Getting the sterics just right: A five-coordinate iridium trisboryl complex that reacts with C-H bonds at room temperature

Article abstract of DOI:10.1039/b914736e

Five-coordinate boryl complexes relevant to Ir mediated C-H borylations have been synthesized, providing a glimpse of the most fundamental step in the catalytic cycle for the first time.

Full text of DOI:10.1039/b914736e

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Getting the sterics just right: a five-coordinate iridium trisboryl complex
that reacts with C–H bonds at room temperaturew
Ghayoor A. Chotana, Britt A. Vanchura, II, Man Kin Tse, Richard J. Staples,
Robert E. Maleczka, Jr* and Milton R. Smith, III*
Received (in Berkeley, CA, USA) 21st July 2009, Accepted 17th August 2009
First published as an Advance Article on the web 4th September 2009
DOI: 10.1039/b914736e
Five-coordinate boryl complexes relevant to Ir mediated C–H
borylations have been synthesized, providing a glimpse of the
most fundamental step in the catalytic cycle for the first time.
In many transition metal catalyzed processes, ligand dissocia-
tion or some other rearrangement of the metal ‘‘catalyst’’ is
required to generate the metal species that reacts with
substrate(s) in the catalytic cycle. Such is the case for
Ir-catalyzed borylations of C–H bonds, where the five-coordinate
boryl complexes believed to be responsible for C–H
functionalization have not been observed.1,2 The closest to
the five-coordinate complexes in phosphine and dipyridyl
ligated systems are the six-coordinate complexes 1 and 2.
While both of these compounds will borylate sp2-hybridized
C–H bonds, ligand dissociation precedes the key C–H inter-
action between the hydrocarbon and the Ir centre (Scheme 1).
Because Ir-catalyzed borylations exhibit unusual chemo-
and regioselectivities, the reactivity of five-coordinate trisboryl
complexes could offer important information regarding the
most fundamental step in the catalytic cycle—C–H bond
scission. Fully cognizant of the pitfalls embodied in Halpern’s
well-known maxim that true reactive intermediates are rarely
isolable,3 we set out to prepare five-coordinate complexes
Scheme 2 Arene displacement route to five-coordinate boryl complexes.
that could react directly with arenes and heterocycles. Our
preliminary results are described herein.4
We expected that the choice of Ir starting material ligand
would be critical for the successful preparation of five-coordinate
complexes. Since compound 2 retains an Z2-olefin from the
starting material, we felt that displacement of an arene with a
bidentate chelating ligand might yield the desired five-coordinate
complexes since Z2-coordination of the expelled arene would
carry the penalty of disrupting its aromaticity (Scheme 2). The
mesitylene trisboryl complex, 3, was selected as the starting
material, since the mesitylene methyl groups block access to
the arene sp2 C–H bonds.1
Complex 3 reacts cleanly with dmpe (1,2-bis(dimethyl-
phosphino)ethane) to yield a new species, 4. 31P NMR spectra
revealed two chemically inequivalent P environments present
1
in a 2 : 1 ratio. H NMR spectra of crude reaction mixtures
showed unreacted 3 was present in addition to resonances for
4 with a 1 : 2 ratio of 3 : 4. At this point, it was clear that 4 was
a dinuclear species, which could be obtained in good yield
by adjusting the stoichiometry (eqn (1)). While equimolar
solutions of 3 and dmpe catalyze C–H borylation, no conversion
is observed when pure compound 4 is used. This is consistent
with our previous observation that catalysis ceases abruptly
when P : Ir ratios reach 3 : 1. The formation of 4 suggests that
a significant portion of the Ir may be sequestered in an inactive
form. Consequently, the efficiency of the active forms of Ir
phosphine catalysts may have been grossly underestimated.
Scheme 1 Generation of five-coordinate, reactive intermediates in
C–H borylations.
Department of Chemistry, Michigan State University,
East Lansing, MI 48824-1322, USA.
E-mail: smithmil@msu.edu, maleczka@chemistry.msu.edu;
Fax: +1 517-353-1793; Tel: +1 517-355-9715 x166/x124
w Electronic supplementary information (ESI) available: Spectral data
for all new compounds, as well as general experimental procedures.
