Selective cleavage of the C-C bonds of aminoethyl groups, via a multistep pathway, by a pincer iridium complex

Article abstract of DOI:10.1021/ja051300p

A pincer-ligated iridium complex is found to react with N-ethylamines, HN(Et)R (R = cyclohexyl, tert-butyl, ethyl), to give the corresponding iridium isocyanide complexes (PCP)Ir(CH₃)(H)(CNR) (PCP = κ³-2,6-(^tBu₂PCH₂)₂C₆H₃). This novel, regioselective C-C bond cleavage reaction occurs readily under mild conditions (25-45 °C). The reaction is shown to proceed via initial dehydrogenation of the amine to give the corresponding imine (N-ethylidenealkylamine). The ethylidene sp² C-H bond then undergoes addition to iridium, followed by methyl migration. Copyright

Full text of DOI:10.1021/ja051300p

Published on Web 05/19/2005
Selective Cleavage of the C-C Bonds of Aminoethyl Groups, via a Multistep
Pathway, by a Pincer Iridium Complex
Xiawei Zhang, Thomas J. Emge, Rajshekhar Ghosh, and Alan S. Goldman*
Department of Chemistry, Rutgers, The State UniVersity of New Jersey, Piscataway, New Jersey 08854
Received March 2, 2005; E-mail: agoldman@rutchem.rutgers.edu
C-H and C-C bonds are the two most fundamental linkages
of organic chemistry. Major efforts toward the activation of C-H
bonds by soluble transition-metal complexes have reaped great
rewards in recent years. The metal-mediated activation of C-C
bonds has proven to be an even more challenging problem;
nevertheless, significant progress in this area has been achieved
via numerous approaches (or combinations thereof), including ring
strain relief, aromatization, chelation, and â-alkyl elimination.1
Figure 1. ORTEP diagrams of 1a, 2a, and 3b. Most hydrogen atoms are
omitted for clarity.
These successes notwithstanding, the ability to cleave “unactivated”
C-C bonds, particularly with regioselectivity in a functionalized
organic molecule, remains a major challenge to organic and
inorganic chemists.
(PCP)Ir(NBE), under the same conditions as above, reacted
analogously with N-ethyl-tert-butylamine (2 equiv), yielding the
new complex 2a in 94% yield (the minor product 2b, observed in
<1% yield, slowly grew in after the initial reaction was complete).
2a was characterized by X-ray diffraction (Figure 1). In analogy
with 1a, the methyl ligand of 2a is trans to the hydride. Likewise,
2b is assigned as a coordination isomer of 2a with the methyl group
cis to the hydride.
The reaction of the (PCP)Ir precursor with diethylamine pro-
ceeded in close analogy to the reactions of N-ethylcyclohexylamine
and N-ethyl-tert-butylamine, although the former reaction proceeded
more slowly and gave a significantly different product ratio. After
2 h at 45 °C, complexes 3a and 3b were formed in 90% yield,
in a ratio of 2.0:1 ((5%), and characterized as isomers of
(PCP)Ir(H)(Me)(CNEt) by 31P and 1H NMR spectroscopy, in
analogy with 1a, 1b, 2a, and 2b. Complexes 3a and 3b are assigned
as isomers with methyl and hydride ligands mutually trans and
mutually cis, respectively. The 3a/3b mixture undergoes slow
isomerization to give predominantly 3b. The X-ray structure of 3b
reveals the methyl group to be trans to the PCP carbon.9
All six complexes, 1a-3a and 1b-3b, undergo slow decomposi-
tion at 90 °C (ca. 15 h) to give the corresponding four-coordinate
isocyanide complexes (PCP)Ir(CNR) and concomitant formation
of methane, as observed by 1H NMR.9 (PCP)Ir(CNtBu) was further
reacted with CO to give (PCP)Ir(CO),12 liberating tert-butyl
isocyanide.
Among the most effective catalysts to date for the functional-
ization of C-H bonds, and specifically for the dehydrogenation of
alkanes, are “pincer”-ligated iridium complexes.2-5 Precursors of
(PCP)Ir (PCP ) κ3-2,6-(tBu2PCH2)2C6H3) can readily cleave not
only hydrocarbon C-H bonds (stoichiometrically or catalytically)6
but also the O-H bond of water7 and the N-H bonds of anilines.8
Herein we report the activation of an unstrained sp3-sp3 C-C single
bond by this pincer-ligated iridium fragment; unlike the aforemen-
tioned E-H bond activations, however, this reaction is found to
proceed via a multistep pathway.
As part of an effort to isolate products of the N-H addition of
aliphatic amines, N-ethylcyclohexylamine (2 equiv) was added to
a p-xylene solution of (PCP)Ir(NBE)9,10 (NBE ) norbornene; this
complex, generated by the reaction of 2 equiv NBE with (PCP)IrH2,
has previously been established to act as a precursor of the 14-
electron fragment (PCP)Ir). After 10 min at ambient temperature
an orange solution was obtained (eq 1). A major species, 1a, was
Jensen and co-workers have reported that (PCP)IrH2 can catalyti-
cally dehydrogenate secondary amines to give imines.13 The
temperature required for this dehydrogenation (200 °C) is surpris-
ingly high; such high temperatures might be required to overcome
product inhibition. Accordingly, we considered amine dehydroge-
nation to give imine as the initial step toward the formation of 1-3.
The resulting imines possess sp2 C-H bonds; we have previously
shown that vinyl and aryl sp2 C-H bonds readily undergo oxidative
addition to (PCP)Ir.6,10 Such C-H addition in the case of the imines,
