Iridium-mediated borylation of benzylic C-H bonds by borohydride

Article abstract of DOI:10.1002/anie.201006320

Simple source: An intramolecular iridium-mediated C-H borylation proceeds through transfer of a BH₃ fragment from borohydride to a benzylic carbon center (see scheme; coe=cyclooctene). Simple and inexpensive LiBH ₄ is thus utilized as the boron source in C-H to C-B conversion.

Full text of DOI:10.1002/anie.201006320

DOI: 10.1002/anie.201006320
À
C H Borylation
À
Iridium-Mediated Borylation of Benzylic C H Bonds by
Borohydride**
Christina Y. Tang, William Smith, Amber L. Thompson, Dragoslav Vidovic, and
Simon Aldridge*
À
À
The transition-metal-mediated conversion of C H to C B
bonds is an exciting recent development in the functionaliza-
tion of both saturated and unsaturated hydrocarbons.[1] In
part this reflects the fact that the resulting borylated
compounds (boronic esters or acids) are attractive substrates
for further chemistry through a range of established proto-
cols.[2] C H to C B conversion in arenes/heteroarenes
catalyzed by [{Ir(cod)X}2]/4,4’-di-tert-butylbipyridine systems
(X = Cl, OMe, indenyl; cod = cyclooctadiene) has been
particularly well developed,[1,3] in some cases achieving
selectivity for substitution patterns which have proved
difficult to access using classical synthetic methods.[4] Typi-
cally these borylation protocols utilize HBpin or B2pin2 as the
boron reagent of choice (pin = pinacolato, OCMe2CMe2O),
with IrIII–tris(Bpin) complexes thought to be key catalytic
À
À
Scheme 1. Syntheses of 2 and 3 through borane complexation with or
À
without additional C H activation. Key reagents and conditions:
a) LiBH4 (10 equiv), diethyl ether, 208C, 6 h, 75%; b) [{Ir(coe)2Cl}2]
(0.25 equiv), THF, then LiBH4 (40 equiv), diethyl ether, 7 d, 42%.
intermediates.[5] C B bond formation proceeds through
À
either M B/C H s bond metathesis or through distinct C
The formation of 3 is suggested by 11B NMR spectroscopy
À
À
À
1
À
H oxidative addition/B C reductive elimination steps in an
which reveals two quartet resonances (at dB À35.1, JBH
=
IrIII/IrV cycle.[1,5,6] An alternative mechanism implicating a
mono(Bpin) complex and a RhI/RhIII catalytic cycle has been
proposed for benzylic borylation using HBpin.[7]
81 Hz and À27.4 ppm, 1JBH = 78 Hz), the former being similar
1
to that reported for 2 (dB À36.8 ppm, JBH = 88 Hz),[12b] the
latter consistent with other examples of [RBH3]À species [e.g.
1
À
In recent work we have examined the interaction of
rhodium and iridium complexes containing bis(N-hetero-
cyclic carbene) (NHC) ligand sets with boranes.[8,9] In doing so
dB À26.8 ppm, JBH = 79 Hz for (2-naphthyl)BH3 ].[13] These
spectroscopic inferences were subsequently confirmed by
crystallographic studies, with 3 being shown to exist as a
centrosymmetric dimer in the solid state (Figure 1). Each
lithium center interacts with six BH hydrogen atoms (with
distances in the range 1.86–2.24 ꢀ), two of which originate
from each of the carbene.BH3 and [ArCH2BH3]À units of one
[(IMes’BH3)BH3]À moiety, and the other two in the
À
we have discovered an unusual intramolecular C H boryla-
tion process mediated by [{Ir(coe)2Cl}2] (coe = cyclooctene)
which leads to the transfer of a BH3 fragment from LiBH4 to a
benzylic carbon center.[7,10,11] Here, we investigate the funda-
mental mechanistic steps which lead to this chemistry.
