One-pot preparation of hydroxylated potassium organotrifluoroborates and subsequent Jones oxidation to potassium organocarbonyltrifluoroborates

Article abstract of DOI:10.1016/j.tet.2010.12.049

Alcohol-containing potassium organotrifluoroborates as starting reagents were prepared from their corresponding dibromobenzenes through a sequential one-pot reaction. The oxidation reactions of these substrates, which were carried out using 3.0 equiv of 8

Full text of DOI:10.1016/j.tet.2010.12.049

Tetrahedron 67 (2011) 1062e1070
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One-pot preparation of hydroxylated potassium organotrifluoroborates and
subsequent Jones oxidation to potassium organocarbonyltrifluoroborates
,
,b,
Dong-Su Kim a, Krishnavenu Bolla a b, Seokjoon Lee c, Jungyeob Ham a
*
a Marine Chemomics Laboratory, Natural Products Research Center, Korea Institute of Science and Technology, Gangneung 210-340, South Korea
b Department of Medicinal and Pharmaceutical Chemistry, University of Science & Technology, Daejeon 305-350, South Korea
c College of Medicine, Kwandong University, Gangneung 210-701, South Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Alcohol-containing potassium organotrifluoroborates as starting reagents were prepared from their
corresponding dibromobenzenes through a sequential one-pot reaction. The oxidation reactions of these
substrates, which were carried out using 3.0 equiv of 8 N Jones reagent in acetone at 0 ꢀC, provided a high
yield of the desired carbonyl-functionalized compounds. In addition, the cross-coupling reactions of
these organocarbonyltrifluoroborates were successfully performed in the presence of 3 mol % of Pd
(PPh3)4 catalyst at 100 ꢀC.
Received 8 November 2010
Received in revised form 15 December 2010
Accepted 15 December 2010
Available online 21 December 2010
Keywords:
One-pot reaction
Ó 2010 Elsevier Ltd. All rights reserved.
Hydroxylated potassium
organotrifluoroborate
Jones oxidation
Potassium organocarbonyltrifluoroborate
SuzukieMiyaura cross-coupling reaction
1. Introduction
may be difficult to prepare by conventional syntheses of organo-
boron reagents.3bed,4
Carbonyl-substituted compounds have attracted much atten-
tion because of their applications as versatile functional groups in
synthetic organic chemistry.1 Thus, a number of methods have been
developed for the formation of carbonyl moieties on various
pharmaceutical, biological, and industrial compounds. Among
them, the method used most widely involves the oxidation of
primary and secondary alcohols to the corresponding carbonyl
compounds.2 For example, the selective oxidative transformation of
alcohols has been performed routinely using oxidizing agents, such
as oxochromium (VI) reagents (PCC, Jones, and Collins reagents),
permanganate, active manganese dioxide, activated DMSO with
TFAA or oxalyl chloride (Swern oxidation), DessMartin periodinane
(DMP), and 2-iodoxybenzoic acid (IBX).2
On the other hand, organotrifluoroborate salts have been rec-
ognized as useful synthetic reagents in the SuzukieMiyaura cross-
coupling reaction.3 Recently, methods for the direct functionaliza-
tion of organotrifluoroborates, using their property of inertness
under various reaction conditions, has been developed and used for
the preparation of more complex organotrifluoroborates, which
In 2006, Molander and Petrillo first reported the direct oxidation
of hydroxylated organotrifluoroborates using tetra-n-propy-
lammonium perruthenate (TPAP), DMP, IBX, and the Swern oxida-
tion.5 However, depending on the counterions (potassium or tetra-
n-butylammonium (TBA)) of organotrifluoroborates, this procedure
requires long reaction times, high reaction temperatures, and excess
oxidizing reagents to obtain satisfactory results. Moreover, pure al-
dehyde-functionalized potassium organotrifluoroborates could not
be prepared from the corresponding primary alcohol-containing
organotrifluoroborates because of unisolated IBX byproducts.
Therefore, the oxidative transformation of primary and secondary
alcohol-containing organotrifluoroborates using a cheap and easily
available oxidizing reagent would be very useful for the preparation
of various carbonyl-functionalized organoboron compounds.
In a recent paper, Burke and Gillis reported that benzoic acid-
containing MIDA (N-methyliminodiacetic acid) boronate could be
prepared from the corresponding primary alcohol-substituted
MIDA boronate via Jones oxidation.6 However, boronic acid, pinacol
boronate ester, 1,8-diaminonaphtalene-masked boronamide, tetra-
n-butylammoniumtrifluoroborate, and N-methyldiethanolamine
boronate were all decomposed under the same conditions. More-
over, in their paper, Jones oxidation using potassium organo-
trifluoroborate as a starting material has not been reported.
* Corresponding author. Tel.: þ82 33 650 3502; fax: þ82 33 650 3629; e-mail
address: ham0606@kist.re.kr (J. Ham).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.12.049

D.-S. Kim et al. / Tetrahedron 67 (2011) 1062e1070
1063
Table 1
As part of the study to prepare functionalized potassium orga-
notrifluoroborates for use as new coupling reagents in the Suzu-
kieMiyaura cross-coupling reaction, we discovered that potassium
organocarbonyltrifluoroborates are readily obtained from the
treatment of primary or secondary alcohol-containing organo-
trifluoroborates with Jones reagent. The Jones oxidation is generally
performed in acetone as a solvent in which potassium organo-
trifluoroborate salts are soluble. Thus, potassium counterion salts
can be used immediately without the need for converting them into
TBA salts. Also, we confirmed that these hydroxylated potassium
organotrifluoroborates can tolerate under Jones oxidation condi-
tions contrary to other organoboron derivatives.
Sequential one-pot preparation of secondary alcohol-substituted potassium orga-
notrifluoroborates from dibromobenzenes and aldehydes
OH
Br
One-pot reaction
Br
R
BF3K
13 examples
2 mmol scale
i) t-BuLi (2 equiv) / -78 oC / THF
R
CHO
ii)
v) 1 N KHF2
O Li
O Li
R
iii) t-BuLi (2 equiv) / -78 oC
Li
R
i
iv) B(-O Pr)3 / -78 oC to rt
Br
B(-OiPr)3
In this paper, we report a facile one-pot synthesis of secondary
alcohol-containing organotrifluoroborates from their correspond-
ing dibromobenzenes, followed by the convenient preparation of
potassium organocarbonyltrifluoroborates via Jones oxidation.
Entry
1
Aldehyde
HOeRBF3K
Isolated yield (%)
83
2. Results and discussion
2
3
4
66
As a starting point, we tested two reactions for the preparation
of alcohol-containing organotrifluoroborates using potassium 4-
bromophenyltrifluoroborate (Scheme 1, Eq. 1) or potassium
(4-formylphenyl)trifluoroborate (Scheme 1, Eq. 2).
dec
87
OH
i) n-BuLi / THF
Br
-78 oC / 1 h
(1)
R
O
ii)
BF3K
BF3K
H
R
5
68
65
83
76
78
75
46
52
R = H, F, OMe
iii) 1 N KHF2
OH
i) t-BuLi / THF
Br
-78 oC / 1 h
6
(
2)
R
R
O
ii)
BF3K
H
R = H, OMe
BF3K
iii) 1 N KHF2
7
Scheme 1. General preparation of secondary alcohol-substituted potassium
organotrifluoroborates.
8
Although the desired compounds were obtained in the lith-
iumehalogen exchange reaction using potassium 4-bromophe-
nyltrifluoroborate as a starting material (Scheme 1, Eq. 1),7 all of the
products were contaminated with potassium phenyltrifluoroborate
as a byproduct, which is not separable (data not shown). When
potassium (4-formylphenyl)trifluoroborate was used as the elec-
trophile (Scheme 1, Eq. 2), the target products were produced in
much lower yields because of the poor solubility of the electrophile,
i.e., trifluoroborate salt, in THF (data not shown). Thus, we discov-
ered the one-pot, sequential reaction for the preparation of various
secondary alcohol-containing organotrifluoroborates from the
corresponding dibromobenzenes and aldehydes via a lithiumehal-
ogen exchange reaction with t-BuLi (Table 1).
9
10
11
12
As expected, when dibromobenzenes were used as starting
materials, the yields for the desired products ranged from good to
excellent, except when 1,2-dibromobenzene was used (Table 1,
entries 1e3). Aliphatic aldehydes as well as benzaldehydes reacted
readily to give good yields of corresponding secondary alcohol-
containing organotrifluoroborates (Table 1, entries 8e10). However,
when conjugated and heterocyclic aldehydes were used as elec-
trophiles, the yields of the target compounds decreased (Table 1,
entries 11e13).