if followed by methyl migration (i.e., deinsertion of isocyanide),
would give the observed products 1-3 (Scheme 1).
obtained in 91% yield, with a minor product, 1b, in 3% yield (as
1
determined by 31P and H NMR).9
The spectroscopic data indicated that products 1a and 1b are
six-coordinate (κ3-PCP)Ir complexes, each possessing one hydride
and one methyl ligand.11 Slow evaporation of pentane solvent
yielded crystals of complex 1a. Structure determination by X-ray
diffraction9 (Figure 1) revealed the presence of a cyclohexyl
isocyanide ligand trans to the PCP carbon and a methyl group trans
to a hydride. The 31P and 1H NMR spectroscopic data of the minor
complex 1b closely resemble those of 1a and are all consistent
with the assignment of 1b as an isomer of 1a with the methyl group
cis to the hydride ligand.9
Reactions of low-valent metals in which alcohols afford metal
carbonyls are well established.14 However, whereas alkyl migration
from acyl ligands is commonly facile, in the case of isocyanides,
alkyl migrations are only well-known in the direction of insertion.15
9
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J. AM. CHEM. SOC. 2005, 127, 8250-8251
10.1021/ja051300p CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Proposed Mechanism of Eq 1
bond. The present system, in which an amine is converted to an
isocyanide, constitutes another example suggesting that prior
dehydrogenation may prove to be a general and valuable approach
toward the regioselective cleavage of C-C bonds of functionalized
organics.
In conclusion, we report the regioselective cleavage of the
unstrained and untethered C-C bond of amines, under very mild
conditions, to give coordinated isocyanides. The reaction proceeds
through amine dehydrogenation, followed by sp2 C-H addition of
the imine product and subsequent methyl migration. Further study
of the applicability and scope of this reaction is underway.
Acknowledgment. We thank the NSF for support of this work
under the auspices of the Center for the Activation and Transforma-
tion of Strong Bonds (CATSB).
We are aware of only one example of alkyl migration proceeding
in the direction of isocyanide deinsertion. In a report by Caulton
and co-workers16 it was found that “RuHCl(PiPr3)2” underwent
imine C-H addition and isocyanide deinsertion. The same ruth-
enium fragment also dehydrogenated Me2NH, indicating that
properties favoring amine dehydrogenation and isocyanide abstrac-
tion from imines are closely related.
To test the mechanistic hypothesis of Scheme 1, we reacted 2
equiv of the imine N-ethylideneethylamine with (PCP)Ir(NBE).
Complexes 3a and 3b formed quantitatively within 10 min at
ambient temperature. Significant further support for the interme-
diacy of the imine is derived from the observation that the ratio of
3a to 3b, obtained from the reaction with imine, was identical with
that obtained from the reaction of (PCP)Ir with diethylamine (2.1:1
((5%)).
A mechanistic alternative to the pathway of Scheme 1 may be
considered in which (PCP)Ir undergoes direct addition of an imine
sp2-sp3 C-C bond. Jun et al. have reported such additions of the
C-C bond of imine groups tethered to rhodium.17 If this were the
case in the present system, the resulting iminoformyl intermediate
could then undergo H migration to give products 1a-3a. However,
the concomitant formation of complexes 1b-3b, in which the
hydride is trans to the isocyanide ligand, argues strongly against
such an alternative pathway (whereas the formation of both “a”
and “b” isomers is entirely consistent with the pathway of Scheme
1).
The direct oxidative addition of an unstrained, untethered sp3-
sp3 C-C bond by (PCP)Ir would undoubtedly be precluded by both
unfavorable thermodynamics and, additionally, a high kinetic
barrier.18 We suspect that sp3-sp3 C-C addition to any metal center
that might be generated in solution may be unlikely, if only due to
competition with C-H addition. Further, even if direct C-C bond
addition were to prove feasible, regioselectivity would undoubtedly
be a major challenge. In the present system, the cleavage of the
C-C bond is made possible by prior dehydrogenation; the
regioselectivity is dictated by the dehydrogenation and perhaps,
initially, by addition of the N-H bond (which is more favorable
than C-H bond addition to (PCP)Ir8). The first examples of
dehydrogenation-initiated sp3-sp3 C-C bond activation were
reported by Crabtree for alkanes.19 Most closely related to the
present work, Jun has reported that dehydrogenation of primary
amines can be followed by trans imination by rhodium-coordinated
2-amino-3-picoline to give a tethered imine group.20 The rhodium
center can then catalyze insertion of olefins into the imino C-H
Supporting Information Available: Experimental details and NMR
and crystallographic data. This material is available free of charge via
the Internet at http://pubs.acs.org.
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(t, JPH ) 16.4 Hz, 1H, Ir-H); 2a, δ -0.14 (t, JPH ) 3.4 Hz, 3H, CH3),
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