Chelated assisted metal-mediated N-H bond activation of β-lactams: Preparation of irida-, rhoda-, osma-, and ruthenatrinems

Article abstract of DOI:10.1021/om500162m

2-Azetidinones substituted with pyridine (2a), quinoline (2b), isoquinoline (2c), imidazole (2d), and benzimidazole (2e) at the 4-position of the four-membered ring have been prepared in order to synthesize tribactams containing a transition metal and its associated ligands, L_nM, at the 2-position of the tricyclic skeleton. The developed procedure is compatible with a wide range of transition-metal starting complexes. Thus, the iridium and rhodium dimers [M(η⁵-C₅Me₅)Cl ₂]₂ react with 2a-e, in the presence of sodium acetate, to afford irida- and rhodatrinems (1a-j) containing the half-sandwich d ⁶ metal fragments M(η⁵-C₅Me₅)Cl (M = Ir, Rh). The reactions of [M(μ-OMe)(η⁴-COD)]₂ (M = Ir, Rh) with 2a lead to irida- and rhodatrinems (1k,l) with the d ⁸ moieties M(η⁴-COD). The coordination sphere and oxidation state of the metal center in these compounds can be modified, without affecting the 2-azetidinone backbone, by means of substitution and oxidative addition reactions. As a proof of concept, metallatrinems with the M(CO) ₂ (M = Ir (1m), Rh (1n)) and Ir(Me)I(CO)₂ (1o) units are also reported. Osmatrinems 1p,q containing the d⁴ metal fragment OsH₃(PⁱPr₃)₂ have been obtained starting from the d² hexahydride OsH₆(PⁱPr ₃)₂, by reaction with 2a,b, whereas the treatment of the tetrahydroborate complexes MH(η²-H₂BH ₂)(CO)(PⁱPr₃)₂ (M = Os, Ru) with 2a yields osma- and ruthenatrinems (1r,s) containing six-coordinate bis(phosphine) d⁶ metal fragments. The IR stretching frequency of the lactamic carbonyl, the bent angle between the five- and four-membered rings of the tricycle, and the N-CO bond length in the lactamic ring are clearly infuenced by the L_nM fragment.

Full text of DOI:10.1021/om500162m

Article
pubs.acs.org/Organometallics
Chelated Assisted Metal-Mediated N−H Bond Activation of
β‑Lactams: Preparation of Irida‑, Rhoda‑, Osma‑, and Ruthenatrinems
Luis Casarrubios,† Miguel A. Esteruelas,*,‡ Carmen Larramona,‡ Jaime G. Muntaner,† Montserrat Olivan,†
́
Enrique Onate,‡ and Miguel A. Sierra*,†
̃
†
́
́
́
Departamento de Quımica Organica, Facultad de Ciencias Quımicas, Universidad Complutense, 28040 Madrid, Spain
́
‡
́
́
Departamento de Quımica Inorganica, Instituto de Sıntesis Quımica y Catalisis Homogenea (ISQCH), Universidad de
́
́
́
Zaragoza-CSIC, 50009 Zaragoza, Spain
S
* Supporting Information
ABSTRACT: 2-Azetidinones substituted with pyridine (2a),
quinoline (2b), isoquinoline (2c), imidazole (2d), and
benzimidazole (2e) at the 4-position of the four-membered
ring have been prepared in order to synthesize tribactams
containing a transition metal and its associated ligands, LnM, at
the 2-position of the tricyclic skeleton. The developed
procedure is compatible with a wide range of transition-metal
starting complexes. Thus, the iridium and rhodium dimers
[M(η5-C5Me5)Cl2]2 react with 2a−e, in the presence of sodium
acetate, to afford irida- and rhodatrinems (1a−j) containing the
half-sandwich d6 metal fragments M(η5-C5Me5)Cl (M = Ir,
Rh). The reactions of [M(μ-OMe)(η4-COD)]2 (M = Ir, Rh) with 2a lead to irida- and rhodatrinems (1k,l) with the d8 moieties
M(η4-COD). The coordination sphere and oxidation state of the metal center in these compounds can be modified, without
affecting the 2-azetidinone backbone, by means of substitution and oxidative addition reactions. As a proof of concept,
metallatrinems with the M(CO)2 (M = Ir (1m), Rh (1n)) and Ir(Me)I(CO)2 (1o) units are also reported. Osmatrinems 1p,q
containing the d4 metal fragment OsH3(PiPr3)2 have been obtained starting from the d2 hexahydride OsH6(PiPr3)2, by reaction
with 2a,b, whereas the treatment of the tetrahydroborate complexes MH(η2-H2BH2)(CO)(PiPr3)2 (M = Os, Ru) with 2a yields
osma- and ruthenatrinems (1r,s) containing six-coordinate bis(phosphine) d6 metal fragments. The IR stretching frequency of
the lactamic carbonyl, the bent angle between the five- and four-membered rings of the tricycle, and the N−CO bond length in
the lactamic ring are clearly infuenced by the LnM fragment.
by far the most efficient is the use of β-lactamases.5 These
INTRODUCTION
■
enzymes catalyze the irreversible hydrolysis of the amide bond
of the β-lactam ring, yielding the antibiotic inactive. Several
classes of β-lactamases have been characterized, leading to the
clinical answer of using the combination of the active β-lactam
antibiotic and one agent to inactivate the hydrolytic enzyme.6
Tricyclic β-lactams known as tribactams or trinems7 are
among the more promising candidates to act as β-lactamase
inhibitors. Nevertheless, these inhibitors have a skeleton closely
related to the natural and synthetic β-lactam antibiotics, which
make them potential targets for the evolution of new β-
lactamases. Therefore, a drastically different approach to the
problem is required. The incorporation of a transition metal8
and its associated ligands as a constituent of the tribactam
skeleton is certainly a promising alternative. In this context, it
should be noted that there are no analogues in nature and the
metal fragment can afford a wide electronic and structural
diversity, as a result of the wide range of coordination numbers
and polyhedrons of the derivatives of these elements, which can
The neverending fight of mankind with bacteria has taken
advantage of the evolutionary arsenal provided by fungi (one of
the natural enemies of the bacteria) in the form, among others,
of β-lactam antibiotics.1 However, the evolutionary pressure
derived from the indiscriminate use of such as antibacterial
agents has resulted in the apparition of bacteria strains capable
of resisting the action, not only of the commonly used
antibiotics but also of many of their synthetic analogues.2 In
fact, several opinions have appeared pointing that humanity is
losing its battle against these pathogens.3 Response to this
situation follows two main trends. The first one is to prepare
new antibacterial agents able to keep their activity in the
presence of bacteria resistant to the already inactive
antibacterial agents. The second front is to develop novel
compounds to inactivate the mechanisms through which
bacteria render useless the antibiotics. Both lines of action are
a worldwide priority, since bacterial resistance is reaching
unseen levels not only in underdeveloped countries but also in
first-world countries.4
Bacteria have evolved several strategies to quench the
bactericide action of β-lactam antibiotics: the main one and
Received: February 13, 2014
Published: April 1, 2014
© 2014 American Chemical Society
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be further modified through specific reactions. In addition, a
plethora of useful starting complexes are available as metal
precursors. The electronic and structural diversity introduced
by the metal fragment should allow these systems to be used
not only as inhibitors of β-lactamases but also as active
antibacterial agents.
Scheme 2
This paper shows the first metallatrinems, which include
four-, six-, and seven-coordinate transition-metal derivatives of
Ir(III), Rh(III), Ir(I), Rh(I), Os(IV), Os(II), and Ru(II) ions as
a member of the tricyclic system.
RESULTS AND DISCUSSION
■
Synthetic Strategy. The available electron density of an
amidate group is mainly centered on the nitrogen atom. Due to
its high basicity, metal ion hydrolysis often competes with
nitrogen ion coordination.9 As a consequence, the formation of
stable nitrogen-coordinated amidate transition-metal derivatives
is rare, in particular when β-lactams are involved,10 although
complexes containing ligands with this moiety as a substituent
are known.11 The balance shifts to the metal ion coordination
when one or more anchors occur so that favorable five- or six-
membered chelate rings can be formed.9,12 Keeping this in
mind, we designed 2-azetidinones substituted at the 4-position
with an aromatic nitrogen donor group, which should bring the
N−H bond to an electrophilic metal center to promote its
activation. These metal centers activate σ bonds in a heterolytic
manner using an external base or alternatively a ligand with
sufficiently basic free electron pairs or hydride.13
of the PMP group occurred uneventfully with cerium(IV)
ammonium nitrate (CAN) to yield N−H 2-azetidinones 2a−c
in acceptable to good yields (Scheme 3). Oxidation of the
Scheme 3
We planned a four-step procedure for the synthesis of
metallatribactams 1 having a metal at the 2-position of the
tricyclic skeleton, with the aim of developing a flexible and easy
route to these compounds (Scheme 1). The incorporation of
Scheme 1
heterocyclic nitrogen did not take place. Extensive decom-
position of the starting materials to unknown mixtures of
products was observed, however, when the reaction was tested
with 2-azetidinones having five-membered heterocycles at the
4-position of the four-membered ring and an allyl group at the
nitrogen (3d,e). For these cases, the deprotection methodology
described by Alcaide and Almendros involving the sequential
use of Grubbs carbene (isomerization) and RuCl3 (oxidation)
was employed.14 Treatment of compounds 3d,e with Ru(
CHPh)Cl2(PCy3)2 (5 mol % per mol of 2-azetidinone 3)
yielded compounds 5a,b having the N-1 allyl bond isomerized
to the methylvinyl moiety, which were subsequently oxidized
(RuCl3/NaIO4) to the corresponding N−H 2-azetidinones
2d,e. Yields of this oxidation were poor, probably due to
oxidation of the five-membered ring at the 4-position (Scheme
4).
Irida- and Rhodatrinems Containing Six-Coordinate
Half-Sandwich d6 Metal Fragments. The feasibility of the
synthesis of the metallatrinems was initially checked by reacting
the 2-azetidinone 2a with the dimers [M(η5-C5Me5)Cl2]2 (M =
Ir, Rh), using conditions similar to those previously employed
to promote the chelated assisted aryl C−H bond activation,15
which do not produce the fragmentation of the four-membered
the metal in the tricyclic skeleton 1 takes place by means of an
assisted chelated heterolytic N−H bond activation of the 2-
azetidinones 2. These substrates were accessed by N-1
deprotection of β-lactams 3 prepared through a Staudinger
cycloaddition between the appropriate imine 4 and phenox-
yacetyl chloride.
Preparation of 2-Azetidinones. Imines 4a−d (Scheme 2)
were reacted with phenoxyacetyl chloride, in the presence of
Et3N, at −78 °C in dichloromethane, yielding the correspond-
ing 2-azetidinones 3a−d in good to excellent yields as single cis
isomers.11e Imine 4e required a modification of the procedure,
involving boiling toluene instead of dichloromethane at −78
°C. The corresponding 2-azetidinone 3e was obtained as a 1/4
cis/trans mixture in an overall 39% yield, from which trans-3e
was separated to be isolated in 31% yield.
Compounds 3a−e bear either a p-MeOC6H4 (PMP) (3a−c)
group or an allyl substituent (3d,e) at N-1. The election of the
N-1 protecting group was critical to perform the next step. The
compatibility of the heterocycle at the 4-position with the
method used to remove the N-1 group was the pivotal feature
of the synthesis of the 2-azetidinones. Thus, oxidative removal
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occupying three sites of a face, whereas the pyridylamidate
moiety lies in the opposite site with a bite angle of 75.0(3)°.
The separation between the iridium center and the amidic
nitrogen atom of 1.989(9) Å (Ir−N(1)) is about 0.2 Å shorter
than that between the metal and the pyridinic nitrogen atom
(Ir−N(2) = 2.168(8) Å). Both bond lengths are consistent with
those reported for N-arylpicolinamidate iridium(III) deriva-
tives.17 The lactamic N(1)−C(1) and C(1)−O(1) distances of
1.428(14) and 1.222(13) Å, respectively, agree with those
found in the scarce pure organic trinems characterized by X-ray
diffraction analysis.16,18
Scheme 4
Metallatrinems 1a,b exist in solution as 5/1 mixtures of the
two pairs of diastereoisomers resulting from the chirality of the
metal center and both CH carbon atoms of the lactamic four-
membered ring. The most noticeable spectroscopic feature of
these compounds is the presence of a singlet at 175.8 ppm for
1a and 177.1 ppm for 1b in the 13C{1H} NMR spectra, in
chloroform-d, corresponding to the lactamic carbonyl group of
the major diastereoisomer, which appears shifted by about 9
ppm toward lower field with regard to that of 2a (167.2 ppm).
In the IR spectra in chloroform, the lactamic ν(CO) absorption
is observed at 1696 cm−1 for 1a and 1684 cm−1 for 1b, in this
case shifted more than 77 cm−1 toward lower frequencies with
regard to that of 2a (1761 cm−1).
ring. In contrast to the lactamic cleavage, the treatment of the
dimers with 1.0 equiv of the 2-azetidinone, in the presence of
2.3 equiv of sodium acetate, in dichloromethane at room
temperature for 12 h leads to the irida- and rhodatrinems 1a,b,
which were isolated as yellow and brown solids in 93% and 90%
yields, respectively (Scheme 5). Their formation can be
rationalized as the heterolytic rupture of the N−H bond of
2a, by action of the external acetate base, according to our
initial hypothesis.
Scheme 5
Having demonstrated that the labile four-membered ring of
2-azetidinone was compatible with the N-directed N−H
activation, the scope of the reaction with regard to the
substituents at the 4-position of the four-membered ring was
studied next. Under the experimental conditions previously
mentioned, azetidinones 2b,c with quinoline and isoquinoline
substituents, respectively, react with the iridium and rhodium
dimers to give the respective metallatrinems 1c−f (Scheme 6)
Iridatrinem 1a was characterized by X-ray diffraction analysis.
Scheme 6
Figure 1 gives a drawing of the molecule. The structure proves
Figure 1. ORTEP diagram of complex 1a (50% probability ellipsoids).
Hydrogen atoms (except those of the lactamic ring) are omitted for
clarity. Selected bond lengths (Å) and angles (deg): Ir−Cl(1) =
2.434(3), Ir−N(1) = 1.989(9), Ir−N(2) = 2.168(8), N(1)−C(1) =
1.428(14), C(1)−O(1) = 1.222(13); N(1)−Ir(1)−N(2) = 75.0(3).
the formation of the tricyclic skeleton with a dihedral angle
between the five-membered metallacycle and the four-
membered lactamic ring of 55.55°, which compares well with
the related angle in allyl (4S,8S,9R)-10-[(E)-ethylidene]-4-
methoxy-11-oxo-1-azatricyclo[7.2.0.03,8]undec-2-ene-2-carbox-
ylate (53.74°),16 the immediate synthetic precursor of the β-
lactamase inhibitor sodium (8R,9R)-10-[(E)-ethylidene]-4-
methoxy-11-oxo-1-azatricyclo[7.2.0.03,8]undec-2-ene-2-carbox-
ylate (Lek157). The geometry around the metal center is close
to octahedral, with the pentamethylcyclopentadienyl ligand
in excellent yields (80−96%). The reactions of 2d,e, having
five-membered heterocyclic rings at the 4-position of the four-
membered ring, with the metal dimers analogously lead to the
tetracyclic (2d) and tricyclic (2e) 2-metalla-β-lactams 1g−j also
in excellent yields (90−96%). In agreement with the case for
1a,b, the 13C{1H} NMR spectra in chloroform-d of these
compounds contain singlets between 177.0 and 179.0 ppm due
to the lactamic carbonyl group, whereas the ν(CO) absorptions
in the IR spectra are observed in the range 1685−1703 cm−1.
