CuCl/bipyridine-catalyzed addition reactions of arylboroxines with aldehydes, α,β-unsaturated ketones, and N-tosyl aldimines

Article abstract of DOI:10.1021/jo201338v

CuCl/bipyridine-catalyzed addition reactions of arylboroxines with aldehydes and α,β-unsaturated ketones at elevated temperatures were described. By using the microwave energy, CuCl/bipyridine-catalyzed addition reactions of arylboroxines with aldimines were also realized.

Full text of DOI:10.1021/jo201338v

NOTE
pubs.acs.org/joc
CuCl/Bipyridine-Catalyzed Addition Reactions of Arylboroxines
with Aldehydes, r,β-Unsaturated Ketones, and N-Tosyl Aldimines
Yuan-Xi Liao and Qiao-Sheng Hu*
Department of Chemistry, College of Staten Island and the Graduate Center of the City University of New York, Staten Island, New York
10314, United States
S Supporting Information
b
ABSTRACT: CuCl/bipyridine-catalyzed addition reactions of
arylboroxines with aldehydes and R,β-unsaturated ketones at
elevated temperatures were described. By using the microwave
energy, CuCl/bipyridine-catalyzed addition reactions of aryl-
boroxines with aldimines were also realized.
ver the past decade, transition-metal-catalyzed addition
reactions of arylboron reagents with aldehydes have emerged
O
as useful transformations in organic synthesis.1ꢀ9 Transition metal
catalysts including Rh(I)/(II),2 Pd(II),3 Ni(0)/(II),4 Cu(I)/(II),5
Fe(III)6 complexes, and more recently Ru(II)7 and Co(II)8
complexes have been reported to catalyze this type of addition
reaction. Although enormous success, including promising en-
antioselectivity, has been achieved, most of the transition metal
catalysts are expensive and/or require air-free handling operation.
The search for operationally convenient and cost-effective cata-
lysts for this type of addition reaction continues.
Figure 1. Type I metalacycles.
Scheme 1
In our laboratory, we are interested in employing readily
available transition metal complexes as catalysts for this type of
addition reaction. In this context, we have recently documented
air/moisture-stable anionic four-electron donor-based (type I)
metalacycles (Figure 1),10 a large family of cyclic organometallic
compounds, as catalysts for the addition reactions of arylboronic
acids with aldehydes, R,β-unsaturated ketones, R-keto esters, and
aldimines.11,12 We have also reported [Rh(COD)Cl]2 and Ni-
(COD)2/4-RCOC6H4Cl-catalyzed addition reactions of arylbor-
ons with aldehydes.13 During our study, we became interested in
using Cu(I)/Cu(II) complexes as catalysts for this type of addition
reaction because Cu(I) or Cu(II) salts such as CuCl or CuCl2 are
inexpensive. So far, two Cu catalysts have been reported for
addition reactions. CuF2/(R)-5,50-bis[di(3,5-di-tert-butyl-4-meth-
oxyphenyl)phosphino]-4,40-bi-1,3-benzodioxole with tetrabutylam-
monium difluorotriphenylsilicate (TBAT) as additive was reported
for the addition reaction of arylborates with aldehydes.5a Recently,
the Cu(OAc)2/dppf complex was also reported as the catalyst for
the addition reaction of arylboronic acids with activated aromatic
aldehydes.5b While these protocols are useful, there are drawbacks
associated with them, such as the requirement of additives and/or
limited substrate scope. In our early study, we found low conversions
(<5%) were observed for the addition reaction of phenylboronic
acid with benzaldehyde (Scheme 1), presumably because of the
decomposition of the catalyst under the reaction condition.
During our study of using type I palladacycles as addition
reaction catalysts, we discovered that addition reactions can
efficiently occur under anhydrous conditions and the palladacycle
catalysts were very stable under such anhydrous conditions.11d
We thus surmised that Cu(I)/(II) catalysts might also be long-
lived under the anhydrous condition and might be able to function
as efficient catalysts for the addition reactions. Herein, we report
our study on such addition reactions with simple Cu(I)/(II)
complexes as catalysts, specifically, CuCl/bipyridine-catalyzed
addition reactions of arylboroxines with aldehydes, R,β-unsatu-
rated ketones, and N-tosyl aldimines.
