Double geminal C-H activation and reversible α-elimination in 2-aminopyridine iridium(III) complexes: The role of hydrides and solvent in flattening the free energy surface

Article abstract of DOI:10.1021/ja048473j

[H₂Ir(OCMe₂)₂L₂]BF₄ (1) (L = PPh₃), a preferred catalyst for tritiation of pharmaceuticals, reacts with model substrate 2-(dimethylamino)pyridine (py-NMe₂; py = 2-pyridyl) to give chelate carbene [H ₂Ir(py-N(Me)CH=)L₂]BF₄ (2a) via cyclometalation, H₂ loss, and reversible α-elimination. Agostic intermediate [H₂Ir(py-N(Me)CH₂-H)L₂]BF ₄ (4a), seen by NMR, is predicted (DFT(B3PW91) computations) to give C-H oxidative addition to form the alkyl intermediate [(H)(η²- H₂)Ir(py-N(Me)CH₂-)L₂]BF₄. Loss of H₂ leads to the fully characterized alkyl [HIr(OCMe ₂)(py-N(Me)CH₂-)L₂]BF₄ (3a ^Me2CO), which loses acetone to give alkylidene hydride 2a by rapid reversible α-elimination. 2a rapidly reacts with excess H₂ in d₆-acetone to generate [H₂Ir(OC(CD₃) ₂)₂L₂]BF₄ (1-d₁₂), 3a^(CD3)2CO, and py-NMe₂ in a 1:1:1 ratio, showing reversibility and accounting for the selective isotope exchange catalyzed by 1. Reaction of 1 with py-N(CH₂)₄ gives the fully characterized carbene 2c. A cis-L₂ carbene intermediate, cis-2c, observed by NMR, reacts with CO via retro α-elimination to give the alkyl 3c^CO, while the trans isomer, 2c, does not react; retro α-elimination thus requires the Ir-H bond to be orthogonal to the carbene plane. Consistent with experiment, computational studies show a particularly flat PE surface with activation of the agostic C-H bond giving a less stable H₂ complex, then formation of a kinetic carbene complex with cis-L, only seen experimentally for py-N(CH₂)₄. Hydrides at key positions, together with gain or loss of solvent and H₂, flatten the PE (AG) surfaces to allow fast catalysis.

Full text of DOI:10.1021/ja048473j

Published on Web 06/24/2004
Double Geminal C-H Activation and Reversible r-Elimination
in 2-Aminopyridine Iridium(III) Complexes: The Role of
Hydrides and Solvent in Flattening the Free Energy Surface
Eric Clot,‡ Junyi Chen,† Dong-Heon Lee,§ So Young Sung,§ Leah N. Appelhans,†
Jack W. Faller,*,† Robert H. Crabtree,*,† and Odile Eisenstein*,‡
Contribution from the Sterling Chemistry Laboratory, Yale UniVersity,
New HaVen, Connecticut 06520-810; LSDSMS, UMR 5636, UniVersite´ Montpellier 2,
34095 Montpellier Cedex 5, France; and Department of Chemistry,
Chonbuk National UniVersity, Chonju, 561-756, Korea
Received March 17, 2004; E-mail: jack.faller@yale.edu; robert.crabtree@yale.edu; odile.eisenstein@univ-montp2.fr
Abstract: [H2Ir(OCMe2)2L2]BF4 (1) (L ) PPh3), a preferred catalyst for tritiation of pharmaceuticals, reacts
with model substrate 2-(dimethylamino)pyridine (py-NMe2; py ) 2-pyridyl) to give chelate carbene [H2Ir(py-
N(Me)CHd)L2]BF4 (2a) via cyclometalation, H2 loss, and reversible R-elimination. Agostic intermediate
[H2Ir(py-N(Me)CH2sH)L2]BF4 (4a), seen by NMR, is predicted (DFT(B3PW91) computations) to give CsH
oxidative addition to form the alkyl intermediate [(H)(η2-H2)Ir(py-N(Me)CH2s)L2]BF4. Loss of H2 leads to
the fully characterized alkyl [HIr(OCMe2)(py-N(Me)CH2s)L2]BF4 (3aMe CO), which loses acetone to give
2
alkylidene hydride 2a by rapid reversible R-elimination. 2a rapidly reacts with excess H2 in d6-acetone to
generate [H2Ir(OC(CD3)2)2L2]BF4 (1-d12), 3a(CD ) CO, and py-NMe2 in a 1:1:1 ratio, showing reversibility and
accounting for the selective isotope exchange catalyzed by 1. Reaction of 1 with py-N(CH2)4 gives the fully
characterized carbene 2c. A cis-L2 carbene intermediate, cis-2c, observed by NMR, reacts with CO via
retro R-elimination to give the alkyl 3cCO, while the trans isomer, 2c, does not react; retro R-elimination
thus requires the IrsH bond to be orthogonal to the carbene plane. Consistent with experiment,
computational studies show a particularly flat PE surface with activation of the agostic CsH bond giving a
less stable H2 complex, then formation of a kinetic carbene complex with cis-L, only seen experimentally
for py-N(CH2)4. Hydrides at key positions, together with gain or loss of solvent and H2, flatten the PE (∆G)
surfaces to allow fast catalysis.
3
2
Introduction
occurs, however. DFT calculations show that the presence of
hydrides at key positions in the catalyst intermediates together
[H2Ir(OCMe2)2L2]BF4 (1) (L ) PPh3), or its precursor
[Ir(cod)L2]BF4, is a preferred catalyst for the commercial
tritiation of pharmaceuticals.1,2 A reversible cyclometalation
involving coordination at a substrate lone pair and oxidative
addition of an adjacent C-H bond with reversible transfer of
the CH hydrogen to the metal is thought to be responsible for
the selectivity.3 We now find that where the key substrate CH
is activated by an adjacent aliphatic nitrogen, as in 2-(dimethyl-
amino)pyridine (py-NMe2; py ) 2-pyridyl), stoichiometric
reaction with 1 leads to transfer of two hydrogens to the metal
with loss of H2 and formation of a carbene complex. The
presence of this normally very stable species might be expected
to slow the isotope exchange by making the H transfers less
easily reversible. Experimentally, rapid isotope exchange still
with gain or loss of solvent and H2 flatten the Gibbs free energy
surfaces to allow fast reversible R-hydride elimination and
isotope exchange in this system. A preliminary report has
appeared on a small part of this work (Scheme 1).4
Unlike reversible â-hydride elimination, well studied in
catalytic reactions such as olefin isomerization, reversible
R-hydride elimination is rare. Evidence for an equilibrium
between an alkyl complex and alkylidene hydride has generally
involved high oxidation state early transition metal complexes,
notably of tungsten5-9 and tantalum.10-14 An equilibrium
between Cp*2Ta(dCH2)(H) and the unobservable Cp*2TasCH3
(4) Lee, D.-H.; Chen, J.; Faller, J. W.; Crabtree, R. H. Chem. Commun. 2001,
213.
(5) Cooper, N. J.; Green, M. L. H. J. Chem. Soc., Chem. Commun. 1974, 209.
(6) Cooper, N. J.; Green, M. L. H. J. Chem. Soc., Chem. Commun. 1974, 761.
(7) Cooper, N. J.; Green, M. L. H. J. Chem. Soc., Dalton Trans. 1979, 1121.
(8) Shih, K.-Y.; Totland, K.; Seidel, S. W.; Schrock, R. R. J. Am. Chem. Soc.
1994, 116, 12103.
(9) Schrock, R. R.; Seidel, S. W.; Mosch-Zanetti, N. C.; Dobbs, D. A.; Shih,
K.-Y.; Davis, W. M. Organometallics 1997, 16, 5195.
(10) Turner, H. W.; Schrock, R. R. J. Am. Chem. Soc. 1982, 104, 2331.
(11) Turner, H. W.; Schrock, R. R.; Fellman, J. D.; Holmes, S. J. J. Am. Chem.
Soc. 1983, 105, 4942.
(12) Fellman, J. D.; Schrock, R. R.; Traficante, D. D. Organometallics 1982, 1,
481.
† Yale University.
‡ Universite´ Montpellier 2.
§ Chonbuk National University.
(1) Saljoughian, M.; Williams, P. G. Curr. Pharm. Des. 2000, 6, 1029.
(2) Shu, A. Y. L.; Saunders, D.; Levinson, S. M.; Landwatter, S. W.; Mahoney,
A.; Senderoff, S. G.; Mack, J. F.; Heys, J. R. J. Labelled Compd.
Radiopharm. 1999, 42, 797.
(3) Crabtree, R. H.; Holt, E. A.; Lavin, M.; Morehouse, S. M. Inorg. Chem.
1985, 24, 1986.
9
10.1021/ja048473j CCC: $27.50 © 2004 American Chemical Society
J. AM. CHEM. SOC. 2004, 126, 8795-8804
8795

A R T I C L E S
Clot et al.
Scheme 1
Figure 1. Crystal structure of the cation of the carbene complex 2b.
assigned to IrdC in the characteristic chemical shift range for
heteroatom stabilized (Fischer) carbenes. Two resonance forms
of 2a are shown in eq 1: 2′′ with an IrsC single bond, usually
dominant in Fischer carbenes, while 2′ has the IrdC double
bond that one would normally expect for a true carbene.