The reactions shown in Schemes 5 and 6 demonstrate that the
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method being developed is amenable to prepare [4,5,6],
[4,5,6,6], [4,5,5], and [4,5,5,6] C-2 metalla analogues of
tribactams.
Irida- and Rhodatrinems Containing Four-Coordinate
d8 Metal Fragments: Modification of the Coordination
Sphere and Oxidation State of the Metal Center. The
square-planar iridium and rhodium dimers [M(μ-OMe)(η4-
COD)]2 (M = Ir, Rh; COD = 1,5-cyclooctadiene) are useful
starting materials to introduce M(η4-COD) moieties at the 2-
position of a tricyclic β-lactam system. Treatment of these
dimers with 1.0 equiv of 2a, in pentane, at room temperature
for 4−6 h leads to the metallatrinems 1k,l, containing a four-
coordinate d8 metal fragment (Scheme 7), which were isolated
Figure 2. ORTEP diagram of complex 1m (50% probability
ellipsoids). Hydrogen atoms (except those of the β-lactamic ring)
are omitted for clarity. Selected bond lengths (Å) and angles (deg):
Ir−N(1) = 2.111(4), Ir−N(2) = 2.028(4), N(2)−C(8) = 1.340(6),
C(8)−O(1) = 1.235(5); N(1)−Ir−N(2) = 77.72(15).
Scheme 7
bite angle of 77.72(15)°. The separation between the iridium
center and the amidic nitrogen atom N(2) of 2.028(4) Å
compares well with that of 1a and is about 0.1 Å shorter than
the separation between the metal and the pyridinic N(1)
nitrogen atom of 2.111(4) Å. Interestingly, the N(2)−C(8)
bond length of 1.340(6) Å is about 0.1 Å shorter than the
related parameter of 1a (N(1)−C(1)), suggesting that the
replacement of the Ir(η5-C5Me5)Cl fragment by the Ir(CO)2
unit produces a strength increase of the N−carbonyl bond
within the four-membered lactamic ring. In contrast to the
N(2)−C(8) distance, the C(8)−O(1) bond length of 1.235(5)
Å is statistically identical with the related parameter of 1a. A
as orange and bright yellow solids in 77% and 69% yields,
respectively. Their formation can be rationalized as the
pyridine-assisted heterolytic N−H bond activation of the
four-membered ring of 2a promoted by the internal methoxy
base, although homolytic N−H addition to the metal center,
followed by reductive elimination of methanol, should not be
totally ruled out, since the square-planar iridium(I) and
rhodium(I) complexes have Lewis base character.19 As
expected due to the bent nature of the tricyclic unit, four
olefinic resonances at 5.71, 5.36, 3.68, and 3.61 ppm (1k) and
5.65, 4.69, 4.03, and 3.91 ppm (1l) in the 1H NMR spectra and
at 67.8, 65.9, 63.6, and 62.2 ppm (1k) and 81.5, 79.9, 79.5, and
79.2 ppm (1l) in the 13C{1H} NMR spectra are characteristic
for these compounds, in dichloromethane-d2, at room temper-
ature. In agreement with the case for 1a−j, the 13C{1H} NMR
spectra also show singlets at 172.6 (1k) and 174.5 ppm (1l)
due to the lactamic carbonyl group, whereas the ν(CO)
absorptions in the IR spectra are observed at 1687 (1k) and
1680 cm−1 (1l).
The possibility of modifying the coordination sphere of the
metal center of the tricycle was also explored. From a
conceptual point of view, this should afford a general
methodology to prepare metallatrinems with not only different
metals but also β-lactams having the same metal with properties
tunable by changes in its coordination sphere. As a proof of
concept, we performed the substitution of the diolefin of 1k,l
by CO. Bubbling this gas through dichloromethane solutions of
the diolefinic species leads to the cis-dicarbonyl derivatives
1m,n, keeping the tricyclic skeleton unaltered (Scheme 7).
These compounds were isolated as orange solids in 90% yields
in both cases.
noticeable feature of the structure is also the association of two
20
2
2
molecules through an Ir(dz )−Ir(dz ) interaction (Figure 3).
Figure 3. Association of two molecules of complex 1m through an
2
2
Ir(dz )−Ir(dz ) interaction (Ir−Ir = 3.1821(4) Å).
The resulting dimer shows an intermolecular metal−metal
distance of 3.1821(4) Å, which compares well with that
reported for the anion [Ir(Tcbiim)(CO)2]− (3.183(1) Å;
Tcbiim = 4,4′,5,5′-tetracyano-2,2-biimidazolate).21 The carbon-
yl ligands of one molecule eclipse the polycyclic system of the
other molecule, whereas the lactamic four-membered rings are
disposed in an antiparallel manner.
The IR and 13C{1H} NMR spectra of 1m,n, in dichloro-
methane-d2, at room temperature are consistent with the
structure shown in Figure 2. As expected for the cis-dicarbonyl
nature of the metal fragments, the IR spectra show two bands at
2061 and 1991 cm−1 for 1m and 2073 and 2007 cm−1 for 1n
along with the lactamic ν(CO) absorption at 1706 cm−1 for 1m
and 1705 cm−1 for 1n. In the 13C{1H} NMR spectra, the
carbonyl ligands display singlets at 178.9 and 171.9 ppm for 1m
and doublets at 186.8 (JC−Rh = 63.0 Hz) and 185.5 ppm (JC−Rh
= 74.0 Hz) for 1n. The lactamic CO resonance appears at 173.8
ppm for 1m and 174.6 ppm for 1n.
Iridatrinem 1m was characterized by X-ray diffraction
analysis. The structure (Figure 2) proves the tricyclic nature
of the species, which displays a dihedral angle between the five-
membered metallacycle and the four-membered lactamic ring
of 53.57°, similar to that of 1a. The coordination geometry
around the iridium atom is almost square planar, with the metal
0.0822 Å out of the best plane defined by the Ir(1), N(1),
N(2), C(15), and C(16) atoms. The main distortion of the
idealized geometry is due to the pyridylamidate N(1)−Ir−N(2)
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The tricyclic systems, including the lactamic four-membered
ring, tolerate not only external and internal bases but also
electrophilic reagents. As a consequence, it is possible to modify
simultaneously the coordination sphere and the oxidation state
of the metal center without affecting the sensitive 2-azetidinone
backbone. Stirring of 1m in methyl iodide for 5 h at room
temperature affords the six-coordinate iridium(III) derivative
1o, resulting from the SN2 oxidative addition of the alkyl halide
to the iridium(I) center of the starting metallatrinem. Tricycle
1o was isolated as a white solid in 79% yield. In solution it
exists as a 4/6 mixture of the diastereoisomers shown in
Scheme 8. The presence of both species is strongly supported
which were isolated as white solids in 82% and 71% yields,
respectively. Under the reaction conditions, the starting
hexahydride undergoes the reductive elimination of molecular
hydrogen to afford the unsaturated d4 tetrahydride
OsH4(PiPr3)2,25 which promotes the heterolytic N−H cleavage
of the lactam by the action of one of the hydride ligands. The
resulting trihydride intermediates are stabilized by coordination
of the nitrogen atom of the heterocyclic substituent at the 4-
position of the lactamic ring. The formation of 1p,q is new
evidence of the wide versatility in coordination number, type of
ligands, metal elements, and electronic and geometrical
environments that it is possible to reach in the metal fragment
of this novel type of tribactams through the synthetic
methodology designed in Scheme 1.
Scheme 8
Osmatrinem 1p has been characterized by X-ray diffraction
analysis. Figure 4 gives a drawing of the tricycle, which shows a
by the 1H and 13C{1H} NMR spectra in dichloromethane-d2, at
room temperature. The most noticeable feature in the 1H NMR
spectrum is the presence of two singlets at 1.51 and 1.41 ppm,
corresponding to the methyl ligand, which show a 4/6 intensity
ratio. According to the proposed structures the 13C{1H} NMR
spectrum contains four Ir−CO resonances at 163.5, 163.4,
158.4, and 158.3 ppm, in addition to the lactamic CO signals at
174.4 and 173.2 ppm and the methyl resonances at −10.2 and
−12.0 ppm.
Figure 4. ORTEP diagram of complex 1p (50% probability ellipsoids).
Hydrogen atoms (except hydrides) are omitted for clarity. Selected
bond lengths (Å) and angles (deg): Os−N(1) = 2.2062(8), Os−N(2)
= 2.1218(19), N(2)−C(8) = 1.347(3), C(8)−O(2) = 1.223(3);
P(1)−Os−P(2) = 163.08(2), N(1)−Os−N(2) = 73.70(7).
Osmatrinems Containing a Seven-Coordinate d4
Metal Fragment: Hydride as Promoter of the N−H
Bond Activation. The saturated hexahydride d2 complex
OsH6(PiPr3)2 activates C−H bonds of a wide range of organic
molecules.22 By protonation with weak Brønsted acids, it
releases molecular hydrogen to afford osmium hydride d4
species which contain the corresponding conjugated base as a
ligand.23 Furthermore, it has been recently shown that it also
activates N−H bonds adjacent to a cyclic carbonyl group such
as those of thymine, uracil, 1-methylthymine, 1-methyluracil,
and cytosine.24 In agreement with this, the treatment of toluene
solutions of this polyhydride with 1.0 equiv of 2a,b, under
reflux, for 12 h leads to the osmatrinems 1p,q (Scheme 9),
dihedral angle between the five-membered metallacycle and the
four-membered lactamic ring significantly more closed (45.00°)
than those of 1a,m. The geometry around the osmium atom
can be rationalized as a distorted pentagonal bipyramid with the
phosphine ligands occupying axial positions (P(1)−Os−P(2) =
163.08(2)°). The metal coordination sphere is completed by
the pyridylamidate moiety, which in this case acts with a N(1)−
Os−N(2) bite angle of 73.70(7)°, and the hydride ligands. The
separation between the metal center and the amidic nitrogen
atom N(2) of 2.1218(19) Å compares well with those reported
for osmium amidate compounds26 and is about 0.08 Å shorter
than the pyridinic Os−N(1) bond length of 2.2062(8) Å. The
lactamic N(2)−C(8) and C(8)−O(2) distances of 1.347(3)
and 1.223(3) Å, respectively, are statistically identical with the
related parameters of 1m. Because of the bent nature of the
tricyclic system, the phosphine ligands of the metal fragment
are inequivalent. According to this, the 31P{1H} NMR spectra
of 1p,q, in toluene, at room temperature show AB spin systems
centered at 27.3 ppm in both cases and defined by Δν = 2873
Hz and JA‑B = 680 Hz (1p) and Δν = 1691 Hz and JA‑B = 670
Scheme 9
1
Hz (1q). In the H NMR spectra at room temperature, the
most noticeable feature is a hydride resonance at −11.72 ppm
for 1p and at −11.70 ppm for 1q, which suggests the operation
of two thermally activated site exchange processes for the
inequivalent hydride ligands of each molecule. In agreement
1
with this, the H{31P} NMR spectrum of 1p at 183 K contains
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at −11.48 ppm an AB spin system, defined by Δν = 778 Hz and
JA‑B = 77.5 Hz, and at −12.56 ppm a singlet (see the Supporting
Information). The high value of the JA‑B coupling constant, for
two cisoid disposed hydrides, indicates that HA and HB undergo
quantum exchange coupling27 in addition to the thermally
activated site exchange. Lactamic CO resonances at 175.2 ppm
(1p) and 175.8 ppm (1q) in the 13C{1H} NMR spectra and
ν(CO) bands at 1684 (1p) and 1681 cm−1 (1q) in the IR
spectra are also characteristic of these compounds.
Osma- and Ruthenatrinems Containing Six-Coordi-
nate Bis(phosphine) d6 Metal Fragments: Tetrahydro-
borate Complexes as Introducers of the Metal Frag-
ment. Complexes containing a tetrahydroborate ligand
attached to the metal through two bridging hydrogen atoms
are known for the most of the transition metals.28 In solution,
they are in equilibrium with the M(η1-H-BH3) species, resulting
from the breaking of a bridge.29 In agreement with this, most
commonly BH3 is lost from the [BH4]− ligand, generating
unsaturated hydride compounds.30 The wide range of
transition-metal tetrahydroborate complexes known and the
fact proved in Scheme 9 that a hydride ligand promotes the
heterolytic N−H bond activation of the lactam without
affecting the four-membered ring prompted us to perform the
reactions of the tetrahydroborate complexes MH(η2-H2BH2)-
(CO)(PiPr3)2 (M = Os, Ru)31 with 2a, in order to asseverate
the wide versatility of the procedure.
Figure 5. ORTEP diagram of complex 1s (50% probability ellipsoids).
Hydrogen atoms (except the hydride) are omitted for clarity. Selected
bond lengths (Å) and angles (deg): Ru−N(1) = 2.117(2), Ru−N(2) =
2.247(2), N(1)−C(1) = 1.350(3), C(1)−O(1) = 1.229(3); P(1)−Ru-
P(2) = 162.33(2), N(1)−Ru−N(2) = 75.11(8), H(01)−Ru−N(2) =
169.4(10), C(15)−Ru−N(1) = 176.50(10).
occupying trans positions (P(1)−Ru−P(2) = 162.33(2)°).
The perpendicular plane is formed by the amidic N(1) and the
pyridinic N(2) nitrogen atoms of the pyridylamidate moiety,
which acts with a N(1)−Ru−N(2) bite angle of 75.11(8)°, the
hydride ligand disposed trans to N(2) (H(01)−Ru−N(2) =
169.4(10)°), and the carbonyl group located trans to N(1)
(C(15)−Ru−N(1) = 176.50(10)°). The Ru−N(1) bond
length of 2.117(2) Å compares well with the Ru−N distances
reported for ruthenium amidate compounds26c,32 and is 0.13 Å
shorter than the Ru−N(2) bond length of 2.247(2) Å. The
lactamic N(1)−C(1) and C(1)−O(1) distances of 1.350(3)
and 1.229(3) Å, respectively, are statistically identical with the
related parameters of 1p.