Our study began with the testing of several copper(I)/(II)
complexes as catalysts for the addition reaction of phenylboron
compounds with benzaldehyde under anhydrous conditions.
By using dry K3PO4, toluene, and dry phenylboronic acid
(phenylboroxine), we found that although low efficiency was
observed by using CuCl2, CuCl, CuCl2/dppf, CuCl2/4,7-di-
phenyl-1,10-phenanthroline, CuCl2/tetramethylethane-1,2-diamine,
or CuCl2/pyridine complex (Table 1, entries 1ꢀ6), CuCl2/
bipyridine exhibited moderate catalytic activity (Table 1, entry
Received: June 30, 2011
Published: August 09, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/jo201338v J. Org. Chem. 2011, 76, 7602–7607
|

The Journal of Organic Chemistry
NOTE
Table 1. Copper(I)/Cu(II)-Catalyzed Addition Reaction of
Phenylboron Reagents with Benzaldehyde a
Table 2. CuCl/Bipyridine-Catalyzed Addition Reactions of
Arylboroxines with Aldehydes a
a Reaction conditions: benzaldehyde (0.25 mmol), phenylboron reagent
(2.0 equiv), base (3.0 equiv), 10 mol % of Cu catalyst, 20 mol % of ligand,
110 °C, 6 h. b Based on 1H NMR analysis. c o-Xylene was used as solvent
at 135 °C.
a Reaction conditions: aldehydes (1.0 equiv), arylboroxine (0.66 equiv).
A: 10 mol % of CuCl, 20 mol % of bipyridine, o-xylene, 135 °C, 6ꢀ8 h. B:
10 mol % of CuCl, 20 mol % of bipyridine, toluene, 110 °C, 6 h. C: 20
mol % of CuCl, 40 mol % of bipyridine, o-xylene, 135 °C, 6 h. b Isolated
yields. c 3-Substituted phthalides as the products.
7). Further study revealed that CuCl/bipyridine was the most
active complex and NaOAc was the best base (Table 1, entries
7ꢀ15). The CuCl/bipyridine catalyst system showed higher
activity at higher temperature with o-xylene as the solvent
(Table 1, entry 16). We also examined other phenylboron
reagents and found that only phenylboroxine showed reactivity
(Table 1, entries 17ꢀ20).
With 10 mol % of CuCl/20 mol % of bipyridine as the catalyst,
NaOAc as the base, and o-xylene as solvent, different arylborox-
ines and aldehydes for the addition reactions were examined, and
our results are listed in Table 2. As shown in Table 2, arylbor-
oxines with electron-donating and electron-withdrawing substit-
uents smoothly react with different aldehydes to give corres-
ponding diarylmethanols in good yields. Our study showed that
aromatic aldehydes bearing electron-withdrawing groups were
more reactive than aromatic aldehydes bearing electron-donating
groups and aliphatic aldehydes. With aromatic aldehydes bearing
electron-withdrawing groups as substrates, the addition reaction
could occur at lower temperature (Table 2, entries 6ꢀ8). With
aromatic aldehydes bearing electron-donating groups and ali-
phatic aldehyde as substrates, good yields were obtained by using
20 mol % of CuCl/40 mol % of bipyridine as the catalyst
(Table 2, entries 9ꢀ15).
Recently, we reported Pd(II)-, Pt(II)-, and Rh(I)-catalyzed
addition reactions of arylboronic acids with alkyl 2-formylbenzo-
ates followed by lactonization to access 3-substituted phthalides.14
After establishing that CuCl/bipyridine could catalyze addition
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The Journal of Organic Chemistry
NOTE
Table 3. CuCl/Bipyridine-Catalyzed Addition Reactions of
substrates. Our study represents the first examples of Cu-
catalyzed 1,4-addition reactions of arylborons with R,β-unsatu-
rated ketones.16
Arylboroxines with r,β-Unsaturated Ketonesa
We also examined the addition reaction of arylboroxines with
N-tosyl aldimines.17 We found that the addition reaction of
arylboroxines with N-tosyl benzaldimine occurred slower and up
to 84% conversion was observed with toluene/4-chlorotoluene
as cosolvents (Table 4, entries 1ꢀ3). Complete conversions and
good yields were achieved with the assistance of microwave
energy (Table 4, entries 4ꢀ9). To our knowledge, this represents
the first example of Cu-complex-catalyzed addition reactions of
organoborons with aldimines.
