by
iodide. Similarly, it was found that the formal substitution of
Rh by Ir as the central metal furnished 7 in appreciable yield;18
although the chosen anionic ligands still exert some influence,
the effect seems to be less pronounced in the Ir series.
6619b
96
4-MeOC6H4-
4-MeOC6H4-
4-(MeOOC)C6H4-
PhCH=CH-
PhCH=CH-
83
85
88
5019b
98
10 6b
EtCH=CH-
a
Unless stated otherwise, all reactions were carried out in CH2Cl2 at
b
c
ambient temperature; in refluxing CH2Cl2; yield of isolated prod-
uct, unless stated otherwise
The same trend was observed in reactions with aromatic alde-
hydes, which are known to give epoxides when reacted with
certain metal carbenes generated in situ.19-22 Because the reac-
tion is thought to commence with attack of the C=O hetero-
nucleophile onto the carbene to give a carbonyl ylide interme-
diate, we conjectured that Rh(+3) half-sandwich carbenes
might be particularly well suited because of their high oxida-
tion state (Table 2). To our surprise, however, [Cp*RhCl2]2 led
to hardly any conversion (entry 1), whereas [Cp*RhI2]2 af-
forded 8 in good yield as a single diastereomer (entry 2). The
The strong correlation between efficiency and the nature of the
halide ligand X manifest in these examples stands in striking
contrast to the results for the catalyzed insertion of 6 into the
O−H bond of methanol (Table 3): all tested Cp*MX2 precata-
lysts − independent of their anionic ligand − afforded product
9 in good to excellent yield; even an Ir(I) complex proved
effective.
Table 3. Catalyst Screening: -OH Insertion Reactiona
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X
X
placement of the donor/acceptor entity of transient 10a by an
MeOH (10 equiv.)
CH2Cl2, RT
O
O
inherently less electrophilic donor/donor carbene15a,30 would
also prevent such a spontaneous insertion step from occurring.
In fact, reaction of [Cp*RhCl2]2 with 5b furnished complex
12, in which both chlorides remain bound to the Rh(+3) center
and the carbene unit is fully intact (Scheme 2 and Figure 2).
As one might expect, the Rh1−C1 distance (2.014(3) Å) of 12
is somewhat longer than that of 10c (1.970(3) Å).17
1
2
3
4
5
6
7
8
9
OR
OR
N2
OMe
6
9
Entry
X
Catalyst (1 mol%)
[Cp*RhCl2]2
[Cp*RhI2]2
Yield (%)b
1
2
3
4
5
83c
88
74
76
90
98c
−OMe
−OMe
−OMe
−OMe
[Cp*IrCl2]2
[Cp*IrI2]2
[Cp*IrI2]2
−COOMe
−OMe
Scheme 2. Preparation of Half-Sandwich Rh(+3) Car-
benesa
6
[(cod)IrCl]2
a
10
11
12
13
14
15
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All reactions were carried out in CH2Cl2 or pentane at ambient
temperature; yield of isolated product, unless stated otherwise;
NMR yield
b
c
5b
6a
[Cp*RhX2]2
OMe
X
X
Rh
a)
b)
X = Cl
MeO
[
10a
, X = Cl]
These strikingly different trends could not be reconciled at the
outset of the project. Therefore it was deemed necessary to
characterize the purported half-sandwich carbene intermedi-
ates of type B in more detail.
O
10b
,
X = Br
10c
, X = I
X = Cl
NMe2
Structures of Cp*M Carbene Complexes (M = Rh, Ir) in
the Solid State. Despite the tremendous preparative im-
portance, carbene complexes A derived from dirhodium tetra-
carboxylate precatalysts had defied all attempts at experi-
mental characterization for decades; only recently have spec-
tral and crystallographic data of a representative set of reactive
intermediates of this type been obtained.15,17,24 In concord with
computational results,25 the gathered information suggests that
the second rhodium atom exerts a stabilizing function as an
integral part of the three center/four electron Rh(+2)-
−Rh(+2)−CR2 core.26 In recognition of the critical role of
metal-metal bonding, it was expected that mono-nuclear com-
plexes of type B might be even more fragile because such
assistance by a neighboring metal center is missing and the
oxidation state of rhodium is also higher (+3 in B versus +2 in
A).