[ArCH2BH3]À unit of the second. The C B distances asso-
ciated with the two different carbon donors are marginally
different [1.587(3) and 1.634(3) ꢀ] with the shorter bond
À
The reaction of IMes [N,N’-bis(2,4,6-trimethylphenyl)-
imidazol-2-ylidene; 1] with excess LiBH4 in diethyl ether
generates the known compound IMes.BH3 (2) in 75%
yield.[12] By contrast, the reaction of 1 with [{Ir(coe)2Cl}2]
(0.25 equiv of dimer)/excess LiBH4, leads to the formation of
the lithium salt 3, in which one of the ortho-methyl
À
substituents has undergone additional C H activation,
thereby generating an [ArCH2BH3]À function (Scheme 1).
[*] Dr. C. Y. Tang, W. Smith, Dr. A. L. Thompson, Dr. D. Vidovic,
Dr. S. Aldridge
Inorganic Chemistry Laboratory, Department of Chemistry
University of Oxford, South Parks Road, Oxford, OX1 3QR (UK)
Fax: (+44)1865-272-690
E-mail: simon.aldridge@chem.ox.ac.uk
Homepage: http://users.ox.ac.uk/~quee1989/
[**] We thank the EPSRC for funding and for access to the National
Mass Spectrometry facility, Swansea University.
Figure 1. Molecular structure of dinuclear 3·C6H5F. Hydrogen atoms
[except those attached to C(15), B(16) and B(30)] and fluorobenzene
solvate omitted (and unactivated mesityl groups shown in wireframe
format) for clarity; thermal ellipsoids set at the 40% proability level.
Key distances [ꢀ]: C(17)–B(30) 1.587(3), C(15)–B(16) 1.634(3).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201006320.
Angew. Chem. Int. Ed. 2011, 50, 1359 –1362
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1359

Communications
being associated with neutral NHC donor [cf. 1.596(4) ꢀ for
2].[12a]
In order to probe the mechanistic steps leading to benzylic
borylation in 3, the stepwise reactions of 1 with [{Ir(coe)2Cl}2]
and LiBH4 have been investigated (Scheme 2). Thus, the
plex 6 features trans bis(NHC) and benzyl/chloride ligand
pairs within a pseudo-octahedral complex. Moreover the
PMe3 ligand gives rise to a doublet in the 31P NMR spectrum,
with a coupling constant (2JPH = 185 Hz) characteristic of
mutually trans hydride and phosphine ligands.[15]
The reaction of 5 with LiBH4 (40 equiv) in diethyl ether
leads to the formation of the bis(hydrido)IrIII benzyltri-
1
hydroborate complex 8. H and 11B NMR measurements are
consistent with the proposed structure. The former reveals
five high-field signals at 208C [at dH À19.60, À18.25, À7.14,
À6.74, and À0.42 ppm (all 1H)] assigned to the two IrH, two
IrHB, and one BH protons, respectively. The 11B spectrum
shows a broad resonance at dB À38.7 ppm, consistent the
formation of an [RBH3]À system (cf. À27.4 ppm for 3).[13] With
due allowance for the lower symmetry, the chemical shifts of
the four highest field 1H NMR resonances are strongly
reminiscent of those found for related IrIII complexes featur-
ing h2-coordinated (charge neutral) aminoboranes {for exam-
ple, dH À15.50 (2H, IrH), À5.83 ppm (2H, IrHB) for [Ir-
(IMes)2(H)2(h2-H2B.NiPr2)]+} and the solid-state structure of
8 (Figure 2) features a similar Ir…B distance for the h2-bound
Scheme 2. Iridium-mediated conversion of 1 to 3. Key reagents and
conditions: a) [{Ir(coe)2Cl}2] (0.47 equiv of dimer), THF, 7 d at 208C,
45%; b) (from 1) [{Ir(coe)2Cl}2] (0.23 equiv of dimer), THF, 12 h at
208C, 85%; c) (from 4b) thermolysis at 658C, toluene, 24 h, quantita-
tive by NMR analysis; (from 1) [{Ir(coe)2Cl}2] (0.25 equiv of dimer),
THF, 60 h at 208C, 68%; d) PMe3 (excess), toluene, 1 h at 208C, 61%;
e,f) (from 5) LiBH4 (4 equiv), diethyl ether, 12 h at 208C, 48%;
g) (from 5) LiBH4 (40 equiv), diethyl ether, 7 d at 208C, 45%.
