Cyclic triolborates: Air- and water-stable ate complexes of organoboronic acids

Article abstract of DOI:10.1002/anie.200704162

(Chemical Equation Presented) A borate in the hand is a convenient reagent for palladium- and copper-catalyzed C-C and C-N bond-forming reactions, especially when, like the title bench-stable complexes, it demonstrates high transmetalation efficiency. Cyclic triolborates can be synthesized readily from organoboronic acids (see scheme), can be handled and stored without special precautions, and are relatively soluble in organic solvents.

Full text of DOI:10.1002/anie.200704162

Communications
DOI: 10.1002/anie.200704162
Organoboron Compounds
Cyclic Triolborates: Air- and Water-Stable Ate Complexes of
Organoboronic Acids
Yasunori Yamamoto,* Miho Takizawa, Xiao-Qiang Yu, and Norio Miyaura*
À
The C B bond of organoboronic acids is totally covalent and
therefore inert to ionic reactions; however, the nucleophilic-
ity of organic groups attached to a boron atom is enhanced
significantly by quaternarization with an anionic ligand.[1]
Thus, tetracoordinated ate complexes have been used suc-
cessfully for most nucleophilic addition and coupling reac-
tions of organoboron compounds, including metal-catalyzed
reactions of organoboronic acids.[1,2] Although the in situ
preparation of such complexes from an organoborane and a
base is most common, the method has limitations. Therefore,
attempts have been made to prepare stable ate complexes.
Air- and water-stable trifluoroborates M[RBF3] (M = K,
NR4)[3] are typical compounds that exist as pure and water-
stable crystalline materials and have advantages over boronic
acids in terms of their preparation and handling. However,
their metal-catalyzed bond-forming reactions are very slow in
the absence of a base because of the low nucleophilicity of the
organic group owing to the high electronegativity of the
fluorine atoms.[3] Sodium trihydroxyborates [RB(OH)3]Na
were synthesized recently as isolated discrete species for
cross-coupling in anhydrous solvents without the aid of an
additional base.[4] Other isolable ate complexes are 1-alkynyl
[5]
ꢀ
borates Li[RC CB(OiPr)3]
and tetraaryl borates M-
[Ar4B].[6] We describe herein novel cyclic triolborates[7] that
are exceptionally stable in air and water and more soluble in
organic solvents than potassium trifluoroborates. We also
demonstrate the high transmetalation efficiency of lithium
Scheme 1. Synthesis of potassium, lithium, and ammonium triol-
borates.
and potassium triolborates in palladium- and copper-cata-
[2]
lyzed C C and C N[8] bond-forming reactions.
B(OiPr)3 (5b) with RLi, followed by the removal of MeOH or
iPrOH through ester exchange with 2a. By using this
À
À
We developed methods for the synthesis of the cyclic
triolborates 4 and 6 (Scheme 1). The azeotropic removal of
water upon the treatment of organoboronic acids 1 with the
triol 2a gave boronic esters 3, which were converted readily
into triolborates 4 by treatment with KOH. Compounds 4
were also obtained in high yields when the esterification was
followed directly by quarternization with KOH in the same
flask without the isolation of 3. The triolborates 4 are
insoluble in toluene (the solvent used) and precipitated as
white solids in high yields. The corresponding lithium salts 6
were synthesized by the alkylation of B(OMe)3 (5a) or
À
protocol, the 2-pyridyl borate 6c, which is sensitive to B C
bond cleavage in the presence of water, was obtained in high
yield. The treatment of PhB(OH)2 with the triol 2b followed
by nBu4NOH afforded a single crystal of the ammonium salt
monohydrate[9] (NBu4)[C6H5B(OCH2)3CCH2CH3]·H2O (7)
for X-ray crystal analysis.
An ORTEP plot of 7 showed that the molecular structure
contains a bicyclo[2.2.2]octane ring that includes a tetrahedral
À
boron atom (Figure 1). The C B bond (1.60 Š) is slightly
longer than that of neutral PhB(OR)2 (R = H, alkyl; 1.56 Š)
as a result of the sp3 hybridization of the boron atom.[10] There
is some distortion of the three boatlike rings owing to
hydrogen bonding between a hydrogen atom of the water
molecule and one of the three borate oxygen atoms.
Triolborates 4 and 6 are bench-stable ate complexes that