Unfortunately, no suitable crystals of 2a could be grown for
crystallographic study.
was detected by trapping the alkyl complex with small, two-
electron donor ligands. Complex Cp*2(H)TadCdCH2/Cp*2Tas
CHdCH2 decomposes via both R-elimination and â-H-
elimination, but R-elimination is favored by a factor of 108,
owing to a highly strained transition state for â-H-elimination.14
In complexes [{N3N}Mo(alkyl)] (N3N3- ) [(Me3SiNCH2-
CH2)3N]3-; alkyl ) cyclopentyl, cyclohexyl), R-elimination is
faster than â-H-elimination; however, no products of R- and
â-H-elimination were observed.15 In some iridium complexes,
R-elimination was proposed to be faster than â-H-elimination
from D labeling,16 but later work showed that the results were
better explained on the basis of a strongly bound alkane complex
as an intermediate.17 A heteroatom greatly facilitates both CH
oxidative addition and R-elimination to give a carbene. Irrevers-
ible geminal R-dehydrogenation of several cyclic ethers and
amines such as dioxolane, furan, and pyrrolidine by RuHCl-
(PiPr3)2 and OsH3Cl(PiPr3)2 has been observed.18
The case of py-NMe2 gave no opportunity for â-elimination,
so we moved to py-NEt2, where that possibility does now exist.
The same reaction proved possible for 2-diethylaminopyridine
(py-NEt2) to give the analogous carbene 2b at 25 °C after 15
1
Results
min in CH2Cl2 solution in 80% yield (eq 1). The H NMR
spectrum of 2b contains two terminal IrH resonances at -10.73
δ (trans to C) and -17.85 δ (trans to N) that are both mutually
coupled (2JHH ) 4.5 Hz) and coupled to the cis PPh3 ligands
(2JPH ) 21.4 Hz). The 13C NMR resonance at 265.9 δ is charac-
teristic of a Fischer carbene. Complex 2b was characterized by
an X-ray structure determination (Figure 1). The Ir-C distance
of 2.018 Å is consistent with predominant single bond character,
while the C-N bond distance of 1.322 Å indicates substantial
multiple bond character as expected from the resonance form
2′′ generally preferred by Fischer carbenes (eq 1).
The cyclic derivative 2-pyrrolidinopyridine, py-N(CH2)4,
gives the analogous carbene 2c at 25 °C in 53% yield but only
after 7 h (eq 1). The 1H NMR spectrum of 2c exhibits two high
field resonances -9.96 δ (trans to C) and -17.85 δ (trans to
N) with coupling constants 2JPH ) 20.9 Hz and 2JHH′ ) 4.7 Hz.
The carbene C resonated in the 13C NMR spectrum at 258.3 δ.
Complex 2c was characterized by an X-ray structure determi-
nation (Figure 2). The Ir-C distance of 2.151 Å is slightly
longer than that in 2b (2.018 Å), but the C-N bond distances
(2c, 1.345 Å; 2b, 1.322 Å) are comparable.
Double Dehydrogenation. A stoichiometric reaction of
2-(dimethylamino)pyridine (py-NMe2) and [H2Ir(OCMe2)2-
(PPh3)2]BF4 (1) yields the cyclic heteroatom-stabilized carbene
complex 2a (Scheme 1). The product is isolated as an air-stable
1
solid in 78% yield after 15 min at 25 °C in CH2Cl2. The H
NMR spectrum of 2a contains a low field singlet of unit intensity
at 11.63 δ assigned to CHdIr and a singlet at 3.39 δ of intensity
3H assigned to the NsMe group. The two inequivalent hydrides
resonate at -10.03 δ (trans to C) and -17.85 δ (trans to N) as
triplets of doublets (2JPH ) 17.0 Hz, 2JHH′ ) 4.3 Hz) indicating
each hydride is cis to the two phosphines. The 13C NMR
spectrum of 2a exhibits a low-field resonance at 250.5 δ
(13) van Asselt, A.; Burger, B. J.; Gibson, V. C.; Bercaw, J. E. J. Am. Chem.
Soc. 1986, 108, 5347.
(14) Parkin, G.; Bunel, E.; Burger, B. J.; Trimmer, M. S.; van Asselt, A.; Bercaw,
J. E. J. Mol. Catal. 1987, 41, 21.
(15) Schrock, R. R.; Seidel, S. W.; Mosch-Zanetti, N. C.; Shih, K.-Y.;
O’Donoghue, M. B.; Davis, W. M.; Reiff, W. M. J. Am. Chem. Soc. 1997,
119, 11876.
(16) Burk, M. J.; McGrath, M. P.; Crabtree, R. H. J. Am. Chem. Soc. 1988,
110, 620.
(17) Ge´rard, H.; Eisenstein, O.; Lee, D.-H.; Chen, J.; Crabtree, R. H. New J.
Chem. 2001, 25, 1121.
Similarly, cyclic derivatives 2-piperidinopyridine (py-N(CH2)5)
and 2-hexamethyleneiminopyridine (py-N(CH2)6) form the
(18) Ferrando-Miguel, G.; Coalter, J. N., III; Ge´rard, H.; Huffman, J. C.;
Eisenstein, O.; Caulton, K. G. New J. Chem. 2002, 26, 687.
9
8796 J. AM. CHEM. SOC. VOL. 126, NO. 28, 2004

Hydrides/Solvent Role in Free Energy Surface Flattening
A R T I C L E S
Figure 3. Crystal structure of the cation of the alkyl complex 3aMe CO
2
with acetone as the solvent ligand.
Figure 2. Crystal structure of the cation of the carbene complex 2c.
Table 1. 1H and 13C NMR Spectroscopic Data for Carbene
Intermediate Alkyl. The conversion of 1 and py-NMe2 to
2a was also monitored in situ by H NMR spectroscopy, but
Complexesa
1
2
2
no cis-(PR3)2 products were seen in this case. Free dihydrogen
was detected (4.20 δ), consistent with the net loss of H2 on
going from 1 to 2a, in addition to an intermediate alkyl iridium
hydride complex [HIr(solv)(py-N(Me)CH2s)L2]BF4 3a (solv
substrate
(product)
δ(IrsH) δ(IrsH ) JHH JPH 13C(IrdC) d(IrsC) d(CsN)
t
c
(ppm)
(ppm) (Hz) (Hz)
(ppm) (X-ray, Å) (X-ray, Å)
Py-NMe2 (2a)
Py-NEt2 (2b)
-10.03 -17.85 4.3 17.0 250.5
-10.73 -17.85 4.5 21.4 265.9
Py-N(CH2) 4 (2c) -9.96 -17.85 4.7 20.9 258.3
Py-N(CH2) 5 (2d) -10.52 -18.06 4.2 18.4 263.2
Py-N(CH2) 6 (2e) -10.85 -17.89 4.3 18.5 260.4
2.018 1.322
2.151 1.345
) Me2CO), denoted 3aMe CO, which disappeared as 2a was
2
formed. Complex 3aMe CO could be independently prepared in
2
almost quantitative yield by dissolving a pure sample of 2a in
a Ht is the hydride atom trans to the alkyl carbon, and Hc is the hydride
cis to Ir-C
acetone, and in this way, 3aMe CO was isolated and fully
2
1
characterized (eq 3, L′ ) Me2CO). In the H NMR spectrum,
the terminal hydride of 3aMe CO resonates as a triplet of unit
2
carbene complexes 2d and 2e, respectively, at 25 °C after 1 h
in the reaction with 1. Their 1H and 13C NMR data along with
those of 2a-c are presented in Table 1.
intensity at -16.07 δ, in the range expected for a hydride trans
to N, with 2JPH ) 15 Hz. No carbene resonance is observed in
the 13C NMR spectrum. The molecular structure of 3aMe CO from
2
A cis Intermediate. Computational work described in a
separate section predicted that the initial kinetic product of the
dehydrogenation reaction should have cis-PR3 groups, not trans
as at first observed. An effort was therefore made to monitor
the reaction to see if any kinetic products could be seen. When
the reaction of 1 with py-N(CH2)4 was monitored in situ by 1H
NMR spectroscopy, a second isomer, cis-2c, was indeed
identified as the initial kinetic product (eq 2) after 2 h. One
hydride in cis-2c must be trans to a phosphine because it appears
as a broad centrosymmetric 1H NMR multiplet (ddd) at -10.83
δ with JPH ) 106 Hz (trans P) and 35 Hz (cis P). An irregular
intensity pattern, approximately 2:3:3:2, is observed, due to
second-order effects caused by the coupled phosphorus nuclei
with nearly identical chemical shifts and coupling to protons
with different relative signs. The other hydride appears as a
triplet of doublets at -18.82 δ with cis coupling constants JPH
≈ JP′H ) 16 Hz and JHH ) 3 Hz. The chemical shift of the
latter is typical of H trans to N rather than C as illustrated by
a comparison with 2a for which the values are -10.03 δ, trans
to C, and -17.85 δ, trans to N. This is definitely a cis-(PR3)2
compound with the stereochemistry shown being the most
probable. As the reaction proceeds, the thermodynamic product
2c grows in at the expense of cis-2c (t{1/2} ) 3.0 h at 18 °C).