In summary, on the basis of the consideration that Cu(I) or
Cu(II) catalysts could be more stable under the anhydrous
conditions than in the presence of water, we demonstrated that
readily available CuCl/bipyridine complex was a good catalyst
for the addition reactions of arylboroxines with aldehydes and
R,β-unsaturated ketones by using dry base and solvent. With the
assistance of microwave energy, the CuCl/bipyridine complex
also catalyzed the addition reactions of arylboroxines with N-
tosyl aldimines. Our study provided an inexpensive transition
metal catalyst for the addition reactions of arylboroxines with
aldehydes, R,β-unsaturated ketones, and N-tosyl aldimines. Our
future work will be directed toward the elucidation of the detailed
mechanism for such CuCl/bipyridine-catalyzed addition reac-
tions and to further examine the effect of water on the longevity
of other transition metal catalysts.
a Reaction conditions: ketone (1.0 equiv), arylboroxine (0.66 equiv), 10 mol
% of CuCl, 20 mol % of bipyridine, o-xylene, 135 °C, 6ꢀ8 h.b Isolated yields.
reactions of aldehydes with arylboroxines, it was necessary to
determine whether or not this catalyst system might be useful for
addition reactions of arylboroxines with methyl 2-formylbenzo-
ates to access 3-substituted phthalides. Our study showed that
CuCl/bipyridine-catalyzed addition reactions of arylboroxines
with methyl 2-formylbenzoates occurred smoothly and 3-sub-
stituted phthalides were obtained in good to excellent yields
(Table 2, entries 16ꢀ19).
’ EXPERIMENTAL SECTION
General. NMR spectra were recorded on 300 or 600 MHz spectro-
1
meters (300 or 600 MHz for H NMR, 150 MHz for 13C NMR, and
287 MHz for 19F NMR) with CDCl3 as the solvent. The microwave-
assisted reactions were conducted in 10 mL sealed pressure reaction
vessels, with a CEM Discover S-class microwave reactor that is equipped
with an infrared temperature detector. The temperatures were controlled
within less than (1ꢀ2 οC in the temperature-controlled microwave-
assisted reactions. Arylboroxines were prepared by azeotropic distillation
of arylboronic acids with dry toluene for 6 h. The bases were dried by
baking well-ground base powder at 140 °C under vacuum for 6 h. Other
chemicals were used directly as received from commercial sources.
Our success of using CuCl/bipyridine as the catalyst for
addition reactions of arylboroxines with aldehydes prompted
us to examine other types of substrates for the addition reactions.
We next examined R,β-unsaturated ketones as substrates for 1,4-
addition reactions of arylboroxines.1,15 We found that CuCl/
bipyridine was also an efficient catalyst for the 1,4-addition
reaction of arylboroxines with R,β-unsaturated ketones. Com-
plete conversions and high yields were obtained for all tested
Table 4. Microwave-Assisted, CuCl/Bipyridine-Catalyzed Addition Reactions of Arylboroxines with N-Tosyl Aldiminea
entry
Ar
Ar0
solvent
temp (°C)
yield (%)b
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
toluene
110c
135c
135c
50d
52d
84d
70
o-xylene
toluene/4-chlorotoluene
toluene/4-chlorotoluene
toluene/4-chlorotoluene
toluene/4-chlorotoluene
toluene/4-chlorotoluene
toluene/4-chlorotoluene
toluene/4-chlorotoluene
180 (μw)
180 (μw)
180 (μw)
180 (μw)
180 (μw)
180 (μw)
4-CH3C6H4
2-CH3C6H4
4-CH3OC6H4
Ph
61
65
62
4-CH3C6H4
4-ClC6H4
58
Ph
69
a Reaction conditions: aldehydes (1.0 equiv), arylboroxine (0.66 equiv), 10 mol % of CuCl, 20 mol % of bipyridine, NaOAc (3.0 equiv), oil bath heating,
6 h or microwave heating at 180 °C for 30 min. b Isolated yields. c Conventional heating by oil bath for 6 h. d Conversion based on 1H NMR analysis.