can be handled and stored without special precautions. When
4e was dissolved in D2O/CD3OD, a 11B NMR signal charac-
teristic of tetrahedral boron species was observed at d =
6.76 ppm, and there was no change in the 1H NMR spectrum
due to any hydrolysis of 4e.
[*] Dr. Y. Yamamoto, M. Takizawa, Dr. X.-Q. Yu, Prof. Dr. N. Miyaura
Division of Chemical Process Engineering
Graduate School of Engineering, Hokkaido University
Sapporo 060-8628 (Japan)
Fax : (+81)11-706-6561
E-mail: yasuyama@eng.hokudai.ac.jp
miyaura@eng.hokudai.ac.jp
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
928
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Chemie
[19]
À
competitive hydrolytic B C bond cleavage. 2-Pyridyl- and
2-thiophenylboronic acid and their boronic ester derivatives
are typical boron compounds for which such cleavage with
water occurs during cross-coupling reactions.[19] However, the
triolborates 6b–c reacted quantitatively with bromoarenes in
anhydrous DMF (Scheme 2). The presence of CuI led to an
increase in the coupling yield with the 2-pyridyl boronate
6c.[19c]
Figure 1. An ORTEP plot of the anion of 7. Thermal ellipsoids at 50%
probability.
Such borate anions are key intermediates for transmet-
alation between organoboron compounds and complexes of
the type NiII–X,[11,12] PdII–X,[13–15] PtII–X,[16] RhI–X,[17] and
CuI–X[18] during metal-catalyzed C C or carbon–heteroatom
À
bond-forming reactions. It became apparent immediately that
these borates can be used conveniently for palladium- and
copper-catalyzed coupling reactions. The cross-coupling reac-
tion of the 4-tolyl triolborate 4e with representative bro-
moarenes was complete within 5 h at room temperature in the
presence of Pd(OAc)2. The ligand johnphos (10) was also
added for the reaction with 4-chloroacetophenone (Table 1,
entry 4) and hindered 2,6-dimethylbromobenzene (entry 14).
The use of aqueous N,N-dimethylformamide (DMF) to give a
homogeneous solution was critical for the reactions carried
out at room temperature.
Scheme 2. Coupling reactions of triolborates that are sensitive to
protodeboronation.
The copper-promoted coupling of aryl boronic acids with
heteroatoms reported by Lam et al.[20a] has found broad
[8]
À
À
À
application in the arylation of N H, O H, and S H bonds.
The simple protocol in air at room temperature was expanded
to catalytic reactions by using a reoxidant of the copper
species.[20b] The catalytic arylation of the N H bond of
À
Low yields are often observed for cross-coupling reactions
of aryl boronic acids in aqueous solvents as a result of
isopropylamine, piperidine, and benzoyl amide provided the
aryl amines 13–15 in high yields in the presence of Cu(OAc)2
(10–20 mol%) under an atmosphere of oxygen (Scheme 3).
Again, the 2-pyridyl boronate 6c underwent the desired
coupling reaction to afford the product in good yield. In both
catalytic and stoichiometric reactions, aryl boronic acids
undergo coupling with water as a side reaction to provide
phenol and diaryl ether by-products.[20,21] Such by-products
were also formed in yields of a few percent in the reactions of
the triolborates, but their formation is prevented completely
in the presence of molecular sieves.
Table 1: Biaryl cross-coupling of the triolborate 4e.[a]
In conclusion, we have described a simple and practical
synthetic approach to stable ate complexes of organoboronic
acids. As such complexes are key species in various ionic
Entry
X
FG
Catalyst
t [h]
Yield [%][b]
1
2
3
4
5
6
7
8
9
10
11
12[c]
13
14
Br
Br
Br
Cl
4-NO2
4-CF3
4-COMe
4-COMe
4-CO2Me
4-Cl
2-OMe
3-OMe
4-OMe
4-OMe
4-OH
4-NH2
4-NMe2
2,6-Me2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2/10
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2/10
5
5
5
22
5
5
5
5
5
22
5
99
93
99
90
99
99
98
98
97
89
96
92
92
80
Br
Br
Br
Br
Br
OTf
Br
Br
Br
Br
5
22
5
[a] Reaction conditions:
8 (1 mmol), 4e (1.1 mmol), Pd(OAc)2
(3 mol%), 10 (6.6 mol%, if used), DMF/H2O (5:1), 208C. [b] Yield of
the isolated product after chromatography. [c] The reaction was carried
out at 508C. FG=functional group.
À
Scheme 3. Copper-catalyzed arylation of N H bonds. M.S. = molec-
ular sieves.
Angew. Chem. Int. Ed. 2008, 47, 928 –931
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929