Next, we investigated the oxidation of various hydroxylated
potassium organotrifluoroborates using 8 N Jones reagent. The
various reaction conditions explored are summarized in Table 2.
When compound 14 was treated with 1.0 equiv of 8 N Jones reagent
13
62
at 0 ꢀC for 10 min followed by solvent removal in the absence of
a base, product 18 completely decomposed because of residual
sulfuric acid in the reaction mixture (Table 2, entry 1). Using K2CO3
as a neutralizing agent, we were able to prepare the oxidized
product 18 (Table 2, entries 2e5). When 3.0 equiv of Jones reagent

1064
D.-S. Kim et al. / Tetrahedron 67 (2011) 1062e1070
Table 2
As expected, all of the carbonyl compounds were quickly pre-
pared from the corresponding alcohols. The yields of the product
increased in the order of para->meta->ortho-substituted tri-
fluoroborates (Table 3, entries 1e5). Interestingly, the presence of
strong electron-withdrawing group, such as fluorine in the aro-
matic ring of benzyl alcohol moieties led to the increased yields of
oxidized products (Table 3, entries 6e8). Further, the reactions of
aliphatic alcohol-containing trifluoroborates produced good yields
of their corresponding products (Table 3, entries 10e12). However,
the oxidations of allylic- (13) and furanyl-substituted (15) alcohols
were not successful under the same reaction conditions (Table 3,
entries 13 and 15). Interestingly, although we could not obtain the
aldehyde product under the optimized reaction conditions when
potassium 4-(2-hydroxyethyl)phenyltrifluoroborate8 was used as
a starting material, we obtained a moderate yield of the carboxylic
acid-containing product 33 in the presence of 9.0 equiv Jones re-
agent at 0 ꢀC within 30 min (Table 3, entry 16).
Optimization of Jones oxidation for the preparation of potassium (4-formylphenyl)
trifluoroborate (18)
i) acetone 2 mL / 0 o
C
OH
O
8 N Jones reagent
H
ii) quenched with K2CO3
BF3K
0.2 mmol scale (14)
BF3K
(18)
Entry
Equiv of 8 N
Equiv of
Time
Conversion
yield (%)b
a
Jones reagent
K2CO3
(min)
1
2
3
4
5
6
1.0
1.0
1.0
2.0
2.0
3.0
None
1.0
1.0
2.0
2.0
10
10
30
10
30
10
dec
53
48
81
82
3.0
100 (77)c
a
Neutralizing agent.
b
The conversion yield estimated on the basis of 1H NMR data of crude reaction
Finally, we focused our attention on the optimization of cross-
coupling reaction conditions using various potassium organo-
carbonyltrifluoroborates (Table 4).
mixture (4.49 ppm of 14 and 9.94 ppm of 18 in acetone-d6).
c
Isolated yield, average of three runs.
In the study of reaction solvents, 20% aqueous 1,4-dioxane was
confirmed to be the optimal solvent, whereas methanol9 and es-
pecially 20% aqueous toluene showed lower isolated yields during
the same reaction times (Table 4, entries 1, 2, 6, and 7). A number of
different Pd catalysts, such as Pd(OAc)2/PPh3, Pd(OAc)2/XPhos,
PdCl2(dppf)$CH2Cl2, and Pd(PPh3)4, were screened for their effec-
tiveness in accomplishing the SuzukieMiyaura cross-coupling re-
action (Table 4, entries 3e6), and it was found that Pd(PPh3)4
provided the highest isolated yield (Table 4, entry 6). By changing
the base from Cs2CO3 to K2CO3, the product yield declined (Table 4,
entry 8). Although attempts to vary the heating source from an oil
bath to a microwave did not improve the reaction yield (Table 4,
was used, the starting material was completely converted to the
desired compound 18 (Table 2, entry 6).
However, increasing the reaction times under the same reaction
conditions did not improve the conversion yields (Table 2, entries 3
and 5). On the other hand, over-oxidized byproducts, such as po-
tassium (4-carboxyphenyl)trifluoroborate were not generated.
Using the optimized conditions determined in the preparation
of 18 (Table 2, entry 6), we carried out the Jones oxidation of various
primary and secondary alcohol-containing potassium organo-
trifluoroborates, and the results are summarized in Table 3.
Table 3
Preparation of carbonyl-containing potassium organotrifluoroborates via Jones oxidation
i) 8 N Jones reagent (3.0 equiv)
acetone (10 mL) / 0 oC / 10 min
HO
O
R
ii) quenched with K2CO3 (3.0 equiv)
R
BF3K
BF3K
16 examples
1.0 mmol scale
Entry
1
AldehydeeBF3K
Product
Isolated yield (%)
79
2
73
3
4
65
67
5
6
61
87
7
82

D.-S. Kim et al. / Tetrahedron 67 (2011) 1062e1070
1065
Table 3 (continued )
Entry
AldehydeeBF3K
Product
Isolated yield (%)
8
9
71
68
10
67
11
12
65
89
13
14
dec
87
15
dec
53
16a
a
Reaction was performed with 9.0 equiv of 8 N Jones reagent at 0 ꢀC for 30 min.
entry 9), a satisfactory cross-coupling product yield of 93% could be
achieved by increasing the reaction temperature from 80 ꢀC to
100 ꢀC in an oil bath (Table 4, entry 10).
The coupling reactions led to the corresponding products in
good to excellent yields. When 4-bromobenzene containing an
electron-withdrawing group (CN) was used following the same
conditions, a high yield (92%) was obtained (Table 5, entry 1). Also,
the coupling reaction using meta-substituted organo-
carbonyltrifluoroborate 22 gave the desired product in 73% yield
(Table 5, entry 4). However, attempts to react 4-bromobenzonitrile
with electron poor trifluoroborate 23 resulted in low yield of the
coupled product (Table 5, entry 5).
Table 4
Optimization of cross-coupling reaction conditionsa
Br
O
(0.1 mmol)
O
CN
3 mol % of Pd cat.
(6 mol % of ligand)
Cs2CO3 (3.0 equiv)
aq 1,4-dioxane / 80 oC
MeO
MeO
BF3K
34
21
(
)
(
)
CN
0.1 mmol scale
3. Conclusion
Entry
Pd catalyst/ligand
Time (h)
Isolated yield (%)
In summary, we have developed a facile one-pot synthesis of
secondary alcohol-containing organotrifluoroborates from their
corresponding dibromobenzenes and successfully prepared novel
potassium organocarbonyltrifluoroborates from the hydroxylated
trifluoroborates via the Jones oxidation. Moreover, we found that
the potassium organotrifluoroborates canwithstand vigorous acidic
and oxidative conditions. The SuzukieMiyaura cross-coupling re-
action with these compounds occurs in high yield with carbonyl
group tolerance. Further applications and developments of orga-
nocarbonyltrifluoroborates are currently under investigation.
1
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2/PPh3
Pd(OAc)2/XPhos
PdCl2(dppf)$CH2Cl2
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
2
2
2
2
2
2
2
2
1
1
65
42
67
74
73
83
32
67
73
93
2b
3
4
5
6
7c
8d
9e
10f
a
All reactions were performed on a 0.1 mmol scale in 1.0 mL of 20% aqueous 1,4-
dioxane in an oil bath.
b
Reaction solvent was MeOH.9
Reaction solvent was 20% aqueous toluene.
4. Experimental
c
d
K2CO3 (3.0 equiv) as a base was used instead of Cs2CO3.
4.1. General considerations
e
Initial microwave irradiation of 80 W was used at 80 ꢀC for 1 h.
f
Reaction temperature was 100 ꢀC in an oil bath.
1H, 13C, and 19F NMR spectra were recorded at 400, 100, and
376 MHz, respectively. 19F NMR chemical shifts were referenced to
external CFCl3 (0.0 ppm). 11B NMR spectra at 128 MHz were
Under optimal reaction conditions, we also examined the
SuzukieMiyaura cross-coupling reaction of various organo-
carbonyltrifluoroborates with aryl and alkenyl bromides, and the
results are presented in Table 5.
obtained on
a spectrometer equipped with the appropriate
decoupling accessories. All 11B NMR chemical shifts were

1066
D.-S. Kim et al. / Tetrahedron 67 (2011) 1062e1070
Table 5
Cross-coupling reactions
R2 Br (0.2 mmol)
3 mol % of Pd(TPP)4
O
O
1R
1R
BF3K
R2
3.0 equiv of C CO3
s2
aq 1,4-dioxane / 1 h
100 oC / oil bath
7 examples
0.2 mmol scale
Entry
1
R1-BF3K
R2-Br
Product
Isolated
yield (%)
21
92
74
2
3
21
21
84
4
5
22
23
73
72
6
7
27
31
81
87
referenced to external BF3$OEt2 (0.0 ppm) with a negative sign
indicating an up-field shift. Mass spectra of potassium organo-
trifluoroborates were performed using negative FAB at the mass
spectrometry facilities at the Seoul National University. FTIR spectra
were recorded on ATR plate. 1,4-Dioxane and H2O were distilled
and degassed under argon. Commercially available reagents were
used without further purification.
for 3 h. The residual solid was dissolved in dry acetone (20 mL), and
the insoluble salts were filtered off through Celite. The solvent was
concentrated on a rotary evaporator and the addition of diethyl
ether (8.0 mL) led to precipitation of the product. The product was
filtered, collected, and dried in vacuum to obtain the desired pure
compound 1 as an ivory solid (532 mg, 83% yield). Mp¼68e70 ꢀC.
