N-H versus C-H activation of a pyrrole imine at {Cp*Ir}: A computational and experimental study

Article abstract of DOI:10.1021/om060863m

Reaction of a pyrrole imine with [IrCl₂Cp*] ₂/NaOAc leads to N-H activation in preference to C - H activation at the pyrrole; however, with the N-methylated ligand C-H activation occurs. Density functional calculations show that N-H bond activation is both kinetically and thermodynamically preferred to C-H activation. Both reactions occur with relatively low energy barriers by an electrophilic agostic interaction with the metal with simultaneous intramolecular hydrogen bonding with acetate leading to deprotonation via a six-membered transition state.

Full text of DOI:10.1021/om060863m

5976
Organometallics 2006, 25, 5976-5978
N-H versus C-H Activation of a Pyrrole Imine at {Cp*Ir}: A
Computational and Experimental Study
David L. Davies,*,† Steven M. A. Donald,‡ Omar Al-Duaij,† John Fawcett,†
Craig Little,‡ and Stuart A. Macgregor*,‡
Department of Chemistry, UniVersity of Leicester, Leicester LE1 7RH, U.K., and School of Engineering
and Physical Sciences, William Perkin Building, Heriot-Watt UniVersity, Edinburgh EH14 4AS, U.K.
ReceiVed September 21, 2006
Scheme 1
Summary: Reaction of a pyrrole imine with [IrCl2Cp*]2/NaOAc
leads to N-H actiVation in preference to C-H actiVation at
the pyrrole; howeVer, with the N-methylated ligand C-H
actiVation occurs. Density functional calculations show that
N-H bond actiVation is both kinetically and thermodynamically
preferred to C-H actiVation. Both reactions occur with
relatiVely low energy barriers by an electrophilic agostic
interaction with the metal with simultaneous intramolecular
hydrogen bonding with acetate leading to deprotonation Via a
six-membered transition state.
In 2003 we reported the facile cyclometalation of nitrogen
donor ligands with [MCl2Cp*]2 (M ) Rh, Ir) or [RuCl2(p-
cymene)]2 in the presence of sodium acetate.1 Subsequent
density functional calculations on the cyclometalation of di-
methylbenzylamine with [Pd(OAc)2]2 and [IrCl2Cp*]23 showed
both these reactions to proceed via six-membered transition
states with significant intramolecular H bonding to coordinated
acetate and some degree of agostic C-H interaction with the
metal. Thus, the metal acetate provides electrophilic activation
of the C-H bond and acts as an intramolecular base for the
deprotonation. Other computational and experimental studies
have suggested an important role for H bonding to acetate in
orienting a substrate.4 The use of carboxylate to facilitate C-H
activation has also been demonstrated recently in the activation
of benzene by platinum(II) complexes.5 We report here the
extension of our work to the activation of N-H bonds which
provides further insight into the nature of these acetate-assisted
bond activation processes.
such processes have been studied computationally,8 though more
recently a σ-bond metathesis pathway has also been proposed.9
Proton transfer to a bound ligand is well-known with lanthanide
metals, being a key step in hydroamination catalysis; however,
these involve highly basic metal alkyls or amides.10 Previous
studies of activation of pyrrole have generally shown that N-H
activation is favored over C-H activation, at least for low-
oxidation-state complexes.11 In contrast, Sames has recently
reported the rhodium(III)-catalyzed arylation of pyrrole and
indoles in which C-H activation is preferred over N-H
activation.12 In this case a coordinated pivalate is thought to
play a key role in this process. Thus, we decided to study the
cyclometalation of pyrrole imines L1 and L2, derived from
pyrrole-2-carboxaldehyde, with [IrCl2Cp*]2/NaOAc (Scheme 1).
L1 has both a C-H and an N-H bond available for activation
and so is an ideal system in which to assess the competition
between these two processes, while L2 only has a C-H bond
available. Density functional calculations have also been used
to quantify the energetics of the competing N-H and C-H bond
activation.