X-ray diffraction is shown in Figure 3. The d(IrsC) of 2.072
Å in complex 3aMe CO lies between those of 2b (2.018 Å) and
2
2c (2.151 Å). The d(CsN) of 1.480 Å in 3aMe CO is substantially
2
longer than those in 2b (1.322 Å) and 2c (1.345 Å), indicating
a single bond character (typical d(CsN) ) 1.47 Å).19
Agostic Intermediate. The reaction of 1 and py-NMe2 was
1
monitored at low temperature by H NMR spectroscopy in an
attempt to identify intermediates that occur earlier than 3aMe CO
.
2
At -80 °C in CD2Cl2 solution, an agostic species, 4a, was
identified in addition to 3aMe CO (Scheme 1). After 40 min at 0
2
°C, species 4a had disappeared, while complexes 3aMe CO and
2
1
2a appeared in the H NMR spectrum. Further reaction and
warming led to complete conversion to 2a. Comparison of 4a
with the related structurally characterized authentic agostic
complex 4b,3 made from 8-methylquinoline via the route shown
in Scheme 2, shows close 1H NMR spectral similarities,
suggesting 4a has the agostic (C-H-Ir bridging) structure
shown in Scheme 2. For example, the inequivalent hydrides
resonate as a pair of signals {4a, -20.69 δ (doublet of triplets,
(19) Huheey, J. E.; Keiter, R. L.; Keiter, R. L. Inorganic Chemistry: Principles
of Structure and ReactiVity, 4th ed; Harper Collins College Publishers: New
York, 1993.
9
J. AM. CHEM. SOC. VOL. 126, NO. 28, 2004 8797

A R T I C L E S
Clot et al.
Scheme 2
colorless solution of alkyl hydride [HIr(OCMe2)(py-N(Me)-
CH2-)L2]BF4 (3a(CD ) CO), as confirmed by its 31P NMR
3 2
resonance at 17.78 δ. After hydrogen was bubbled through this
solution for 30 min, the formation sequence was almost com-
pletely reversed to give dihydride [IrH2(OC(CD3))2(PPh3)2]BF4
(1-d12), alkyl hydride 3a(CD ) CO, and free py-NMe2 in a 1:1:1
3 2
ratio, identified from their 1H and 31P NMR spectra. This
reversibility of py-NMe2 binding is of course required for isotope
exchange catalysis to occur.
H/D Exchange. Deuterium labeling experiments were carried
out to determine the fate of the terminal hydrides of 1 during
the reaction with substrates py-NMe2, py-NEt2, and py-N(CH2)4
to generate complexes 2a-c, respectively. Complex [D2Ir-
(OCMe2)2(PPh3)2]BF4 (1-d2), prepared from [Ir(cod)(PPh3)2]BF4
and D2 in acetone, reacted with py-NMe2 in CH2Cl2 solution
IrH trans to N) and -29.84 δ (doublet of triplets, IrH trans to
C-H...Ir) compared with 4b, -19.20 δ (dt) and -28.60 δ (dt)}
2
coupled both to the two cis phosphines (4a, JPH ) 17.1 Hz;
2
4b, JPH ) 15.0 Hz) and to each other (4a, JHH ) 7.9 Hz; 4b,
JHH ) 8.0 Hz). For 4a a singlet at 2.60 δ is assigned to the
rapidly exchanging py-NMe2 methyl groups. No broadening of
this peak is observed in the 1H NMR spectrum even at -80 °C
in CD2Cl2, so -NMe2 group rotation is fast. In contrast to 4a,
4b, having no R-N atom, does not cyclometalate or form a
carbene. This means that the nitrogen R to the methyl group in
4a favors both cyclometalation to give the alkyl as well as
R-elimination to give the carbene.
over 15 min to yield 3a(CD ) CO. The 1H NMR data for the NMe
3 2
region of 3a(CD ) CO show that 4% of the NMe sites are
3 2
deuterated, as confirmed by the appearance of a singlet at 3.46
δ in the 2H NMR spectrum. There were no Ir-D resonances in
2
the high field region of the H NMR spectrum. Similar results
were obtained from 1-d2 and py-NEt2, where deuterium
incorporation occurred to some extent (5%) at the NEt meth-
ylene group.
Equilibration of 2 and 3. We find an equilibrium between
3aMe CO and 2a that is highly sensitive to acetone concentration
2
In the case of py-N(CH2)6, the methylene protons adjacent
to the carbene carbon were also slightly deuterated (ca. 5%)
(eq 3, L′ ) Me2CO; Scheme 1). The colorless alkyl complex
3aMe CO dissolved in CD2Cl2 loses acetone within seconds to
2
2
appearing as a singlet at 3.59 δ in the H NMR spectrum. No
give the yellow carbene 2a. Addition of 4, 6, and 8 equiv of
deuterium incorporation was observed at the â-carbon position
for either the py-NEt2 or py-N(CH2)4 cases, demonstrating the
selectivity of the deuterium incorporation for complex 1-d2.
acetone to a CD2Cl2 solution of 2a yield a 3aMe CO/2a ratio of
2
2:1, 3.2:1, and 4.3:1, respectively, qualitatively demonstrating
the equilibration. The equilibrium between 3aMe CO and 2a was
2
also studied more quantitatively using variable temperature 31
P
CO Experiments. During the computational study, it became
clear that dissociation of the pyridine arm of the chelate might
be of importance. To check this, we passed CO (1 atm) through
CH2Cl2 solutions of the carbene complexes 2a-c. The carbenes
from acyclic py-NMe2 and py-NEt2 underwent immediate
reaction (seconds) to give [HIr(CO)(py-N(Me)CH2-)L2]BF4,
3aCO, (eq 3, L′ ) CO) the CO analogue of the acetone complex,
NMR spectroscopy in 1,2-dichlorobenzene solution with the
result that ∆H° ) -13.0 ( 0.2 kcal mol-1 and ∆S° ) -35.0
( 1.0 cal K-1 mol-1. The Gibbs free energy difference between
3a and 2a at 298 K is therefore ∆G°298K ) -3 kcal mol-1
.
We failed to detect any iridium(III) alkyl intermediates in
the reaction of 1 with py-NEt2, py-N(CH2)4, N(CH2)5, or
N(CH2)6, in CD2Cl2 or from 2b-e in acetone. Using the more
basic solvent d3-acetonitrile, the alkyl hydride trans-[(H)Ir-
3aMe CO. The cyclic carbene 2c derived from py-N(CH2)4 was
2
completely inert even after a 10 h reaction time. The lack of
reactivity of the latter implies that either (i) the pyridine is never
labile at all or, more probably, (ii) that the pyridine is labile
but the bulk of the pyridine, held by the five-membered ring in
a conformation that forces the pyridine to point to the metal,
cannot freely rotate to become coplanar with the ML2(carbene)
plane as would be required for the R-H transfer to occur
(Scheme 3). Models show that the pyridine is far more free to
move so as to point away from the metal in the acyclic cases
(2a-b) but is severely restricted in the five-membered cyclic
case (2c). We therefore propose that pyridine is lost in these
acyclic complexes, allowing CO to bind. After carbene rotation,
retro R-elimination would lead directly to the observed carbonyl
(Scheme 3, L′ ) CO).
Confirmation of this picture came from the reaction of CO
with the cis carbene, cis-2c, observed after short reaction times
from 1 and py-N(CH2)4. cis-2c reacts with CO (1 atm, 10 min)
to undergo retro R-elimination to give the previously unobserved
alkyl as the CO adduct, 3cCO. In contrast, under the same
conditions, the trans carbene, 2c, is entirely unreactive. This
implies that retro R-elimination requires the reacting Ir-H bond
to be orthogonal to the carbene plane and aligned with the empty
p-orbital of the carbene carbon, as in cis-2c.
(MeCN-d3)(-CH(CH3)N(Et)py)(PPh3)]BF4 (3bCD CN) was formed
3
from 2b over 150 min via a retro R-elimination analogous to
1
that of eq 3 with L′ ) CD3CN. The H NMR spectrum of
3bCD CN is similar to that of 3aMe CO including a characteristic
high field Ir-H resonance (trans to N) at -16.44 δ with
3
2
2
coupling constant JPH ) 15.2 Hz. Attempts to isolate other
iridium(III) alkyl complexes from dissolution of 2c in a variety
of donor solvents were unsuccessful, but on the other hand, the
alkyl complexes 3dCD CN (from py-N(CH2)5) and 3eCD CN (from
py-N(CH2)6) were detected from their respective carbenes 2d
and 2e in d3-acetonitrile solvent, forming over a time period of
ca. 5 h. The reason that reversible R-elimination is not observed
with 2c, having a five-membered ring, but only with the acyclic
amines (2a-2b) and the larger cyclic amines (2d-e), is
probably the ring strain that would occur if the alkyl complex
formed from 2c. This alkyl would have a strained fused 5:5
ring system, while those from 2d-e would have less strained
5:6 or 5:7 ring systems; the acyclic cases, lacking ring fusion,
would be even less strained.
3
3
The reversibility of the reaction in eq 3 (L′ ) Me2CO) was
monitored by in situ 1H and by 31P NMR experiments.
Dissolution of yellow crystals of 2a in d6-acetone yields a
9
8798 J. AM. CHEM. SOC. VOL. 126, NO. 28, 2004

Hydrides/Solvent Role in Free Energy Surface Flattening
A R T I C L E S
Scheme 3
Figure 4. Energy profile (kcal mol-1) for C-H activation from [H2Ir(py-
NMe2)(PH3)2]+, 4t. Gibbs free energies are given in parentheses.