Figure 2. Molecular structure of 8. Hydrogen atoms [except those
attached to Ir(25), C(34) and B(342)] omitted and unactivated mesityl
groups shown in wireframe format for clarity; thermal ellipsoids set at
the 40% probability level. Key distances [ꢀ] and angle [8]: Ir(25)···B(342)
2.253(7), C(34)–B(342) 1.679(10); C(1)-Ir(25)-C(26) 174.7(2).
interaction of 1 with [{Ir(coe)2Cl}2] in THF under a dinitrogen
atmosphere proceeds sequentially to the formation of the
planar tetra-coordinate IrI complexes [Ir(IMes)(N2)(h2-
coe)Cl] (4a) and [Ir(IMes)2(h2-coe)Cl] (4b), respectively
(see Supporting Information for details of both compounds).
The structure of 4a is characterized by a trans disposition of
IMes and coe ligands, while in 4b the IMes and coe ligands are
cis, presumably to accommodate the bulky IMes ligands in a
mutually trans arrangement. Prolonged reaction in THF leads
to loss of the remaining coe ligand and the formation of the
IrIII complex [Ir(IMes)(IMes’)HCl] (5). Complex 5 features
the chelating NHC/benzyl IMes’ ligand, formed by oxidative
benzyltrihydroborate ligand to related amineborane com-
plexes [2.253(7) ꢀ vs., for example, 2.230(2) ꢀ for [Ir-
(IMes)2(H)2(h2-H3B.NMe3)]+).[9b,16] In the case of 8, the
borylated product can be liberated from the metal coordina-
tion sphere by the use of excess LiBH4 and extended reaction
times, thereby generating the bis(BH3) system 3; the second
equivalent of borane presumably offers a potent alternative
Lewis acid center for NHC coordination [cf. IrIII].
À
addition of one of the C H bonds of a mesityl ortho-methyl
Of interest mechanistically is the route for the formation
of 8 from 5. One possibility is initial salt metathesis to yield
the borohydride complex 7, followed by an intramolecular
migration of the tethered benzyl function from iridium to
boron. Precedent for a structural motif akin to 7 comes from
the crystallographically characterized complex [Ir(IMes)-
(IMes’)(H)(h2-H2BNCy2)]+, which features the neutral ami-
noborane H2BNCy2 h2-ligated to the same [Ir(IMes)-
substituent.[8,14] As such, a mechanism for borylation through
À
À
initial C H oxidative addition is plausible. The resulting Ir H
linkage is characterized by a 1H NMR resonance at dH
À33.14 ppm; methyl activation is also signaled by a signifi-
cantly more complex pattern of signals in the aliphatic region,
and the heavy atom skeleton of 5 was subsequently confirmed
crystallographically. Although the location of the hydride
ligand could not be determined reliably, further evidence for
the identity of 5 was obtained from a trapping reaction with
PMe3 which yields [Ir(IMes)(IMes’)HCl(PMe3)] (6). Com-
À
(IMes’)(H)]+ fragment.[9b] That said, the anionic BH4
ligand is known to be more strongly reducing than neutral
aminoboranes, and given the paucity of mononuclear IrIII
1360
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Angew. Chem. Int. Ed. 2011, 50, 1359 –1362

tions [F2 > 2s(F2)] and R1 = 0.0422, wR2 = 0.1071 for all unique
borohydride derivatives in the chemical literature,[17,18] we
sought to independently verify the viability of a system of the
type [Ir(IMes)2(H)(X)(h2-BH4)]. To this end we have been
successful in synthesizing [Ir(IMes)2(H)2(h2-BH4)] (9) by
reaction of 4b with the more soluble borohydride source
[nBu4N][BH4] in diethyl ether. Crystallographic and spectro-
scopic studies of this complex (Figure 3) are consistent with
reflections. Max./min. residual electron densities: 0.18/À0.25 eꢀÀ3
.