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NOTE
General Procedure for CuCl/Bipyridine-Catalyzed Addi-
tion Reactions of Arylboroxines with Aldehydes. To a vial
containing aldehyde (0.25 mmol), arylboroxine (0.168 mmol), base
(NaOAc, 0.75 mmol), and CuCl/bipyridine (conditions A, B, or
D: 0.025 mmol/0.05 mmol; condition C: 0.05 mmol/0.1 mmol) was
added solvent (1.0 mL, condition A or C: o-xylene; condition B:
toluene). After the mixture was stirred at 110 °C (condition B) or
135 °C (condition A or C) for 6ꢀ8 h, the reaction was quenched by 4 N
HCl (2 mL) aqueous solution. The mixture was extracted with CH2Cl2
(3 ꢁ 15 mL). The organic layers were combined. After evaporation of
the organic solvents, the residue was subjected to column chromato-
graphy [silica gel, ethyl acetate/hexane (v/v = 1:10) as eluent] to afford
the products.
(s, 3H), 2.17 (d, J = 4.2 Hz, 1H); 13C NMR δ 142.8, 141.4, 135.3, 130.5,
128.4, 127.5(2C), 127.1, 126.2, 126.1, 73.3, 19.4.
o-Tolyl(p-tolyl)methanol11d (Table 2, entries 12 and 13): 1H NMR δ
7.51 (d, J = 7.2 Hz, 1H), 7.25ꢀ7.17 (m, 3H), 7.11ꢀ7.10 (m, 4H), 5.91
(s, 1H), 2.31 (s, 3H), 2.22 (s, 1H), 2.20 (s, 3H); 13C NMR δ 141.5,
139.9, 137.2, 135.2, 130.4, 129.1, 127.3, 127.0, 126.0, 73.1, 21.1, 19.3.
(4-Methoxyphenyl)(p-tolyl)methanol11d (Table 2, entry 14): 1H
NMR δ 7.24 (d, J = 9.0 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 7.11 (d,
J = 8.4 Hz, 2H), 6.83 (d, J = 8.4 Hz, 2H), 5.72 (s, 1H), 3.75 (s, 3H), 2.31
(s, 4H); 13C NMR δ 158.9, 141.1, 137.0, 136.3, 129.0, 127.7, 126.3,
113.7, 75.5, 55.2, 21.0.
Cyclohexyl(phenyl)methanol11a (Table 2, entry 15): 1H NMR δ 7.32
(t, J = 7.2 Hz, 2H), 7.28ꢀ7.24 (m, 3H), 4.27 (dd, J = 3.0, 7.2 Hz, 1H),
1.98ꢀ1.96 (m, 1H), 1.93 (d, J = 3.0 Hz, 2H), 1.77ꢀ1.74 (m, 1H),
1.66ꢀ1.57 (m, 3H), 1.37ꢀ1.35 (m, 1H), 1.25ꢀ1.00 (m, 4H),
0.95ꢀ0.89 (m, 1H); 13C NMR δ 143.6, 128.1, 127.3, 126.6, 79.3,
44.9, 29.2, 28.8, 26.4, 26.0, 25.9.
Diphenylmethanol13a (Table 2, entry 1): 1H NMR δ 7.33ꢀ7.28 (m,
8H), 7.23 (t, J = 7.2 Hz, 2H), 5.74 (s, 1H), 2.45 (s, 1H); 13C NMR δ
143.7, 128.4, 127.5, 126.5, 76.1.