Scheme 4
complex 4t, the agostic C-H bond of the py-NMe2 that is close
to the metal has Ir...C ) 2.766 Å and Ir...H ) 2.013 Å (Figure
4). The C-H bond is twisted out of the Ir-py-N plane to allow
the metal to bind side-on to access the C-H bond electronic
density and avoid the Ir...H distance being too short. The
transition state for cleaving the C-H bond, designated as
<4t_3tH2>, has been located at ∆E ) 11.6 kcal mol-1 (∆G )
10.2 kcal mol-1) above 4t and has IrV character20 with the angles
between the five ligands in the equatorial plane ranging from
90° to 46°, the latter being C-Ir-H of the C-H bond to be
cleaved (Figure 4). The distances between the three hydrogens
are longer than 1.8 Å, and the C...H distance of the activated
bond is 1.617 Å. The Ir-C (2.246 Å) as well as the Ir-H bonds
(1.603 Å) are almost fully formed, with the latter being very
close to the two other d(Ir-H). This transition state <4t_3tH2>
leads to a dihydrogen complex, 3tH2, isoenergetic with complex
4t (∆E ) 0. kcal mol-1, ∆G ) -1.0 kcal mol-1). In 3tH2, the
dihydrogen is trans to the Ir-C bond and lies in the py-N-C
plane (Figure 4). The Ir-C bond is short (2.086 Å) because
the trans H2 ligand has a very weak trans influence. The
geometry of the complex is essentially octahedral. H2 with its
weak binding energy (∆E ) 17.9 kcal mol-1, ∆G ) 5.1 kcal
mol-1) is easily lost, and therefore the acetone lost earlier can
readily bind. In agreement with experiment, the acetone complex
This in turn implies that slow pyridine dissociation is the
factor that makes cis to trans isomerization of the product
carbene in the reaction of eq 2 slow in the cyclic case, permitting
observation of a cis intermediate that only slowly (t{1/2} ) 3.0
h at 18 °C) converts to the trans form. In the acyclic case, the
same pathway via the cis intermediate may be followed, but
the subsequent isomerization to the observed trans compound
is now very fast because the pyridine is very labile and rotation
around the Ir-C single bond is facile (Scheme 4).
Computational Studies. Unless stated, all the complexes in
the DFT study involve PH3 and py-NMe2 and are designated
with the experimental numbering scheme followed by t (1t,
2t,...). The experimental species have been calculated including
all atoms at the DFT level. Selected structures have been
calculated with PMe3 and PPh3 at the DFT level. We give both
E and G values because G is indispensable here, owing to the
gain or loss of ligands during the overall process.
3tMe CO is calculated to be more stable than 3tH (∆E ) -8
kcal mol-1, ∆G ) -2.7 kcal mol-1).
2
2
From this point two pathways can be envisaged, one via 3tH
2
and the other from 3tMe CO. Despite our efforts, no pathway
could be identified leading from 3tMe CO to the carbene complex
2
2
2t. In the first pathway, when H2 is lost from 3tH2, the empty
coordination site of the octahedron, represented by an open
square 0, in the resulting 16-e square pyramid 3t0, is trans to
the alkyl ligand, so no vacant cis site is available for the R-H
migration and a geometrical rearrangement is thus needed
(Figure 5). The pyridine cannot dissociate because the resulting
14-e species would be very unstable, so the only way to create
an empty site cis to the Ir-CH2 bond is to move one of the
phosphine ligands toward the empty site created by the departure
of H2. The appropriate transition state, <3t0_cis-2t>, for the
resulting C-H cleavage has been located only 3.6 kcal mol-1
In complex 1t, the two cis ketone ligands each have typical
Ir-O-C angles of ca. 130°. Replacement of the two ketones
by a py-NMe2 with bound pyridine and agostic C-H, 4t,
destabilizes the system by ∆E ) 14 kcal mol-1. However the
change in free energy is only ∆G ) 3.1 kcal mol-1 because of
the favorable entropy for decoordination of two acetone
molecules. This py-NMe2 agostic complex, 4t, the starting point
for the mechanistic study, is the energy reference for E and G
(E ) -14.0 kcal mol-1 and G ) -3.1 kcal mol-1 for 1t). In
(20) Lam, W. H.; Jia, G.; Lin, Z.; Lau, C. P.; Eisenstein, O. Chem.sEur. J.
2003, 9, 2775.
9
J. AM. CHEM. SOC. VOL. 126, NO. 28, 2004 8799

A R T I C L E S
Clot et al.
Figure 7. DFT(B3PW91) optimized geometries for [(H)2Ir(py-NMe-
CH-)(L)2]+, 2t and cis-2t, for L ) PPh3.
Table 2. Selected Full DFT(B3PW91) Optimized Structural
Parameters of [H2Ir(pyr-NMe-CHd)L2]+, 2t, with trans and cis L
Ligandsa
Figure 5. Energy profile (kcal mol-1) for R-C-H migration from [HIr(py-
NMe-CH2-)(PH3)2]+, 3t0. Gibbs free energies are given in parentheses.
L ) PH
L ) PMe3
L ) PPh3
trans
3
trans
cis
trans
cis
cis
Ir-C6
2.004
2.177
1.338
1.583
1.655
2.308
2.308
153.9
1.949
2.190
1.335
1.582
1.608
2.370
2.382
94.1
1.980
2.172
1.350
1.581
1.663
2.336
2.336
153.2
1.941
2.199
1.343
1.579
1.615
2.400
2.405
96.7
1.991
2.166
1.342
1.576
1.649
2.357
2.341
156.8
1.940
2.208
1.336
1.607
1.607
2.431
2.449
104.5
Ir-N1
C6-N2
Ir-H1
Ir-H2
Ir-P1
Ir-P2
P1-Ir-P2
∆E
0.0
-5.4
0.0
+1.7
0.0
+4.3
a Energy differences, ∆E, in kcal mol-1. The numbering scheme is that
shown in Figure 1.
(1.452 Å) to cis-2t (1.338 Å). The C-N bond distance is
marginally longer than the experimental value of 1.322 Å. This
illustrates the strong donation by N and Ir into the empty carbene
orbital. The energy of cis-2t is calculated to be 8.3 kcal mol-1
(∆G ) -9.7 kcal mol-1) below the 16-e complex 3t0. The
cleavage of the C-H bond in the alkyl complex is thus
favorable, having a small energy barrier. The complex having
two trans phosphine ligands, 2t, is found 5.4 kcal mol-1 (∆G
) 5 kcal mol-1) above cis-2t.
Alternate pathways for the C-H cleavage starting from the
18-e alkyl Ir complex, 3tH2, could in principle be initiated by
loss of either phosphine or pyridine (Figure 6). Transition states
associated with the C-H cleavage in these 16-e species with a
dissociated phosphine (TS-Phos-1) or dissociated pyridine
(TS-Pyr-1) have been located 18.6 kcal mol -1 (∆G ) 15.6
kcal mol-1) and 30 kcal mol-1 (∆G ) 39.2 kcal mol-1) above
the transition state <3t0_cis-2t>. The high values rule out loss
of these ligands and clearly indicate a preferential passage
through <3t0_cis-2t> for the R-migration of H from the alkyl
complex 3tH2. The initial dissociation of H2 is thus favored.
Because of the high energies of TS-Phos-1 and TS-Pyr-1, no
16-e complexes from the dissociation of the phosphine or the
pyridine were optimized.
Figure 6. Relative energy (kcal mol-1) of the TS for R-C-H migration
associated with loss of a ligand (H2 (top), PH3 (middle), or pyridine
(bottom)) from [H(H2)Ir(py-NMe-CH2-)(PH3)2]+, 3tH . Gibbs free energies
2
are given in parentheses.
(∆G ) 2.1 kcal mol-1) above the 16-e complex 3t0 (Figure 5).
In this transition structure, the two phosphine ligands are cis
(P-Ir-P ) 93.6°). In complex 3t0, the dihedral angles
C-N(py)-Ir-P are 107° and 70° indicating that the two
phosphines could be considered as being perpendicular to the
py-N-Ir plane. In <3t0_cis-2t>, these two angles have
become 67° and 30°, which shows that both the phosphines
move significantly relative to the pyridine plane during the R-H
migration. The C-H bond is only moderately elongated (1.347
Å), and the newly forming Ir-H bond is 1.779 Å. The Ir-C
bond has shortened from 2.040 Å in 3t0 to 1.967 Å in <3t0_cis-
2t>. This transition state connects with a dihydrido-carbene
complex cis-2t, having two cis phosphines. Complex cis-2t is
octahedral with all the high trans influence ligands, carbene and
hydride, trans to weak trans influence ligands, phosphine and
pyridine, a favorable arrangement. The Ir-C bond length (2.005
Å) is essentially the same as the experimental value of 2.018
Å. The C-N bond has also shortened significantly from 3t0
The relative energies of the cis and trans isomers cis-2t and
2t vary with the nature of the phosphine. While the cis isomer
is favored by 5.4 kcal mol-1 for PH3, the trans isomer is favored
by 1.7 kcal mol-1 and 4.3 kcal mol-1 for PMe3 and PPh3,
respectively (see Figure 7 and Table 2). The angle P-Ir-P in
the cis complex increases with the size of the phosphine (94.1°
for PH3, 96.7° for PMe3, 104.5° for PPh3), supporting an
9
8800 J. AM. CHEM. SOC. VOL. 126, NO. 28, 2004

Hydrides/Solvent Role in Free Energy Surface Flattening
A R T I C L E S
electronic preference for the cis isomer, overcome by steric
effects.21 The preference for the cis isomer is associated with
the optimal relative positioning of strong and weak ligands.
very stable IrH5L2.22 The overall transformation of 4 to 3 can
thus be viewed as H transfer from an alkyl group to a hydride
ligand. The calculations indicate that an oxidative addition/
reductive elimination is preferred over the alternative σ-
metathesis process. The formation of a dihydrogen complex and
the loss of H2 during the reaction path are supported experi-
mentally by the observation of H2. Another rationalization of
the equivalent energies of 4 and 3 is the optimal distribution of
strong and weak trans influence ligands around the metal.23 In
4, the weak trans influence agostic ligand is trans to a high
trans influence hydride. In 3, the agostic ligand converts to a
high trans influence alkyl group, but trans to this alkyl is now
the H2 group with the smallest trans influence of all ligands. In
this transformation, the high and low trans influence ligands
just trade places via H migration.