1H NMR (400 MHz, acetone-d6)
d
7.42 (d, 2H, J¼8.0 Hz), 7.30 (d, 2H,
J¼8.8 Hz), 7.14 (d, 2H, J¼7.6 Hz), 6.84 (d, 2H, J¼8.8 Hz), 5.68 (s, 1H),
4.2. Preparation of secondary alcohol-substituted potassium
organotrifluoroborates
4.37 (s, 1H), 3.76 (s, 3H). 13C NMR (100 MHz, acetone-d6)
d
159.4,
143.1, 139.3, 132.2, 128.5, 125.4, 114.0, 76.2, 55.4. 19F NMR (376 MHz,
acetone-d6)
d
ꢁ142.4. 11B NMR (128 MHz, acetone-d6)
d 3.62. FTIR
4.2.1. Potassium
4-(hydroxy(4-methoxyphenyl)methyl)phenyl-
(ATR) n 3418, 3069, 3010, 2950, 2933, 2837, 1610, 1509, 1216, 1170,
trifluoroborate (1). To a solution of 1,4-dibromobenzene (472 mg,
2.0 mmol) in THF (12 mL) was slowly added t-BuLi (1.7 M solution
in pentane, 2.4 mL, 4.0 mmol) at ꢁ78 ꢀC under N2. After 1 h, 4-
methoxybenzaldehyde (300 mg, 2.2 mmol) was slowly added and
then the reaction mixture was slowly warmed to 0 ꢀC for 30 min.
The reaction mixture was repeatedly cooled to ꢁ78 ꢀC and then t-
BuLi (1.7 M solution in pentane, 2.4 mL, 4.0 mmol) was slowly
added. After 30 min, triisopropyl borate (376 mg, 2 mmol) was
added and the reaction mixture was slowly warmed to room
temperature for 40 min. After the reaction was completed, 1 N KHF2
(6.0 mL, 6.0 mmol) was added at room temperature. After stirring
for 20 min, the suspension was concentrated and dried in vacuum
953, 802, 579 cmꢁ1. HRFABMS: m/z calcd for C14H13BF3O2 [MꢁKþ]ꢁ
281.0961, found 281.0965.
4.2.2. Potassium 3-(hydroxy(4-methoxyphenyl)methyl)phenyltri-
fluoroborate (2). The title compound was obtained as an ivory
solid (423 mg, 66% yield) using 1,3-dibromobenzene (472 mg,
2.0 mmol) and 4-methoxybenzaldehyde (300 mg, 2.2 mmol).
Mp¼167e170 ꢀC. 1H NMR (400 MHz, acetone-d6)
d 7.52 (s, 1H),
7.34 (d, 1H, J¼7.6 Hz), 7.31 (d, 2H, J¼8.4 Hz), 7.10 (dt, 1H, J¼5.6,
2.0 Hz), 7.05 (t, 1H, J¼7.2 Hz), 6.83 (d, 2H, J¼8.8 Hz), 5.68 (d, 1H,
J¼4.0 Hz), 4.36 (d, 1H, J¼4.0 Hz), 3.75 (s, 3H). 13C NMR (100 MHz,
acetone-d6)
d 158.4, 143.0, 138.5130.3, 130.0, 127.5, 125.9, 123.3,

D.-S. Kim et al. / Tetrahedron 67 (2011) 1062e1070
1067
113.0, 75.8, 54.5. 19F NMR (376 MHz, acetone-d6)
NMR (128 MHz, acetone-d6) 3.75. FTIR (ATR)
d
ꢁ142.2. 11B
3.78 (br s, 1H), 1.67 (m, 2H), 1.42 (m, 1H), 1.29 (m, 5H), 0.87 (t, 3H,
d
n
3526, 3004,
J¼6.8 Hz). 13C NMR (100 MHz, acetone-d6)
d
142.7, 131.3, 123.9, 73.9,
ꢁ142.2.
11B NMR (128 MHz, acetone-d6)
d 3.78. FTIR (ATR) n 3559, 3399,
2933, 2835, 1610, 1510, 1234, 1156, 989, 902, 799, 713, 604 cmꢁ1
.
39.6, 31.8, 25.5, 22.4, 13.4. 19F NMR (376 MHz, acetone-d6)
d
HRFABMS: m/z calcd for C14H13BF3O2 [MꢁKþ]ꢁ 281.0961, found
281.0965.
3014, 2957, 2928, 2858, 1608, 1228, 964, 914, 826, 745, 576 cmꢁ1
.
HRFABMS: m/z calcd for C12H17BF3O [MꢁKþ]ꢁ 245.1325, found
4.2.3. Potassium 4-((4-fluorophenyl)hydroxymethyl)phenyltrifluoro-
borate (4). The title compound was obtained as a white solid
(536 mg, 87% yield) using 1,4-dibromobenzene (472 mg, 2.0 mmol)
and 4-fluorobenzaldehyde (273 mg, 2.2 mmol). Mp¼228e231 ꢀC. 1H
245.1325.
4.2.8. Potassium 4-(cyclohexyl(hydroxyl)methyl)phenyltrifluoroborate
(9)7. The title compound was obtained as a white solid (462 mg,
78% yield) using 1,4-dibromobenzene (472 mg, 2.0 mmol) and
cyclohexanecarboxaldehyde (247 mg, 2.2 mmol). Mp>250 ꢀC. 1H
NMR (400 MHz, acetone-d6)
d
7.43 (m, 4H), 7.15 (d, 2H, J¼8.0 Hz),
7.04 (t, 2H, J¼8.8 Hz), 5.74 (d,1H, J¼4.0 Hz), 4.62 (d,1H, J¼4.0 Hz). 13C
NMR (100 MHz, acetone-d6)
d
161.5 (d, J¼240.6 Hz), 142.4 (d,
NMR (400 MHz, acetone-d6)
d
7.43 (d, 2H, J¼8.0 Hz), 7.06 (d, 2H,
J¼2.9 Hz), 141.8, 131.4, 128.1 (d, J¼7.9 Hz), 124.6, 114.3 (d, J¼21.2 Hz),
J¼7.6 Hz), 4.22 (d, 1H, J¼7.2 Hz), 3.66 (br s, 1H), 2.02 (m, 1H), 1.73
75.1. 19F NMR (376 MHz, acetone-d6)
d
ꢁ118.5, ꢁ142.4. 11B NMR
(m,1H),1.62 (m, 2H), 1.53 (m,1H),1.40 (m, 1H),1.18 (m, 3H),1.05 (m,
(128 MHz, acetone-d6)
d
3.72. FTIR (ATR)
n
3527, 3331, 3073, 3029,
1H), 0.92 (m, 1H). 13C NMR (100 MHz, acetone-d6)
d 142.2, 132.0,
2884, 1604, 1506, 1398,1217, 954, 818, 775, 566 cmꢁ1. HRFABMS: m/z
calcd for C13H10BF4O [MꢁKþ]ꢁ 269.0761, found 269.0758.
125.6, 79.5, 46.3, 27.4, 27.0, 26.9. 19F NMR (376 MHz, acetone-d6)
d
ꢁ142.2. 11B NMR (128 MHz, acetone-d6)
d 3.76. FTIR (ATR) n 3342,
3017, 2921, 2850, 1224, 957, 816, 588 cmꢁ1. HRFABMS: m/z calcd for
C13H17BF3O [MꢁKþ]ꢁ 257.1325, found 257.1320.