Cl Rh
Cl
OMe
Rh
Cl
MeOOC Cl
12
11
Me2N
a
Reagents and conditions: (a) 6a, CH2Cl2/FC6H5, 0°C →
−20°C, see ref. 17; (b) 5b, CH2Cl2/FC6H5, 0°C → −20°C
In fact, it required considerable experimentation until we
managed to isolate the donor/acceptor carbene complexes 10
derived from the diazo ester derivative 6a and [Cp*RhX2]2 (X
= Cl, Br, I) (Scheme 2). As previously reported, compounds
10b (X = Br) and 10c (X = I) represent the first true half-
sandwich donor/acceptor carbene complexes of Rh(+3) to be
fully characterized.17 In contrast, the chloride analogue 10a (X
= Cl) escaped all attempts at isolation: although there is no
doubt that this species is transiently formed, the nascent car-
bene unit inserts into one of the Rh−Cl bonds even at
−50°C.27,28 The structure of the resulting product 11 in the
solid state shows a functionalized C-metalated rhodium eno-
late;29 alternatively, this species can be viewed as a rhodium
carbenoid because it comprises a C-atom carrying a metal
atom and chloride as a potential leaving group.17 The metalat-
ed center resonates at δC = 70.6 ppm (CD2Cl2, −50°C), where-
as the true carbene complexes 10b,c have the expected low-
field NMR signatures (δC = 314.2 ppm (X = Br), 316.4 ppm
(X = I)). Interestingly, these resonances are significantly
downfield from those of all dirhodium carbene complexes of
type A characterized so far (ca. 235-270 ppm).17,24
Figure 2. Structure of the donor/donor Cp*Rh(+3) carbene complex
12 in the solid state
Scheme 3. Preparation of Iridium-Carbene Complexesa
O
6c
6a
OMe
X
X
Ir
Cl
Cl
Ir
[Cp*IrX2]2
OMe
b)
a)
EtO
MeO
14a, X = Cl
13
O
O
b
, X = I
Cl
Cl
COOMe
COOMe
Ir
Ir
6a
[(cod)IrCl]2
c)
15
OMe
OMe
a
Reagents and Conditions: a) 6a, CH2Cl2/FC6H5, 0°C →
−20°C; (b) 6c, CH2Cl2/FC6H5, 0°C → −20°C; c) 6a,
CH2Cl2/FC6H5, 0°C → −20°C; cod = 1,5-cyclooctadiene
The spontaneous formation of 11 at cryogenic conditions
suggests that the chloride ligands render the carbene center of
transient 10a so electrophilic that spontaneous 1,2-migratory
insertion will ensue; in contrast, the somewhat less electroneg-
ative bromide or iodide ligands are incapable of triggering this
process. Under this premise it seemed likely that formal re-
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NMR spectra of 15 are also broad due to hindered rotation
1
2
3
4
5
6
7
8
about the C1−C4 bond. The partial double bond character
manifest in this spectral feature corresponds well to the crys-
tallographic data, which show a short C1−C4 distance and an
almost perfect alignment of the arene with the carbene “emp-
ty” orbital (Figure 4). As in 13, it is largely the arene substitu-
ent that imparts (meta)stability onto this donor/acceptor car-
bene via delocalization of charge density within the aromatic
π-cloud.15,17 In line with the lower oxidation state of and hence
higher electron density at the central metal, the Ir1−C1 car-
bene bond (1.912(3) Å) of 15 is shorter than that of the Ir(+3)
species 13 (1.960(2) Å).34 Yet, the dynamic behavior observed
by NMR proves that even in 15 the carbene unit has little
double bond character; the bond order of its Ir(+3) sibling 13
must therefore be even lower.
