On the basis of this, we hypothesized that boron-carbon
bonds could also be activated by NHC complexation.6
Here we report that stable complexes of the common NHC
bis-2,6-diisopropylphenyl imidazolylidinene (IPr) with BPh3
and BEt3 participate in base-free Suzuki-Miyaura cou-
plings.7 The findings significantly extend the potential uses
of NHC-boranes in organic synthesis; they are in effect a
new class of boron reagents amenable to Pd-catalyzed
couplings. As such, they complement boranes, boronic acids,
and organotrifluoroborates.8
Table 1. Results for sp2-sp2 Coupling: Aryl Transfer
To start, we selected complexes 1 and 2 because they were
readily available and stable (Figure 1). Triphenyl derivative
Figure 1. Structures of NHC-borane complexes used in this work
with formal charges indicated.
a Conditions: PdCl2(dppf) (6 mol %), THF-H2O, 60 °C, 1 h. b Reaction
was run with BPh3 instead of 1. c No palladium complex was added.
d Conditions: PdCl2(dppf) (6 mol %), THF-H2O, 60 °C, 8 h. e Conditions:
Pd(OAc)2 (5 mol %), XPhos (10 mol %), toluene-H2O (10:1), 80 °C, 24 h.
f Conditions: Pd(OAc)2 (10 mol %), RuPhos (20 mol %), toluene-H2O
(10:1), 80 °C, 24 h.
1 was chosen to assess aryl-aryl coupling, while triethyl
derivative 2 was selected to illustrate alkyl-aryl couplings.
The reagents were assembled by deprotonation of the
corresponding imidazolium hydrochloride salt to generate
the IPr carbene,9 followed by addition of the boranes (see
Supporting Information). Complexation of the boranes to the
carbene was evidenced by large upfield shifts in the 11B NMR
spectra (from 86 ppm in BPh3 to -0.9 ppm in 1 and from
70 ppm in BEt3 to -13.2 ppm in 2).
Clearly, the carbene plays a crucial role. In addition, no
reaction occurred when the catalyst was omitted (entry 3).
We next investigated the possibility of transferring more
than one phenyl group from 1. Reaction of 0.34 equiv of 1
with the triflate of cyclohexyl 4-hydroxybenzoate in the
absence of base did not give coupled product in high yield.
However, the yield increased to 96% when 3 equiv of K2CO3
was added (entry 4).
Iodides (entries 5-6 and 11-12), bromides (entries 7-8
and 13-14), and chlorides (entries 9-10 and 15-16) were
also suitable partners for cross coupling. For Br and Cl, we
used the preferred ligands for Suzuki-Miyaura couplings
(XPhos10 for Br and RuPhos11 for Cl). In each case, a single
phenyl group was transferred in good yield without base,
and all three phenyl groups were transferred when base was
added.
The palladium-catalyzed sp2-sp2 C-C couplings with
IPr-borane 1 are summarized in Table 1. In a typical
experiment, the triflate of cyclohexyl 4-hydroxybenzoate was
heated at 60 °C in wet THF together with 6 mol % of
PdCl2(dppf) for 1 h. Full conversion to the corresponding
biaryl was achieved (Table 1, entry 1). Wet solvents (10%
vol.) were required to ensure reproducible results. In addition,
no base was required for the reaction, in contrast to the usual
Suzuki-Miyaura conditions.
A control experiment with uncomplexed BPh3 showed that
no reaction took place under the same conditions (entry 2).
To extend the method to sp2-sp3 couplings, we probed
the transfer of ethyl groups from triethylborane complex 2
(IPr-BEt3) with triflates and halides. These results are
summarized in Table 2.
Reactions with triflates were carried out in wet toluene at
80 °C with Pd(OAc)2/XPhos (Table 2, entries 1-2, condi-
tions A). 2-Iodobenzyl heptyl ether gave the expected
coupling product in 65% yield with PdCl2(dppf) (Conditions
(6) For an NHC-activated opening of oxiranes by organoaluminum
reagents, see: Zhou, H.; Campbell, E. J.; Nguyen, S. T. Org. Lett. 2001, 3,
2229–2231.
(7) (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457–2483. (b)
Chemler, S. R.; Trauner, D.; Danishefsky, S. J. Angew. Chem., Int. Ed.
2001, 40, 4544–4568.
(8) Organotrifluoroborates are more stable than boronic acids but are
believed to hydrolyze to the boronates under the coupling conditions. See:
(a) Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 40, 275–286. (b)
Darses, S.; Geneˆt, J.-P. Chem. ReV. 2008, 108, 288–325. For another
approach using modified boronic acids, see: (c) Gillis, E. P.; Burke, M. D.
J. Am. Chem. Soc. 2007, 129, 6716–6717. (d) Knapp, D. M.; Gillis, E. P.;
Burke, M. D. J. Am. Chem. Soc. 2009, 131, 6961–6963. (e) Yamamoto,
Y.; Takizawa, M.; Yu, X.-Q.; Miyaura, N. Angew. Chem., Int. Ed. 2008,
47, 928–931.
(10) Huang, X.; Anderson, K. W.; Zim, D.; Jiang, L.; Klapars, A.;
Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 6653–6655.
(11) Milne, J. E.; Buchwald, S. L. J. Am. Chem. Soc. 2004, 126, 13028–
13032.
(9) IPr is commercially available. Nonetheless, the IPr used in this work
was prepared in our laboratories.
Org. Lett., Vol. 11, No. 21, 2009
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