N-H activation is an extremely important reaction in alkene
amination6 and hydrodenitrogenation.7 For middle to late
transition metals N-H activation usually occurs via oxidative
addition to an electron-rich low-oxidation-state complex and
Pyrrole imine L1 reacted with [IrCl2Cp*]2 and NaOAc in
1
dichloromethane at room temperature. The H NMR spectrum
* To whom correspondence should be addressed. E-mail: dld3@
leicester.ac.uk (D.L.D.); s.a.macgregor@hw.ac.uk (S.A.M.).
† University of Leicester.
of the product shows a 1:1 ratio of the Cp* and the pyrrole
ligand. Three multiplets, each having an integration of 1H, are
observed at δ 6.38, 6.78, and 7.17 in the region expected for
pyrrole ring protons, suggesting formation of the N,N chelating
product 1a (the alternative C,N product 1b would only show
‡ Heriot-Watt University.
(1) Davies, D. L.; Al-Duaij, O.; Fawcett, J.; Giardiello, M.; Hilton, S.
T.; Russell, D. R. Dalton Trans. 2003, 4132.
(2) Davies, D. L.; Donald, S. M. A.; Macgregor, S. A. J. Am. Chem.
Soc. 2005, 127, 13754.
(3) Davies, D. L.; Donald, S. M. A.; Al-Duaij, O.; Macgregor, S. A.;
Polleth, M. J. Am. Chem. Soc. 2006, 128, 4210.
(4) (a) Privalov, T.; Linde, C.; Zetterberg, K.; Moberg, C. Organo-
metallics 2005, 24, 885. (b) Steinhoff, B. A.; Guzei, I. A.; Stahl, S. S. J.
Am. Chem. Soc. 2004, 126, 11268. (c) Mueller, J. A.; Goller, C. P.; Sigman,
M. S. J. Am. Chem. Soc. 2004, 126, 9724.
(5) Ziatdinov, V. R.; Oxgaard, J.; Mironov, O. A.; Young, K. J. H.;
Goddard, W. A.; Periana, R. A. J. Am. Chem. Soc. 2006, 128, 7404.
(6) For reviews see for example: (a) Muller, T. E.; Beller, M. Chem.
ReV. 1998, 98, 675. (b) Brunet, J.-J.; Neibecker, D. In Catalytic Hetero-
functionalization; Togni, A., Gru¨tzmacher, H., Eds.; Wiley-VCH: Wein-
heim, Germany, 2001; p 91.
(8) Macgregor, S. A. Organometallics 2001, 20, 1860.
(9) Pittard, K. A.; Cundari, T. R.; Gunnoe, T. B.; Day, C. S.; Petersen,
J. L. Organometallics 2005, 24, 5015.
(10) Gagne´, M. R.; Marks, T. J. J. Am. Chem. Soc. 1989, 4108. Gagne´,
M. R.; Stern, C. L.; Marks, T. J. J. Am. Chem. Soc. 1991, 114, 275.
(11) (a) Ladipo, F. T.; Merola, J. S. Inorg. Chem. 1990, 29, 4172. (b)
Jones, W. D.; Dong, L.; Myers, A. W. Organometallics 1995, 14, 855. (c)
Morikita, T.; Hirano, M.; Sasaki, A.; Komiya, S. Inorg. Chim. Acta 1999,
291, 341. (d) Lopez, C.; Baron, G.; Arevalo, A.; Munoz-Hernandez, M.
A.; Garcia, J. J. J. Organomet. Chem. 2002, 664, 170. (e) Hirano, M.; Onuki,
K.; Kimura, Y.; Komiya, S. Inorg. Chim. Acta 2003, 352, 160.
(12) Wang, X.; Lane, B. S.; Sames, D. J. Am. Chem. Soc. 2005, 127,
4996.