9
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12
13
14
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Figure 3. Structure of the Ir(+3) half-sandwich carbene complex 13 in
the solid state; disordered fluorobenzene in the unit cell is not shown
for clarity
Not unexpectedly, the preparation of complexes 14a,b was
even more challenging as they carry an electron-withdrawing
ester function (rather than a MeO- substituent) on the aryl ring
(Figure 5).35 The emerging “acceptor/acceptor” character is
manifest in the structural data of 14a in the solid state: as a
deactivated arene is obviously less capable of compensating
the electron deficiency of the adjacent carbene, the C1−C5
bond (1.460(4) Å) is markedly longer than that in the do-
nor/acceptor carbene 13 (1.429(3) Å). As a consequence,
back-donation from [Cp*Ir] is upregulated, which results in a
significant contraction of the carbene Ir1−C1 bond to 1.914(3)
Å in 14a (versus 1.960(2) Å in 13).
Figure 4. Structure of the Ir(+1) donor/acceptor carbene complex 15
Formal replacement of Rh(+3) by Ir(+3) as the central metal
also suppressed the ligand coupling (Scheme 3). Complex 13
is the iridium analogue of the transient rhodium carbene 10a
that had defied characterization (Figure 3).31 Interestingly, the
carbene center of 13 resonates at δC = 275.9 ppm (CD2Cl2) and
is hence much less deshielded than those of the rhodium spe-
cies 10b (314.2 ppm) and 10c (316.4 ppm). Moreover, the
Ir1−C1 carbene bond (1.960(2) Å) is shorter than the Rh1−C1
bonds in 10c (1.970(3) Å),17 which speaks for stronger back-
bonding from Ir(+3) into the “empty” carbene orbital. The
arene ring in 13 is aligned for maximal orbital overlap be-
tween the π-system and the carbene; as a consequence, the
C1−C4 bond is markedly contracted to 1.429(3) Å. These
structural attributes showcase that the donor substituent large-
ly accounts for the stabilization of highly electrophilic species
of this type. In contrast, the electron-withdrawing ester group
is almost orthogonal to the carbene as to prevent any further
destabilization of the already highly electron deficient site; the
decoupling is also manifest in the rather long C1−C2 distance
(1.510(3) Å).
Figure 5. Structure of the half-sandwich “acceptor/acceptor” carbene
14a in the solid state; CH2Cl2 in the unit cell is not shown for clarity
These insights into the subtle interplay between the central
metal and the ligand framework allowed the reactivity trends
to be rationalized that had surfaced during the initial screen-
ing. The striking correlation between the halide ligand X in the
precatalyst and the efficiency of the cyclopropanation of ole-
fins (Table 1) and the Darzens-type reactions of aromatic
aldehydes (Table 2) likely has its origins in the distinct migra-
tory aptitudes of X (Cl >> Br ≈ I) and hence the largely differ-
ent stability of the carbene complexes of type B: the chloride-
containing Cp*Rh(+3) carbene 10a is only transiently formed:
intramolecular carbene insertion into the Rh−Cl bond is evi-
dently faster than the intermolecular attack of the C=O group
of an aldehyde partner, which prevents carbonyl ylide E from
forming and hence brings epoxidation to a halt. The resulting
“carbenoid” 11 is also unlikely to cyclopropanate styrene,
We also managed to isolate the analogous Ir(+1) carbene 15;
the interest in this species was nurtured by the fact that
[(cod)IrCl]2 had proven competent in –OH insertion reactions
(Table 3, entry 6).32,33 The 13C NMR spectrum of 15 shows
four pairs of differently broadened lines for the cod ligand.
This observation suggests twofold symmetry, whereby the
broadening comes from the dynamic averaging about the
symmetry axis. The resonances of the aromatic signals in the
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certainly not under mild conditions.28 For 10b,c (M = Rh, X =
unsymmetrical azobenzene derivative confirmed this conclu-
sion (see below, Scheme 4).