Treatment of toluene solutions of the aforementioned
osmium and ruthenium tetrahydroborate compounds with 1.0
equiv of 2a, under reflux, for 12 h leads to the osma- and
ruthenatrinems derivatives 1r,s (Scheme 10), containing six-
Scheme 10
1
The H, 31P{1H}, and 13C{1H} NMR spectra of 1r,s, in
benzene-d6, at room temperature are consistent with the
structure shown in Figure 5. In agreement with the presence of
1
a hydride ligand in these compounds, the H NMR spectra in
the high-field region contain at −14.69 (1r) and −13.33 ppm
(1s) triplets with H−P coupling constants of 21.3 and 24.0 Hz,
respectively. As expected for inequivalent phosphine ligands,
resulting from the bent nature of the tricycles, 31P{1H} NMR
spectra show AB spin systems centered at 24.9 (1r) and 52.4
ppm (1s) and defined by Δν = 2341 Hz and JA‑B = 634 Hz and
Δν = 2395 Hz and JA‑B = 676 Hz, respectively. In the 13C{1H}
NMR spectra, the lactamic CO resonances appear at 174.6 (1r)
and 175.6 ppm (1s), whereas the ν(CO) bands are observed at
1679 (1r) and 1670 cm−1 (1s) in the IR spectra, along with the
ν(MCO) absorptions at 1866 (1r) and 1881 cm−1 (1s).
coordinate bis(phosphine) d6 metal fragments at the 2-positon
of the tricycle, which were isolated as brown solids in 67% and
78% yields, respectively. Their formation involves the
heterolytic N−H bond activation of the lactam promoted by
one of the hydride ligands of the unsaturated five-coordinate
dihydride species MH2(CO)(PiPr3)2, which are generated as a
consequence of the BH3 release from the starting complexes
according to the previously mentioned general behavior of
these types of compounds. As for 1p, the coordination of the
pyridyl substituent of the four-membered ring stabilizes the
resulting unsaturated monohydride intermediates.
Ruthenatrinem 1s was characterized by an X-ray diffraction
analysis. Figure 5 shows a view of the tricycle, which displays a
bent angle between the five- and four membered rings of
37.92°. This angle is more closed than those of 1a,m,p by about
18, 16, and 7°, respectively. The comparison points out that the
transition metal at the 2-position and its associated ligands
exercise a marked influence on the bent angle of the tricycle.
The coordination geometry around the ruthenium atom can be
rationalized as derived from a distorted octahedron with the
phosphorus atoms of the triisopropylphosphine ligands
CONCLUDING REMARKS
■
This paper shows the discovery of an unprecedented class of
tribactams containing a transition metal and its associated
ligands at the 2-position of the tricyclic skeleton and reveals
that these metallatrinems can be formed through chelated
assisted heterolytic N−H bond activation of 2-azetidinones
substituted at the 4-position of the four-membered ring with an
N-heterocycle, including pyridine, quinoline, isoquinoline,
imidazole, and benzimidazole. The procedure is compatible
with a wide range of transition-metal starting complexes (half-
sandwich and diolefin dimers, polyhydride or tetrahydroborate
derivatives) and external and internal bases, including the
hydride ligand. This versatility allows polycycles to be built
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Organometallics
Article
z): calcd for C17H15N2O [M + H]+ 263.1179, found 263.1160. IR
containing a variety of saturated and unsaturated metal
fragments and four-, six-, and even seven-coordinated metal
ions (d4, d6, d8). Furthermore, once the metallatrinem has been
formed, the coordination sphere and oxidation state of the
metal center can be modified, without affecting the sensitive 2-
azetidinone backbone, through reactions of substitution and
oxidative addition, respectively. The metal fragment certainly
has a significant influence on relevant parameters of the
tribactam such as the IR stretching frequency of the lactamic
carbonyl, which ranges from 1670 to 1710 cm−1, the bent angle
between the five- and four-membered rings of the tricycle,
which changes from 55.55 to 37.92° for the studied cases, and
the N−CO bond length in the lactamic ring, which undergoes a
notable shortening by replacement of Ir(η5-C5Me5)Cl by
Ir(CO)2, OsH3(PiPr3)2, or RuH(CO)(PiPr3)2.
It is clear that hard work now needs to be done in order to
fully understand the influence of the metal fragment on the
relevant parameters of this novel family of tribactams, in
particular those determining their activity as inhibitors or
antibiotics,33 because the potentiality of their components is
impressive given the versatility of metal complexes that can be
used to introduce the metal fragment into the polycycle and the
possibility of modifying the coordination sphere of the metal
through simple reactions.
1
(CH2Cl2, cm−1): ν (CN) 1618, 1582, 1503. H NMR (300 MHz,
CDCl3, 298 K): δ 9.70−9.64 (m, 1H, isoqn), 9.07 (s, 1H, CHN),
8.67 (d, JH−H = 5.6, 1H, isoqn), 7.90−7.84 (m, 1H, isoqn), 7.75−7.68
(m, 3H, isoqn), 7.47−7.42 (m, 2H, PMP), 7.03−6.97 (m, 2H, PMP),
3.86 (s, 3H, CH3O). 13C{1H} NMR (75.5 MHz, CDCl3, 298 K): δ
160.1 (s, C isoquin), 159.0 (s, C PMP), 152.2 (s, CHN), 144.1 (s,
C PMP), 142.1 (s, C isoqn), 136.9 (s, C isoqn), 130.2 (s, CH isoqn),
128.5 (s, CH isoqn), 127.2 (s, CH isoqn), 127.1 (s, CH isoqn), 127.0
(s, CH isoqn), 122.6 (s, CH PMP), 122.4 (s, CH isoqn), 114.4 (s, CH
PMP), 55.4 (s, CH3O).
Preparation of N-((1-Methyl-1H-benzo[d]imidazol-2-yl)-
methylene)prop-2-en-1-amine (4d). A solution of allylamine
(1.73 g, 30.28 mmol) and 1-methyl-1H-benzo[d]imidazole-2-carbal-
dehyde39 (0.80 g, 6.05 mmol) in dichloromethane (12 mL) was stirred
at room temperature for 15 h in the presence of 6.05 g of anhydrous
Na2SO4. The mixture was then filtered and evaporated to yield a
yellow solid (1.2 g, quantitative). HRMS (electrospray, m/z): calcd for
C12H13NaN3 [M + Na]+ 222.1002, found 222.0985. IR (CH2Cl2,
1
cm−1): ν(CN) 1649. H NMR (300 MHz, CDCl3, 298 K): δ 8.55
(s, 1H, CHN), 7.85−7.82 (m, 1H, bzim), 7.45−7.28 (m, 3H, bzim),
6.17−6.02 (m, 1H, CH), 5.33−5.18 (m, 2H, CH2), 4.36−4.33
(m, 2H, CH2N), 4.19 (s, 3H, CH3N). 13C{1H} NMR (75.5 MHz,
CDCl3, 298 K): δ 155.3 (s, CHN), 147.5 (s, C bzim), 142.6 (s, C
bzim), 137.0 (s, C bzim), 135.1 (s, CH), 124.4 (s, CH bzim), 122.7
(s, CH bzim), 120.6 (s, CH bzim), 116.5 (s, CH2), 109.9 (s, CH
bzim), 64.0 (s, CH2N), 31.9 (s, CH3N).
Preparation of N-((1-Methyl-1H-imidazol-2-yl)methylene)-
prop-2-en-1-amine (4e). This compound was prepared as described
for 4d starting from allylamine (3.20 g, 56.7 mmol), 1-methyl-1H-
imidazole-2-carbaldehyde (1.25 g, 11.35 mmol), and 11.35 g of
anhydrous Na2SO4 in dichloromethane (25 mL). Yield (white solid):
1.69 g (quantitative). HRMS (electrospray, m/z): calcd for C8H12N3
[M + H]+ 150.1026, found 150.0999. IR (CH2Cl2, cm−1): ν(CN)
EXPERIMENTAL SECTION
■
General Information. All reactions involving the use of metallic
complexes were carried out with rigorous exclusion of air using
Schlenk-tube techniques. Solvents were obtained free of oxygen and
water from a solvent purification apparatus. Et3N was distilled over
CaH2 and stored under argon prior to use. Acid chlorides were
1
1
1650. H NMR (300 MHz, CDCl3, 298 K): δ 8.33 (s, 1H, CHN),
distilled under argon prior to use. H, 13C{1H}, and 31P{1H} NMR
7.12 (s, 1H, imid), 6.94 (s, 1H, imid), 6.12−5.97 (m, 1H, CH),
5.26−5.12 (m, 2H, CH2), 4.25−4.20 (m, 2H, CH2N), 4.01 (s, 3H,
CH3N). 13C{1H} NMR (75.5 MHz, CDCl3, 298 K): δ 153.6 (s, CH
N), 142.8 (s, C im), 135.4 (s, CH), 128.8 (s, CH im), 124.5 (s, CH
im), 115.5 (s, CH2), 63.3 (s, CH2N), 35.0 (s, CH3N).
spectra were recorded on 300, 400, and 500 MHz spectrometers.
Chemical shifts (expressed in parts per million) are referenced to
residual solvent peaks (1H, 13C{1H}) or external 85% H3PO4
(31P{1H}). Coupling constants J and N are given in hertz. Attenuated
total reflection infrared spectra (ATR-IR) of solid samples were run on
a FT-IR spectrometer. C, H, and N analyses were carried out with a
CHNS/O analyzer. High-resolution electrospray mass spectra were
acquired using a hybrid quadrupole time-of-flight spectrometer. 4-
Methoxy-N-(pyridin-2-ylmethylene)aniline (4a),34 [M(η5-C5Me5)-
Cl2]2 (M = Ir, Rh),35 [M(μ-OMe)(η4-COD)]2 (M = Ir, Rh),36
OsH6(PiPr3)2,37 and MH(η2-H2BH2)(CO)(PiPr3)2 (M = Os, Ru)31a
were prepared by published methods.
Preparation of ( )-cis-1-(4-Methoxyphenyl)-3-phenoxy-4-
(pyridin-2-yl)azetidin-2-one (3a). A solution of phenoxyacetyl
chloride (3.32 g, 19.48 mmol) in anhydrous dichloromethane (5 mL)
was purged with argon and cooled to −78 °C. A solution of
triethylamine (3.03 g, 29.94 mmol) in dichloromethane (2.5 mL) was
added dropwise. The mixture was stirred for 30 min at −78 °C, and a
solution of 4-methoxy-N-(pyridin-2-ylmethylene)aniline (4a; 3.18 g,
14.98 mmol) in dichloromethane (2.5 mL) was slowly added by
dropping. Upon completion of the addition, the cooling bath was
removed; the reaction mixture was stirred at room temperature for 16
h and quenched with 2 mL of MeOH. The crude mixture was diluted
with 15 mL of CH2Cl2 and washed with NaHCO3 (10 mL) and brine
(10 mL). The organic layer was dried over anhydrous Na2SO4 and the
solvent evaporated. SiO2 chromatography (Hex/EtOAc 4/6) yielded
analytically pure 3a (3.84 g, 74%) as a single cis isomer. HRMS
(electrospray, m/z): calcd for C21H18NaN2O3 [M + Na]+ 369.1210,
Preparation of 4-Methoxy-N-(quinolin-2-ylmethylene)-
aniline (4b). A solution of 1.55 g (9.84 mmol) of quinoline-2-
carbaldehyde and 0.88 g (7.13 mmol) of 4-methoxyaniline in 20 mL of
EtOH was stirred at room temperature for 10 h. The formed solid was
filtered and redissolved in Et2O (40 mL). Filtration and evaporation of
the solvent yielded pure 4b (1.49 g, 5.70 mmol, 80%) as an orange
solid. HRMS (electrospray, m/z): calcd for C17H15N2O [M + H]+
263.1179, found 263.1129. IR (CH2Cl2, cm−1): ν (CN) 1622, 1599,
1
1591. H NMR (300 MHz, CDCl3, 298 K): δ 8.75 (s, 1H, CHN),
1
found 369.1174. IR (CHCl3, cm−1): ν(CO) 1756. H NMR (300
8.25 (d, JH−H = 8.6, 1H, quin), 8.10 (d, JH−H = 8.5, 1H, quin), 8.03 (d,
JH−H = 8.6, 1H, quin), 7.69−7.53 (m, 2H, quin), 7.46−7.39 (m, 1H,
quin), 7.36−7.31 (m, 2H, PMP), 6.89−6.83 (m, 2H, PMP), 3.68 (s,
3H, CH3O). 13C{1H} NMR (75.5 MHz, CDCl3, 298 K): δ 158.7 (s, C,
PMP), 157.7 (s, C quin), 154.7 (s, CHN), 147.5 (s, C quin), 143.0
(s, C PMP), 136.0 (s, C qn), 129.4 (s, CH qn), 129.1 (s, CH qn),
128.3 (s, CH qn), 127.3 (s, CH qn), 127.0 (s, CH qn), 122.5 (s, CH
PMP), 118.1 (s, CH qn), 114.1 (s, CH PMP), 55.0 (s, CH3O).
Preparation of (E)-N-(Isoquinolin-1-ylmethylene)-4-methox-
yaniline (4c). A solution of 0.58 g (3.70 mmol) of isoquinoline-1-
carbaldehyde38 and 0.46 g (3.70 mmol) of 4-methoxyaniline in 8 mL
of EtOH was stirred at room temperature for 10 h. The formed solid
was filtered, washed with cold EtOH (2 × 2 mL), and dried to give
pure 4c (0.97 g, quantitative) as a red solid. HRMS (electrospray, m/
MHz, CDCl3, 298 K): δ 8.54−8.50 (m, 1H, py), 7.60 (td, JH−H = 7.7,
1.8, 1H, py), 7.42 (d, JH−H = 7.9, 1H, py), 7.34−7.29 (m, 2H, PMP),
7.21−7.13 (m, 3H, py + Ph), 6.94−6.87 (m, 1H, Ph), 6.86−6.79 (m,
4H, PMP + Ph), 5.61 (d, JH−H = 4.9, 1H, −CH), 5.55 (d, JH−H = 4.9,
1H, −CH), 3.74 (s, 3H, CH3O). 13C{1H} NMR (75 MHz, CDCl3,
298 K): δ 162.2 (CO), 156.9 (s, C PMP), 156.6 (s, C Ph), 153.6 (s,
C py), 149.3 (s, CH py), 136.3 (s, CH py), 130.3 (s, C PMP), 129.2
(s, CH Ph), 123.3 (s, CH py), 122.6 (s, CH py), 122.2 (s, CH Ph),
118.7 (s, CH PMP), 115.8 (s, CH Ph), 114.5 (s, CH PMP), 81.5 (s,
−CH), 63.4 (s, −CH), 55.4 (CH3O).
Preparation of ( )-cis-1-(4-Methoxyphenyl)-3-phenoxy-4-
(quinolin-2-yl)azetidin-2-one (3b). This compound was prepared
as described for 3a starting from phenoxyacetyl chloride (1.36 g, 7.97
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mmol), 4b (1.40 g, 5.33 mmol), and Et3N (1.61 g, 15.91 mmol). 3b
was obtained as a single cis isomer after purification by SiO2
chromatography (Hex/EtOAc 8/2). Yield (white solid): 1.48 g
(70%). HRMS (electrospray, m/z): calcd for C25H21N2O3 [M + H]+
(CHCl3, cm−1): ν(CO) 1763. 1H NMR (300 MHz, CDCl3, 298 K):
δ 7.29−7.18 (m, 2H, Ph), 7.09 (s, 1H, im), 7.00−6.93 (m, 1H, Ph),
6.92−6.80 (m, 3H, Ph + im), 5.76−5.61 (m, 1H, CH), 5.56 (bs, 1H,
−CH), 5.18− 5.05 (m, 2H, CH2), 4.65 (bs, 1H, −CH), 4.24−4.13
(m, 1H, CH2N), 4.59−4.50 (m, 1H, CH2N), 3.56 (s, 3H, CH3N).