(7) Bianchini, C.; Meli, A.; Vizza, F. Eur. J. Inorg. Chem. 2001, 43.
10.1021/om060863m CCC: $33.50 © 2006 American Chemical Society
Publication on Web 11/23/2006

Communications
Organometallics, Vol. 25, No. 26, 2006 5977
Figure 1. X-ray structures of 1a and 2. Selected bond lengths (Å)
and bond angles (deg) are as follows. 1a: Ir-N(1), 2.069(3); Ir-
N(2), 2.123(3); N(1)-Ir-N(2), 76.4(1). 2: Ir-C(1), 2.019(5); Ir-
N(2), 2.094(4); C(1)-Ir-N(2), 77.7(2). All H atoms have been
omitted for clarity.
two doublets in this region). The absence of a ν(N-H) band in
the infrared spectrum is also consistent with the deprotonation
of the N-H group and coordination of the pyrrole nitrogen to
the metal. Hence, in this case N-H activation seems to be
preferred to C-H activation.
Figure 2. Computed reaction profiles (kcal/mol) for N-H (lower)
and C-H activation in [Ir(HNdCHNC4H4)(κ2-OAc)Cp]+. Non-
participating H atoms are omitted for clarity, and distances are given
in angstroms.
To test whether C-H activation was indeed possible with
this system, reaction of the N-methylated pyrrole imine L2 with
[IrCl2Cp*]2 and NaOAc was attempted. The C-H activated
1
product 2 was obtained in good yield. The H NMR spectrum
In the alternative intermediate, 4 (E ) +2.6 kcal/mol), the
C(3)-H bond is directed toward the OAc ligand (C-H‚‚‚O )
2.62 Å) and so allows for C-H activation at this position via
TS4-6 (E ) +23.2 kcal/mol). In TS4-6 the distance between
the transferring H and the Ir center is shorter (2.27 Å) and that
shows only two doublets at δ 6.41 and 6.78 due to the pyrrole
ring protons, confirming that cyclometalation has occurred and
that activation of a pyrrole C-H bond is also energetically
accessible in this system.
The X-ray structures of 1a and 2 have been determined and
are shown in Figure 1 with selected bond lengths and angles.
The structures are very similar, though the Ir-N distances in
1a are slightly longer than the corresponding Ir-N and Ir-C
distances in 2. In both complexes there is some distortion in
the Cp* ligand with two long Ir-C bonds trans to the pyrrolide
nitrogen or metalated carbon, as found in other cyclometalated
complexes.1
Our previous work on cyclometalation using [IrCl2Cp*]2
identified a key role for intermediates of the type [Ir(substrate)-
(κ2-OAc)Cp*]+. Bond activation then proceeds via intra-
molecular proton transfer to one arm of the OAc ligand, and
the most accessible route always features a six-membered
transition state.3 This is the basis of the present study, where
density functional calculations13 have been used to assess the
energetics of N-H vs C-H bond activation for the model
substrate HNdCHNC4H4.
to the accepting OAc oxygen is longer (1.97 Å) than in TS3-5
.
Thus, the balance between H bonding (to O) and an agostic
interaction (to Ir) shifts in the two transition states, with more
H bonding in TS3-5 reflecting the more acidic nature of the
N-H bond compared to the C-H one. In neither transition state
is there much elongation of the X-H bond being activated.