1
2
3
4
5
6
7
8
I, Br) as well as for all Cp*Ir(+3) complexes, in contrast, this
migratory process has not been observed; such species are
therefore competent partners in the cited transformations. The
fact that the reaction with methanol seems largely unaffected
by such changes in the precatalyst (Table 3) is understood if
one considers that even a carbenoid such as 11 will react with
an alcohol substrate.17
Table 4. Catalytic Metathesis of Azobenzene
Nr Catalyst
(2 mol%)
solvent
T
LEDa
Yield
(%)b
Catalytic Azo-Metathesis. The ability of certain Fischer
carbene complexes to cleave the −N=N− bond of an azoben-
zene derivative has previously been demonstrated;36-38 to the
best of our knowledge, however, this transformation has never
been translated into a catalytic process that would open a
relevant new entry into α-imino esters. Compounds of this
type find many different applications, which have recently
been covered in a comprehensive review;39 therefore it may
suffice to mention that asymmetric reduction of α-imino esters
provides rapid access to amino acid building blocks, whereas
many organometallic reagents attack their imine entity at
nitrogen (rather than at carbon) and, in doing so, lead to valu-
able N-substituted amino acid derivatives.39,40
9
1
2
3
4
5
6
7
8
9
[Cp*RhCl2]2
toluene
toluene
toluene
toluene
THF
RT
< 1
13
8
−
+
−
o
o
o
o
+
+
+
+
+
+
+
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
RTc
RT
[Cp*RhI2]2
≤ 69d
< 1
14
80°C
80°C
80°C
80°C
RTc
RTc
RTc
RTc
RTc
RTc
RTc
MeCN
DCE
48
98 (91)
98
72
93
96
16
16
toluene
toluene
toluene
toluene
toluene
toluene
toluene
[Cp*RhBr2]2
10 [Rh2(OAc)4]
11 [Cp*IrCl2]2
12 [Cp*IrI2]2
13 [(cod)IrCl]2
Although condensation of an α-oxo-ester with the appropriate
amine partner seems to be the obvious way for making α-
imino esters such as 17, numerous alternative methods have
been developed in the past.39 Especially when it comes to
reacting poorly nucleophilic amines and/or sensitive α-oxo
esters, recourse to a phosphine–mediated Staudinger ligation
of an azide precursor with the carbonyl is often the method of
choice, despite the poor atom economy of this process.41 More
recently, α-imino esters were prepared from donor/acceptor
dirhodium carbenes upon reaction with aryl azides.42,43
14 [Cu(MeCN)4]PF6
a
+: irradiation with light emitted by commercial blue LED; −: the
reaction was carried out in the dark; o: daylight; b NMR yield (isolated
yield); c despite irradiation, the internal temperature was only slightly
above RT when the reaction was carried out in toluene; d poor repro-
ducibility on scale up, see Text
A brief screening showed once again a striking correlation
between catalytic activity and the nature of the anionic ligands
(I ≈ Br >> Cl) when working with half-sandwich rhodium
precatalysts of type [Cp*MX2]2; this effect basically vanished
for M = Ir(+3) (Table 4). In view of the structural data out-
lined above, these trends suggest the intervention of true car-
bene intermediates. In line with this notion, [Rh2(OAc)4] was
also found effective (entry 10), although the yield was lower
and the functional group tolerance definitely inferior (see
below); in contrast, Ir(+1) as well as Cu(+1) proved inade-
quate (entries 13, 14).
Compared to azides, azoarenes have many obvious advantages
as possible source of an [Ar−N=] fragment, because they are
stable, safe, benign and readily available in functionalized
form; for their role as classical dyes, a sizeable number of such
compounds is available even in bulk quantities. Therefore it
seemed warranted to investigate whether catalytic metathesis
of azobenzene derivatives opens a potentially orthogonal
gateway to α-imino esters that are difficult to make otherwise.