Crystallographic data (for 8): C42H51BIrN4, Mr 814.92, triclinic,
¯
P1, a = 11.0741(2), b = 11.4654(3), c = 16.8691(5) ꢀ, a = 94.860(1),
b = 93.489(1), g = 117.875(1)8, V= 1874.2(1) ꢀ3, Z = 2, 1c =
1.444 mgmÀ3, T= 150 K, l = 0.71073 ꢀ. 26047 reflections collected,
8430 independent [R(int) = 0.044], which were used in all calcula-
tions. R1 = 0.0408, wR2 = 0.1824 for observed unique reflections [F2 >
2s(F2)] and R1 = 0.0681, wR2 = 0.1824 for all unique reflections. Max./
min. residual electron densities: 1.02/À0.96 eꢀÀ3
.
Crystallographic data (for 9): C42H54BIrN4, Mr 817.91, monoclinic,
P21/n, a = 12.6789(1), b = 11.1796(1), c = 28.2664(3) ꢀ, b =
96.567(1)8, V= 3980.3(1) ꢀ3, Z = 4, 1c = 1.365 mgmÀ3, T= 150 K, l =
0.71073 ꢀ. 51436 reflections collected, 9057 independent [R(int) =
0.031], which were used in all calculations. R1 = 0.0334, wR2 = 0.0628
for observed unique reflections [F2 > 2s(F2)] and R1 = 0.0482, wR2 =
0.0707 for all unique reflections. Max./min. residual electron den-
sities: 1.77/À1.39 eꢀÀ3
.
Further details on the crystal structure investigations may be
obtained from the Fachinformationszentrum Karlsruhe (e-mail:
crysdata@fiz-karlsruhe.de), on quoting the depository numbers
CSD 795296 (3), 795300 (8), and 805002 (9).
Figure 3. Molecular structure of 9. Hydrogen atoms [except those
attached to Ir(1) and B(48)] omitted and unactivated mesityl groups
shown in wireframe format for clarity; thermal ellipsoids set at the
40% probability level. Key distance [ꢀ] and angle [8]: Ir(1)···B(48)
2.248(5); C(2)-Ir(1)-C(25) 173.0(2).
Received: October 8, 2010
Published online: December 29, 2010
À
Keywords: boron · borylation · C H activation · iridium ·
N-heterocyclic ligands
.
trans-Ir(IMes)2, cis-Ir(H)(X) and Ir(h2-BH4) motifs analogous
to those proposed for 7. Moreover, the alkyl migration step
converting the proposed intermediate 7 into 8 finds precedent
among d6 5d metal complexes in the recent work of
Vedernikov and co-workers, who report methyl and phenyl
group migration between hexa-coordinate PtIV and tetra-
coordinate boron centers.[19] Related migration of alkyl
substituents from f-block metals to boron to give alkyltrihy-
droborates has also been reported:[20]
À
[1] For a comprehensive recent review of C H borylation chemistry,
see: I. A. I. Mkhalid, J. H. Barnard, T. B. Marder, J. M. Murphy,
J. F. Hartwig, Chem. Rev. 2010, 110, 890 – 931.
[2] See, for example: Boronic Acids: Preparation and Applications
in Organic Synthesis and Medicine (Ed.: D. G. Hall), Wiley-
VCH, Weinheim, 2005.
[3] a) J.-Y. Cho, M. K. Tse, D. Holmes, R. E. Maleczka, Jr., M. R.
Smith III, Science 2002, 295, 305 – 308; b) T. Ishiyama, J. Takagi,
K. Ishida, N. Miyaura, N. R. Anastasi, J. F. Hartwig, J. Am.
Chem. Soc. 2002, 124, 390 – 391.
[4] For representative examples, see: a) R. E. Maleczka, Jr., F. Shi,
D. Holmes, M. R. Smith III, J. Am. Chem. Soc. 2003, 125, 7792 –
7793; b) D. N. Coventry, A. S. Batsanov, A. E. Goeta, J. A. K.