CCDC 741048 and 741049. For ESI and crystallographic data in CIF
or other electronic format see DOI: 10.1039/b914736e
(1)
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Chem. Commun., 2009, 5731–5733 | 5731

The most obvious tact for preparing a five-coordinate
complex is to increase the steric demands of the phosphine
ligand. Indeed, 3 reacts cleanly with 1,2-bis(di-tert-butyl-
phosphino)ethane (dtbpe) in cyclohexane or THF to afford a
the Ir centre, compound 6, the isopropyl analogue of 5, was
prepared in analogous fashion. The spectroscopic data for 6
are similar to those for 5 (Fig. 1). Refinement of the X-ray
crystal structure was less straightforward as the boryl group
containing B2 exhibited rotational disorder about the Ir–B2
vector. The conformer population was optimized by least-
squares analysis in the usual way and the structure of the
major conformer (73% of the total population) is the one
shown in Fig. 1. The closest Ir–C methyl contact (3.419 A) is
even longer than that in 5, reflecting a bona fide five-coordinate
structure for 6.
1
new complex, 5, whose 31P NMR and H NMR spectra were
consistent with a five-coordinate structure (eqn (2)). This was
confirmed by X-ray crystallography and the structure of 5 is
shown in Fig. 1.z The geometry about Ir is a distorted square
pyramid. The Ir atom lies only 0.14 A above the least-squares
plane defined by the phosphorus and basal boron atoms. The
apical boron atom shows the most pronounced distortion as
the Ir–B1 vector is B151 away from being normal to the basal
plane, canting towards the boryl groups and away from
the phosphine ligand. Unique boryl resonances cannot be
discerned in low temperature 1H NMR spectra, indicating
either isochronous chemical shifts or rapidly exchanging boryl
environments. Likewise, a single resonance is observed for the
tert-butyl methyl groups down to ꢁ80 1C.
Relative to 5, 6 is significantly more reactive at room
temperature as the borylation with 1,3-C6H4(CF3)2 in
Scheme 3 attests, and borylation of 2-methylthiophene by 6
is even more facile, which is consistent with the greater
reactivities of aromatic heterocycles in C–H borylations.1,13
While the reactions are very clean with respect to the organic
1
substrates and products, it is evident from H and 31P NMR
spectra that a number of Ir hydride species form.14 The
differences in relative reactivities also translate to catalytic
reactions. Specifically, borylations of 2-methylthiophene
were examined in cyclohexane-d12 solutions at 100 1C. When
catalysts were generated in situ by adding 10 mol% of the
diphosphine ligand to 10 mol% (Z5-indenyl)Ir(Z4-1,5-cyclo-
octadiene), 93% conversion was observed for the dippe
catalyst after 2 h, whereas the analogous reaction with the
dtbpe catalysts yielded only 12% conversion. Similar relative
rates were seen using isolated compounds 5 and 6, although
the absolute rates approximately doubled. This is not surprising
since in situ generation will have an induction period and the
conversion of the precatalyst to its active form may not be
quantitative.
ð2Þ
The structure of 5 differs substantially from the most closely
related boron compound, trans-IrCl(BCat)2(PEt3)2 (Cat =
catecholate), which is a distorted trigonal bipyramid with
trans axial phosphines.5 Given that many nominally five-
coordinate d6 transition metal structures are stabilized by
agostic interactions from C–H bonds in their ligand periphery,6
we have examined this possibility for 5. NMR and IR spectra
lack the signatures associated with agostic C–H interactions,
which is consistent with the solid state structure where
the closest Ir–C distance of 3.169(9) A falls outside the range
of 2.65–2.94 A for Ir compounds with bona fide agostic
interactions,7–12 and is B0.5 A longer than the agostic
C–H distances for five-coordinate IrIII examples.7,11
The enhanced reactivity of 6 relative to 5 arises from steric
relief in the metal coordination sphere that is incumbent with
removing four methyl groups from the diphosphine ligand.