To this end, however, −N=N− bond cleavage must outperform
directed ortho-metalation of the azobenzene substrate.44 This
is a non-trivial task since the directing effect of the −N=N−
bridge onto rhodium complexes is well established and has
already served heterocycle synthesis in the past.45
Under the optimized conditions, the reaction shows a broad
scope and appreciable compatibility with polar and apolar
substituents; moreover, it was found to scale well. As can be
seen from Table 5, the azobenzene derivative to be metathe-
sized can be electron rich or electron poor, even though the
latter usually require higher temperatures. The need for more
forcing conditions suggests that the reaction commences with
attack of an N-atom of the azo-bridge onto the electrophilic
carbene center, which is obviously less favorable for electron
deficient substrates. In any case, the new methods allows α-
imino esters such as 20-22, 25, 28, 33 and 36 to be made,
which are difficult to access by conventional carbonyl conden-
sation since the required aniline derivatives are poorly nucleo-
philic and therefore do not react well with an α-oxo-ester. The
substituents can be placed ortho, meta or para to the azo
bridge with little change in efficiency; only the 2,6-
disubstituted derivative 27 did not form, most likely because
the −N=N− unit is too shielded for attack onto the rhodium
intermediate. Donor/acceptor carbenes of the structural type
discussed in the previous sections of this paper gave the best
results; electron donating or withdrawing substituents on their
aryl rings do not matter much. The more stabilized do-
Gratifyingly though, the reaction of diazo derivative 6b with
azobenzene 16 in the presence of catalytic [Cp*RhI2]2 in tolu-
ene furnished traces of the desired α-imino ester 17 (Table 4,
entry 3; for the product structure, see Figure S3); although a
better yield was obtained at reflux temperature, the outcome
proved erratic upon attempted scale-up (entry 4). We surmised
that light might play a role in triggering isomerization of the
largely E-configured azo derivative 16 to the potentially more
nucleophilic and sterically less hindered Z-isomer.46,47 This
assumption proved correct in that essentially quantitative
conversion was reached when the diazo derivative was added
over the course of 2 h to the mixture irradiated with light emit-
ted by a commercial blue LED; the 91% yield of pure 17 ob-
tained under these conditions proved well reproducible (entry
8). As no other product derived from the azobenzene substrate
was detected in the crude material, both halves of 16 must
have ended up in the product. A control experiment using an
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Journal of the American Chemical Society
Page 6 of 10
nor/donor carbenes react reluctantly (see product 37): their tives reported in the literature had been explained in analogy
1
2
3
4
5
6
7
8
carbene center is less electrophilic and hence less susceptible
to attack by the −N=N− bridge. In contrast, diazo derivatives
with only electron withdrawing substituents such as diazoma-
lonate are not decomposed by [Cp*MX2]2 and therefore cannot
be used at the current stage of development. Moreover, an
attempt at using this reaction for the ring opening of pyri-
dazine, a heteroaromatic “azo”-derivative, met with failure,
because this and related substrates form stable adducts with
the [Cp*RhCl2] fragment.48
to canonical olefin metathesis by invoking metal-nitrenes and
metallacyclic intermediates.36,37 Although rhodium nitrene
complexes could not be excluded as the propagating species at
the outset of our investigation, the lack of any scrambling of
the azobenzene derivatives 39 and 40 in the control experi-
ment shown in Scheme 4 argued against such a scenario.
Scheme 4. Control Experiments
9
Me
N2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
CF3
Me
+
2
Table 5. Selection of imines formed by azobenzene metathesisa
Ph
COOMe
N
N
N
[Cp*RhI2]2 (2 mol%)
toluene, reflux
N
Ph
COOMe
Ph
COOMe
b
85% (18:22, 1:1.05, NMR)
20 89% (R = COOC8H17
)
COOMe
COOMe
21
91% (R = F)
22 84% (R = CF3)b
38
23
85%
CF3
F
R
Me
MeO
N2
Me
N
Ph
COOMe
F
N
N
N
Me
(1.5 equiv.)