4.2.4. Potassium 4-((3-fluorophenyl)hydroxymethyl)phenyltrifluoro-
borate (5). The title compound was obtained as an ivory solid
(419 mg, 68% yield) using 1,4-dibromobenzene (472 mg, 2.0 mmol)
and 3-fluorobenzaldehyde (273 mg, 2.2 mmol). Mp¼228e231 ꢀC. 1H
4.2.9. Potassium 4-(1-hydroxy-3-methylbutyl)phenyltrifluoroborate
(10). The title compound was obtained as awhite solid (405 mg, 75%
yield) using 1,4-dibromobenzene (472 mg, 2.0 mmol) and iso-
valeraldehyde (190 mg, 2.2 mmol). Mp¼238e241 ꢀC. 1H NMR
NMR (400 MHz, acetone-d6)
d
7.44 (d, 2H, J¼8.0 Hz), 7.30 (m, 1H),
7.20 (m, 2H), 7.15 (d, 2H, J¼7.6 Hz), 6.93 (m, 1H), 5.74 (s, 1H). 13C NMR
(100 MHz, acetone-d6)
d
163.6 (d, J¼242.0 Hz), 150.3 (d, J¼24.0 Hz),
(400 MHz, acetone-d6)
d
7.43 (d, 2H, J¼8.0 Hz), 7.11 (d, 2H, J¼7.6 Hz),
142.2, 132.4, 130.4 (d, J¼8.0 Hz), 125.5, 123.1 (d, J¼2.0), 113.8 (d,
4.61 (m,1H), 3.67 (d,1H, J¼4.0 Hz),1.70 (m, 2H),1.43 (m,1H), 0.93 (d,
J¼3.0 Hz), 113.6 (d, J¼4.0 Hz), 75.9. 19F NMR (376 MHz, acetone-d6)
6H, J¼6.4 Hz). 13C NMR (100 MHz, acetone-d6)
d
143.0, 131.3, 123.8,
ꢁ142.3.
11B NMR (128 MHz, acetone-d6)
d 3.81. FTIR (ATR) n 3554, 3391, 3017,
d
ꢁ115.5, ꢁ142.4. 11B NMR (128 MHz, acetone-d6)
d
3.77. FTIR (ATR)
n
72.0, 49.0, 24.5, 22.6, 21.8. 19F NMR (376 MHz, acetone-d6)
d
3542, 3382, 3074, 2879, 1701, 1589, 1216, 953, 762, 702 cmꢁ1
.
HRFABMS: m/z calcd for C13H10BF4O [MꢁKþ]ꢁ 269.0761, found
2956, 2926, 2870, 1608, 1220, 957, 824, 575 cmꢁ1. HRFABMS: m/z
calcd for C11H15BF3O [MꢁKþ]ꢁ 231.1168, found 231.1165.
269.0764.
4.2.5. Potassium 4-((2-fluorophenyl)hydroxymethyl)phenyltrifluoro-
borate (6). The title compound was obtained as an ivory solid
(401 mg, 65% yield) using 1,4-dibromobenzene (472 mg, 2.0 mmol)
and 2-fluorobenzaldehyde (273 mg, 2.2 mmol). Mp¼229e232 ꢀC.
4.2.10. Potassium 4-(1-hydroxy-3,7-dimethylocta-2,6-dienyl)phenyl-
trifluoroborate (11). The title compound was obtained as an ivory
solid (309 mg, 46% yield) using 1,4-dibromobenzene (472 mg,
2.0 mmol) and citral (335 mg, 2.2 mmol). Mp¼122e124 ꢀC. 1H NMR
1H NMR (400 MHz, acetone-d6)
d
7.67 (td, 1H, J¼7.6, 1.6 Hz), 7.42 (d,
(400 MHz, acetone-d6)
d
7.44 (d, 2H, J¼7.6 Hz), 7.19 (d, 2H, J¼7.6 Hz),
2H, J¼8.0 Hz), 7.25 (m, 1H), 7.17 (td, 1H, J¼7.6, 1.2 Hz), 7.16 (d, 2H,
7.56 (d, 1H, J¼16.0 Hz), 6.26 (d, 1H, J¼16.0 Hz), 5.15 (m, 1H), 3.53 (s,
J¼7.6 Hz), 7.01 (ddd, 1H, J¼10.8, 8.4, 1.2 Hz), 6.04 (d, 1H, J¼3.2 Hz),
1H), 2.09 (m, 2H), 1.65 (s, 3H), 1.62 (m, 2H), 1.59 (s, 3H), 1.34 (s, 3H).
4.65 (d, 1H, J¼4.0 Hz). 13C NMR (100 MHz, acetone-d6)
d
159.6 (d,
13C NMR (100 MHz, acetone-d6)
d 134.8, 134.3, 131.8, 130.4, 127.5,
J¼242.7 Hz), 140.6, 133.2 (d, J¼13.5 Hz), 131.4, 128.1 (d, J¼8.2 Hz),
127.8 (d, J¼4.4 Hz), 124.5, 123.9 (d, J¼3.3 Hz), 114.6 (d, J¼21.9 Hz),
125.0, 124.4, 71.8, 43.1, 27.9, 24.9, 22.7, 16.7. 19F NMR (376 MHz,
acetone-d6)
d
ꢁ142.4. 11B NMR (128 MHz, acetone-d6)
d 3.75. FTIR
69.1. 19F NMR (376 MHz, acetone-d6)
d
ꢁ120.1, ꢁ142.4. 11B NMR
(ATR) n .
3542, 3401, 3017, 2968, 2925, 1606, 1217, 955, 809 cmꢁ1
(128 MHz, acetone-d6)
d
3.56. FTIR (ATR)
n
3525, 3073, 3045, 2921,
HRFABMS: m/z calcd for C16H21BF3O [MꢁKþ]ꢁ 297.1638, found
1613, 1486, 1215, 954, 754 cmꢁ1
.
HRFABMS: m/z calcd for
297.1640.
C13H10BF4O [MꢁKþ]ꢁ 269.0761, found 269.0765.
4.2.11. Potassium 4-(hydroxy(thiophen-2-yl)methyl)phenyltrifluoro-
borate (12). The title compound was obtained as a yellow solid
(308 mg, 52% yield) using 1,4-dibromobenzene (472 mg, 2.0 mmol)
and 2-thiophenecarboxaldehyde (247 mg, 2.2 mmol) at ꢁ78 ꢀC.
4.2.6. Potassium 4-((2,3-dimethoxyphenyl)hydroxymethyl)phenyl-
trifluoroborate (7). The title compound was obtained as a white
solid (581 mg, 83% yield) using 1,4-dibromobenzene (472 mg,
2.0 mmol) and 2,3-dimethoxybenzaldehyde (366 mg, 2.2 mmol).
Mp¼219 ꢀC (dec). 1H NMR (400 MHz, acetone-d6)
d 7.46 (d, 2H,
Mp¼207 ꢀC. 1H NMR (400 MHz, acetone-d6)
d
7.42 (d, 2H, J¼8.0 Hz),
J¼8.0 Hz), 7.28 (dd, 1H, J¼4.8, 1.2 Hz), 7.21 (d, 2H, J¼8.0 Hz), 6.90
(dd, 1H, J¼5.2, 3.6 Hz), 6.83 (dt, 1H, J¼3.6, 1.2 Hz), 5.94 (d, 1H,
J¼4.4 Hz), 4.83 (d, 1H, J¼4.0 Hz). 13C NMR (100 MHz, acetone-d6)
7.16 (m, 3H), 7.03 (t, 1H, J¼8.0 Hz), 6.89 (dd, 1H, J¼8.0, 1.2 Hz), 6.07
(s, 1H), 3.82 (s, 3H), 3.61 (s, 3H). 13C NMR (100 MHz, acetone-d6)
d
153.4, 146.9, 142.9, 140.5, 132.0, 125.7, 124.2, 120.1, 111.9, 71.0, 60.4,
d
151.1, 141.2, 131.4, 126.0, 124.3, 124.0, 123.5, 72.3. 19F NMR
56.0. 19F NMR (376 MHz, acetone-d6)
d
ꢁ142.2. 11B NMR (128 MHz,
(376 MHz, acetone-d6)
d
ꢁ142.5. 11B NMR (128 MHz, acetone-d6)
acetone-d6)
d
3.76. FTIR (ATR)
n
3500, 3073, 3014, 2939, 2836, 1586,
d 3.75. FTIR (ATR) n 3619, 3520, 3100, 3069, 3021, 2879, 1608, 1221,
1478, 1214, 953, 759 cmꢁ1. HRFABMS: m/z calcd for C15H15BF3O3
[MꢁKþ]ꢁ 311.1066, found 311.1067.
955, 707, 602 cmꢁ1. HRFABMS: m/z calcd for C11H9BF3OS [MꢁKþ]ꢁ
257.0419, found 257.0421.