Similarly the Ir‚‚‚H distances are very long (>2.25 Å), implying
very little oxidative character in the transition state. These results
differ from the σ-bond metathesis transition states located in a
ruthenium system where C-H and N-H distances of 1.463 and
1.326 Å were calculated along with short Ru‚‚‚H contacts below
1.9 Å.9,14 Most importantly, in the present study TS3-5 is 6.4
kcal/mol more stable than TS4-6, indicating a kinetic preference
for N-H over C-H bond activation. In addition, product 5 is
4.1 kcal/mol more stable than 6 and so N-H bond activation
is also thermodynamically preferred.15
We have interpreted acetate-assisted C-H bond activation
as an electrophilic mechanism involving intramolecular depro-
tonation. In the activation of pyrrole the lower pKa of the N-H
bond is expected to facilitate deprotonation; hence, N-H
activation is expected to be kinetically favored over C-H
activation. It is perhaps surprising, given its nonpolar nature,
that the barrier to activation of a C-H bond is only 6.4 kcal/
mol greater. We propose that these results reflect the synergic
nature of acetate-assisted X-H activation, where both X-H‚‚‚O
H bonding and X-H‚‚‚M agostic interactions reinforce each
other to facilitate the bond activation process. Thus, for the more
Two forms of the precursor complex [Ir(HNdCHNC4H4)-
(κ2-OAc)Cp*]+, 3 and 4, were located which differ in the
orientation of the pyrrole moiety (see Figure 2). 3 is slightly
more stable and exhibits H bonding between the pyrrole N-H
and the OAc ligand (N-H‚‚‚O ) 1.92 Å). As such, 3 is perfectly
set up for N-H bond activation, and this proceeds in one step
via TS3-5 (E ) +16.8 kcal/mol). The geometry of TS3-5 reflects
a displacement of the proximal OAc arm from the metal center
by the approaching N-H bond. The N-H‚‚‚O distance also
decreases to 1.53 Å, and a slight elongation of the N-H distance
to 1.10 Å is computed. However, the activating N-H bond
remains remote from the Ir center, with Ir‚‚‚N and Ir‚‚‚H
distances in excess of 2.5 Å.
(14) Similar σ-bond metathesis transition states were obtained in the
present study by considering the reactions of (Ir(HNdCHNC4H4)(κ1-OAc)-
Cp*]+. H transfer to the remaining coordinated oxygen entailed activation
barriers (relative to 3) of 21.2 kcal/mol (N-H activation) and 31.3 kcal/
mol (C-H activation). See the Supporting Information for details.
(15) Experimentally, the observed products form via displacement of
HOAc by Cl- and calculations on models of these species indicate the N-H
bond activation product is the more stable one by 9.1 kcal/mol.
(13) Frisch, M.; et al. Gaussian 03, revision C.02; Gaussian, Inc.:
Wallingford, CT, 2004. Calculations used the BP86 functional. Ir and Cl
were described using the Stuttgart RECPs and the associated basis sets.
6-31G** basis sets were used for C, N, O, and H atoms. Zero-point energy
corrections are included. See the Supporting Information for details.

5978 Organometallics, Vol. 25, No. 26, 2006
Communications
acidic N-H bond significant H bonding creates a more electron-
rich N-H bond that is better able to undergo an agostic
interaction with Ir. For the C-H bond the agostic interaction
increases the acidity, leading to more efficient C-H‚‚‚O H
bonding. Both interactions thus work synergistically to break
the X-H bond.
The rather small difference in activation energies for acetate-
assisted N-H and C-H activation may account for the different
selectivities observed by Sames with a rhodium(III) carbox-
ylate.12 In that case the pyrrole is not constrained by chelation
and an η2 bonding mode may be possible (as indeed suggested
by Sames). Such an interaction may constrain the geometry to
provide a hydrogen bond to the C-H. Our work demonstrates
that under these conditions the activation of a C-H bond can
readily occur.
Acknowledgment. We thank Heriot-Watt University and the
University of Leicester for support and the Saudi Arabian
government for a studentship to O.A.-D.
Supporting Information Available: Text giving experimental
procedures and spectroscopic details, CIF files and tables giving
crystallographic data, atomic coordinates, thermal parameters, and
bond distances and angles for 1a and 2, tables giving computed
Cartesian coordinates and energies of all stationary points, and text
giving the full ref 13. This material is available free of charge via
the Internet at http:/pubs.acs.org.
OM060863M