Howard, T. B. Marder, R. N. Perutz, Chem. Commun. 2005,
2172 – 2174; c) J. M. Murphy, X. Liao, J. F. Hartwig, J. Am.
Chem. Soc. 2007, 129, 15434 – 15435; d) C. C. Tzschucke, J. M.
Murphy, J. F. Hartwig, Org. Lett. 2007, 9, 761 – 764.
[5] For relevant iridium–tris(Bpin) and related complexes see
reference [3b] and: a) P. Nguyen, H. P. Blom, S. A. Westcott,
N. J. Taylor, T. B. Marder, J. Am. Chem. Soc. 1993, 115, 9329 –
9330; b) T. M. Boller, J. M. Murphy, M. Hapke, T. Ishiyama, N.
Miyaura, J. F. Hartwig, J. Am. Chem. Soc. 2005, 127, 14263 –
14278; c) C. W. Liskey, C. S. Wei, D. R. Pahls, J. F. Hartwig,
Chem. Commun. 2009, 5603 – 5605; d) G. A. Chotana, B. A.
VanchuraII, M. K. Tse, R. J. Staples, R. E. Maleczka, Jr., M. R.
Smith III, Chem. Commun. 2009, 5731 – 5733.
In summary, we report an intramolecular benzylic bor-
ylation occurring at the ortho-methyl substituent of an
À
ancillary NHC ligand. While selective C H borylation
chemistry is becoming a more widely exploited synthetic
method, the current example is intriguing in exploiting simple
(and inexpensive) LiBH4 as the boron source. Mechanisti-
À
cally, this chemistry appears to proceed through C H
oxidative addition and subsequent Ir-to-B benzyl migration
steps. Further studies aimed at accessing related chemistry for
non-tethered substrates [for example, by partnering borohy-
I
À
dride sources with Ir systems capable of intermolecular C H
activation] are currently being investigated and will be
reported in due course.
[6] H. Tamura, H. Yamazaki, H. Sato, S. Sakaki, J. Am. Chem. Soc.
2003, 125, 16114 – 16126.
Experimental Section
Included here are crystallographic data for compounds 3, 8, and 9.
Synthetic and characterizing data for all new compounds and
crystallographic data for 4a, 4b, 5, and 6 are included in the
Supporting Information.
[7] a) S. Shimada, A. S. Batsanov, J. A. K. Howard, T. B. Marder,
Angew. Chem. 2001, 113, 2226 – 2229; Angew. Chem. Int. Ed.
2001, 40, 2168 – 2171; b) W. H. Lam, K. C. Lam, Z. Lin, S.
Shimada, R. N. Perutz, T. B. Marder, Dalton Trans. 2004, 1556 –
1562.
[8] C. Y. Tang, W. Smith, D. Vidovic, A. L. Thompson, A. B.
Chaplin, S. Aldridge, Organometallics 2009, 28, 3059 – 3066.
[9] a) C. Y. Tang, A. L. Thompson, S. Aldridge, Angew. Chem. 2010,
122, 933 – 937; Angew. Chem. Int. Ed. 2010, 49, 921 – 925; Angew.
Crystallographic data (for 3.C6H5F): C48H63B4FLi2N4, Mr 772.18,
tetragonal, P41212, a = 17.3197(2), c = 16.1346(2) ꢀ, V= 4839.9(1) ꢀ3,
Z = 4, 1c = 1.060 mgmÀ3, T= 150 K, l = 0.71073 ꢀ. 65879 reflections
collected, 3156 independent [R(int) = 0.032], which were used in all
calculations. R1 = 0.0643, wR2 = 0.1128 for observed unique reflec-
Angew. Chem. Int. Ed. 2011, 50, 1359 –1362
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www.angewandte.org
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Communications
À
Chem. 2010, 122, 933 – 937; b) C. Y. Tang, A. L. Thompson, S.