4.2.7. Potassium 4-(1-hydroxyhexyl)phenyltrifluoroborate (8). The
title compound was obtained as a white solid (432 mg, 76% yield)
using 1,4-dibromobenzene (472 mg, 2.0 mmol) and hexanal
(220 mg, 2.2 mmol). Mp>250 ꢀC. 1H NMR (400 MHz, acetone-d6)
4.2.12. Potassium 4-(furan-2-yl(hydroxy)methyl)phenyltrifluoroborate
(13). The title compound was obtained as a yellow solid (347 mg,
62% yield) using 1,4-dibromobenzene (472 mg, 2.0 mmol) and 2-
furaldehyde (211 mg, 2.2 mmol) at ꢁ78 ꢀC. Mp¼116e120 ꢀC. 1H
d
7.43 (d, 2H, J¼7.6 Hz), 7.10 (d, 2H, J¼7.6 Hz), 4.52 (t, 1H, J¼6.8 Hz),
NMR (400 MHz, acetone-d6)
d
7.47 (d, 2H, J¼8.0 Hz), 7.41 (dd, 1H,

1068
D.-S. Kim et al. / Tetrahedron 67 (2011) 1062e1070
J¼2.0, 0.8 Hz), 7.19 (d, 2H, J¼8.0 Hz), 6.32 (dd, 1H, J¼3.2, 1.6 Hz), 6.11
(dt, 1H, J¼3.2, 0.8 Hz), 5.68 (d, 1H, J¼4.0 Hz), 4.54 (d, 1H, J¼4.4 Hz).
131.1, 127.7,113.3, 54.9. 19F NMR (376 MHz, acetone-d6)
d
ꢁ143.4. 11
B
NMR (128 MHz, acetone-d6)
d 3.35. FTIR (ATR) n 2974, 2903, 2840,
13C NMR (100 MHz, acetone-d6)
d
158.5, 141.5, 138.9, 131.3, 124.6,
1649, 1595, 1318, 1260, 952, 852, 767, 686, 600 cmꢁ1. HRFABMS: m/z
calcd for C14H11BF3O2 [MꢁKþ]ꢁ 279.0804, found 279.0810.
109.8, 105.8, 70.1. 19F NMR (376 MHz, acetone-d6)
d
ꢁ142.4. 11B NMR
(128 MHz, acetone-d6)
d 3.67. FTIR (ATR) n 3518, 3151, 3120, 3072,
3021, 2871, 1610,1397, 1216, 955, 819, 741, 597 cmꢁ1. HRFABMS: m/z
calcd for C11H9BF3O2 [MꢁKþ]ꢁ 241.0648, found 241.0651.
4.4.5. Potassium 3-(4-methoxybenzoyl)phenyltrifluoroborate (22).
The title compound was obtained as a yellow solid (194 mg, 61%
yield) using potassium 3-(hydroxy(4-methoxyphenyl)methyl)phe-
nyltrifluoroborate (2, 320 mg, 1.0 mmol). Mp¼164e168 ꢀC. 1H NMR
4.3. Preparation of 8 N Jones reagent2b
(400 MHz, acetone-d6)
d
7.91 (s, 1H), 7.80 (d, 2H, J¼8.8 Hz), 7.74 (d,
Chromium(VI) oxide 10 g (0.1 mol) was dissolved in water
(15 mL), and concentrated sulfuric acid (8.6 mL) was slowly added
in an ice water bath. The mixture solution was diluted with water
up to 37.5 mL.
1H, J¼6.4 Hz), 7.47 (d, 1H, J¼7.2 Hz), 7.27 (t, 1H, J¼7.2 Hz), 7.05 (d,
2H, J¼8.8 Hz), 3.91 (s, 3H). 13C NMR (100 MHz, acetone-d6)
d 196.0,
162.8, 136.3, 135.5, 133.0, 132.0, 131.1, 126.4, 126.0, 113.3, 54.9. 19F
NMR (376 MHz, acetone-d6)
d
ꢁ143.3. 11B NMR (128 MHz, acetone-
d6) 3.30. FTIR (ATR) n 3049, 2969, 2930, 2839, 1643, 1597, 1256,
d
4.4. Preparation of carbonyl-functionalized potassium
organotrifluoroboartes via Jones oxidation
1212, 1168, 1002, 759, 601 cmꢁ1
. HRFABMS: m/z calcd for
C14H11BF3O2 [MꢁKþ]ꢁ 279.0804, found 279.0806.
4.4.1. Potassium 4-formylphenyltrifluoroborate (18)10. To a solution
of 4-(hydroxymethyl)phenyltrifluoroborate8 (14, 214 mg, 1.0 mmol)
in acetone (10 mL) was slowly added 8 N Jones reagent (0.38 mL,
3.0 mmol) at 0 ꢀC. The reaction mixture was stirred for 10 min at
4.4.6. Potassium 4-(4-fluorobenzoyl)phenyltrifluoroborate (23). The
title compound was obtained as a white solid (266 mg, 87% yield)
using potassium 4-((4-fluorophenyl)hydroxymethyl)phenyltrifluo-
roborate (4, 308 mg, 1.0 mmol). Mp>250 ꢀC. 1H NMR (400 MHz, ac-
0
ꢀC. After 10 min, K2CO3 (415 mg, 3.0 mmol) was added. After
etone-d6)
d
7.86 (dd, 2H, J¼9.2, 5.6 Hz), 7.65 (d, 2H, J¼8.0 Hz), 7.56 (d,
stirring for 5 min at room temperature, the insoluble salts were
filtered off through Celite with charcoal. The solvent was concen-
trated on a rotary evaporator and then redissolved in a minimal
amount of acetone. The addition of diethyl ether (5.0 mL) led to
precipitation of the product. The product was filtered, collected,
and dried in vacuum to obtain the desired pure compound 18 as
a white solid (168 mg, 79% yield). Mp>250 ꢀC. 1H NMR (400 MHz,
2H, J¼8.0 Hz), 7.30 (t, 2H, J¼8.8 Hz). 13C NMR (100 MHz, acetone-d6)
d
194.9, 164.8 (d, J¼248.8 Hz), 135.1 (d, J¼3.2 Hz), 134.4, 132.3 (d,
J¼8.9 Hz), 131.5, 127.9, 115.0 (d, J¼21.8 Hz). 19F NMR (376 MHz, ace-
tone-d6)
(ATR)
d
ꢁ109.6, ꢁ143.5. 11B NMR (128 MHz, acetone-d6)
d 3.37. FTIR
n
3104, 3071, 3017, 1655, 1596, 1285, 1208, 928, 765, 685 cmꢁ1
.
HRFABMS: m/z calcd for C13H8BF4O [MꢁKþ]ꢁ 267.0604, found
267.0598.
acetone-d6)
d
9.94 (s, 1H), 7.69 (d, 2H, J¼8.0 Hz), 7.66 (d, 2H,
J¼8.0 Hz). 13C NMR (100 MHz, acetone-d6)
d
192.5, 134.5, 132.1,
4.4.7. Potassium 4-(3-fluorobenzoyl)phenyltrifluoroborate (24). The
title compound was obtained as an ivory solid (251 mg, 82% yield)
using potassium 4-((3-fluorophenyl)hydroxymethyl)phenyltrifluo-
roborate (5, 308 mg, 1.0 mmol). Mp>250 ꢀC. 1H NMR (400 MHz,
127.6. 19F NMR (376 MHz, acetone-d6)
d
ꢁ143.6. 11B NMR (128 MHz,
acetone-d6)
d
3.02 (q, J¼50.2 Hz). FTIR (ATR)
n 3050, 2851, 2762,
1683, 1221, 949, 819, 698, 542 cmꢁ1. HRFABMS: m/z calcd for
C7H5BF3O [MꢁKþ]ꢁ 173.0386, found 173.0388.
acetone-d6)
d
7.66 (d, 2H, J¼8.0 Hz), 7.58 (m, 4H), 7.48 (m, 1H), 7.40
(m, 1H). 13C NMR (100 MHz, acetone-d6)
d
194.9, 162.4 (d, J¼244.0),
4.4.2. Potassium 3-formylphenyltrifluoroborate (19)10. The title
compound was obtained as a white solid (155 mg, 73% yield) using
potassium 3-(hydroxymethyl)phenyltrifluoroborate8 (15, 214 mg,
141.1 (d, J¼7.0 Hz), 133.9, 131.5, 130.1 (d, J¼7.0 Hz), 128.0, 125.6 (d,
J¼3.0 Hz), 118.3 (d, J¼21.0 Hz), 115.8 (d, J¼22.0 Hz). 19F NMR
(376 MHz, acetone-d6)
d
ꢁ114.2, ꢁ143.5. 11B NMR (128 MHz, ace-
1.0 mmol). Mp¼212e214 ꢀC.1H NMR (400 MHz, acetone-d6)
d
9.98 (s,
tone-d6) d 3.18. FTIR (ATR) n 3075, 3033, 1653, 1205, 948, 759,
1H), 8.03 (s,1H), 7.80 (d,1H, J¼7.2 Hz), 7.62 (dt,1H, J¼7.2,1.6 Hz), 7.32
715 cmꢁ1. HRFABMS: m/z calcd for C13H8BF4O [MꢁKþ]ꢁ 267.0604,
(t,1H, J¼7.6 Hz). 13C NMR (100 MHz, acetone-d6)
d
193.3, 138.0, 135.2,
d
found 267.0609.