13C{1H} NMR (75 MHz, CDCl3, 298 K): δ 164.7 (s, CO), 156.9 (s,
1
397.1547, found 397.1501. IR (CHCl3, cm−1): ν(CO) 1755. H
NMR (300 MHz, CDCl3, 298 K): δ 8.10 (t, JH−H = 8.9, 2H, qn), 7.80
(dd, JH−H = 8.1, 1.4, 1H, qn), 7.76−7.71 (m, 1H, qn), 7.62−7.52 (m,
2H, qn), 7.38−7.33 (m, 2H, PMP), 7.17−7.09 (m, 2H, Ph), 6.90−6.78
C Ph), 141.8 (s, C im), 131.3 (s, CH), 129.6 (s, CH Ph), 128.7 (s,
CH im), 122.2 (s, CH im), 122.1 (s, CH Ph), 118.8 (s, CH2), 115.1
(s, CH Ph), 84.9 (s, −CH), 53.9 (s, −CH), 43.2 (s, CH2N), 32.6 (s,
CH3N).
(m, 5H, Ph + PMP), 5.74 (d, JH−H = 5.0, 1H, −CH), 5.71 (d, JH−H
=
5.0, 1H, −CH), 3.74 (s, 3H, CH3O). 13C{1H} NMR (75 MHz,
CDCl3, 298 K): δ 162.5 (s, CO), 157.0 (s, C PMP), 156.7 (s, C
Ph), 154.6 (s, C qn), 147.7 (s, C qn), 136.6 (s, C qn), 130.4 (s, C
PMP), 129.8 (s, CH qn), 129.2 (s, CH Ph), 129.0 (s, CH qn), 127.8
(s, CH qn), 127.7 (s, CH qn), 126.9 (s, CH qn), 122.4 (s, CH Ph),
119.7 (s, CH qn), 118.7 (s, CH PMP), 115.9 (s, CH Ph), 114.5 (s, CH
PMP), 81.9 (s, −CH), 64.0 (s, −CH), 55.4 (s, CH3O).
Isomerization of 3d into ( )-cis-4-(1-Methyl-1H-benzo[d]-
imidazol-2-yl)-3-phenoxy-1-(prop-1-enyl)azetidin-2-one (5a).
To a sunlight -protected solution of 3d (0.55 g, 1.65 mmol) in
anhydrous toluene (6 mL) was added RuCl2(CHPh)(PCy3)2 (67.9
mg, 0.082 mmol) in portions, under argon. The mixture was refluxed
and monitored by thin-layer chromatography (TLC). After
completion, the solvent was eliminated and the crude product was
purified by SiO2 chromatography (Hex/EtOAc 7/3) to obtain
analytically pure 5a as 1.6/1 E/Z mixture. Yield (yellow solid): 0.34
Preparation of ( )-cis-4-(Isoquinolin-1-yl)-1-(4-methoxy-
phenyl)-3-phenoxyazetidin-2-one (3c). This compound was
prepared as described for 3a starting from phenoxyacetyl chloride
(0.90 g, 5.28 mmol), 4c (0.92 g, 3.52 mmol), and Et3N (1.07 g, 10.56
mmol). 3c was obtained as a single cis isomer after purification by SiO2
chromatography (Hex/EtOAc 4/6). Yield (white solid): 0.76 g (54%).
HRMS (electrospray, m/z): calcd for C25H21N2O3 [M + H]+
1
g (62%). IR (CHCl3, cm−1): ν(CO) 1758. H NMR (300 MHz,
CDCl3, 298 K): δ 7.79−7.74 (m, 2H, bzim, E+Z), 7.40−7.26 (m, 6H,
bzim, E+Z), 7.22−7.14 (m, 4H, Ph, E+Z), 6.98−6.86 (m, 6H, Ph, E
+Z), 6.64 (dd, JH−H = 14.3, 1.7, 1H, =CHN, E), 6.33 (dd, JH−H = 9.3,
1.8, 1H, CHN, Z), 5.87 (d, JH−H = 5.0, 1H, −CH, Z), 5.71 (d, JH−H
= 5.0, 1H, −CH, Z), 5.66 (s, 2H, 2 x −CH, E), 5.17−4.98 (m, 2H, 
1
397.1547, found 397.1508. IR (CHCl3, cm−1): ν(CO) 1746. H
NMR (300 MHz, CDCl3, 298 K): δ 8.52 (d, JH−H = 5.7, 1H, isoqn),
8.16 (bd, JH−H = 7.9, 1H, isoqn), 7.86 (d, JH−H = 8.3, 1H, isoqn), 7.69
(t, JH−H = 7.6, 1H, isoqn), 7.63−7.55 (m, 2H, isoqn), 7.37−7.34 (m,
2H, PMP), 7.07 (t, JH−H = 8.0, 2H, Ph), 6.88−6.78 (m, 3H, Ph), 6.68
(d, JH−H = 8.1, 2H, PMP), 6.21 (d, JH−H = 5.2, 1H, −CH), 5.82 (d,
JH−H = 5.2, 1H, −CH), 3.76 (s, 3H, CH3O). 13C{1H} NMR (75 MHz,
CDCl3, 298 K): δ 162.3 (s, CO), 157.2 (s, C PMP), 156.4 (s, C
Ph), 151.8 (s, C isoqn), 142.1 (s, C isoqn), 136.2 (s, C isoqn), 131.1
(s, CH isoqn), 129.9 (s, C PMP), 129.1 (s, C Ph), 127.5 (s, CH
isoqn), 127.4 (s, CH isoqn), 127.2 (s, CH isoqn), 123.8 (s, CH isoqn),
122.3 (s, CH Ph), 121.0 (s, CH isoqn), 118.9 (s, CH PMP), 116.2 (s,
CH Ph), 114.3 (s, CH PMP), 82.2 (s, −CH), 55.4 (s, −CH), 53.4 (s,
CH3O).
CHCH3, E+Z), 3.88 (d, JH−H = 1.6, 6H, CH3N, E+Z), 1.61 (dd, JH−H
=
7.0, 1.7, 6H, CH3CH, E+Z). 13C{1H} NMR (75 MHz, CDCl3, 298
K, E+Z): δ 163.1 (s, CO, E), 161.4 (s, CO, Z), 156.8 (s, C Ph,
E), 156.8 (s, C Ph, Z), 147.1 (s, C bzim, Z), 146.4 (s, C bzim, E),
142.2 (s, C bzim, E+Z), 137.0 (s, C bzim, E), 136.9 (s, C bzim, Z),
129.6 (s, C Ph, E), 129.5 (s, CH Ph, Z), 123.3 (s, CH Ph, Z), 123.2 (s,
CHN, Z), 122.9 (s, CHN, E), 122.3 (s, CH Ph, E), 120.8 (s, CH
bzim, E), 120.0 (s, CH bzim, Z), 119.9 (s, CH bzim, E), 119.5 (s, CH
bzim, Z), 116.0 (s, CH Ph, Z), 115.9 (s, CH Ph, E), 113.5 (s, 
CHCH3, Z), 111.8 (s, CHCH3, E), 109.4 (s, CH bzim, Z), 109.3 (s,
CH bzim, E), 83.6 (s, −CH, Z), 83.0 (s, −CH, E), 60.2 (s, −CH, E),
58.1 (s, −CH, Z), 30.8 (s, CH3N, E+Z), 14.9 (s, CH3CH, E), 12.8
(s, CH3CH, Z).
Preparation of ( )-cis-1-Allyl-4-(1-methyl-1H-benzo[d]-
imidazol-2-yl)-3-phenoxyazetidin-2-one (3d). This compound
was prepared as described for 3a starting from phenoxyacetyl chloride
(1.03 g, 6.03 mmol), 4d (0.60 g, 3.01 mmol), and Et3N (1.22 g, 12.05
mmol). 3d was obtained as a single cis isomer after purification by SiO2
chromatography (Hex/EtOAc 4/6). Yield (orange solid): 0.59 g
(59%). HRMS (electrospray, m/z): calcd for C20H20N3O2 [M + H]+
Isomerization of trans-3e into ( )-trans-4-(1-Methyl-1H-
imidazol-2-yl)-3-phenoxy-1-(prop-1-enyl)azetidin-2-one (5b).
This compound was prepared as described for 5a starting from
trans-3e (1.10 g, 3.88 mmol) and RuCl2(CHPh)(PCy3)2 (159.6 mg,
0.194 mmol). Pure 5b was obtained as a 1/6 E/Z mixture after
purification by SiO2 chromatography (Hex/EtOAc 4/6). Yield (yellow
oil): 0.70 g (64%). IR (CHCl3, cm−1): ν(CO) 1754. 1H NMR (300
1
334.1550, found 334.1524. IR (CHCl3, cm−1): ν(CO) 1762. H
NMR (300 MHz, CDCl3, 298 K): δ 7.82−7.76 (m, 1H, bzim), 7.37−
7.26 (m, 3H, bzim), 7.21−7.14 (m, 2H, Ph), 6.94 (t, JH−H = 7.6, 1H,
Ph), 6.91−6.86 (m, 2H, Ph), 5.86−5.71 (m, 1H, CH), 5.65 (d, JH−H
= 4.8, 1H, −CH), 5.40 (d, JH−H = 4.8, 1H, −CH), 5.26−5.17 (m, 2H,
CH2), 4.41−4.33 (m, 1H, CH2N), 3.95−3.87 (m, 1H, CH2N), 3.78
(s, 3H, CH3N). 13C{1H} NMR (75 MHz, CDCl3, 298 K): δ 164.8 (s,
CO), 156.8 (s, C Ph), 147.3 (s, C bzim), 142.3 (s, C bzim), 136.5
(s, C bzim), 130.1 (s, CH), 129.4 (s, CH Ph), 123.0, 122.6, 122.1
(all s, CH bzim), 120.0 (s, CH2), 119.9 (s, CH Ph), 115.8 (s, CH
Ph), 109.1 (s, CH bzim), 82.8 (s, −CH), 55.9 (s, −CH), 43.8 (s,
CH2N), 30.4 (s, CH3N).
MHz, CDCl3, 298 K): δ 7.31−7.23 (m, 4H, Ph, E+Z), 7.13 (d, JH−H
=
1.2, 2H, im, E+Z), 7.05−6.98 (m, 2H, Ph, E+Z), 6.95−6.85 (m, 6H,
Ph + im, E+Z), 6.48 (dd, JH−H = 14.3, 1.8, 1H, CHN, E), 6.02 (dd,
JH−H = 9.0, 1.7, 1H, CHN, Z), 5.50 (d, JH−H = 1.8, 1H, −CH, Z),
5.45 (d, JH−H = 1.9, 1H, −CH, E), 5.18−5.08 (m, 1H, CHCH3, Z),
5.03 (d, JH−H = 1.9, 1H, −CH, Z), 5.01−4.91 (m, 1H, CHCH3, E),
4.90 (d, JH−H = 1.9, 1H, −CH, E), 3.68 (s, 3H, CH3N, E), 3.65 (s, 3H,
CH3N, Z), 1.63−1.60 (m, 3H, CH3CH, E), 1.60 (dd, JH−H = 7.2,
1.7, 3H, CH3CH, Z). 13C{1H} NMR (75 MHz, CDCl3, 298 K, Z): δ
162.4 (s, CO), 157.0 (s, C Ph), 142.0 (s, C im), 129.7 (s, CH Ph),
129.0 (s, CHN), 122.5 (s, CH Ph), 122.4 (s, CH im), 120.1 (s, CH
im), 116.8 (s, CHCH3), 115.3 (s, CH Ph), 85.5 (s, −CH), 57.3 (s,
−CH), 32.8 (CH3N), 12.8 (CH3CH).
Preparation of ( )-trans-1-Allyl-4-(1-methyl-1H-imidazol-2-
yl)-3-phenoxyazetidin-2-one (trans-3e). A solution of phenox-
yacetyl chloride (4.50 g, 26.80 mmol) in 5 mL of anhydrous toluene
was added dropwise via syringe to a solution of 4e (2.00 g, 13.40
mmol) and Et3N (5.40 g, 53.60 mmol) in 2.5 mL of refluxing toluene
under argon. The resulting mixture was refluxed for 10 h. The crude
mixture was diluted with 15 mL of CH2Cl2 and washed with saturated
NaHCO3 (10 mL) and brine (10 mL). The organic layer was dried
over anhydrous Na2SO4 and the solvent evaporated under vacuum.
The crude mixture (1/4 cis-/trans-3e) was purified by SiO2
chromatography (Hex/EtOAc 3/7) to yield analytically pure lactam
trans-3e. Yield (yellow solid): 1.20 g (31%). A 1.50 g portion (39%) of
the cis/trans mixture was also recovered. HRMS (electrospray, m/z):
calcd for C16H18N3O2 [M + H]+ 284.1394, found 284.1364. IR
Preparation of ( )-cis-3-Phenoxy-4-(pyridin-2-yl)azetidin-2-
one (2a). To an ice-cooled solution of 3a (1.00 g, 2.88 mmol) in
CH3CN (90 mL) was slowly added a solution of cerium(IV)
ammonium nitrate (CAN, 4.74 g, 8.66 mmol) in H2O (30 mL).
The reaction mixture was kept at 0 °C, and progress was monitored by
TLC until total consumption of the starting material. After
completion, AcOEt, saturated aqueous NaHCO3, and saturated
aqueous Na2SO3 were added to the reaction mixture and the two
layers separated. The aqueous layer was extracted with AcOEt, and the
combined organics were washed with brine and dried over Na2SO4.
The solvent was removed under reduced pressure, and the crude
mixture was purified by SiO2 chromatography (Hex/EtOAc 4/6) to
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yield analytically pure 2a. Yield (white solid): 0.41 g (60%). HRMS
(electrospray, m/z): calcd for C14H13N2O2 [M + H]+ 241.0972, found
122.4 (s, CH Ph), 119.9 (s, CH bzim), 116.1 (s, CH Ph), 109.2 (s, CH
bzim), 84.2 (s, −CH), 52.5 (s, −CH), 30.4 (s, CH3N).
1
241.0976. IR (CHCl3, cm−1): ν(CO) 1761. H NMR (300 MHz,
Preparation of ( )-trans-4-(1-Methyl-1H-imidazol-2-yl)-3-
phenoxyazetidin-2-one (2e). This compound was prepared as
described for 2d starting from 5b (0.66 g, 2.33 mmol), RuCl3 (17 mg,
0.08 mmol), NaIO4 (0.97 g, 4.66 mmol) in 1,2-DCE (11 mL), and
H2O (11 mL). Pure 2e was obtained after purification by SiO2
chromatography (EtOAc) as a reddish solid. Yield: 90 mg (16%).
HRMS (electrospray, m/z): calcd for C13H14N3O2 [M + H]+
CDCl3, 298 K): δ 8.46 (bd, JH−H = 4.8, 1H, py), 7.69−7.63 (m, 1H,
py), 7.51 (d, JH−H = 7.8, 1H, py), 7.20−7.10 (m, 3H, py + Ph), 6.90 (t,
JH−H = 7.3, 1H, Ph), 6.79 (d, JH−H = 8.1, 2H, Ph), 6.42 (bs, 1H, NH),
5.54 (dd, JH−H = 4.8, 2.6, 1H, −CH), 5.22 (d, JH−H = 4.8, 1H, −CH).