Me
COOMe
N
N
N
MeO
COOMe
COOMe
N
F
[Cp*RhI2]2 (1 mol%)
LED, toluene, RT
N
not detected
24 99% (R = OMe)
25 86% (R = COOC8H17
27 0%
26 95%
)
39
40
OMe
O
N3
Scheme 5. Formation and Evolution of a Diaziridine In-
termediate
N
N
N
N
N
COOMe
COOMe
COOMe
NOE
28 83%b
O
29 65%
30 71%
MeO
N
(Z)-16
OMe
I
Rh
MeO
N
R
R
CD2Cl2, -40°C
I
O
N
10c
N
N
MeO
COOMe
41
COOEt
MeO
MeO
31 97% (R = H)
10c
Ph
N
O
67%e
34
35
36
90% (R = H)
66% (R = OMe)
92% (NMR, R = COOC8H17
37
32
33
2
69% (R = OMe)
41
COOMe
31
b
)
b,c,d
65% (R = COOC8H17
)
-40°C to RT
MeO
a unless stated otherwise, all compounds were made using [Cp*RhI2]2
(1 mol%) in toluene at ambient temperature under irradiation with
light emitted by blue LED’s; b at 90°C; using [Cp*IrI2]2 as the cata-
c
lyst; d the product is subject to partial hydrolysis during flash chroma-
tography; e addition of the diazo derivative over 5 h
Compounds 28-30 nicely illustrate the favorable chemoselec-
tivity profile of this new transformation. An imine such as 28
bearing an unprotected ketone on its backbone is neither ac-
cessible from an α-oxo-ester by ordinary condensation chem-
istry nor by Staudinger ligation. Furthermore, the intact alkyne
in compound 29 shows that catalytic −N=N− cleavage is faster
than cyclopropene formation.17 Arguably most notable, how-
ever, is the synthesis of product 30: the fact that [Cp*RhI2]2
cleaved the azo bridge while leaving the azide intact sets this
catalyst apart from many other metal complexes (including
[Rh2(OAc)4] and other dirhodium tetracarboxylate complexes),
which readily react with azides to form highly reactive metal
nitrene intermediates.49,50
Figure 6. Structure of diaziridine 41 in the solid state
We conjectured that the new catalytic metathesis reaction of
azobenzene derivatives described herein might commence by
attack of an N-atom of the −N=N− bridge onto the half-
Mechanistic Studies. The stoichiometric reactions of Fischer
carbene complexes of tungsten or chromium with azo deriva-
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Journal of the American Chemical Society
sandwich rhodium (iridium) carbene to form an ylide interme- azobenzene, provided the latter is (Z)-configured. This step is
1
2
3
4
5
6
7
8
diate in the first place. With samples of pure crystalline car-
benes in hand, we were in a positon to test this hypothesis.
likely reversible even at low temperature and leads to isomeri-
zation of the substrate, which therefore constantly needs to be
photo-isomerized back to the active form to ensure complete
conversion in the catalytic set-up. The resulting ylide F
evolves into diaziridine G, such that the transannular interac-
tions between the aryl substituents are minimized. Attack by a
second carbene B affords an intermediate of type H which
breaks down, presumably via a cheletropic process, to give
two equivalents of the α-imino ester product.53
To this end, a sample of (Z)-16 was prepared according to the
literature,51 as the preparative results had clearly indicated that
only this geometric isomer engages in metathetic N=N bond
cleavage. Slow warming of a 1:1 mixture of (Z)-16 and com-
plex 10c in CD2Cl2 solution in the dark from −78°C to ambient
temperature afforded the expected α-imino ester 31 and unre-
acted azobenzene in a ≈ 2.9:1 ratio (NMR) (Scheme 5); im-
portantly, recovered 16 had completely isomerized to the
thermodynamically more stable (E)-isomer. This outcome
shows that the reaction pathway involves a reversible step
generating the unreactive azobenzene isomer and hence ex-
9
Overall, the stepwise scission of the −N=N− bond of azoben-
zene by a metal carbene described herein is reminiscent of the
equally stepwise metathetic cleavage of the −N≡N triple bond
of aryldiazonium salts by metal alkylidynes recently described
by our group.54 Though certainly overshadowed by the im-
mense success of alkene55,56 and alkyne metathesis,57 these and
other unorthodox manifestations showcase that metathesis in
general continues to provide many opportunities for methodo-
logical innovation.58
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
plains why constant light-driven E→Z isomerization is neces-
sary for full conversion in a catalytic set-up. Treatment of (Z)-
16 with two equivalents of 10c led to clean formation of 31 as
the only product detected by NMR. This experiment proved
that both halves of the azobenzene convert into product; the
use of the unsymmetrical substrate 38 confirmed this conclu-
sion (Scheme 4).