Aldridge, J. Am. Chem. Soc. 2010, 132, 10578 – 10591.
metallics 2000, 19, 1194 – 1197. For related IMes C H activation
chemistry, see: b) R. F. R. Jazzar, S. A. Macgregor, M. F. Mahon,
S. P. Richards, M. K. Whittlesey, J. Am. Chem. Soc. 2002, 124,
4944 – 4945; c) O. Torres, M. Martꢂn, E. Sola, Organometallics
2009, 28, 863 – 870.
À
[10] For previous reports of benzylic C H borylation see refer-
ence [7] and: a) J.-Y. Cho, C. N. Iverson, M. R. Smith III, J. Am.
Chem. Soc. 2000, 122, 12868 – 12869; b) T. Ishiyama, K. Ishida, J.
Takagi, N. Miyaura, Chem. Lett. 2001, 30, 1082 – 1083.
[11] For a report of arene borylation using HBpin and [(NHC)2M-
(cod)]+ complexes (M = Rh or Ir) see: G. D. Frey, C. F.
Rentzsch, D. von Preysing, T. Scherg, M. Mꢁhlhofer, E. Herdt-
weck, W. A. Herrmann, J. Organomet. Chem. 2006, 691, 5725 –
5738.
2
[15] By means of comparison, a trans JPH coupling constant of
153.5 Hz has been reported for mer-[Ir(PMe3)3H(2-py)Cl]: H. E.
Selnau, J. S. Merola, Organometallics 1993, 12, 1583 – 1591.
[16] One other example of an h2-benzyltrihydroborate complex has
been structurally characterized: S. Nlate, P. Guenot, S. Sinband-
hit, L. Toupet, C. Lapinte, V. Guerchais, Angew. Chem. 1994,
106, 2294 – 2296; Angew. Chem. Int. Ed. Engl. 1994, 33, 2218 –
2219.
.
[12] IMes·BH3 has previously been prepared from BH3 thf or
.
BH3 SMe2. Synthesis and crystal structure: a) T. Ramnial, H.
Jong, I. D. McKenzie, M. Jennings, J. A. C. Clyburne, Chem.
Commun. 2003, 1722 – 1723; 11B NMR data: b) Y. Yamaguchi, T.
Kashiwabara, K. Ogata, Y. Miura, Y. Nakamura, K. Kobayashi,
T. Ito, Chem. Commun. 2004, 2160 – 2161.
[17] The sole example of a structurally characterized IrIII borohydride
complex reported to date, features a dinuclear Ir(m:h1,h1-BH4)Ir
unit: T. M. Gilbert, F. J. Hollander, R. G. Bergman, J. Am.
Chem. Soc. 1985, 107, 3508 – 3516.
[18] A number of systems of the type [Ir(PR3)2(H)2(BH4)] have been
reported in conjunction with bulky phosphines and their thermal
decomposition pathways analyzed, although no structural data
are available: a) H. D. Empsall, E. Mentzer, B. L. Shaw, J. Chem.
Soc. Chem. Commun. 1975, 861 – 862; b) T. J. Marks, J. R. Kolb,
Chem. Rev. 1976, 76, 263 – 293.
[13] 11B resonances at À27 and À36 ppm have been reported for (2-
À
naphthyl)BH3 and (C6F5)BH3À, respectively: a) M. R. Biscoe,
R. Breslow, J. Am. Chem. Soc. 2003, 125, 12718 – 12719; 11B
signals in the range + 2 to À7 ppm have been reported for h2-
bound PhBH3À ligands: b) F.-C. Liu, J.-H. Chen, S.-C. Chen, K.-
Y. Chen, G.-H. Lee, S.-M. Peng, J. Organomet. Chem. 2005, 690,
291 – 300.
[19] E. Khaskin, P. Y. Zavalij, A. N. Vedernikov, J. Am. Chem. Soc.
2008, 130, 10088 – 10089.
[20] G. Rossetto, M. Porchia, F. Ossola, P. Zanella, R. D. Fischer, J.
Chem. Soc. Chem. Commun. 1985, 1460 – 1461.
[14] The analogous rhodium complex [Rh(IMes)(IMes’)HCl] has
previously been reported by Nolan and co-workers under similar
conditions: a) J. Huang, E. D. Stevens, S. P. Nolan, Organo-
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