Discussion
The calculations predicted that the cis-phosphine isomer is
initially formed, a proposal subsequently supported by the
experimental evidence for py-N(CH2)4. However, the cyclic
amine, py-N(CH2)4, is the only one for which the cis-phosphine
intermediate cis-2t was observed. Two possibilities exist. Either
the other amines go directly to the trans complex or all go via
the cis intermediate but the cis to trans isomerization is very
fast. The CO experiments only test for the presence of an empty
coordination site and so cannot safely distinguish between the
two pathways because both require such an empty site.
The energies of the alkyl and the carbene complexes are
similar because the N lone pair stabilizes the carbene group. In
related geminal dehydrogenations of furan and pyrrolidine by
[RuHCl(PiPr3)2]2 and OsH3Cl(PiPr3), calculations have shown
why the reaction is feasible.18
The reversibility of the reaction is also supported by the H/D
scrambling and the tritiation catalysis whereby D(T) originally
on the metal is transferred to the Me group of the amine. The
H/D scrambling is made possible by the very facile H/H′
exchange in species such as 3. This includes a rotation of the
H2 ligand and H/H′ exchange between the hydride and H2. We
did not study this computationally in this species, but there are
ample examples in similar complexes.24
The cis and trans (PR3)2 are close in energy because of the
bulk of the phosphine ligand. The cis isomer has the best
distribution of strong and weak trans influence ligands in the
coordination sphere of Ir and is favored electronically; the trans
isomer becomes favored solely on steric grounds. This explains
why the difference in energy between these two isomers is not
very large even for PPh3. Apart from illustrating the limitations
and advantages of using PH3 as model phosphine, this work
suggests that it may sometimes be necessary to search for kinetic
isomers with cis phosphines in mechanistic studies even if both
reagents and products have trans phosphines. This may occur
if the isomerization produces a favorable distribution of strong
and weak trans influence ligands.
The first possibility, a direct trans process, cannot be excluded
(although despite numerous attempts, no corresponding transi-
tion state could be located) because once the pyridine dissociated
in 3tMe CO, the alkyl can rotate so as to allow the R-H migration
2
to occur without phosphines having to move (Scheme 3). If so,
py-N(CH2)4 is unable to follow this direct trans pathway. We
propose that the conformational constraints of the cyclic amine
py-N(CH2)4 prevent the dissociated pyridine from rotating away
from the metal, a rotation that would be required in order for
the carbene to achieve a conformation suitable for the R-H
migration with Ir-H aligned with the vacant carbene p-orbital.
In this required conformation, the pyridine group would collide
with the trans PPh3 groups. This steric problem which only
occurs for the conformationally restrained py-N(CH2)4 case also
explains why CO does not react with 2c, while the acyclic cases
2a-b give the alkyl complex 3CO
.
The second possibility, that cis to trans isomerization is fast,
should also be considered because a pathway for such a process
involving decoordination of the pyridine exists (Scheme 4). In
this proposal, the conformationally mobile cases (2a-b, 2e-
d) give fast rearrangement, but the 2c case (py-N(CH2)4) is slow
because of steric hindrance of Ir-C bond rotation by the
dissociated pyridine. An alternative pathway for cis to trans
isomerization, with rate-determining loss of PPh3, can be
excluded because this pathway should not show a large rate
difference between cis-2c and cis-2a-b. In addition, the
observed rate of isomerization is unaffected by the addition of
PPh3 (5 equiv).
Experimental Section
All preparations and manipulations were carried out under oxygen-
free nitrogen or argon following conventional Schlenk techniques.
Dichloromethane was freshly distilled from CaH2 and degassed before
use. Diethyl ether was dried over sodium and benzophenone and
degassed before use. Deionized water was used. 2-(Dimethylamino)-
pyridine, 2-chloropyridine, and pyrrolidine were purchased from
Aldrich. 2-Diethylaminopyridine was obtained from ITC Corp. Cyclic
pyridines (py-N(CH2)n)25 and the complexes [IrH2(OCMe2)2L2]BF4 (1)26
and [Ir(COD)L2]BF4 (2) (L ) PPh3)27 were prepared according to
literature procedures. 1H NMR, 13C{1H} NMR,31P{1H} NMR, and
As expected, the free energy G, which includes the entropy
changes associated with the gain or loss of ligands during the
reaction, should be considered in preference to the energy E.
The calculations show that the difference in free energy between
the most stable product 3tMe CO and the highest transition state
2
<3t0_cis-2t> is only 10.9 kcal mol-1, while the difference in
energy E is 29.5 kcal mol-1. This is consistent with the
reversibility of the reactions, implied by the catalysis and directly
observed for species 3Me CO and 2.
2
The energies of 4 and 3 are the same because the C-H and
H-H as well as Ir-C and Ir-H bond energies are similar and
because the Ir-N-C-N-C five-membered ring is unstrained.
The transition state is relatively low due to the accessibility of
IrV for iridium with strongly σ-donating ligands, such as in the
(22) Garlaschelli, L.; Khan, S. I.; Bau, R.; Longoni, G.; Koetzle, T. F. J. Am.
Chem. Soc. 1985, 107, 7212.
(23) Matthes, J.; Gru¨ndemann, S.; Toner, A.; Guari, Y.; Donnadieu, B.; Spandl,
J.; Sabo-Etienne, S.; Clot, E.; Limbach, H.-H.; Chaudret, B. Organometallics
2004, 23, 1424.
(24) Maseras, F.; Lledo´s, A.; Clot, E.; Eisenstein, O. Chem. ReV. 2000, 100,
601.
(25) Hassner, A.; Krepski, L. R.; Alexanian, V. Tetrahedron 1978, 34, 978.
(26) Crabtree, R. H.; Demou, P. C.; Eden, D.; Mihelcic, J. M.; Parnell, C. A.;
Quirk, J. M.; Morris, G. E. J. Am. Chem. Soc. 1982, 104, 6994.
(27) Crabtree, R. H. Synth. React. Inorg. Met. -Org. Chem. 1982, 12, 407.
(21) QM/MM calculations of the cis versus trans 2a (L ) PPh3) predict a
preference for the cis form in disagreement both with experiment and with
the full DFT calculations. The origins of this discrepancy are under study.
9
J. AM. CHEM. SOC. VOL. 126, NO. 28, 2004 8801

A R T I C L E S
Clot et al.
heteronuclear two-dimensional NMR were recorded on Bruker 400,
Bruker 500, GE-Omega 300, or GE-Omega 500 spectrometers. Micro-
analyses were carried out by Robertson Microlit Laboratories.
cis,trans-[Dihydridobis(triphenylphosphine)(N,C-2-(dimethyl-
amino)pyridine-1′-ylidene)iridium(III)] Fluoroborate (2a). Method
1: The fluoroborate salt of [H2Ir(OCMe2)2(PPh3)2]+ (1) (280 mg, 0.30
mmol) was dissolved in degassed CH2Cl2 (4 mL), and 2-(dimethyl-
amino)pyridine (py-NMe2, 37 mg, 0.30 mmol) was added. The resulting
clear yellow solution was stirred for 15 min. Slow addition of diethyl
ether (ca. 10 mL) gave a light yellow precipitate. The solution was
then filtered, and the light yellow powder was washed with Et2O (15
mL) and dried in vacuo to give pure product. The complex was
recrystallized from CH2Cl2/Et2O. Yield: 217 mg (78%).
Method 2: to a clear red CH2Cl2 (10 mL) solution of [Ir(COD)-
(PPh3)2]BF4 (2) (352 mg, 0.38 mmol) was syringed py-NMe2 (50 mg,
0.38 mmol). H2 gas was passed for 10 min at 0 °C, and the solution
turned bright yellow. After warming to room temperature, diethyl ether
(10 mL) was added to give a yellow solid, which was filtered, washed
with diethyl ether (3 × 8 mL), and dried in vacuo. Yield: 140 mg
(40%).