13C{1H} NMR (75 MHz, CDCl3, 298 K): δ 167.2 (s, CO), 157.0 (s,
C Ph), 155.6 (s, C py), 149.1 (s, CH py), 136.6 (s, CH py), 129.4 (s,
CH Ph), 123.4 (s, CH py), 122.5 (s, CH py), 122.4 (s, CH Ph), 115.9
(s, CH Ph), 83.7 (s, −CH), 59.8 (s, −CH).
1
244.1081, found 244.1083. IR (CHCl3, cm−1): ν(CO) 1769. H
NMR (300 MHz, CDCl3, 298 K): δ 7.55 (bs, 1H, NH), 7.31−7.25 (m,
2H, Ph), 7.07−6.97 (m, 4H, Ph + imid), 6.91 (bs, 1H, im), 5.47 (bs,
1H, −CH), 4.82 (d, JH−H = 1.8, 1H, −CH), 3.62 (s, 3H, CH3N).
13C{1H} NMR (75 MHz, CDCl3, 298 K): δ 165.6 (s, CO), 157.1 (s,
C Ph), 143.7 (s, C im), 129.7 (s, C Ph), 128.1 (s, CH im), 122.5 (s,
CH im), 122.4 (s, CH Ph), 115.6 (s, CH Ph), 86.3 (s, −CH), 51.7 (s,
−CH), 32.8 (s, CH3N).
Preparation of ( )-cis-3-Phenoxy-4-(quinolin-2-yl)azetidin-
2-one (2b). This compound was prepared as described for 2a starting
from 3b (0.70 g, 1.76 mmol) in CH3CN (60 mL) and CAN (2.90 g,
5.30 mmol) in H2O (18 mL). Pure 2b was obtained after purification
by SiO2 chromatography (Hex/EtOAc 6/4) as a pale brown solid.
Yield: 0.38 g (75%). HRMS (electrospray, m/z): calcd for
C18H15N2O2 [M + H]+ 291.1128, found 291.1129. IR (CHCl3,
Reaction of [Ir(η5-C5Me5)Cl2]2 with 2a: Preparation of 1a. A
mixture of [Ir(η5-C5Me5)Cl2]2 (33.4 mg, 0.042 mmol), 2a (20 mg,
0.084 mmol), and NaOAc (16.1 mg, 0.196 mmol) in dichloromethane
(10 mL) was stirred overnight at room temperature. After this time,
the crude mixture was filtered through Celite and evaporated to
dryness. The obtained residue was dissolved in the minimum amount
of dichloromethane, and diethyl ether was added to afford a yellow
solid that was dried in vacuo. Yield: 46 mg (93%). This complex was
isolated as a 5/1 diastereomeric mixture. The diastereomeric ratio was
1
cm−1): ν(CO) 1764. H NMR (300 MHz, CDCl3, 298 K): δ 8.18
(d, JH−H = 8.5, 1H, qn), 8.03 (d, JH−H = 8.5, 1H, qn), 7.82 (d, JH−H
=
8.1, 1H, qn), 7.74−7.68 (m, 1H, qn), 7.65 (d, JH−H = 8.6, 1H, qn),
7.58−7.52 (m, 1H, qn), 7.17−7.10 (m, 2H, Ph), 6.92−6.82 (m, 3H,
Ph), 6.75 (bs, 1H, NH), 5.66 (dd, JH−H = 4.8, 2.5, 1H, −CH), 5.40 (d,
JH−H = 4.8, 1H, −CH). 13C{1H} NMR (75 MHz, CDCl3, 298 K): δ
166.7 (s, CO), 157.0 (s, C Ph), 155.8 (s, C qn), 147.4 (s, C qn),
136.4 (s, C qn), 129.8 (s, CH qn), 129.3 (s, CH Ph), 129.0 (s, CH
qn), 127.7 (s, CH qn), 126.8 (s, CH qn), 122.3 (s, CH Ph), 119.6 (s,
CH qn), 115.8 (s, CH Ph), 83.9 (s, −CH), 60.0 (s, −CH).
1
determined by integration of well-resolved signals in the H NMR
spectra and indicated as [M] for the major and [m] for the minor.
Separation of the diastereoisomers was not possible by SiO2
chromatography or any other means. HRMS (electrospray, m/z):
calcd for C24H26IrN2O2 [M − Cl]+ 567.1619, found 567.1632. IR
(CHCl3, cm−1): ν(CO) 1696 (s). 1H NMR (300 MHz, CDCl3, 298
K): δ 8.88 (d, JH−H = 5.6, 1H, py, [m]), 8.59 (d, JH−H = 5.6, 1H, py
[M]), 7.71 (td, J = 7.7, 1.6, 2H, py, [M+m]), 7.40−7.20 (m, 8H, py +
Ph, [M+m]), 7.13−7.05 (m, 4H, Ph, [M+m]), 7.02−6.94 (m, 2H, Ph,
[M+m]), 5.75 (d, JH−H = 4.5, 1H, −CH, [M]), 5.74 (d, JH−H = 4.4, 1H,
−CH, [m]), 5.14 (d, JH−H = 4.5, 1H, −CH, [M]), 4.89 (d, JH−H = 4.4,
1H, −CH, [m]), 1.87 (s, 15H, Cp*, [M]), 1.82 (s, 15H, Cp*, [m]).
13C{1H} NMR (75 MHz, CDCl3, 298 K, [M]): δ 175.8 (s, CO),
162.5 (s, C py), 158.0 (s, C Ph), 150.3 (s, CH py), 137.8 (s, CH py),
129.5 (s, CH Ph), 124.5 (s, CH py), 122.5 (s, CH Ph), 121.8 (s, CH
py), 115.7 (s, CH Ph), 86.5 (s, −CH), 82.7 (s, C Cp*), 65.6 (s,
−CH), 9.8 (s, CH3 Cp*).
Preparation of ( )-cis-4-(Isoquinolin-1-yl)-3-phenoxyazeti-
din-2-one (2c). This compound was prepared as described for 2a
starting from 3c (0.35 g, 0.88 mmol) in CH3CN (30 mL) and CAN
(1.45 g, 2.65 mmol) in H2O (9 mL). Pure 2c was obtained after
purification by SiO2 chromatography (Hex/EtOAc 6/4) as a slightly
colored solid. Yield: 0.11 g (41%). HRMS (electrospray, m/z): calcd
for C18H15N2O2 [M + H]+ 291.1128, found 291.1130. IR (CHCl3,
1
cm−1): ν(CO) 1759. H NMR (300 MHz, DMSO-d6, 298 K): δ
9.05 (s, 1H, NH), 8.52 (d, JH−H = 5.6, 1H, isoqn), 8.20 (d, JH−H = 8.4,
1H, isoqn), 7.96 (d, JH−H = 8.1, 1H, isoqn), 7.78 (d, JH−H = 5.7, 1H,
isoqn), 7.73 (dd, JH−H = 8.4, 6.7, 1H, isoqn), 7.59 (dd, JH−H = 8.4, 6.7,
1H, isoqn), 7.08 (dd, JH−H = 8.6, 7.3, 2H, Ph), 6.85−6.80 (m, 1H, Ph),
6.63 (dd, JH−H = 7.6, 1.6, 2H, Ph), 5.96 (dd, JH−H = 5.0, 1.4, 1H,
−CH), 5.92 (d, JH−H = 5.0, 1H, −CH). 13C{1H} NMR (75 MHz,
DMSO-d6, 298 K): δ 166.0 (s, CO), 157.1 (s, C Ph), 155.2 (s, C
isoqn), 141.4 (s, C isoqn), 135.2 (s, C isoqn), 130.1 (s, CH isoqn),
129.2 (s, CH Ph), 127.2, 127.0, 126.3, 124.5 (all s, CH isoqn), 121.8
(s, CH Ph), 120.4 (s, CH isoqn), 115.7 (s, CH Ph), 83.5 (s, −CH),
55.3 (s, −CH).
Reaction of [Rh(η5-C5Me5)Cl2]2 with 2a: Preparation of 1b.
This complex was prepared as described for 1a starting from [Rh(η5-
C5Me5)Cl2]2 (25.9 mg, 0.042 mmol), 2a (20.0 mg, 0.083 mmol), and
NaOAc (16.1 mg, 0.196 mmol) in dichloromethane (4 mL). Yield
(brown solid): 38 mg (90%). This complex was isolated as a 5/1
diastereomeric mixture. HRMS (electrospray, m/z): calcd for
C24H26N2O2Rh [M − Cl]+ 477.1044, found 477.1051. IR (CHCl3,
Preparation of ( )-cis-4-(1-Methyl-1H-benzo[d]imidazol-2-
yl)-3-phenoxyazetidin-2-one (2d). Aqueous RuCl3 (0.30 g, 0.90
mmol) and solid NaIO4 (0.38 g, 1.80 mmol) were sequentially added
to a solution of 5a (0.30 g, 0.90 mmol) in a 1,2-dichloroethane/water
mixture (8 mL, 1/1). The reaction mixture was stirred at room
temperature until completion (TLC). The mixture was quenched with
aqueous Na2S2O3 and extracted with EtOAc. The organic phase was
concentrated, and the resulting residue was dissolved in acetone and
stirred with saturated aqueous NaHCO3 (0.33 mL) and Na2CO3 (0.02
mmol). The mixture was extracted with EtOAc, and the extract was
washed with water, dried over MgSO4, filtered, and concentrated. The
crude mixture was purified by SiO2 chromatography (EtOAc) to yield
analytically pure 2d as a pale brown solid. Yield: 30 mg (13%). HRMS
(electrospray, m/z): calcd for C17H16N3O2 [M + H]+ 294.1237, found
1
cm−1): ν(CO) 1684 (s). H NMR (300 MHz, CDCl3, 298 K): δ
8.88 (d, JH−H = 5.6, 1H, py, [m]), 8.56 (d, JH−H = 5.6, 1H, py, [M]),
7.68 (td, JH−H = 7.7, 1.5, 2H, py, [M+m]), 7.38−7.14 (m, 8H, py + Ph,
[M+m]), 7.11−7.05 (m, 4H, Ph, [M+m]), 6.96 (td, JH−H = 7.3, 1.2,
2H, Ph, [M+m]), 5.66 (d, JH−H = 4.5, 1H, −CH, [M]), 5.65 (d, JH−H
=
4.5, 1H, −CH, [m]), 4.85 (d, JH−H = 4.5, 1H, −CH, [M]), 4.58 (d,
JH−H = 4.5, 1H, −CH, [m]), 1.89 (s, 15H, Cp*, [M]), 1.83 (s, 15H,
Cp*, [m]).13C{1H} NMR (75 MHz, CDCl3, 298 K, [M]): δ 177.1 (s,
CO), 161.6 (s, C py), 158.1 (s, C Ph), 149.7 (s, CH py), 137.5 (s,
CH py), 129.5 (s, CH Ph), 124.2 (s, CH py), 122.9 (s, CH Ph), 121.7
(s, CH py), 115.7 (s, CH Ph), 94.8 (d, JC−Rh = 8.3, C Cp*), 83.2 (s,
−CH), 64.7 (s, −CH), 9.9 (s, CH3 Cp*).
1
294.1238. IR (CHCl3, cm−1): ν(CO) 1772 cm−1. H NMR (300
Reaction of [Ir(η5-C5Me5)Cl2]2 with 2b: Preparation of 1c.
This complex was prepared as described for 1a starting from [Ir(η5-
C5Me5)Cl2]2 (27.1 mg, 0.034 mmol), 2b (20.0 mg, 0.069 mmol), and
NaOAc (13.4 mg, 0.163 mmol) in dichloromethane (3 mL). Yield
(yellow solid): 43.1 mg (96%). This complex was isolated as a 1/1
diastereomeric mixture. HRMS (electrospray, m/z): calcd for
C28H28IrN2O2 [M − Cl]+ 617.1776, found 617.1787. IR (CHCl3,
MHz, CDCl3, 298 K): δ 7.80 (d, JH−H = 7.3, 1H, bzim), 7.44 (bs, 1H,
NH), 7.38−7.27 (m, 3H, bzim), 7.22 (dd, JH−H = 8.6, 7.3, 2H, Ph),
7.00 (d, JH−H = 7.4, 1H, Ph), 6.94 (d, JH−H = 7.7, 2H, Ph), 5.71 (bd,
JH−H = 4.7, 1H, −CH), 5.40 (d, JH−H = 4.7, 1H, −CH), 3.77 (s, 3H,
CH3N). 13C{1H} NMR (75 MHz, CDCl3, 298 K): δ 165.6 (s, CO),
157.0 (s, C Ph), 148.9 (s, C bzim), 142.1 (s, C bzim), 136.7 (s, C
bzim), 129.6 (s, CH Ph), 123.2 (s, CH bzim), 122.9 (s, CH bzim),
1
cm−1): ν(CO) 1697. H NMR (300 MHz, CDCl3, 298 K): δ 8.64
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(d, JH−H = 8.7, 1H, qn), 8.39 (d, JH−H = 8.7, 1H, qn), 8.18 (d, JH−H
=
−CH, [M]), 5.06 (d, JH−H = 4.5, 1H, −CH, [m]), 1.95 (s, 15H, Cp*,
[M]), 1.90 (s, 15H, [m]). 13C{1H} NMR (126 MHz, CDCl3, 298 K,
[M]): δ 177.3 (s, CO), 163.8 (s, C isoqn), 158.3 (s, C Ph), 141.8 (s,
C isoqn), 135.9 (s, C isoqn), 132.0 (s, CH isoqn), 129.2 (s, CH Ph),
127.9, 127.7, 126.4, 126.0, 122.9 (all s, CH isoqn), 121.8 (s, CH Ph),
116.5 (s, CH Ph), 94.8 (d, JC−Rh = 8.3, C Cp*), 86.2 (s, −CH), 65.2
(s, −CH), 9.9 (s, CH3 Cp*).
8.4, 1H, qn), 8.11 (d, JH−H = 8.4, 1H, qn), 7.92−7.72 (m, 5H, qn),
7.67−7.51 (m, 3H, qn), 7.38−7.20 (m, 6H, Ph), 7.09−6.91 (m, 4H,
Ph), 6.14 (d, JH−H = 4.3, 1H, −CH), 5.92 (d, JH−H = 4.5, 1H, −CH),
5.34 (d, JH−H = 4.5, 1H, −CH), 5.17 (d, JH−H = 4.3, 1H, −CH), 1.88
(s, 15H, Cp*), 1.70 (s, 15H, Cp*). 13C{1H} NMR (75 MHz, CDCl3,
298 K): δ 176.6 (s, CO), 175.0 (s, CO), 163.8 (s, C qn), 163.8
(s, C qn), 158.3 (s, C Ph), 158.0 (s, C Ph), 146.3 (s, C qn), 145.7 (s,
C qn), 138.2 (s, C qn), 138.0 (s, C qn), 132.3, 131.0, 130.1 (all s, CH
qn), 129.6 (s, CH Ph), 129.3 (s, CH Ph), 129.1, 128.3, 128.2, 127.6,
127.4, 121.9, 121.6 (all s, CH qn), 119.1 (s, CH Ph), 118.7 (s, CH
Ph), 115.9 (s, CH Ph), 87.3 (s, −CH), 86.3 (s, C Cp*), 86.3 (s, C
Cp*), 83.2 (s, −CH), 68.6 (s, −CH), 67.9 (s, −CH), 10.5 (s, CH3
Cp*), 9.7 (s, CH3 Cp*).