Fig. 2 depicts a putative transition state 7 for the C–H cleavage
Complex 5 reacts only slowly with arenes at room tempera-
ture. This is not surprising considering the crowded environ-
ment at the metal centre (Fig. 1). This is also consistent with
the low catalytic activity of in situ generated catalysts using
dtbpe as the chelating ligand. To ease the steric crowding at
Fig. 1 X-Ray structures of compounds 5 and 6 with BPin methyl
groups omitted. The white carbons are those with the closest Ir
contacts (Irꢂ ꢂ ꢂC = 3.169 A in 5 and 3.419 A in 6). In both cases,
the Ir–C distances are significantly longer than those in compounds
with Ir C–H agostic interactions.
Scheme 3 Relative reactivities of 5 and 6 with 1,3-bis(trifluoromethyl)-
benzene and 6 with 2-methylthiophene at 25 1C.
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5732 | Chem. Commun., 2009, 5731–5733

We thank BASF, Inc. for a gift of HBPin, Professor
Gregory Hillhouse for a gift of dtbpe, and the Michigan
Economic Development Corp., the NIH (GM63188 to
M.R.S.), the Pharmaceutical Roundtable of the ACS
Green Chemistry Institute, Pfizer, Inc., and the Astellas
USA Foundation (to R.E.M.) for generous financial support.
Fig. 2 A comparison of the orientation for the B2 boryl ligands
in structures 5 and 6 with the qualitative transition state 7. For
compound 5, rotation about the Ir–B bond is required to reach the
transition state, whereas the boryl orientation in 6 is nearly ideal for
cleaving the arene C–H bond.
Notes and references
ꢀ
z Crystal data for 5. C36H76O6B3P2Ir, M = 891.54, triclinic, P1,
a = 11.651(4), b = 12.035(4), c = 17.151(4) A, a = 73.82(3)1,
b = 76.42(3)1, g = 69.37(2)1, V = 2136.6(11) A3, T = 293(2) K,
Z = 2, 9677 reflections measured, 6106 unique (Rint = 0.0668), which
were used in all calculations. The final R1 and wR2 were 0.0581 and
0.1428. CCDC 741048. Crystal data for 6. C32H68O6B3P2Ir,
M = 835.43, monoclinic, P21/c, a = 17.821(4), b = 12.668(3),
c = 18.491(4) A, b = 104.80(3)1, V = 4035.9(14) A3, T = 173(2)
K, Z = 4, 34 198 reflections measured, 5816 unique (Rint = 0.0803),
which were used in all calculations. The final R1 and wR2 were 0.0474
and 0.1035. CCDC 741049.
step. It is similar to that found by Sakaki in his computational
studies of related complexes with chelating nitrogen ligands
where the hydrogen is transferred from the arene to one of the
boryl ligands.15,16 For compound 6, the isopropyl substituents
make the metal centre more accessible for arene approach
relative to 5. Fig. 2 points out a subtler feature that may
contribute to the lowered barrier—namely, the orientation of
the boryl ligands. In Sakaki’s transition state, the boryl ligand
that facilitates transfer must be oriented such that the boron
and its pinacolate oxygen atoms lie in the basal plane of the
square pyramid. As seen in Fig. 2, the dihedral angle f
between the plane defined by B2 and its oxygen atoms and
the basal plane in 5 is significantly larger (f = 481) than the
corresponding angle in 6 (f = 211). Thus, transition state 7
should be more readily accessible from structure 6 relative to
5. The disorder of the BPin ligand containing B2 in compound
6 is also consistent with greater flexibility afforded by the
isopropyl-substituted diphosphinoethane as no similar disorder
was evident in the tert-butyl analogue, 5. Despite these
observations, the fact remains that compounds 5 and 6 are
fluxional, indicating that barriers for boryl reorientation are
small, and we hesitate to ascribe too much significance to the
boryl orientations in these ground states on the relative
transition state energies.
1 J. Y. Cho, M. K. Tse, D. Holmes, R. E. Maleczka, Jr and
M. R. Smith, III, Science, 2002, 295, 305–308.
2 T. Ishiyama, J. Takagi, K. Ishida, N. Miyaura, N. R. Anastasi and
J. F. Hartwig, J. Am. Chem. Soc., 2002, 124, 390–391.
3 J. Halpern, Science, 1982, 217, 401–407.
4 We previously outlined this strategy for preparing 5-coordinate
boryl complexes: G. A. Chotana, R. E. Maleczka, Jr and
M. R. Smith, III, Abstracts of Papers, 233rd ACS National
Meeting, Chicago, IL, United States, March 25–29, 2007, 2007,
INOR-188.