1H NMR (CD2Cl2) δ 11.63 (s, 1H, dCH), 7.65 (t, 1H, JH-H ) 7.9
Hz, pyridinesH), 7.50 (d, 1H, JH-H ) 6.1 Hz, pyridinesH), 7.28 (m,
31H, PPh3 and pyridinesH), 6.48 (t, 1H, JH-H ) 6.7 Hz, pyridines
H), 3.39 (s, 1H, IrdC(H)N(Me)py), -10.03 (td, 1H, JP-H ) 17.0 Hz,
JH-H ) 4.3 Hz, IrsH (trans to IrdCH)), -17.85 (td, 1H, JP-H ) 17.0
Hz, JH-H ) 4.3 Hz, IrsH (trans to IrsN)); 13C{1H} NMR (CD2Cl2) δ
250.46 (s, IrdC), 154.82 (s, Cpy2), 154.41 (s, Cpy6), 137.99 (s, Cpy5),
132.62 (s, CPh1), 132.28 (t, JP-C ) 6.0 Hz, CPh2,6), 129.80 (s, CPh4),
127.60 (t, JP-C ) 6.0 Hz CPh3,5), 123.23 (s, Cpy4), 113.22 (s, Cpy3),
46.46 (s, IrdC(H)N(Me)py). 31P{1H} NMR (CD2Cl2) δ 21.80. Anal.
Calcd for C43H40N2P2IrBF4‚O1C4H10: C, 56.46; H, 5.00; N, 2.80.
Found: C, 56.62; H, 4.68; N, 2.91.
cis,trans-[Dihydridobis(triphenylphosphine)(N,C-2-diethyl-
aminopyridine-1′-ylidene)iridium(III)] Fluoroborate (2b). To [H2Ir-
(OCMe2)2(PPh3)2]BF4 (1) (350 mg, 0.38 mmol) dissolved in 5 mL of
CH2Cl2 2-diethylaminopyridine (py-NEt2, 60 mg, 0.38 mmol) was
added. After 15 min of stirring at room temperature, 10 mL of diethyl
ether was added dropwise to give a bright yellow solid. The solution
was then filtered leaving a yellow solid, which was washed with diethyl
ether (3 × 5 mL) followed by drying in vacuo. The complex was
recrystallized from CH2Cl2/Et2O. Yield: 290 mg (80%).
2b can also be prepared by Method 2 from 1 (100 mg, 0.11 mmol)
and py-NEt2 (17 mg, 0.11 mmol) in 10 mL of CH2Cl2. 2b was isolated
upon addition of 50 mL of diethyl ether after 10 min of H2 treatment
at 0 °C and recrystalized from CH2Cl2/Et2O. Yield: 48 mg (46%).
1H NMR (CD2Cl2) δ 7.78 (t, 1H, JH-H ) 7.9 Hz, pyridinesH), 7.71
(d, 1H, JH-H ) 4.9 Hz, pyridinesH), 7.37 (m, 31H, PPh3 and pyridines
H), 6.53 (t, 1H, JH-H ) 6.1 Hz, pyridinesH), 3.72 (q, JH-H ) 7.3 Hz,
2H, IrdC(Me)N(CH2CH3)py), 2.24 (s, 3H, IrdC(Me)N(CH2CH3)py),
1.11 (t, JH-H ) 7.3 Hz, 3H, IrdC(Me)N(CH2CH3)py), -10.73 (td, 1H,
JP-H ) 21.4 Hz, JH-H ) 4.5 Hz, IrsH (trans to IrdC)), -17.85 (td,
1H, JP-H ) 21.4 Hz, JH-H ) 4.5 Hz, IrsH (trans to IrsN)); 13C{1H}
NMR (CD2Cl2) δ 265.88 (s, IrdC), 158.48 (s, Cpy2), 155.77 (s, Cpy6),
139.78 (s, Cpy5), 133.84 (t, JP-C ) 6.0 Hz, CPh2,6), 133.60 (s, CPh1),
131.27 (s, CPh4), 129.08 (t, JP-C ) 6.0 Hz, CPh3,5), 123.85(s, Cpy4),
115.18 (s, Cpy3), 44.66 (s, IrdC(Me)N(CH2CH3)py), 37.95 (s,
IrdC(Me)N(CH2CH3)py), 13.22 (s, IrdC(Me)N(CH2CH3)py); 31P{1H}
NMR (CD2Cl2) δ 20.85. Anal. Calcd for C45H44N2P2IrBF4: C, 56.61;
H, 4.61; N, 2.94. Found: C, 56.06; H, 4.61; N, 2.85.
5 mL) followed by drying in vacuo. The complex was recrystallized
from CH2Cl2/Et2O. Yield: 110 mg (53%).
1H NMR (CD2Cl2) δ 7.83 (d, 1H, JH-H ) 5.3 Hz, pyridinesH),
7.82 (t, 1H, JH-H ) 8.0 Hz, pyridinesH), 7.37 (m, 30H, PPh3), 7.17
(d, 1H, JH-H ) 7.5 Hz, pyridinesH), 7.61 (t, 1H, JH-H ) 6.4 Hz,
pyridinesH), 3.64 (t, JH-H ) 8.0 Hz, 2H, Ir(dCCH2CH2CH2)), 2.43
(t, JH-H ) 7.5 Hz, 2H, Ir(dCCH2CH2CH2)), 1.64 (t, J ) 8.0 Hz, 2H,
Ir(dCCH2CH2CH2)), -9.96 (td, 1H, JP-H ) 20.9 Hz, JH-H ) 4.7 Hz,
IrsH (trans to IrdC)), -17.85 (td, 1H, JP-H ) 20.9 Hz, JH-H ) 4.7
Hz, IrsH (trans to IrsN)); 13C{1H} NMR (CD2Cl2) δ 258.34 (s, IrdC),
155.13 (s, Cpy6), 154.76 (s, Cpy2), 139.78 (s, Cpy5), 133.36 (t, JP-C
6.0 Hz, CPh3,5), 133.08 (s, CPh1), 130.86 (s, CPh4), 128.66 (t, JP-C
)
)
6.0 Hz, CPh3,5), 123.26 (s, Cpy4), 114.50 (s, Cpy3), 54.62 (s, IrdC(CH2-
CH2CH2)Npy), 49.45 (s, IrdC(CH2CH2CH2)Npy), 21.94 (s, IrdC(CH2-
CH2CH2)Npy). 31P{1H} NMR (CD2Cl2): δ 20.06. Anal. Calcd for
C45H42N2P2IrBF4: C, 56.73; H, 4.41; N, 2.94. Found: C, 56.46; H,
4.40; N, 2.83.
cis,trans-[Dihydridobis(triphenylphosphine)(N,C-2-piperidino-
pyridine-1′-ylidene)iridium(III)] Fluoroborate (2d). [H2Ir(OCMe2)2-
(PPh3)2]PF6 (440 mg, 0.45 mmol) was dissolved in degassed CH2Cl2
(4 mL), and 2-piperidinopyridine (py-N(CH2)5, 73 mg, 0.45 mmol) was
added. The resulting clear yellow solution was stirred for 60 min. Slow
addition of hexanes (ca. 20 mL) gave a light yellow precipitate. The
solution was then filtered, and the light yellow powder was washed
with hexanes 3 times (3 × 15 mL) and dried in vacuo to give pure
product. The complex was also recrystallized from CH2Cl2/hexane.
Yield: 400 mg (90%).
1H NMR (CD2Cl2, 400 MHz) δ 7.93 (m, 1H), 7.80 (t, 1H, J ) 8
Hz), 7.36 (m, 31H), 6.67 (t, 1H, J ) 8 Hz), 3.41 (t, 2H, J ) 6 Hz,
NCH2), 2.67 (m, 2H, dCCH2), 1.45, 0.83 (m, 2H each, NCH2 (CH2)
2), -10.52 (td, 1H, JP-H ) 20 Hz, JH-H′ ) 4 Hz, IrsH), -18.06 (td,
1H, JP-H ) 16 Hz, JH-H′ ) 4 Hz, IrsH); 13C{1H} NMR (CD2Cl2, 100
MHz) δ 262.2 (s, IrdC), 159.1 (s, Cpy), 154.6 (s, Cpy), 139.3 (s, Cpy),
133.2 (t, JP-C ) 6.4 Hz, CPh2,6), 132.8 (s, CPh1), 130.7 (s, CPh4), 128.6
(t, JP-C ) 6.4 Hz, CPh3,5), 123.3 (s, Cpy), 113.7 (s, Cpy), 49.5 (s, NCH2),
48.1 (s, dCCH2), 21.1, 18.4 (s, NCH2(CH2)2); 31P{1H} NMR (CD2Cl2)
δ 20.95. Anal. Calcd for C46H44N2P3IrF6: C, 53.96; H, 4.33; N, 2.74.
Found: C, 54.13; H, 4.30; N, 2.79.
cis,trans-[Dihydridobis(triphenylphosphine)(N,C-2-hexamethyl-
eneiminopyridine-1′-ylidene)iridium(III)] Fluoroborate (2e). [H2Ir-
(OCMe2)2(PPh3)2]BF4 (150 mg, 0.16 mmol) was dissolved in degassed
CH2Cl2 (6 mL), and 2-hexamethyleneiminopyridine (py-N(CH2)6, 28
mg, 0.16 mmol) was added. The resulting clear yellow solution was
stirred for 60 min. Slow addition of hexane (ca. 20 mL) gave a light
yellow precipitate. The solution was then filtered, and the light yellow
powder was washed with hexane 3 times (3 × 10 mL) and dried in
vacuo to give pure product. The complex was recrystallized from
CH2Cl2/hexane. Yield: 127 mg (80%).