133.7, 126.8, 125.9. 19F NMR (376 MHz, acetone-d6)
ꢁ143.4. 11B NMR
(128 MHz, acetone-d6)
d
3.24 (q, J¼52.2 Hz). FTIR (ATR)
n
3052, 2823,
4.4.8. Potassium 4-(2-fluorobenzoyl)phenyltrifluoroborate (25). The
title compound was obtained as an ivory solid (217 mg, 71% yield)
using potassium 4-((2-fluorophenyl)hydroxymethyl)phenyltriflu-
oroborate (6, 308 mg, 1.0 mmol). Mp¼243 ꢀC (dec). 1H NMR
2726, 1706,1593,1245, 1150, 957, 780, 692, 606 cmꢁ1. HRFABMS: m/z
calcd for C7H5BF3O [MꢁKþ]ꢁ 173.0386, found 173.0384.
4.4.3. Potassium 2-formylphenyltrifluoroborate (20)10a,b,11. The title
compound was obtained as a white solid (138 mg, 65% yield) using
potassium 2-(hydroxymethyl)phenyltrifluoroborate8 (16, 214 mg,
1.0 mmol). Mp¼204e206 ꢀC. 1H NMR (400 MHz, acetone-d6)
(400 MHz, acetone-d6)
d
7.62 (m, 5H), 7.51 (td, 1H, J¼7.6, 2.0 Hz), 7.35
(td, 1H, J¼7.6, 1.2 Hz), 7.28 (ddd, 1H, J¼9.6, 8.4, 0.8 Hz). 13C NMR
(100 MHz, acetone-d6)
d
193.0, 159.6 (d, J¼246.7 Hz), 134.4, 132.2 (d,
J¼8.1 Hz),131.7,130.1 (d, J¼3.3 Hz),128.3 (d, J¼16.1 Hz),127.7,124.5 (d,
d
10.61 (s, 1H), 7.76, (m, 2H), 7.37 (t, 1H, J¼7.2 Hz), 7.20 (t, 1H,
J¼3.6 Hz), 115.8 (d, J¼21.7 Hz). 19F NMR (376 MHz, acetone-d6)
J¼7.6 Hz). 13C NMR (100 MHz, acetone-d6)
d
197.0, 140.0, 133.1,
d
ꢁ114.7, ꢁ143.6. 11B NMR (128 MHz, acetone-d6)
d 3.11. FTIR (ATR) n
131.4, 125.4, 124.4. 19F NMR (376 MHz, acetone-d6)
d
ꢁ135.5. 11B
3072, 3029,1655,1612,1217, 956, 844, 753, 657, 545 cmꢁ1. HRFABMS:
NMR (128 MHz, acetone-d6)
d
3.33 (q, J¼53.4 Hz). FTIR (ATR)
n
3053,
m/z calcd for C13H8BF4O [MꢁKþ]ꢁ 267.0604, found 267.0600.
3023, 2897, 2863, 1674, 1592, 1184, 947, 748, 608 cmꢁ1. HRFABMS:
m/z calcd for C7H5BF3O [MꢁKþ]ꢁ 173.0386, found 173.0389.
4.4.9. Potassium 4-(2,3-dimethoxybenzoyl)phenyltrifluoroborate
(26). The title compound was obtained as an ivory solid (237 mg,
68% yield) using potassium 4-((2,3-dimethoxyphenyl)hydrox-
ymethyl)phenyltrifluoroborate (7, 350 mg, 1.0 mmol). Mp¼142e
4.4.4. Potassium 4-(4-methoxybenzoyl)phenyltrifluoroborate (21).
The title compound was obtained as an ivory solid (213 mg, 67%
yield) using potassium 4-(hydroxy(4-methoxyphenyl)methyl)phe-
nyltrifluoroborate (1, 320 mg, 1.0 mmol). Mp¼226 ꢀC (dec). 1H NMR
144 ꢀC. 1H NMR (400 MHz, acetone-d6)
d
7.61 (d, 2H, J¼8.4 Hz), 7.57
(d, 2H, J¼8.4 Hz), 7.16 (m, 2H), 6.83 (dd, 1H, J¼6.8, 2.0 Hz), 3.92 (s,
(400 MHz, acetone-d6)
d
7.79 (d, 2H, J¼8.8 Hz), 7.63 (d, 2H,
3H), 3.66 (s, 3H). 13C NMR (100 MHz, acetone-d6)
d
195.7, 152.8, 146.5,
J¼7.6 Hz), 7.54 (d, 2H, J¼8.0 Hz), 7.06 (d, 2H, J¼8.8 Hz), 3.91 (s, 3H).
135.6, 134.9, 131.4, 127.7, 123.6, 119.7, 113.8, 60.4, 55.3. 19F NMR
13C NMR (100 MHz, acetone-d6)
d
195.1, 162.8, 135.1, 131.9, 131.3,
(376 MHz, acetone-d6)
d
ꢁ143.5. 11B NMR (128 MHz, acetone-d6)

D.-S. Kim et al. / Tetrahedron 67 (2011) 1062e1070
1069
d
3.26. FTIR (ATR)
n
3072, 3017, 2970, 2938, 2836, 1657, 1474, 1316,
acetone-d6)
2H). 13C NMR (100 MHz, acetone-d6)
19F NMR (376 MHz, acetone-d6)
3.29. FTIR (ATR) n 3562, 3076, 3022, 2923, 2646, 2552,
d
7.44 (d, 2H, J¼7.6 Hz), 7.06 (d, 2H, J¼7.6 Hz), 3.50 (s,
1266, 949, 758, 707, 549 cmꢁ1. HRFABMS: m/z calcd for C15H13BF3O3
[MꢁKþ]ꢁ 309.0910, found 309.0905.
d 172.4, 131.7, 130.9, 127.0, 40.7.
d
ꢁ143.2. 11B NMR (128 MHz, ac-
etone-d6)
d
4.4.10. Potassium 4-(hexanoyl)phenyltrifluoroborate (27). The title
compound was obtained as an ivory solid (189 mg, 67% yield) using
potassium 4-(1-hydroxyhexyl)phenyltrifluoroborate (8, 284 mg,
1690, 1610, 1400, 1224, 1185, 958, 804 cmꢁ1. HRFABMS: m/z calcd
for C8H7BF3O2 [MꢁKþ]ꢁ 203.0491, found 203.0489.
1.0 mmol). Mp¼227e230 ꢀC. 1H NMR (400 MHz, acetone-d6)
d
7.77
4.5. SuzukieMiyaura cross-coupling reactions
(d, 2H, J¼8.0 Hz), 7.60 (d, 2H, J¼8.0 Hz), 2.95 (t, 2H, J¼7.2 Hz), 1.69
(m, 2H), 1.37 (m, 4H), 0.91 (t, 3H, J¼7.2 Hz). 13C NMR (100 MHz,
4.5.1. 40-(4-Methoxybenzoyl)biphenyl-4-carbonitrile (34). To a 16ꢂ
90 mm glass vessel containing a stirring bar was added the potas-
sium 4-(4-methoxybenzoyl)phenyltrifluoroborate (21, 63.6 mg,
0.2 mmol), Cs2CO3 (195 mg, 0.6 mmol), Pd(PPh3)4 (6.9 mg,
3ꢂ10ꢁ3 mmol, 3 mol %), and 4-bromobenzonitrile (36.4 mg,
0.2 mmol). The mixture was dissolved in 20% aqueous 1,4-dioxane
(2 mL). The reaction was stirred in an oil bath at 100 ꢀC for 1 h, then
cooled to room temperature. The reaction mixture was extracted
with diethyl ether and H2O, and then organic layer was dried over
MgSO4. The solvent was filtered off through silica gel. The solvent
was concentrated on a rotary evaporator. The crude product was
purified by preparative TLC (0.5 mm, elution with hexane/
EtOAc¼4:1). The pure compound 34 was obtained as a white solid
(57.7 mg, 92% yield). Mp¼153e154 ꢀC. 1H NMR (400 MHz, CDCl3)
acetone-d6) d F
199.8, 134.5, 131.6, 125.9, 37.8, 31.4, 24.1, 22.3, 13.3. 19
NMR (376 MHz, acetone-d6)
d
ꢁ143.5. 11B NMR (128 MHz, acetone-
d6) d 3.34. FTIR (ATR) n 3069, 3029, 2931, 2859, 1672, 1215, 954, 818,
763, 580 cmꢁ1. HRFABMS: m/z calcd for C12H15BF3O [MꢁKþ]ꢁ
243.1168, found 243.1162.