5 W. Clegg, F. J. Lawlor, T. B. Marder, P. Nguyen, N. C. Norman,
A. G. Orpen, M. J. Quayle, C. R. Rice, E. G. Robins, A. J. Scott,
F. E. S. Souza, G. Stringer and G. R. Whittell, J. Chem. Soc.,
Dalton Trans., 1998, 301–309.
6 G. J. Kubas, Metal Dihydrogen and Sigma-Bond Complexes:
Structure, Theory, and Reactivity, Kluwer Academic/Plenum
Publishers, New York, 2001.
7 Y. K. Sau, H. K. Lee, I. D. Williams and W. H. Leung,
Chem.–Eur. J., 2006, 12, 9323–9335.
8 N. M. Scott, V. Pons, E. D. Stevens, D. M. Heinekey and
S. P. Nolan, Angew. Chem., Int. Ed., 2005, 44, 2512–2515.
9 E. Clot, J. Y. Chen, D. H. Lee, S. Y. Sung, L. N. Appelhans,
J. W. Faller, R. H. Crabtree and O. Eisenstein, J. Am. Chem. Soc.,
2004, 126, 8795–8804.
10 R. Dorta, R. Goikhman and D. Milstein, Organometallics, 2003,
22, 2806–2809.
In summary, the steric influence of the chelating diphosphino-
ethane ligands has a dramatic effect on the structures
and reactivities of the trisboryl complexes obtained in their
reactions with arene complex 3. It is interesting that even
though equimolar solutions of 3 and dmpe are catalytically
active for borylation, the major product 4 obtained by
reaction of 3 and dmpe is ineffective. Consequently, it is
conceivable that the active catalytic species for certain
phosphine-supported systems are present in very low
concentration. Perhaps most importantly, the synthesis of
five-coordinate boryl complexes that react directly with arenes
makes it possible to probe the rate-limiting and most
fundamental step in the catalytic cycle, while avoiding the
potential for obfuscation by ligand dissociation that is
incumbent to most precatalysts. We are actively pursuing
further reactivity of compounds 5 and 6, with other arenes
and heterocycles, as well as boranes. In addition, we are
actively developing routes to related five-coordinate structures
with other bidentate ligands.
11 E. Clot, O. Eisenstein, T. Dube, J. W. Faller and R. H. Crabtree,
Organometallics, 2002, 21, 575–580.
12 A. C. Cooper, W. E. Streib, O. Eisenstein and K. G. Caulton,
J. Am. Chem. Soc., 1997, 119, 9069–9070.
13 J. Takagi, K. Sato, J. F. Hartwig, T. Ishiyama and N. Miyaura,
Tetrahedron Lett., 2002, 43, 5649–5651.
14 For example, the compounds (dippe)IrH3(BPin)2 and (dippe)-
IrH4BPin can be seen in the milieu. These have been fully
characterized and details will be published in due course. Some
of these findings have been publicly disseminated. See:
B. A. Vanchura, B. Ramanathan, G. A. Chotana and
M. R. Smith III, Abstracts of Papers, 237th ACS National Meeting,
Salt Lake City, UT, United States, March 22–26, 2009, 2009,
INOR-001.
15 H. Tamura, H. Yamazaki, H. Sato and S. Sakaki, J. Am. Chem.
Soc., 2003, 125, 16114–16126.
16 We find a transition state similar to 7 in computational studies of
the phosphine ligated catalysts: D. A. Singleton and M. R. Smith,
III, manuscript in preparation.
17 Hartwig and co-workers prepared a five-coordinate catecholate
boryl analog of 6 using the route we previously disclosed in ref. 4.
Please see: C. W. Liskey, C. S. Wei, D. R. Pahls and J. F. Hartwig,
Chem. Commun., 2009, DOI: 10.1039/b913949d.
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Chem. Commun., 2009, 5731–5733 | 5733