1H NMR (CD2Cl2, 400 MHz) δ 7.64 (m, 2H), 7.27 (m, 31H), 6.36
(t, 1H, J ) 8 Hz), 3.63 (m, 2H, NCH2), 2.91 (m, 2H, dCCH2), 1.43,
1.31, 0.46 (m, 2H each, NCH2 (CH2)3), -10.84 (td, 1H, JP-H ) 20
Hz, JH-H′ ) 4 Hz, IrsH), -17.89 (td, 1H, JP-H ) 16 Hz, JH-H′ ) 4
Hz, IrsH); 13C{1H} NMR (CD2Cl2, 100 MHz) δ 270.7 (s, IrdC), 158.8
(s, Cpy), 155.4 (s, Cpy), 139.2 (s, Cpy), 134.3 (s, CPh1), 133.4 (t, JP-C
)
6.2 Hz, CPh2,6), 130.8 (s, CPh4), 128.7 (t, JP-C ) 6.4 Hz, CPh3,5), 123.2
(s, Cpy), 114.5 (s, Cpy), 51.1 (s, dCCH2), 50.9 (s, NCH2), 28.9, 24.8,
20.4 (s, NCH2(CH2)3); 31P{1H} NMR (CD2Cl2) δ 21.3. Anal. Calcd
for C47H46N2P2IrBF4: C, 57.61; H, 4.73; N, 2.86. Found: C, 57.54; H,
4.50; N, 2.49.
cis,trans-[Dihydridobis(triphenylphosphine)(N,C-2-pyrrolidino-
pyridine-1′-ylidene)iridium(III)] Fluoroborate (2c). [H2Ir(OCMe2)2-
(PPh3)2]BF4 (1) (200 mg, 0.22 mmol) and py-N(CH2)4 (32 mg, 0.22
mmol) were stirred in CH2Cl2 (10 mL) at room temperature for 7 h.
The solvent was then removed in vacuo. The yellow residue was
redissolved in 10 mL of CH2Cl2. Et2O (25 mL) was added dropwise to
give a very pale yellow precipitate, which was washed with Et2O (3 ×
Observation of the Initial Kinetic Product, cis-2c, from the
Reaction of 2-Pyrrolidinopyridine with [H2Ir(OCMe2)2(PPh3)2]BF4
(1). 1H NMR spectroscopy showed that 2-pyrrolidinopyridine (1 equiv)
reacted with [IrH2(OCMe) 2(PPh3) 2]BF4 in CD2Cl2 at 25 °C to give an
initial cis-PPh3 isomer that slowly isomerizes to the trans isomer at
room temperature over 5 h. The 1H NMR spectrum of the two isomers
shows two distinct pairs of high field iridium hydride resonances. One
9
8802 J. AM. CHEM. SOC. VOL. 126, NO. 28, 2004

Hydrides/Solvent Role in Free Energy Surface Flattening
A R T I C L E S
pair, due to the trans isomer, appear as two triplets of doublets at δ
-9.98 and δ -18.57 (2JP-H ) 20.9 Hz, 2JH-H′ ) 4.7 Hz), each coupled
to two trans phosphine nuclei. The other pair, due to the cis isomer, is
coupled to two cis phosphine nuclei. In particular, one appears as a
broad centrosymmetric multiplet centered at δ -10.83 as a result of
being coupled to one trans and one cis phosphorus nucleus. Second-
order effects due to two coupled phosphorus nuclei with nearly identical
chemical shifts and coupling to protons with different relative signs
give rise to an irregular intensity pattern (2:3:3:2). The second hydride
appears as a triplet of doublets at δ -18.82, as a result of being coupled
to two inequivalent cis phosphine nuclei and the other hydride (2JP-H
completion of the reaction showed >95% formation of the Ir(III)
carbene complex, 2b (for py-NEt2) or 2c (for py-(CH2)4).
1H NMR Study of the Equilibrium of 2a and 3aMe CO. The 31P
2
NMR measurements were taken using a GE-Omega 500 spectrometer
at 202 MHz. Solutions for the thermodynamic study were prepared by
dissolving 2a in 1,2-dichlorobenzene and adding appropriate amounts
of Me2CO (0.27 M stock solution in 1,2-dichlorobenzene) and
perfluorotriphenylphosphine as the internal standard. The analyses of
the equilibrium constants using the required equations were carried out
with a nonlinear least-squares fit. The reported errors correspond to 1
standard deviation.
2
2
≈ JP′-H ) 16 Hz, JH′-H ) 3 Hz).
Reaction of 2a-c with CO. 2a-b (0.30 mmol) was dissolved in
1
trans-[Hydrido(acetone)bis(triphenylphosphine)(N,C-2-(dimethyl-
CD2Cl2 (0.3 mL) and a reference H NMR spectrum was taken prior
amino)pyridine-1′-yl)iridium(III)] Fluoroborate (3aMe CO). Method
2
to bubbling with CO for 30 s. 2a-b showed immediate and quantitative
conversion to compound 3a-bCO. Unlike 2a-b, compound 2c showed
no change on bubbling with CO even after 19 h. 3aCO was prepared in
a pure state as follows: 2a (28 mg, 0.030 mmol) was dissolved in
dichloromethane (8 mL), and CO bubbled for 1 min. Approximately
half the solvent was evaporated with a stream of air and the product,
3aCO (25 mg, 0.026 mmol), was recrystallized from dichloromethane/
1: to a red acetone (10 mL) solution of [Ir(cod)(PPh3)2]BF4 (346 mg,
0.38 mmol) py-NMe2 (50 mg, 0.38 mmol) was added via a syringe.
Upon passing H2 gas for 10 min at 0 °C, the solution turned to very
pale yellow. Diethyl ether (15 mL) was added, and a white precipitate
formed. After filtration, the resulting white solid was washed with
diethyl ether (3 × 10 mL) and dried in vacuo. The complex was
recrystallized from CH2Cl2/Et2O. Yield: 244 mg (65%).
1
ether, forming translucent white, needlelike crystals. Yield: 87% H
3
Method 2: To an acetone (5 mL) solution [H2Ir(OCMe2)2(PPh3)2]-
BF4 (1) (120 mg, 0.13 mmol) py-NMe2 (16 mg, 0.13 mmol) was added.
After 15 min of stirring, the resulting colorless solution was precipitated
by treatment with Et2O (20 mL). The white precipitate was collected
on a glass frit, washed with Et2O (3 × 5 mL) and dried in vacuo.
Yield: 48 mg (37%).
NMR (CD2Cl2, 298 K): δ 7.54 (d, 1H, JHH ) 6.1 Hz, Hpy), 7.51-
7.36 (m, 31H, Har, Hpy), 7.08 (m, 1H, Hpy), 6.11 (m, 1H, Hpy), 3.51 (t,
2H, 3JPH ) 14.1 Hz, IrCH2N), 2.01 (s, 3H, NCH3), -15.08 (t, 1H, 2JPH
) 12.7 Hz, IrH); 31P NMR (CD2Cl2, 298 K) δ10.32; FTIR (CD2Cl2)
ν(CO) 2034 cm-1
.
To observe the reaction of cis-2c with CO, [H2Ir(OCMe2)2(PPh3)2]-
BF4 (100 mg, 1 equiv) was dissolved in dichloromethane (16 mL).
2-Pyrrolidinopyridine (1 equiv) in dichloromethane (4 mL) was
immediately added. The mixture was stirred for 10 min, and then CO
(1 atm) was bubbled (50 mL/min) for 60 min. The resulting compound
3cCO was recrystallized from dichloromethane/diethyl ether to give long
white needles. By analogy with the spectroscopic data for 3aCO (NMR
1H NMR (OCMe2-d6) δ 8.52 (d, 1H, pyridinesH), 7.46 (m, 30H,
PPh3), 7.17 (t, 1H, JH-H ) 8.0 Hz, pyridinesH), 6.48 (t, 1H, JH-H
)
5.9 Hz, pyridinesH), 5.54 (d, 1H, JH-H ) 8.5 Hz, pyridinesH), 4.06
(t, 2H, JH-H ) 12.3 Hz, IrsC(H2)N(Me)py), 2.17 (s, 3H, IrsC(H2)N-
(Me)py), 2.09 (s, 6H, IrsOCMe2), -16.07 (t, 1H, JP-H ) 15 Hz, 1H,
IrsH); 13C{1H} NMR (OCMe2-d6) δ 161.05 (s, Cpy2), 146.18 (s, Cpy6),
138.05 (s, Cpy5), 135.16 (t, JP-C ) 5.3 Hz, CPh2,6), 131.86 (s, CPh4),
130.59 (s, CPh1), 129.75 (t, JP-C ) 4.5 Hz, CPh3,5), 37.21 (s,
IrsC(H2)N(Me)py), 30.38 (s, IrsOCMe2), 15.99 (s, IrsC(H2)N(Me)-
py); 31P{1H} NMR (OCMe2-d6) δ 17.78. Anal. Calcd for C46H48N2P2-
OIrBF4: C, 55.99; H, 4.87; N, 2.84. Found: C, 55.78; H, 4,71; N,
2.85.
fully assigned by 2D experiments), the product was identified as 3cCO
.