Communications
(4 Š; 300 mg), and copper acetate (10 mol%) in toluene (6 mL) was
stirred at room temperature for 20 h under an atmosphere of oxygen.
reactions of boron compounds, including metal-catalyzed
bond-forming reactions, studies towards their application to
other addition and coupling reactions are in progress.
Received: September 10, 2007
Published online: December 14, 2007
À
Keywords: ate complexes · borates · C N coupling ·
cross-coupling · organoboron compounds
Experimental Section
.
4 f: Phenylboronic acid (1 f; 100 mmol) and 1,1,1-tris(hydroxy-
methyl)ethane (2a; 100 mmol) were dissolved in toluene (200 mL).
Water was removed by azeotropic distillation by the Dean–Stark
method for 4 h. The solvents were then removed to give crude 3 f.
1H NMR (400 MHz, [D6]DMSO): d = 0.87 (s, 3H), 3.33 (d, J = 4.9 Hz,
2H), 3.75 (d, J = 10.5 Hz, 2H), 3.94 (d, J = 10.5 Hz, 2H), 4.85 (t, J =
4.9 Hz, 1H), 7.31–7.44 (m, 3H), 7.68 ppm (d, J = 7.8 Hz, 2H);
13C NMR (100 MHz, [D6]DMSO): d = 17.4, 36.7, 63.1, 67.7, 127.8,
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130.9, 133.7 ppm (C B is not observed); 11B NMR (128 MHz,
À
[D6]DMSO): d = 30.1ppm; MS (EI): m/z (%): 43 (14), 57 (36), 72
(39), 78 (16), 91 (14), 105 (100), 117 (55), 122 (38), 132 (43), 151 (17),
159 (15), 173 (35), 188 (16), 206 (83, M+); HRMS (EI): m/z calcd for
C11H15BO3: 206.1114; found: 206.1102. The crude 3 f and KOH
(90 mmol) were dissolved in toluene and heated at reflux for 4 h by
the Dean–Stark method. The potassium triolborate 4 f that precipi-
tated was collected by filtration, washed with acetone, and dried
under reduced pressure. 1H NMR (400 MHz, [D6]DMSO): d = 0.47 (s,
3H), 3.56 (s, 6H), 6.88–6.98 (m, 3H), 7.30 ppm (d, J = 6.8 Hz, 2H);
13C NMR (100 MHz, [D6]DMSO): d = 16.5, 73.9, 124.2, 125.7,
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132.3 ppm (C B is not observed); 11B NMR (128 MHz,
À
[D6]DMSO): d = 4.39 ppm; MS (FABÀ): m/z (%): 56 (5), 104 (100),
148 (27), 205 (10, [MÀK]À); HRMS (FABÀ): m/z calcd for
C11H14BO3À: 205.1041; found: 205.1041; elemental analysis: calcd
(%) for C11H14BKO3: C 54.12, H 5.78; found: C 52.76, H 5.65.
6c: nBuLi (110 mmol) in hexane was added to a stirred solution
of 2-bromopyridine (100 mmol) in THF (400 mL) at À788C. The
resulting mixture was stirred for 1h at À788C, then a solution of
triisopropyl borate (5b; 120 mmol) was added. The mixture was
stirred for 2 h at À788C and then allowed to warm to room
temperature. A solution of 1,1,1-tris(hydroxymethyl)ethane (2a;
100 mmol) in THF (150 mL) was then added, and the resulting
mixture was stirred for 5 h. Concentration to dryness under reduced
1
pressure gave 6c (82%). H NMR (400 MHz, [D6]DMSO): d = 0.54
(s, 3H), 3.67 (s, 6H), 7.06–7.51(m, 3H), 8.24 ppm (br s, 2H);
13C NMR (100 MHz, [D6]DMSO): d = 15.9, 73.5, 120.8, 127.8, 134.4,
146.9 ppm; 11B NMR (128 MHz, [D6]DMSO): d = 3.25 ppm.
7: A solution of nBu4NOH (10 mmol, 1M in H2O) was added to a
solution of 4 f (10 mmol) in MeOH (5 mL) at 08C, and the resulting
mixture was stirred for 2 h at room temperature. The product was
extracted with CH2Cl2, washed with water, dried over MgSO4, and
concentrated in vacuo. The solid obtained was recrystallized from
CH2Cl2/EtOAc to give 7 (98%).
Crystal data for 7: C28H54BO4N, Mr = 479.55, monoclinic, space
group C2/c, a = 22.102(15), b = 16.568(11), c = 17.512(11) Š, b =
107.53(5)8, V= 6115.4(70) Š3, Z = 8, 1calcd = 1.042 gcmÀ3, m(MoKa) =
0.669 cmÀ1; 2qmax = 55.08, 29236 reflections, 7018 unique reflections
(Rint = 0.039), reflection/parameter ratio = 19.39, R1(I>2.00s(I)) =
0.0696; R (all reflections) = 0.1568, wR2 (all reflections) = 0.1991,
goodness-of-fit indicator= 0.980, maximum shift/error in final cycle =
0.00, 1(min/max) = À0.35/0.53 eÀ ŠÀ3. CCDC 669817 contains the
supplementary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
General procedure for cross-coupling reactions: The triolborate
(1.1 mmol), the aryl halide (1.0 mmol), and palladium acetate
(3 mol%) were placed in a flask under an atmosphere of nitrogen.
DMF/H2O (5:1; 3 mL) was added, and the reaction mixture was
stirred at room temperature for 5 h.
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