Scheme 6. Proposed Catalytic Cycle; [Rh] = Cp*RhI2
Monitoring of the 1:1 mixture of 10c and 16 by NMR showed
the build-up of an intermediate, which reached maximum
concentration at −40°C; it proved stable enough for full char-
acterization when kept cold. This compound was unambigu-
ously assigned the diaziridine structure 41 based on extensive
1D and 2D NMR analyses; the trans-disposition of the two
phenyl rings derived from the azobenzene was evident from
the NOESY data and the presence of two signals in the 15N
NMR spectrum. This stereochemical setting implies that
cis/trans-isomerization must have taken place prior to for-
mation of the three-membered ring; the cyclization is therefore
almost certainly a stepwise rather than concerted process. The
assignment was confirmed when crystals of this metastable
intermediate suitable for X-ray diffraction could be grown.
The structure of 41 in the solid state (Figure 6) features an
almost isosceles trianglar core, in which the N1−N2 single
bond (1.481(2) Å) is only slightly longer than C1−N1
(1.459(2) Å) and C1−N2 (1.463(3) Å) bonds and all three
angles are very close to 60°.
Diaziridine 41 reacts with a second equivalent of the rhodium
half-sandwich carbene complex 10c to yield two equivalents
of 3 (Scheme 5). This result suggests that the N-atoms of 41
are sufficiently nucleophilic to attack the carbene center.
CONCLUSIONS
Diaziridines had been formed in modest yields in some of the
stoichiometric reactions of Fischer tungsten carbenes with
(electron deficient) azo compounds, when carried out in polar
solvents such as MeCN.37a,52 Although a possible role in the
stoichiometric metathesis of azobenzene had not been exclud-
ed, the −N=N− cleavage was explained in a canonical fashion
via metal-nitrene complexes and diazametallacyclobutane
derivatives in analogy to the Chauvin cycle of regular olefin
metathesis.37a Actually, it was insinuated at one point that
diaziridine formation and metathesis might be competing
reaction channels.52
Although the net outcome of the reaction between a rhodium
carbene and the hetero-double bond of azobenzene formally
represents a “metathesis” reaction, the underlying mechanism
is distinct from the principles governing alkene metathesis,
which became immensely popular and versatile with the ad-
vent of the well-defined Schrock- and Grubbs-type catalysts.55
In any case, the new manifold increases the portfolio of multi-
ple-bonded substrates amenable to metathesis and provides
access to synthetically valuable α-imino esters, some of which
would be difficult to make otherwise.
In striking contrast to the literature, all available experimental
data suggest that the rhodium catalyzed cleavage of azoben-
zenes described herein passes through a diaziridine as the key
intermediate. We confidently propose that the reaction pro-
ceeds as shown in Scheme 6: the electrophilic rhodium car-
bene B primarily formed succumbs to attack by an N-atom of
The most effective and tolerant precatalysts are half-sandwich
complexes of type [Cp*MX2]2 (M = Rh, Ir), which perform
better than the popular dirhodium tetracarboxylate complexes
that dominate contemporary rhodium carbene chemistry. A
representative set of pertinent half-sandwich Cp*M carbene
complexes has been isolated and fully characterized, despite
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Journal of the American Chemical Society
Page 8 of 10
2233. (b) Hubert, A. J.; Noels, A. F.; Anciaux, A. J.; Teyssié, P.
Synthesis 1976, 600. (c) Demonceau, A.; Noels, A. F.; Hubert, A. J.;
Teyssié, P. J. Chem. Soc. Chem. Commun. 1981, 688.
their sensitivity. The acquired data explain why the reactivity
of this previously unexplored class of intermediates is strongly
correlated with the nature of the halide ligands X; most nota-
bly, the complex derived from [Cp*RhCl2]2 undergoes sponta-
neous migratory insertion of the incipient carbene unit into the
Rh−Cl bond before true carbene reactivity can be harnessed.
This and related results allow a host of preparative data to be
rationalized, and should provide guidance for further explora-
tions of the field.
1
2
3
4
5
6
7
8
(9) For leading studies on Rh(+3) carbenes, see the following and
literature cited therein: (a) Callot, H. J.; Piechocki, Tetrahedron Lett.