1H NMR (CD2Cl2, 298 K) δ 7.6-7.34 (m, 31H, aromatic), 7.22 (ddd,
1H, 3J ) 8.7, 7.1 Hz,4J ) 1.6 Hz, py-H4), 6.22 (ddd, 1H, 3JH-H ) 7.0,
6.1 Hz, 4JH-H ) 0.9 Hz, py-H5), 5.44 (d, 1H, 3JH-H ) 8.7 Hz, py-H3),
3
3
3
4.35 (dddd, 1H, JP-H ) 26.6 Hz, JH-H ) 11.7 Hz, JH-H ) 4.6 Hz,
3JP-H ) 4.6 Hz, Ir-C-H), 2.42 (t, 1H, JH-H,
) JH-H,
) 9.8
3
2
trans
gem
2
Hz, NCH2), 1.89-1.25 (m, 5H, (CH2)3), -14.81 (t, 1H, JP-H ) 13.0
Reaction of cis,trans-[H2Ir(dC(Me)N(Et)py)(PPh3)2]BF4 (2b) with
MeCN-d3. 2b (20 mg, 0.02 mmol) was dissolved in 0.6 mL of MeCN-
Hz); 31P NMR (CD2Cl2, 298 K) 14.70, 4.02, JP-P ) 339.1 Hz. FTIR
2
(CD2Cl2, 298 K): ν(CO) 2035 cm-1. The trans analogue, 2c, was
1
d3 in an NMR tube. The sample, monitored periodically by H NMR,
entirely unreactive under the same conditions.
showed quantitative formation of trans-[(H)Ir(MeCN-d3)(C(HCH3)N-
1
(Et)py)(PPh3)2]BF4 (3bCD CN) after 150 min. H NMR (MeCN-d3) δ
Crystal Structure Determinations of 3aMe CO and 2a were reported
3
2
4.12 (m, 1H, IrsCHMe), 1.80 (q, 2H, JH-H ) 7.3 Hz, NCH2CH3),
1.09 (d, 3H, JH-H ) 7.3 Hz, IrsCHMe), 0.42 (t, 3H, JH-H ) 7.3 Hz,
NCH2CH3), -16.44 (1H, JP-H ) 15.2 Hz, IrsH). A pure solid could
not be obtained.
in ref 4.
3aMe CO: A pale yellow crystal of 3aMe CO, obtained by the slow
2
2
diffusion of diethyl ether into a concentrated solution of 3aMe CO in
2
dichloromethane, was mounted on a Nonius Kappa diffractometer.
Triclinic; P1h (No. 2); a ) 11.8113(4) Å; b ) 12.6330(5) Å; c )
16.5025(7) Å; R ) 100.210(2)°; â ) 107.894(2)°; γ ) 101.536(2)°; V
) 2219.4(2) Å3; Z ) 2; Dcalcd ) 1.551 g/cm3; temperature, 183 K; Mo
KR λ ) 0.710 69 Å; no. reflections (I > 3.0σ(I)) ) 6997; R ) 0.043,
Rw ) 0.042; GOF ) 1.34.
2b: A colorless plate of 2b, obtained by the slow diffusion of diethyl
ether into a concentrated solution of 2b in dichloromethane, was
mounted on a Nonius Kappa diffractometer. Monoclinic; P21 /n (No.
14); a ) 14.4246(6) Å; b ) 14.7760(6) Å; c ) 22.8912(7) Å; â )
107.342°; V ) 4657.2(3) Å3; Z ) 4; Dcalcd ) 1.49 g/cm3; temperature,
183 K; Mo KR λ ) 0.710 69 Å; µ ) 32.19 cm-1. No. reflections (I >
3.0σ(I)) ) 5722; R ) 0.032, Rw ) 0.034; GOF ) 0.81.
Reaction of 2a with H2 in Me2CO-d6. In an NMR tube, 20 mg
(0.02 mmol) of 2a was dissolved in 0.6 mL of Me2CO-d6. The yellow
1
solution turned colorless. H NMR spectrum taken after 60 s showed
quantitative formation of 3a(CD ) CO. A stream of H2 was then bubbled
through the solution for 30 min at room temperature. 1H and 31P NMR
measurements showed complete consumption of 2a with >90%
3
2
conversion to equimolar 1, 3a(CD ) CO, and free py-NMe2.
3
2
H/D Exchange. py-NMe2 (28 mg, 0.30 mmol) and d2-1 were
2
dissolved in 0.6 mL of degassed CH2Cl2 in an NMR tube. H NMR
measurements after 15 min at room temperature showed no resonance
for Ir-D but a singlet at 3.46 δ indicating that the methyl region of
NMe was deuterated. There was also a singlet for 2a at 21 δ in the 31
P
NMR spectrum. Exhaustive vacuum removal of the volatiles, followed
by H NMR assay in CD2Cl2, showed no starting material but only 1
and >95% conversion to 2a.
A similar procedure was followed for both py-NEt2 and py-(CH2)4.
In all cases, both 1H and 31P NMR measurements taken at the
2c: A colorless plate crystal of 2c, obtained by the slow diffusion
of diethyl ether into a concentrated solution of 2c in dichloromethane,
was mounted on a Nonius Kappa diffractometer. Monoclinic; C2/c
(No. 15); a ) 49.8735(11) Å; b ) 10.8667(3) Å; c ) 18.3822(4) Å;
â ) 110.5040°; V ) 9331.3(3) Å3; Z ) 8; Dcalcd ) 1.597 g/cm3;
1
9
J. AM. CHEM. SOC. VOL. 126, NO. 28, 2004 8803

A R T I C L E S
Clot et al.
temperature, 296 K; Mo KR λ ) 0.710 69 Å; µ ) 32.19 cm-1. No.
reflections (I > 3.0σ(I)) ) 5981; R ) 0.057, Rw ) 0.039; GOF )
1.26.
electrons). For these two systems, the frequencies of the located extrema
were not computed.
Conclusions
Computational Details. All calculations were performed with the
Gaussian 98 set of programs28 within the framework of hybrid DFT
(B3PW91).29 The Ir atom was represented by the relativistic effective
core potential (RECP) from the Stuttgart group (17 valence electrons)
and its associated (8s7p6d)/[6s5p3d] basis set,30 augmented by an f
polarization function (R ) 0.95).31 A 6-31G(d,p) basis set32 was used
for all the remaining atoms. Full optimizations of geometry without
any constraint were performed, followed by analytical computation of
the Hessian matrix to confirm the nature of the located extrema as
minima or transition states on the potential energy surface. The
thermodynamic quantities, ∆G and ∆S, were computed for 298 K within
the harmonic oscillator approximation as implemented in Gaussian 98.
In the case of the complexes 2t and cis-2t with PPh3 as a model
phosphine ligand (Figure 7), the 6-31G(d,p) basis set was restricted to
the two N atoms and to the carbene C-H moiety. The rest of the C
and H atoms were treated with a 6-31G basis set due to the already
high computational cost (578 basis functions, 1296 primitives, and 338
A double geminal C-H activation has been observed in the
reaction of [H2Ir(OCMe2)2L2]BF4 (1) with several 2-amino
pyridines. It occurs stepwise by way of successive cyclometa-
lation, H2 loss, and reversible R-elimination. The activation
barriers from DFT(B3PW91) calculations are low, and all
intermediates are at comparable energies, in full agreement with
the observed high kinetic activity and reversibility of the
reactions. The flatness of the free energy surface is shown to
be due to the presence of hydrides at specific positions in the
catalyst intermediates and the gain or loss of solvent as well as
to the stabilizing influence of the donating amino group in the
final carbene complex. Several key intermediates have been
characterized or trapped experimentally. Although the phosphine
ligands are trans both in the reactant and in the final products,
the intermediacy of a kinetic carbene complex with cis-
phosphine ligands, suggested by the calculations, was subse-
quently observed experimentally in the case of pyr-N(CH2)4.
(28) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M.
A.; Cheeseman, J. R.; Zakrzewski, V. G.: Montgomery, J. A.; Stratmann,
R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin,
K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi,
R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.;
Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.;
Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz,
J. V.; Baboul, A. G.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.;
Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham,
M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.;
Gill, P. M. W.; Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L.;
Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 98, rev A7;
Gaussian, Inc.: Pittsburgh, PA, 1998.
Acknowledgment. The U.S. authors thank the U.S. DOE for
funding and Michael Janzen for helpful suggestions. The French
authors thanks the CNRS and Ministe`re of National Education
for financial support. The Korean authors thank KRF(2002-
070-C00053). This paper was completed by R.H.C. and O.E.
while visiting UC Berkeley under Dow Chemical (R.H.C., Dow
Lectures in Organic Chemistry) and Miller Institute sponsorship
(O.E. Miller Visiting Professor).
(29) (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (b) Perdew, J. P.; Wang,
Y. Phys. ReV. B 1992, 82, 284.
(30) Andrae, D.; Ha¨ussermann, U.; Dolg, M.; Stoll, H.; Preuss, H. Theor. Chim.
Acta 1990, 77, 123.
Supporting Information Available: CIF file for 2c. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(31) Ehlers, A. W.; Bo¨hme, M.; Dapprich, S.; Gobbi, A.; Ho¨llwarth, A.; Jonas,
V.; Ko¨hler, K. F.; Stegmann, R.; Veldkamp, A.; Frenking, G. Chem. Phys.
Lett. 1993, 208, 111.
(32) Hariharan, P. C.; Pople, J. A. Theor. Chim. Acta 1973, 28, 213.
JA048473J
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8804 J. AM. CHEM. SOC. VOL. 126, NO. 28, 2004