4.4.11. Potassium
4-(cyclohexanecarbonyl)phenyltrifluoroborate
(28). The title compound was obtained as a white solid (191 mg,
65% yield) using potassium 4-(cyclohexyl(hydroxyl)methyl)phe-
nyltrifluoroborate (9, 296 mg, 1.0 mmol). Mp>250 ꢀC. 1H NMR
(400 MHz, acetone-d6)
d
7.76 (d, 2H, J¼8.0 Hz), 7.60 (d, 2H,
J¼8.0 Hz), 3.36 (m, 1H), 1.83 (m, 4H), 1.72 (m, 1H), 1.45 (m, 4H), 1.26
(m, 1H). 13C NMR (100 MHz, acetone-d6)
44.7, 29.5, 25.9, 25.5. 19F NMR (376 MHz, acetone-d6)
d 203.0, 133.6, 131.7, 126.1,
d
ꢁ143.3. 11
B
d
7.89 (d, 2H, J¼8.0 Hz), 7.88 (d, 2H, J¼8.4 Hz), 7.79 (d, 2H, J¼10.5 Hz),
7.76 (d, 2H, J¼10.5 Hz), 7.71 (d, 2H, J¼8.4 Hz), 7.01 (d, 2H, J¼8.8 Hz),
3.92 (s, 3H). 13C NMR (100 MHz, CDCl3)
194.8, 163.4, 144.5, 142.4,
138.2, 132.7, 132.5, 130.5, 129.9, 127.9, 127.0, 118.7, 113.7, 111.7, 55.5.
NMR (128 MHz, acetone-d6)
d 3.32. FTIR (ATR) n 3072, 3025, 2930,
2853, 1666, 1216, 953, 833, 750 cmꢁ1. HRFABMS: m/z calcd for
C13H15BF3O [MꢁKþ]ꢁ 255.1168, found 255.1168.
d
FTIR (ATR)
n 3075, 3059, 3036, 2922, 2850, 2231, 1644, 1601, 1313,
4.4.12. Potassium 4-(3-methylbutanoyl)phenyltrifluoroborate (29).
The title compound was obtained as an ivory solid (239 mg, 89%
yield) using potassium 4-(1-hydroxy-3-methylbutyl)phenyl-
trifluoroborate (10, 270 mg, 1.0 mmol). Mp¼133 ꢀC (dec). 1H NMR
1260, 764 cmꢁ1. HRFABMS: m/z calcd for C21H16NO2 [MþH]þ
314.1181, found 314.1180.
4.5.2. (4-Methoxyphenyl)(40-methylbiphenyl-4-yl)methanone
(35). The title compound was obtained as a white solid (44.8 mg,
74% yield) using potassium 4-(4-methoxybenzoyl)phenyltrifluo-
roborate (21, 63.6 mg, 0.2 mmol) and 4-bromotoluene (34.2 mg,
(400 MHz, acetone-d6)
d
7.77 (d, 2H, J¼8.0 Hz), 7.60 (d, 2H,
J¼8.0 Hz), 2.83 (d, 2H, J¼6.8 Hz), 2.24 (m,1H), 0.97 (d, 6H, J¼6.8 Hz).
13C NMR (100 MHz, acetone-d6)
25.0, 22.1. 19F NMR (376 MHz, acetone-d6)
d 199.6, 134.9, 131.6, 126.0, 46.8,
d
ꢁ143.4. 11B NMR
0.2 mmol). Mp¼171e172 ꢀC. 1H NMR (400 MHz, CDCl3)
d 7.89 (d,
(128 MHz, acetone-d6)
d
3.36. FTIR (ATR)
n
3072, 3025, 2959, 2930,
2H, J¼8.8 Hz), 7.86 (d, 2H, J¼8.4 Hz), 7.70 (d, 2H, J¼8.0 Hz), 7.58 (d,
2873, 1671, 1221, 944, 816, 705, 584 cmꢁ1. HRFABMS: m/z calcd for
C11H13BF3O [MꢁKþ]ꢁ 229.1012, found 229.1012.
2H, J¼8.0 Hz), 7.31 (d, 2H, J¼8.0 Hz), 7.01 (d, 2H, J¼8.8 Hz), 3.92 (s,
3H), 2.44 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 195.1, 163.1, 144.7,
138.0, 137.1, 136.6, 132.4, 130.4, 130.3, 129.6, 127.1, 126.6, 113.5, 55.5,
4.4.13. Potassium 4-(thiophene-2-carbonyl)phenyltrifluoroborate
(31). The title compound was obtained as an ivory solid (256 mg,
87% yield) using potassium 4-(hydroxy(thiophen-2-yl)methyl)
phenyltrifluoroborate (12, 296 mg, 1.0 mmol). Mp¼117 ꢀC (dec). 1H
21.1. FTIR (ATR) n 3070, 3024, 2918, 2852, 1737, 1639, 1600, 1251,
1175, 1029, 932, 763 cmꢁ1. HRFABMS: m/z calcd for C21H19O2
[MþH]þ 303.1385, found 303.1380.
NMR (400 MHz, acetone-d6)
d
7.92 (dd, 1H, J¼5.2, 1.2 Hz), 7.73 (dd,
4.5.3. (E)-2-(4-(4-Methoxybenzoyl)phenyl)-3-phenylacrylaldehyde
(36). The title compound was obtained as a colorless oil (57.5 mg,
84% yield) using potassium 4-(4-methoxybenzoyl)phenyl-
1H, J¼4.0, 1.2 Hz), 7.68 (d, 2H, J¼8.4 Hz), 7.65 (d, 2H, J¼8.4 Hz), 7.26
(dd, 1H, J¼4.8, 3.6 Hz). 13C NMR (100 MHz, acetone-d6)
d 188.0,
144.3, 135.1, 134.1, 133.3, 131.5, 127.9, 127.1. 19F NMR (376 MHz, ac-
trifluoroborate (21, 63.6 mg, 0.2 mmol) and
a
-bromocinnamalde-
etone-d6)
(ATR)
d
ꢁ143.3. 11B NMR (128 MHz, acetone-d6)
d
3.23. FTIR
hyde (42.2 mg, 0.2 mmol). 1H NMR (400 MHz, CDCl3)
d
9.82 (s, 1H),
n
3107, 3069, 3021, 2974, 2927, 2852, 1700, 1623, 1412, 1218,
7.89 (d, 2H, J¼8.8 Hz), 7.85 (d, 2H, J¼8.4 Hz), 7.49 (s, 1H), 7.34 (m,
3H), 7.26 (m, 4H), 7.00 (d, 2H, J¼9.2 Hz), 3.91 (s, 3H). 13C NMR
956, 835, 761, 706 cmꢁ1. HRFABMS: m/z calcd for C11H7BF3OS
[MꢁKþ]ꢁ 255.0263, found 255.0260.
(100 MHz, CDCl3)
d 195.1, 193.3, 163.3, 151.0, 140.9, 138.0, 137.2,
133.6, 132.6, 130.7, 130.6, 130.2, 130.0, 129.4, 128.7, 113.6, 55.5. FTIR
4.4.14. Potassium 4-(carboxymethyl)phenyltrifluoroborate (33). To
a solution of potassium 4-(2-hydroxyethyl)phenyltrifluoroborate8
(17, 228 mg, 1.0 mmol) in acetone (10 mL) was slowly added 8 N
Jones reagent (1.13 mL, 9.0 mmol) at 0 ꢀC. The reaction mixture was
stirred for 30 min at 0 ꢀC. After 30 min, 3.0 mL of 1 N KHF2 was
added. After stirring for 10 min at room temperature, the suspen-
sion was concentrated and dried in vacuum for 3 h. The residual
solid was dissolved in dry acetone (10 mL), and the insoluble salts
were filtered off through Celite with charcoal. The solvent was
concentrated on a rotary evaporator and the addition of CH2Cl2 led
to precipitation of the product. The product was filtered, collected,
and dried in vacuum to obtain the desired pure compound 33 as an
ivory solid (128 mg, 53% yield). Mp>250 ꢀC. 1H NMR (400 MHz,
(ATR) n 3061, 3006, 2958, 2932, 2839, 2713, 1682, 1651, 1604, 1287,
1172, 929, 743 cmꢁ1. HRFABMS: m/z calcd for C23H19O3 [MþH]þ
343.1334, found 343.1338.