1980, 21, 3489. (b) Callot, H. J.; Metz, F.; Piechocki, C. Tetrahedron
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1991, 32, 2445. (d) Hayashi, T.; Kato, T.; Kaneko, T.; Asai, T.; Ogo-
shi, H. J. Organomet. Chem. 1994, 473, 323. (e) Lo, V. K.-Y.; Thu,
H.-Y.; Chan, Y.-M.; Lam, T.-L.; Yu, W.-Y. ; Che, C.-M. Synlett
2012, 23, 2753. (f) Franssen, N. M. G.; Finger, M.; Reek, J. N. H.; de
Bruin, B. Dalton Trans. 2013, 42, 4139.
9
(10) Chen, W.-W.; Lo, S.-F.; Zhou, Z.; Yu, W.-Y. J. Am. Chem.
Soc. 2012, 134, 13565.
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11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ASSOCIATED CONTENT
(11) (a) Shi, Z.; Koester, D. C.; Boultadakis-Arapinis, M.; Glorius,
F. J. Am. Chem. Soc. 2013, 135, 12204. (b) Hyster, T. K.; Ruhl, K. E.;
Rovis, T. J. Am. Chem. Soc. 2013, 135, 5364. (c) Liang, Y.; Yu, K.;
Li, B.; Xu, S.; Song, H.; Wang, B. Chem. Commun. 2014, 50, 6130.
(d) Jeong, J.; Patel, P.; Hwang, H.; Chang, S. Org. Lett. 2014, 16,
4598. (e) Hu, F.; Xia, Y.; Ye, F.; Liu, Z.; Ma, C.; Zhang, Y.; Wang, J.
Angew. Chem., Int. Ed. 2014, 53, 1364. (f) Ye, B.; Cramer, N. Angew.
Chem., Int. Ed. 2014, 53, 7896. (g) Shi, J.; Yan, Y.; Li, Q.; Xu, H. E.;
Yi, W. Chem. Commun. 2014, 50, 6483. (h) Yang, Y.; Wang, X.; Li,
Y.; Zhou, B. Angew. Chem., Int. Ed. 2015, 54, 15400. (i) Zhou, J.;
Shi, J.; Liu, X.; Jia, J.; Xu, H. E.; Yi, W. Chem. Commun. 2015, 51,
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pov, S. N. Eur. J. Org. Chem. 2015, 4950. (k) Wang, L.; Li, Z.; Qu,
X.; Peng, W.-M.; Hu, S.-Q.; Wang, H.-B. Tetrahedron Lett. 2015, 56,
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Supporting Information. Experimental part including character-
ization data, NMR spectra of new compounds, and supporting
crystallographic information (PDF)
AUTHOR INFORMATION
Corresponding Author
* fuerstner@kofo.mpg.de
ACKNOWLEDGMENT
We thank Mr. S. Größl and Dr. J. Murphy for valuable discus-
sions and the analytical departments of our Institute for excellent
support. Generous financial support by the MPG is gratefully
acknowledged.
Zhou, B. Chem.−Eur. J. 2014, 20, 17653. (m) Zhang, Y.; Zheng, J.;
Cui, S. J. Org. Chem. 2014, 79, 6490. (n) Yu, S.; Liu, S.; Lan, Y.;
Wan, B.; Li, X. J. Am. Chem. Soc. 2015, 137, 1623. (o) Cheng, Y.;
Bolm, C. Angew. Chem., Int. Ed. 2015, 54, 12349. (p) Zhou, B.;
Chen, Z.; Yang, Y.; Ai, W.; Tang, H.; Wu, Y.; Zhu, W.; Li, Y.
Angew. Chem., Int. Ed. 2015, 54, 12121. (q) Lu, Y.-S.; Yu, W.-Y.
Org. Lett. 2016, 18, 1350. (r) Zhang, B.; Li, B.; Zhang, X.; Fan, X.
Org. Lett. 2017, 19, 2294. (s) Halskov, K. S.; Roth, H. S.; Ellman, J.
A. Angew. Chem. 2017, 129, 9311.
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