Reaction of [Ir(η5-C5Me5)Cl2]2 with 2d: Preparation of 1g.
This complex was prepared as described for 1a starting from [Ir(η5-
C5Me5)Cl2]2 (28.5 mg, 0.036 mmol), 2d (21.0 mg, 0.071 mmol), and
NaOAc (13.8 mg, 0.169 mmol) in dichloromethane (3 mL). Yield
(yellow solid): 45.0 mg (96%). This complex was isolated as a single
diastereomer. HRMS (electrospray, m/z): calcd for C27H29IrN3O2 [M
− Cl]+ 620.1885 found 620.1896. IR (CHCl3, cm−1): ν(CO) 1703.
1H NMR (300 MHz, CDCl3, 298 K): δ 7.65−7.60 (m, 1H, bzim),
7.46−7.36 (m, 3H, bzim), 7.32−7.25 (m, 2H, Ph), 7.18 (d, JH−H = 8.0,
2H, Ph), 7.03−6.96 (m, 1H, Ph), 5.82 (d, JH−H = 4.5, 1H, −CH), 5.04
(d, JH−H = 4.5, 1H, −CH), 3.87 (s, 3H, CH3N), 1.99 (s, 15H, Cp*).
13C{1H} NMR (75 MHz, CDCl3, 298 K): δ 175.9 (s, CO), 159.7 (s,
C bzim), 157.8 (s, C Ph), 138.4 (s, C bzim), 137.0 (s, C bzim), 129.5
(s, CH Ph), 123.8 (s, CH bzim), 123.3 (s, CH bzim), 122.0 (s, CH
Ph), 117.4 (s, CH bzim), 115.9 (s, CH Ph), 110.9 (s, CH bzim), 86.2
(s, C Cp*), 83.1 (s, −CH), 56.5 (s, −CH), 32.0 (s, CH3N), 10.6 (s,
CH3 Cp*).
Reaction of [Rh(η5-C5Me5)Cl2]2 with 2b: Preparation of 1d.
This complex was prepared as described for 1a starting from [Rh(η5-
C5Me5)Cl2]2 (26.6 mg, 0.043 mmol), 2b (25.0 mg, 86 mmol), and
NaOAc (16.7 mg, 0.204 mmol) in dichloromethane (4 mL). Yield
(orange solid): 39 mg (80%). This complex was isolated as a 1.3/1
diastereomeric mixture. HRMS (electrospray, m/z): calcd for
C28H28N2O2Rh [M − Cl]+ 527.1200, found 527.1197. IR (CHCl3,
1
cm−1): ν(CO) 1690. H NMR (300 MHz, CDCl3, 298 K, broad
signals): δ 8.73 (s, 1H, qn, [m]), 8.43 (s, 1H, qn, [M]), 8.22−8.11 (m,
2H, qn, [M+m]), 7.98−7.76 (m, 5H, qn, [M+m]), 7.64−7.53 (m, 2H,
qn, [M+m]), 7.45 (s, 1H, qn, [M]), 7.41−7.17 (m, 6H, Ph, [M+m]),
7.14−6.84 (m, 4H, Ph, [M+m]), 5.93 (s, 1H, −CH, [m]), 5.84 (s, 1H,
−CH, [M]), 5.24 (s, 1H, −CH, [m]), 4.98 (s, 1H, −CH, [M]), 1.92
(s, 15H, Cp*, [M]), 1.71 (s, 15H, Cp*, [m]). 13C{1H} NMR (CDCl3,
126 MHz, 298 K, [M+m]): δ 179.0 (s, CO), 176.6 (s, CO),
164.9 (s, C qn), 163.6 (s, C qn), 158.7 (s, C Ph), 158.5 (s, C Ph),
147.1, 146.2, 138.2, 138.0 (all s, C qn), 131.4, 131.0, 130.1 (all s, CH
qn), 129.9 (s, CH Ph), 129.7 (s, CH Ph), 129.6, 129.5, 128.8, 128.5,
127.7, 127.4, 122.2, 121.9 (all s, CH qn), 120.1, 119.7, 116.3 (all s, CH
Ph), 95.9 (d, JC−Rh = 8.3, C Cp*), 94.7 (d, JC−Rh = 8.3, C Cp*), 84.8
(s, −CH), 84.3 (s, −CH), 68.5 (s, −CH), 67.2 (s, −CH), 11.1 (s, CH3
Cp*), 10.1 (s, CH3 Cp*).
Reaction of [Rh(η5-C5Me5)Cl2]2 with 2d: Preparation of 1h.
This complex was prepared as described for 1a starting from [Rh(η5-
C5Me5)Cl2]2 (20.0 mg, 0.032 mmol), 2d (19.0 mg, 0.065 mmol), and
NaOAc (12.6 mg, 0.153 mmol) in dichloromethane (3 mL). Yield
(orange solid): 34.5 mg (94%). This complex was isolated as a single
diastereomer. HRMS (electrospray, m/z): calcd for C27H29N3O2Rh
[M − Cl]+ 530.1309, found 530.1325. IR (CHCl3, cm−1): ν(CO)
1
1690. H NMR (300 MHz, CDCl3, 298 K): δ 7.73−7.68 (m, 1H,
bzim), 7.44−7.35 (m, 4H, bzim + Ph), 7.31−7.25 (m, 1H, Ph), 7.18
(d, JH−H = 8.1, 2H, Ph), 7.01−6.95 (m, 1H, Ph), 5.73 (d, JH−H = 4.5,
1H, −CH), 4.73 (d, JH−H = 4.5, 1H, −CH), 3.78 (s, 3H, CH3N), 1.98
(s, 15H, Cp*). 13C{1H} NMR (CDCl3, 75 MHz, 298 K): δ 177.3 (s,
CO), 157.9 (s, C bzim), 157.5 (s, C Ph), 139.1 (s, C bzim), 137.2
(s, C bzim), 129.5 (s, CH Ph), 123.4 (s, CH bzim), 123.0 (s, CH
bzim), 121.9 (s, CH Ph), 117.2 (s, CH bzim), 115.9 (s, CH Ph), 110.7
(s, CH bzim), 94.5 (d, JC−Rh = 8.6, C Cp*), 83.9 (s, −CH), 56.0 (s,
−CH), 31.6 (s, CH3N), 10.6 (s, CH3 Cp*).
Reaction of [Ir(η5-C5Me5)Cl2]2 with 2c: Preparation of 1e. This
complex was prepared as described for 1a starting from [Ir(η5-
C5Me5)Cl2]2 (26.1 mg, 0.032 mmol), 2c (19.0 mg, 0.065 mmol), and
NaOAc (12.4 mg, 0.152 mmol) in dichloromethane (3 mL). Yield
(yellow solid): 39.8 mg (94%). This complex was isolated as a 7/1
diastereomeric mixture. HRMS (electrospray, m/z): calcd for
C28H28IrN2O2 [M − Cl]+ 617.1776, found 617.1772. IR (CHCl3,
Reaction of [Ir(η5-C5Me5)Cl2]2 with 2e: Preparation of 1i. This
complex was prepared as described for 1a starting from [Ir(η5-
C5Me5)Cl2]2 (37.0 mg, 0.047 mmol), 2e (23.0 mg, 0.094 mmol), and
NaOAc (18.2 mg, 0.222 mmol) in dichloromethane (5 mL). Yield
(yellow solid): 52.3 mg (92%). This complex was isolated as a single
diastereomer. HRMS (electrospray, m/z): calcd for C23H27IrN3O2 [M
− Cl]+ 570.1728, found 570.1734. IR (CHCl3, cm−1): ν(CO) 1695.
1H NMR (300 MHz, CDCl3, 298 K): δ 7.31−7.20 (m, 4H, Ph + im),
7.03−6.92 (m, 3H, Ph + im), 4.92 (d, JH−H = 2.3, 1H, −CH), 4.73 (d,
JH−H = 2.3, 1H, −CH), 3.54 (s, 3H, CH3N), 1.91 (s, 15H, Cp*).
13C{1H} NMR (75 MHz, CDCl3, 298 K): δ 175.2 (s, CO), 157.8 (s,
C Ph), 153.7 (s, C im), 129.5 (s, CH Ph), 124.4 (s, CH im), 122.9 (s,
CH im), 122.2 (s, CH Ph), 117.1 (s, CH Ph), 85.5 (s, C Cp*), 84.9 (s,
−CH), 57.4 (s, −CH), 34.3 (s, CH3N), 9.9 (s, CH3 Cp*).
1
cm−1): ν(CO) 1699. H NMR (500 MHz, CDCl3, 298 K, [M + m
(characteristic signals)]): δ 8.46 (d, JH−H = 6.4, 1H, isoqn, [M]), 8.01
(d, 1H, JH−H = 8.4, isoqn, [M]), 7.91 (d, JH−H = 8.3, 1H, isoqn, [M]),
7.83 (dd, JH−H = 8.1, 6.8, 1H, isoqn, [M]), 7.69 (d, JH−H = 6.4, 1H,
isoqn, [M]), 7.65 (dd, JH−H = 8.3, 6.8, 1H, isoqn, [M]), 7.22 (dd, JH−H
= 8.7, 7.2, 2H, Ph, [M]), 6.99−6.94 (m, 3H, Ph, [M]), 6.04 (d, JH−H
=
4.6, 1H, −CH, [M]), 6.01 (d, JH−H = 4.7, 1H, −CH, [m]), 5.61 (d,
JH−H = 4.6, 1H, −CH, [M]), 5.05 (d, JH−H = 4.7, 1H, −CH [m]), 1.95
(s, 15H, Cp*, [M]), 1.86 (s, 15H, Cp*, [m]). 13C{1H} NMR (126
MHz, CDCl3, 298 K, [M]): δ 176.2 (s, CO), 164.8 (s, C isoqn),
158.3 (s, C Ph), 142.5 (s, C isoqn), 136.0 (s, C isoqn), 132.2 (s, CH
isoqn), 129.3 (s, CH Ph), 128.4, 128.0, 126.4, 125.8, 123.2 (all s, CH
isoqn), 121.9 (s, CH Ph), 116.5 (s, CH Ph), 86.6 (s, C Cp*), 85.7 (s,
−CH), 66.3 (s, −CH), 9.8 (s, CH3 Cp*).
Reaction of [Rh(η5-C5Me5)Cl2]2 with 2e: Preparation of 1j.
This complex was prepared as described for 1a starting from [Rh(η5-
C5Me5)Cl2]2 (28.0 mg, 0.045 mmol), 2e (22.0 mg, 0.090 mmol), and
NaOAc (17.5 mg, 0.210 mmol) in dichloromethane (5 mL). Yield
(orange solid): 41.7 mg (90%). This complex was isolated as a single
diastereomer. HRMS (electrospray, m/z): calcd for C23H27N3O2Rh
[M − Cl]+ 480.1153, found 480.1157. IR (CHCl3, cm−1): ν(CO)
1684. 1H NMR (300 MHz, CDCl3, 298 K): δ 7.26−7.16 (m, 4H, Ph +
im), 7.00−6.90 (m, 3H, Ph + im), 4.93 (d, JH−H = 2.3, 1H, −CH), 4.39
(d, JH−H = 2.5, 1H, −CH), 3.41 (s, 15H, Cp*). 13C{1H} NMR
(CDCl3, 75 MHz, 298 K): δ 177.4 (s, CO), 158.2 (s, C Ph), 151.9
(s, C im), 129.9 (s, CH Ph), 125.0 (s, CH im), 123.4 (s, CH im),
122.6 (s, CH Ph), 117.6 (s, CH Ph), 94.4 (d, JC−Rh = 8.5, C Cp*), 85.8
(s, −CH), 57.3 (s, −CH), 34.3 (s, CH3N), 10.3 (s, CH3 Cp*).
Reaction of [Rh(η5-C5Me5)Cl2]2 with 2c: Preparation of 1f.
This complex was prepared as described for 1a starting from [Rh(η5-
C5Me5)Cl2]2 (19.8 mg, 0.032 mmol), 2c (19.0 mg, 0.065 mmol). and
NaOAc (12.4 mg, 0.152 mmol) in dichloromethane (4 mL). Yield
(orange solid): 33.6 mg (92%). This complex was isolated as a 9/1
diastereomeric mixture. HRMS (electrospray, m/z): calcd for
C28H28N2O2Rh [M − Cl]+: 527.1200, found 527.1219. IR (CHCl3,
1
cm−1): ν(CO) 1688. H NMR (500 MHz, CDCl3, 298 K, [M + m
(characteristic signals)]): δ 8.42 (d, 1H, JH−H = 6.4, isoqn, [M]),
7.91−7.88 (m, 2H, isoqn, [M]), 7.80−7.75 (m, 2H, isoqn, [M]), 7.60
(dd, JH−H = 8.2, 6.8, 1H, isoqn, [M]), 7.20 (dd, JH−H = 8.7, 7.1, 2H, Ph,
[M]), 6.97−6.92 (m, 3H, Ph, [M]), 5.92 (d, JH−H = 4.6, 1H, −CH,
[M]), 5.90 (d, JH−H = 4.5, 1H, −CH, [m]), 5.30 (d, JH−H = 4.6, 1H,
1829
dx.doi.org/10.1021/om500162m | Organometallics 2014, 33, 1820−1833

Organometallics
Article
Reaction of [Ir(μ-OMe)(η4-COD)]2 with 2a: preparation of 1k.
A yellow suspension of [Ir(μ-OMe)(η4-COD)]2 (91.5 mg, 0.138
mmol) in pentane (10 mL) was treated with 2a (66.3 mg, 0.276
mmol), and the resulting suspension was stirred for 4 h at room
temperature. After this time an orange suspension was formed. The
orange solid was washed with pentane (2 × 3 mL) and dried in vacuo.
Yield: 115 mg (77%). Anal. Calcd for C22H23IrN2O2: C, 48.96; H,
4.29; N, 5.19. Found: C, 48.63; H, 4.29; N, 5.14. HRMS (electrospray,
m/z): calcd for C22H23IrN2O2 539.1344, found 539.1306. IR (cm−1):
398.9847. IR (cm−1): ν(CO) 2073 (s), 2007 (s); ν(CO) 1705 (s).
1H NMR (300 MHz, CD2Cl2, 298 K): δ 8.61 (d, JH−H = 5.0, 1H, py),
7.90 (t, 1H, JH−H = 5.0, py), 7.39 (m, 2H, py), 7.29 (t, JH−H = 7.9, 2H,
m-Ph), 7.06−6.98 (m, 3H, o-Ph + p-Ph), 5.72 (d, JH−H = 4.6, 1H,
−CH), 5.10 (d, JH−H = 4.1, 1H, −CH). 13C{1H}-APT plus HSQC and
HMBC NMR (75.4 MHz, CD2Cl2, 298 K): δ 186.8 (d, JC−Rh = 63.0,
Rh-CO), 185.5 (d, JC−Rh = 74.0, Rh-CO), 174.6 (s, CO), 163.5 (s,
C py), 158.2 (s, Cipso Ph), 153.1 (s, CH py), 139.6 (s, CH py), 129.9
(s, CH Ph), 124.0 (s, CH py), 123.1 (s, CH py), 122.0 (s, CH Ph),
115.6 (s, CH Ph), 84.0 (s, CH), 66.2 (s, CH).