4.5.4. 30-(4-Methoxybenzoyl)biphenyl-4-carbonitrile (37). The title
compound was obtained as a colorless oil (45.8 mg, 73% yield) using
potassium 3-(4-methoxybenzoyl)phenyltrifluoroborate (22, 63.6
mg, 0.2 mmol) and 4-bromobenzonitrile (36.4 mg, 0.2 mmol). 1H
NMR (400 MHz, CDCl3)
d
8.00 (t, 1H, J¼1.6 Hz), 7.88 (d, 2H, J¼9.2 Hz),
7.82 (m, 1H), 7.80 (m, 1H), 7.77 (d, 2H, J¼8.4 Hz), 7.74 (d, 2H,
J¼8.8 Hz), 7.61 (t,1H, J¼7.6 Hz), 7.01 (d, 2H, J¼8.8 Hz), 3.92 (s, 3H). 13C
NMR (100 MHz, CDCl3) d 195.0, 163.5, 144.6, 139.3, 139.2, 132.7, 132.5,
130.4, 129.8 (2C), 129.0, 128.3, 127.8, 118.7, 113.7, 111.4, 55.5. FTIR

1070
D.-S. Kim et al. / Tetrahedron 67 (2011) 1062e1070
(ATR)
n
3070, 3019, 2917, 2845, 2222, 1736, 1647, 1597, 1509, 1320,
1616, 1600, 1514, 1410, 1292, 826, 717 cmꢁ1. HRFABMS: m/z calcd for
C18H12NOS [MþH]þ 290.0640, found 290.0638.
1261, 1174, 1016, 844, 759 cmꢁ1. HRFABMS: m/z calcd for C21H16NO2
[MþH]þ 314.1181, found 314.1175.
Acknowledgements
4.5.5. 40-(4-Fluorobenzoyl)biphenyl-4-carbonitrile (38). The title
compound was obtained as a white solid (43.4 mg, 72% yield) using
potassium 4-(4-fluorobenzoyl)phenyltrifluoroborate (23, 61.2 mg,
0.2 mmol) and 4-bromobenzonitrile (36.4 mg, 0.2 mmol).
This research was supported by the KIST Institutional Program
(2Z03401), Republic of Korea. We are grateful to Professor Gary A.
Molander (University of Pennsylvania) for friendly discussions.
Mp¼177e178 ꢀC. 1H NMR (400 MHz, CDCl3)
d 7.91 (m, 4H), 7.81 (d,
2H, J¼8.8 Hz), 7.77 (d, 2H, J¼8.4 Hz), 7.73 (d, 2H, J¼8.4 Hz), 7.21 (t,
2H, J¼8.8 Hz). 13C NMR (100 MHz, CDCl3)
d 194.5, 165.5 (d,
J¼253.4 Hz), 144.3, 143.0, 137.4, 133.6 (d, J¼3.0 Hz), 132.7, 132.6 (d,
Supplementary data
Supplementary data (copies of 1H, 13C, 19F, and 11B NMR spectra
of all new compounds). Supplementary data related to this article
can be found online at doi:10.1016/j.tet.2010.12.049.
J¼9.3 Hz), 130.6, 127.9, 127.2, 118.6, 115.6 (d, J¼21.8 Hz), 111.9. FTIR
(ATR) n 3284, 3061, 2958, 2923, 2852, 2224, 1651, 1592, 1500, 1277,
1151, 929, 854 cmꢁ1. HRFABMS: m/z calcd for C20H13FNO [MþH]þ
302.0981, found 302.0975.
References and notes
4.5.6. 40-Hexanoylbiphenyl-4-carbonitrile (39). The title compound
was obtained as a white solid (45.0 mg, 81% yield) using potassium
4-hexanoylphenyltrifluoroborate (27, 56.4 mg, 0.2 mmol) and 4-
bromobenzonitrile (36.4 mg, 0.2 mmol). Mp¼83e85 ꢀC. 1H NMR
1. (a) The Carbonyl Group; Patai, S., Zabicky, J., Eds.; Wiley: New York, NY, 1966 and
1970; Vols. 1 and 2; (b) Whitesell, J. K. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 6; p 703; (c) Carey, F.
A.; Sundberg, R. J. Advanced Organic Chemistry, 5th ed.; Springer: New York, NY,
2007, Part B, Chapter 2.
2. (a) Ley, S. V.; Madin, A.; Lee, T. V.; Procter, G. In Comprehensive Organic Syn-
thesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 7; p 251, and
references therein; (b) Hudlicky, M. Oxidations in Organic Chemistry. ACS
(400 MHz, CDCl3)
d
8.08 (d, 2H, J¼8.8 Hz), 7.78 (d, 2H, J¼8.4 Hz),
7.74 (d, 2H, J¼8.8 Hz), 7.70 (d, 2H, J¼8.4 Hz), 3.01 (t, 2H, J¼7.6 Hz),
1.79 (m, 2H), 1.41 (m, 4H), 0.94 (t, 3H, J¼6.8 Hz). 13C NMR (100 MHz,
ꢀ
CDCl3)
d 199.9, 144.3, 143.2, 136.9, 132.7, 128.8, 127.9, 127.4, 118.6,
Monograph Series 186; American Chemical Society: Washington, DC, 1990;
p 114.
111.8, 38.7, 31.5, 24.0, 22.5, 13.9. FTIR (ATR)
n 3059, 2958, 2924,
3. (a) Molander, G. A.; Figueroa, R. Aldrichimica Acta 2005, 38, 49; (b) Stefani, H. A.;
Cella, R.; Vieira, A. S. Tetrahedron 2007, 63, 3623; (c) Molander, G. A.; Ellis, N.
Acc. Chem. Res. 2007, 40, 275; (d) Darses, S.; Genet, J.-P. Chem. Rev. 2008, 108,
288; (e) Molander, G. A.; Canturk, B. Angew. Chem., Int. Ed. 2009, 48, 9240; (f)
Molander, G. A.; Sandrock, D. L. Curr. Opin. Drug Discovery Dev. 2009, 12, 811.
4. Kim, D.-S.; Ham, J. Org. Lett. 2010, 12, 1092 and references therein.
5. Molander, G. A.; Petrillo, D. E. J. Am. Chem. Soc. 2006, 128, 9634.
6. Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2008, 130, 14084.
7. Molander, G. A.; Ellis, N. M. J. Org. Chem. 2006, 71, 7491.
8. Park, Y. H.; Ahn, H. R.; Canturk, B.; Jeon, S. I.; Lee, S.; Kang, H.; Molander, G. A.;
Ham, J. Org. Lett. 2008, 10, 1215.
9. Molander, G. A.; Biolatto, B. J. Org. Chem. 2003, 68, 4302.
10. (a) Molander, G. A.; Febo-Ayala, W.; Jean-Gerard, L. Org. Lett. 2009, 11, 3830;
2863, 2237, 1675, 1602, 1202, 819 cmꢁ1. HRFABMS: m/z calcd for
C19H20NO [MþH]þ 278.1545, found 278.1539.
4.5.7. 40-(Thiophene-2-carbonyl)biphenyl-4-carbonitrile (40). The
title compound was obtained as an ivory solid (50.4 mg, 87% yield)
using potassium 4-(thiophene-2-carbonyl)phenyltrifluoroborate
(31, 58.8 mg, 0.2 mmol) and 4-bromobenzonitrile (36.4 mg,
0.2 mmol). Mp¼139 ꢀC. 1H NMR (400 MHz, CDCl3)
d 8.01 (d, 2H,
J¼8.4 Hz), 7.80 (d, 2H, J¼8.8 Hz), 7.75 (m, 5H), 7.71 (dd, 1H, J¼3.6,
ꢀ
0.8 Hz), 7.22 (dd, 1H, J¼4.8, 4.0 Hz). 13C NMR (100 MHz, CDCl3)
(b) Molander, G. A.; Figueroa, R. J. Org. Chem. 2006, 71, 6135; (c) Molander, G. A.;
Fumangalli, T. J. Org. Chem. 2006, 71, 5743.
d
187.4, 144.4, 143.4, 142.8, 138.0, 134.8, 134.5, 132.7, 130.0, 128.0,
127.9, 127.3, 118.6, 111.8. FTIR (ATR)
n
3106, 2923, 2852, 2225, 1628,
11. Yuen, A. K. L.; Hutton, C. A. Tetrahedron Lett. 2005, 46, 7899.