1
ν(CO) 1687 (s). H NMR (400 MHz, CD2Cl2, 298 K): δ 8.05 (d,
JH−H = 5.6, 1H, py), 7.86 (m, 1H, py), 7.50 (d, JH−H = 8.0, 1H, py),
7.34−7.27 (m, 3H, py + m-Ph), 7.07 (d, JH−H = 8.8, 2H, o-Ph), 6.99 (t,
JH−H = 7.8, 1H, p-Ph), 5.71 (d, JH−H = 4.6, 1H, −CH), 5.36 (m, 1H, 
CH COD), 4.95 (d, JH−H = 4.6, 1H, −CH), 4.55 (m, 1H, CH
COD), 3.68 (m, 1H, CH COD), 3.61 (m, 1H, CH COD), 2.32−
1.54 (m, 8H, CH2 COD). 13C{1H}-APT plus HSQC and HMBC
NMR (100.62 MHz, CD2Cl2, 298 K): δ 172.6 (s, CO), 166.0 (s, C
py), 158.3 (s, Cipso Ph), 148.5 (s, CH py), 139.1 (s, CH py), 129.8 (s,
Cmeta Ph), 123.9 (s, CH py), 122.6 (s, Cpara Ph), 122.2 (s, CH py),
115.9 (s, Cortho Ph), 84.1 (s, CH), 67.8 (s, CH COD), 66.9 (s, CH),
65.9, 63.6, 62.2 (all s, CH COD), 32.8, 32.3, 31.9, 30.1 (all s,
−CH2− COD).
Reaction of 1m with CH3I: Preparation of 1o. A dark orange
suspension of 1m (123.0 mg, 0.252 mmol) was treated with CH3I (4
mL), and the resulting suspension was stirred protected from the light
for 5 h at room temperature. After this time, the resulting solution was
evaporated to dryness and pentane was added to afford a white solid
that was washed with pentane (3 × 2 mL) and dried in vacuo. Yield:
122.6 mg (79%). This complex was isolated as a 4/6 diastereomeric
mixture.40 The diastereomeric ratio was determined by integration of
well-resolved signals in the 1H NMR spectra and indicated as [M] for
the major and [m] for the minor isomer. Anal. Calcd for
C17H14IIrN2O4: C, 32.44; H, 2.24; N, 4.45. Found: C, 32.64; H,
2.65; N, 4.25. HRMS (electrospray, m/z): calcd for C17H14IIrN2O4
[M]+ 630.9701, found 630.9761. IR (cm−1): ν(CO) 2113 (s), 2060
(s); ν(CO) 1710 (s). 1H NMR (300 MHz, CD2Cl2, 298 K): δ 8.89
(d, JH−H = 5.3, 1H, py, [M]), 8.66 (d, JH−H = 5.3, 1H, py [m]), 8.08−
8.02 (m, 1H, py, [M]+[m]), 7.61−7.45 (m, 2H, py + Ph, [M]+[m]),
7.38−7.31 (m, 2H, Ph, [M]+[m]), 7.15−7.03 (m, 3H, py + Ph,
[M]+[m]), 5.87 (d, JH−H = 4.4, 1H, −CH [M]), 5.85 (d, JH−H = 4.4,
Reaction of [Rh(μ-OMe)(η4-COD)]2 with 2a: Preparation of 1l.
A pale yellow suspension of [Rh(μ-OMe)(η4-COD)]2 (100.0 mg,
0.149 mmol) in pentane (10 mL) was treated with 2a (72.0 mg, 0.299
mmol), and the resulting suspension was stirred for 6 h at room
temperature. After this time a bright yellow suspension was formed.
The bright yellow solid was washed with pentane (2 × 3 mL) and
dried in vacuo. Yield: 93 mg (69%). Anal. Calcd for C22H23N2O2Rh:
C, 58.67; H, 5.15; N, 6.22. Found: C, 59.04; H, 5.36; N, 5.97. HRMS
(electrospray, m/z): calcd for C22H23N2NaO2Rh [M + Na]+ 473.0707,
found 473.0747. IR (cm−1): ν(CO) 1680 (s). 1H NMR (300 MHz,
CD2Cl2, 298 K): δ 7.73 (m, 2H, py), 7.28 (m, 4H, py + m-Ph), 7.06
(d, JH−H = 7.8, 2H, o-Ph), 6.98 (t, JH−H = 7.3, 1H, p-Ph), 5.65 (m, 1H,
CH COD), 5.59 (d, JH−H = 4.6, 1H, −CH), 4.82 (d, JH−H = 4.6, 1H,
−CH), 4.69 (m, 1H, CH COD), 4.03 (m, 1H, CH COD), 3.91
(m, 1H, CH COD), 2.17−1.75 (m, 8H, CH2 COD). 13C{1H}-APT
plus HSQC and HMBC NMR (75.47 MHz, CD2Cl2, 298 K,): δ 174.5
(s, CO), 164.8 (s C py), 158.5 (s, Cipso Ph), 148.0 (s, CH py), 138.2
(s, CH py), 129.8 (s, Cmeta Ph), 123.5 (s, CH py), 123.0 (s, Cpara Ph),
122.1 (s, CH py), 116.1 (s, Cortho Ph), 83.7 (s, JC−Rh = 2.2, CH), 81.5
(d, JC−Rh = 12.5, CH COD), 79.9 (d, JC−Rh = 11.7, CH COD),
79.5 (d, JC−Rh = 13.2, CH COD) 79.2 (d, JC−Rh = 12.4, CH
COD), 65.6 (s, CH), 31.1, 31.4, 31.2, 29.6 (all s, −CH2− COD).
Reaction of 1k with CO: Preparation of 1m. Carbon monoxide
was bubbled through an orange solution of 1k (200 mg, 0.372 mmol)
in dichloromethane (10 mL) for 10 min. After this time, the resulting
solution was evaporated to dryness and pentane was added to afford a
dark orange solid that was washed with pentane (3 × 2 mL) and dried
in vacuo. Yield: 163 mg (90%). Anal. Calcd for C16H11IrN2O4: C,
39.34; H, 2.27; N, 5.74. Found: C, 38.94; H, 2.55; N, 5.50. HRMS
(electrospray, m/z): calcd for C16H11IrN2O4 [M]+ 511.0253, found
511.0241. IR (cm−1): ν(CO) 2061 (s), 1991 (s); ν(CO) 1706 (s).
1H NMR (400 MHz, CD2Cl2, 298 K): δ 8.85 (d, JH−H = 5.7, 1H, py),
8.00 (m, 1H, py), 7.55 (d, JH−H = 7.8, 1H, py), 7.42 (m, 1H, py), 7.30
(m, 2H, m-Ph), 7.06−7.02 (m, 3H, o-Ph + p-Ph), 5.82 (d, JH−H = 4.8,
1H, −CH), 5.25 (d, JH−H = 4.8, 1H, −CH). 13C{1H}-APT plus HSQC
and HMBC NMR (75.4 MHz, CD2Cl2, 298 K): δ 178.9 (s, Ir-CO),
173.8 (s, CO), 171.9 (s, Ir-CO), 163.4 (s, C py), 158.0 (s, Cipso Ph),
153.9 (s, CH py), 140.9 (s, CH py), 129.9 (s, CH Ph), 125.2 (s, CH
py), 123.6 (s, CH py), 122.6 (s, CH Ph), 116.0 (s, CH Ph), 85.2 (s,
CH), 66.9 (s, CH).
1H, −CH, [m]), 5.46 (d, JH−H = 4.4, 1H, −CH, [m]), 5.37 (d, JH−H
=
4.4, 1H, −CH, [M]), 1.51 (s, 3H, −CH3, [m]), 1.41 (s, 3H, −CH3,
[M]). 13C{1H}-APT plus HSQC and HMBC NMR (75.47 MHz,
CD2Cl2, 298 K, [M] + [m]): δ 174.4, 173.2 (both s, CO), 163.5,
163.4 (both s, Ir-CO), 161.1, 160.2 (both s, C py), 158.4, 158.3 (both
s, Ir-CO), 158.0, 157.9 (both s, Cipso Ph), 153.8, 152.0 (both s, CH
py), 141.0 (s, CH Py), 130.0 (s, CH Ph), 126.5 (s, CH py), 126.3 (s,
CH py), 124.1 (s, CH py), 124.0 (s, CH py), 122.7 (s, CH Ph), 116.2
(s, CH Ph), 116.0 (s, CH Ph), 84.4, 83.2, 69.2, 66.5 (all s, CH), −10.2,
−12.0 (both s, CH3).
Reaction of OsH6(PiPr3)2 with 2a: Preparation of 1p. A
colorless solution of OsH6(PiPr3)2 (100 mg, 0.193 mmol) in toluene
(10 mL) was treated with 2a (46.5 mg, 0.193 mmol) and heated under
reflux during 12 h. After this time, the resulting solution was
evaporated to dryness and pentane was added to afford a white solid
that was washed with pentane (3 × 2 mL) and dried in vacuo. Yield:
117 mg (82%). Anal. Calcd for C32H56N2O2OsP2: C, 51.04; H, 7.50;
N, 3.72. Found: C, 51.64; H, 7.40; N, 3.46. HRMS (electrospray, m/
z): calcd for C32H55N2O2OsP2 [M − H]+ 753.3430, found 753.3350.
IR (cm−1): ν(CO) 1684 (s). 1H NMR (400 MHz, C7D8, 298 K): δ
9.15 (d, JH−H = 6.6, 1H, CH py), 7.48 (d, 2H, JH−H = 7.5, CH Ph),
7.20 (m, 2H, CH py), 7.04 (m, 2H, CH Ph), 6.97 (t, JH−H = 7.6, 1H,
CH Ph), 6.88 (t, JH−H = 6.6, 1H, CH py), 6.31 (t, JH−H = 6.6, 1H, CH
py), 5.63 (d, JH−H = 4.3, 1H, −CH), 4.70 (d, JH−H = 2.4, 1H, −CH),
2.27 (m, 3H, PCH(CH3)2), 1.93 (m, 3H, PCH(CH3)2), 1.20 (dd, JH−H
= 6.8, JH−P = 12.4, 9H, PCH(CH3)2), 1.20 (dd, JH−H = 6.8, JH−P = 12.4,
9H, PCH(CH3)2), 1.02 (dd, JH−H = 7.1, JH−P = 11.8, 9H,
PCH(CH3)2), 0.94 (dd, JH−H = 7.1, JH−P = 11.6, 9H, PCH(CH3)2),
−11.72 (br, 3H, OsH). 1H{31P} NMR (500 MHz, C7D8, 183 K, high-
field region): −11.48 (AB spin system, Δν = 778, JA‑B = 77.5, 2H,
OsH), −12.56 (br s, 1H, OsH). t1(min) (ms, OsH, 500 MHz, C7D8,
233 K); 123 4 (−11.48 ppm); 138 4 (−12.56 ppm). 31P{1H}
NMR (162 MHz, C7D8, 298 K): δ 27.3 (AB spin system, Δν = 2873,
JA‑B = 680). 13C{1H}-APT plus HSQC and HMBC NMR (100.4 MHz,
C7D8, 298 K): δ 175.2 (s, CO), 161.5 (s, C py), 158.8 (s, Cipso Ph),
156.2 (s, CH py), 134.0 (s, CH py), 129.1 (s, CH Ph), 122.4 (s, CH
py), 121.2 (s, CH Ph), 121.1 (s, CH py), 116.5 (s, CH Ph), 84.7 (s,
CH), 68.4 (s, CH), 29.8 (dd, JC−P = 20.6, JC−P = 2.9, PCH(CH3)2),
26.5 (dd, JC−P = 21.3, JC−P = 2.2, PCH(CH3)2), 20.7, 20.4, 19.6, 19.5
(all s, PCH(CH3)2).
Reaction of 1l with CO: Preparation of 1n. Carbon monoxide
was bubbled through a brown solution of 1l (100 mg, 0.186 mmol) in
dichloromethane (10 mL) for 2 h. After this time, the resulting
solution was evaporated to dryness and pentane was added to afford
an orange solid that was washed with pentane (3 × 2 mL) and dried in
vacuo. Yield: 80 mg (90%). Anal. Calcd for C16H12N2O4Rh: C, 48.14;
H, 3.03; N, 7.02. Found: C, 48.33; H, 2.96; N, 7.42. HRMS
(electrospray, m/z): calcd for C16H12N2O4Rh [M]+ 398.9931, found
Reaction of OsH6(PiPr3)2 with 2b: Preparation of 1q. A
colorless solution of OsH6(PiPr3)2 (100 mg, 0.193 mmol) in toluene
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Article
(10 mL) was treated with 2b (56.2 mg, 0.193 mmol) and heated under
reflux for 12 h. After this time, the resulting solution was evaporated to
dryness and pentane was added to afford a white solid that was washed
with pentane (3 × 2 mL) and dried in vacuo. Yield: 110 mg (71%).
Anal. Calcd for C36H57N2O2OsP2: C, 53.91 H, 7.16; N, 3.49. Found:
C, 53.62; H, 6.99; N, 3.68 HRMS (electrospray, m/z): calcd for
C36H58N2O2OsP2 [M − H]+ 803.3507, found 803.3545. IR (cm−1):
−13.33 (t, JH−P = 24.0, 1H, RuH). 31P{1H} NMR (121 MHz, C6D6,
298 K): δ 52.4 (AB spin system, Δν = 2395, JA‑B = 676). 13C{1H}-APT
plus HSQC and HMBC NMR (75.3 MHz, C6D6, 298 K): δ 207.0 (s,
Ru−CO), 175.6 (s, CO), 161.4 (s, C py), 159.2 (s, Cipso Ph),
153.9 (s, CH py), 135.7 (s, CH py), 129.7 (s, CH Ph), 121.9 (s, CH
py), 121.7 (s, CH Ph), 121.5 (s, CH py), 116.8 (s, CH Ph), 84.7 (s,
CH), 66.1 (s, CH), 27.6 (dd, JC−P = 16.6, JC−P = 2.6, PCH(CH3)2),
26.6 (dd, JC−P = 15.7, JC−P = 2.6, PCH(CH3)2), 20.6, 20.4, 19.6, 19.5
(all s, PCH(CH3)2).
Structural Analysis of Complexes 1a,m,p,s. X-ray data were
collected for the complexes on Bruker Smart APEX CCD and Bruker
AXS Smart 100 CCD diffractometers equipped with a normal-focus
2.4 kW sealed-tube source (Mo radiation, λ = 0.71073 Å) operating at
50 kV and 40 mA (1p), 30 mA (1p,s) or 25 mA (1a). Data were
collected over the complete sphere. Each frame exposure time was 10 s
(1a,p,s) or 20 s (1m) covering 0.3° in ω. Data were corrected for
absorption by using a multiscan method applied with the SADABS
program.41 The structures were solved by Patterson or direct methods
and refined by full-matrix least squares on F2 with SHELXL97,42
including isotropic and subsequently anisotropic displacement
parameters. The hydrogen atoms (except hydrides) were observed
in the least-squares Fourier maps or calculated and refined freely or
refined using a restricted riding model. Hydrides of 1p were observed
in the last cycles of refinement but refined too close to metals;
therefore, a restricted refinement model was used. 1m cocrystallizes
with 0.5 molecule of hydroquinone.
1
ν(CO) 1681 (s). H NMR (300 MHz, C6D6, 298 K): δ 9.74 (d,
JH−H = 8.4, 1H, CH py), 7.56−7.06 (m, 9H, CH Py + Ph), 6.87 (t,
JH−H = 7.0, 1H, CH py), 5.83 (d, JH−H = 3.6, 1H, −CH), 4.93 (d, JH−H
= 3.6, 1H, −CH), 2.19 (m, 3H, PCH(CH3)2), 1.85 (m, 3H,
PCH(CH3)2), 1.17 (dd, JH−H = 7.0, JH−P = 12.4, 9H, PCH(CH3)2),
1.07 (dd, JH−H = 7.1, JH−P = 12.2, 9H, PCH(CH3)2), 0.97 (dd, JH−H
=
7.5, JH−P = 12, 9H, PCH(CH3)2), 0.82 (dd, JH−H = 7.1, JH−P = 10.9,
1
9H, PCH(CH3)2), −11.70 (br, 3H, OsH). H{31P} NMR (300 MHz,
C7D8, 183 K, high-field region): −11.04 (br s, 2H, OsH), −13.03 (br,
1H, OsH). t1(min) (ms, OsH, 300 MHz, C7D8, 233 K); 54
(−11.01 ppm); 65
4
4 (−12.97 ppm). 31P{1H} NMR (162 MHz,
C6D6, 298 K): δ 27.3 (AB spin system, Δν = 1691, JA‑B = 670).
13C{1H}-APT plus HSQC and HMBC (75 MHz, C6D6, 298 K): δ
175.8 (s, CO), 163.7 (s, C qn), 159.2 (s, Cipso Ph), 148.3 (s, C qn),
136.2 (s, CH qn), 135.6 (s, CH Ph), 129.7 (s, CH py), 129.1 (s, CH
qn), 128.8 (s, C qn), 128.5 (s, CH qn), 126.7 (s, CH qn), 121.8 (s,
CH qn), 119.9 (s, CH Ph), 116.9 (s, CH Ph), 86.3 (s, CH), 71.6 (s,
CH), 29.8 (dd, JC−P = 20.4, JC−P = 3.1, PCH(CH3)2), 26.7 (dd, JC−P
=
19.8, JC−P = 2.7, PCH(CH3)2), 21.3, 21.0, 20.1 (all s, PCH(CH3)2).
Reaction of OsH(η2-H2BH2)(CO)(PiPr3)2 with 2a: Preparation
of 1r. A colorless solution of OsH(η2-H2BH2)(CO)(PiPr3)2 (100 mg,
0.180 mmol) in toluene (10 mL) was treated with 2a (43.4 mg, 0.180
mmol) and heated under reflux for 12 h. After this time, the resulting
solution was evaporated to dryness and pentane was added to afford a
brown solid that was washed with pentane (3 × 2 mL) and dried in
vacuo. Yield: 105 mg (67%). Anal. Calcd for C33H54N2O3OsP2: C,
50.88; H, 6.99; N, 3.60. Found: C, 50.82; H, 6.90; N, 3.55. HRMS
(electrospray, m/z): calcd for C33H55N2O3OsP2 [M + H]+ 781.3480,
Crystal data for 1a: C24H26ClIrN2O2·0.5C6H6 Mw = 641.17,
yellow, prismatic block (0.18 × 0.16 × 0.07 mm), triclinic, space group
P1, a = 10.853(2) Å, b = 10.896(2) Å, c = 12.009(3)Å, α = 98.514(4)°,
̅
β = 108.068(3)°, γ: =105.722(4)°, V = 1257.1(5) Å3, Z = 2, Z′ = 1,
Dcalcd = 1.694 g cm−3, F(000) = 630, T = 120(2) K, μ = 5.443 mm−1,
9523 measured reflections (2θ = 3−50°, ω scans 0.3°), 4298 unique
reflections (Rint = 0.1015), minimum/maximum transmission factors
0.693/1.000, final agreement factors R1 = 0.0546 (2936 observed
reflections, I > 2σ(I)) and wR2 = 0.1193, 4298/0/265 data/restraints/
parameters, GOF = 0.993, largest peak and hole 2.032 and −1.143 e/
Å3.
1
found 781.3299. IR (cm−1): ν(CO) 1866 (s), ν(CO) 1679 (s). H
NMR (300 MHz, C6D6, 298 K): δ 9.15 (d, JH−H = 5.4, 1H, CH py),
7.47 (d, 2H, JH−H = 7.8, CH Ph), 6.87 (m, 2H, CH py), 6.87 (m, 1H,
CH Ph), 6.29 (td, JH−H = 6.1, JH−P = 1.8, 1H, CH py), 5.47 (d, JH−H
=
Crystal data for 1m: C16H11IrN2O4·0.5C6H6O2, Mw = 542.52,
orange, irregular block (0.16 × 0.04 × 0.04 mm), monoclinic, space
group C2/c, a = 24.6159(14)Å, b = 8.1783(5)Å, c = 17.4801(10)Å, β =
101.6990(10)°, V = 3445.9(3) Å3, Z = 8, Z′ = 1, Dcalcd = 2.091 g cm−3,
F(000) = 2072, T = 100(2) K, μ = 7.784 mm−1, 20493 measured
4.3, 1H, −CH), 4.33 (s, 1H, −CH), 2.71 (m, 3H, PCH(CH3)2), 232
(m, 3H, PCH(CH3)2), 1.31 (dd, JH−H = 6.9, JH−P = 12.9, 9H,
PCH(CH3)2), 1.30 (dd, JH−H = 6.9, JH−P = 12.6, 9H, PCH(CH3)2),
0.99 (dd, JH−H = 6.7, JH−P = 12.5, 9H, PCH(CH3)2), 0.97 (dd, JH−H
=
6.3, JH−P = 12.8, 9H, PCH(CH3)2), −14.69 (t, JH−P = 21.3, 1H, OsH).
31P{1H} NMR (121 MHz, C6D6, 298 K): δ 24.9 (AB spin system, Δν
reflections (2θ = 3−58°, ω scans 0.3°), 4160 unique reflections (Rint
=
= 2341, JA‑B = 634). 13C{1H}-APT plus HSQC and HMBC NMR
(100.4 MHz, C6D6, 298 K): δ 188.3 (t, JC−P = 9.8, Os−CO), 174.6
(s, CO), 161.2 (s, C py), 159.1 (s, Cipso Ph), 154.7 (s, CH py), 135.1
(s, CH py), 129.7 (s, CH Ph), 122.3 (s, CH py), 121.8 (s, CH Ph),
121.2 (s, CH py), 116.8 (s, CH Ph), 84.8 (s, CH), 67.9 (s, CH), 28.4
(dd, JC−P = 21.3, JC−P = 2.2, PCH(CH3)2), 27.4 (dd, JC−P = 21.3, JC−P
= 2.2, PCH(CH3)2), 20.7, 20.4, 19.6, 19.5 (all s, PCH(CH3)2).
Reaction of RuH(η2-H2BH2)(CO)(PiPr3)2 with 2a: Preparation
of 1s. A colorless solution of RuH(η2-H2BH2)(CO)(PiPr3)2 (100 mg,
0.215 mmol) in toluene (10 mL) was treated with 2a (51.6 mg, 0.215
mmol) and heated under reflux for 3 h. After this time, the resulting
solution was evaporated to dryness and pentane was added to afford a
brown solid that was washed with pentane (3 × 2 mL) and dried in
vacuo. Yield: 115 mg (78%). Anal. Calcd for C33H54N2O3P2Ru: C,
57.46; H, 7.89; N, 4.06. Found: C, 57.82; H, 7.57; N, 4.37. HRMS
(electrospray, m/z): calcd for C33H55N2O3P2Ru [M + H]+ 691.2738,
0.0549), minimum/maximum transmission factors 0.598/0.842, final
agreement factors R1 = 0.0332 (3530 observed reflections, I > 2σ(I))
and wR2 = 0.0526, 4160/0/247 data/restraints/parameters, GOF =
1.127, largest peak and hole 0.832 and −1.066 e/Å3.
Crystal data for 1p: C32H56N2O2OsP2, Mw = 752.93, colorless,
irregular block (0.29 × 0.06 × 0.02 mm), monoclinic, space group
P21/c, a = 18.5861(8) Å, b = 12.3352(5) Å, c = 15.5389(7) Å, β =
108.2130(10)°, V = 3384.0(3) Å3, Z = 4, Z′ = 1, Dcalcd = 1.478 g cm−3,
F(000) = 1536, T = 100(2) K, μ = 3.892 mm−1, 50203 measured
reflections (2θ = 3−58°, ω scans 0.3°), 8255 unique reflections (Rint
=
0.0330), minimum/maximum transmission factors 0.588/0.842, final
agreement factors R1 = 0.0205 (7272 observed reflections, I > 2σ(I))
and wR2 = 0.0456, 8255/3/379 data/restraints/parameters, GOF =
1.052, largest peak and hole 1.102 and −0.476 e/Å3.
Crystal data for 1s: C33H54N2O3P2Ru, Mw = 689.79, colorless,
irregular block (0.26 × 0.11 × 0.10 mm), monoclinic, space group
P21/n, a = 14.4769(7) Å, b = 10.6595(5) Å, c = 23.1385(12) Å, β =
101.2010(10)°, V = 3502.6(3) Å3, Z = 4, Z′ = 1, Dcalcd = 1.308 g cm−3,
F(000) = 1456, T = 100(2) K, μ = 0.572 mm−1, 31601 measured
1
found 691.2735. IR (cm−1): ν(CO) 1881 (s), ν(CO) 1670 (s). H
NMR (300 MHz, C6D6, 298 K): δ 9.09 (d, JH−H = 5.4, 1H, CH py),
7.60 (d, 2H, JH−H = 8.7, CH Ph), 7.28 (m, 1H, CH py), 7.01 (m, 2H,
CH Ph), 6.96 (m, 2H, CH Ph), 6.54 (td, JH−H = 5.8, JH−P = 1.8, 1H,
CH py), 5.57 (d, JH−H = 4.1, 1H, −CH), 4.53 (d, JH−H = 4.1, 1H,
−CH), 2.76 (m, 3H, PCH(CH3)2), 2.29 (m, 3H, PCH(CH3)2), 1.43
(dd, JH−H = 6.0, JH−P = 12.0, 9H, PCH(CH3)2), 1.43 (dd, JH−H = 9.0,
JH−P = 15.0, 9H, PCH(CH3)2), 1.13 (dd, JH−H = 6.0, JH−P = 7.2, 9H,
PCH(CH3)2), 1.09 (dd, JH−H = 2.8, JH−P = 7.2, 9H, PCH(CH3)2),
reflections (2θ = 3−58°, ω scans 0.3°), 8342 unique reflections (Rint
=
0.0481), minimum/maximum transmission factors 0.728/0.842, final
agreement factors R1 = 0.0391 (6631 observed reflections, I > 2σ(I))
and wR2 = 0.0816, 8342/0/385 data/restraints/parameters, GOF =
1.056, largest peak and hole 0.628 and −0.677 e/Å3.
1831
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W.; Spencer, J.; Vila, A. J. Acc. Chem. Res. 2006, 39, 721. (d) Wang, J.-
F.; Chou, K.-C. Curr. Top. Med. Chem. 2013, 13, 124.
ASSOCIATED CONTENT
■
S
* Supporting Information
(6) See: Per
3740.
́
ez-Llarena, F. J.; Bou, G. Curr. Med. Chem. 2009, 16,
1
Figures giving H and 13C{1H} NMR spectra of compounds
4b−e, 3a−e, 5a,b, 2a−e, and 1a−j and CIF files giving
positional and displacement parameters, crystallographic data,
and bond lengths and angles of compounds 1a,m,p,s. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(7) Trinems: (a) Mori, M.; Somada, A.; Oida, S. Chem. Pharm. Bull.
2000, 48, 716. (b) Kanno, O.; Shimoji, Y.; Ohya, S.; Kawamoto, I. J.
Antibiot. 2000, 53, 404. (c) Sader, H. S.; Gales, A. C. Drugs 2001, 61,
553. (d) Alcaide, B.; Almendros, P. Curr. Org. Chem. 2002, 6, 245.
(e) Copar, A.; Prevec, T.; Anzic,
̌
B.; Mesar, T.; Selic,
Solmajer, T. Bioorg. Med. Chem. Lett. 2002, 12, 971. (f) Plantan, I.;
Selic, L.; Mesar, T.; Anderluh, P. S.; Oblak, M.; Prezelj, A.; Hesse, L.;
Andrejasi
̌
L.; Vilar, M.;
̌
AUTHOR INFORMATION
Corresponding Authors
*E-mail for M.A.E.: maester@unizar.es.
*E-mail for M.A.S.: sierraor@ucm.es.
̌
̌
■
̌ ̌
c, M.; Vilar, M.; Turk, D.; Kocijan, A.; Prevec, T.; Vilfan, G.;
Kocjan, D.; Copar, A.; Urleb, U.; Solmajer, T. J. Med. Chem. 2007, 50,
4113. (g) Venkatesan, A. M.; Agarwal, A.; Abe, T.; Ushirogochi, H.;
Ado, M.; Tsuyoshi, T.; Dos Santos, O.; Li, Z.; Francisco, G.; Lin, Y. I.;
Petersen, P. J.; Yang, Y.; Weiss, W. J.; Shlaes, D. M.; Mansour, T. S.
Bioorg. Med. Chem. 2008, 16, 1890.
Notes
The authors declare no competing financial interest.
(8) The incorporation of metals into biologically active drugs has
produced several biologically active targets. See: (a) Bioorganometal-
lics: Biomolecules, Labeling, Medicine; Jaouen, G., Ed.; Wiley-VCH:
Weinheim, Germany, 2006. (b) Hartinger, C. G.; Dyson, P. J. Chem.
Soc. Rev. 2009, 38, 391.
ACKNOWLEDGMENTS
■
Financial support from the Spanish MINECO (Projects
CTQ2011-23459, CTQ2010-20714-C02-01/BQU and Con-
solider Ingenio 2010 (CSD2007-00006)), the DGA (E35), the
CAM (S2009/PPQ-1634-AVANCAT), and the European
Social Fund (FSE) is acknowledged. Johnson Matthey Catalysts
is acknowledged for the donation of RhCl3·3H2O and IrCl3·
3H2O.
(9) Sigel, H.; Martin, R. B. Chem. Rev. 1982, 82, 385.
(10) (a) Goodgame, D. M. L.; Khaled, A. M.; O’Mahoney, C. A.;
Williams, D. J. J. Chem. Soc., Chem. Commun. 1990, 851. (b) Good-
game, D. M. L.; Hill, S. P. W.; Williams, D. J. Polyhedron 1992, 11,
1841. (c) Goodgame, D. M. L.; Hill, S. P. W.; Lincoln, R.; Quiros, M.;
Williams, D. J. Polyhedron 1993, 12, 2753. (d) Arndt, P.; Lefeber, C.;
Kempe, R.; Tillack, A.; Rosenthal, U. Chem. Ber. 1996, 129, 1281.
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dx.doi.org/10.1021/om500162m | Organometallics 2014, 33, 1820−1833

Organometallics
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