Naphthalen-2-yl(phenyl)methanol11c (Table 2, entry 2): 1H NMR δ
7.80 (s, 1H), 7.77ꢀ7.75 (m, 2H), 7.72 (d, J = 8.4 Hz, 1H), 7.44ꢀ7.41
(m, 2H), 7.36ꢀ7.33 (m, 3H), 7.27 (t, J = 7.8 Hz, 2H), 7.22 (t, J = 7.2 Hz,
1H), 5.86 (d, J = 3.0 Hz, 1H), 2.61 (s, 1H); 13C NMR δ 143.5, 141.0,
133.2, 132.8, 128.4, 128.2, 128.0, 127.6, 127.5, 126.6, 126.1, 125.9, 124.9,
124.7, 76.2.
3-Phenylisobenzofuran-1(3H)-one14 (Table 2, entry 16): 1H NMR δ
7.95 (d, J = 7.2 Hz, 1H), 7.64 (t, J = 7.2 Hz, 1H), 7.55 (t, J = 7.8 Hz, 1H),
7.38ꢀ7.26 (m, 6H), 6.40 (s, 1H); 13C NMR δ 170.5, 149.6, 136.3, 134.3,
129.3, 129.2, 128.9, 126.9, 125.5, 125.5, 122.8, 82.6.
3-p-Tolylisobenzofuran-1(3H)-one14 (Table 2, entry 17): 1H NMR δ
7.95 (d, J = 8.4 Hz, 1H), 7.63 (t, J = 7.8 Hz, 1H), 7.54 (t, J = 7.8 Hz, 1H),
7.32 (t, J = 7.8 Hz, 1H), 7.18ꢀ7.14 (m, 4H), 6.37 (s, 1H), 2.34 (s, 3H);
13C NMR δ 170.5, 149.7, 139.2, 134.2, 133.3, 129.5, 129.2, 127.0, 125.6,
125.5, 122.8, 21.1.
(4-Chlorophenyl)(2-(trifluoromethyl)phenyl)methanol11d (Table 2,
entry 3): 1H NMR δ 7.67 (d, J = 8.4 Hz,1H), 7.57ꢀ7.52 (m, 2H), 7.39 (t,
J = 7.2 Hz, 1H), 7.28 (s, 4H), 6.25 (s, 1H), 2.46 (d, J = 3.6 Hz, 1H); 13C
NMR δ 141.9, 141.2, 133.3, 132.4, 129.4, 128.5, 128.0, 127.8, 127.6 (q,
J = 29.7 Hz), 125.6 (q, J = 5.6 Hz), 124.3 (q, J = 272.3 Hz), 70.7 (q,
J = 2.3 Hz).
3-o-Tolylisobenzofuran-1(3H)-one14 (Table 2, entry 18): 1H NMR δ
7.97 (d, J = 7.8 Hz, 1H), 7.66 (t, J = 7.2 Hz, 1H), 7.56 (t, J = 7.2 Hz, 1H),
7.33 (d, J = 7.8 Hz, 1H), 7.28ꢀ7.24 (m, 2H), 7.12 (t, J = 7.8 Hz, 1H),
6.91 (d, J = 7.8 Hz, 1H), 6.67 (s, 1H), 2.49 (s, 3H); 13C NMR δ 170.5,
149.2, 137.1, 134.1, 134.0, 131.0, 129.3, 129.2, 127.1, 126.3, 126.3, 125.6,
123.0, 80.4, 19.2.
(4-Chlorophenyl)(4-fluorophenyl)methanol18 (Table 2, entry 4): 1H
NMR δ 7.30ꢀ7.25 (m, 6H), 7.01 (t, J = 9.0 Hz, 2H), 5.75 (s, 1H), 2.42
(d, J = 2.4 Hz, 1H); 13C NMR δ 162.3 (d, J = 245.4 Hz), 142.0, 139.2 (d,
J = 2.9 Hz), 133.4, 128.7, 128.2 (d, J = 7.8 Hz), 127.8, 115.5 (d, J = 21.2
Hz), 74.9.
3-(4-Methoxyphenyl)isobenzofuran-1(3H)-one14 (Table 2, entry
1
19): H NMR δ 7.95 (d, J = 7.8 Hz, 1H), 7.64 (t, J = 7.2 Hz, 1H),
(2,4-Bis(trifluoromethyl)phenyl)(4-chlorophenyl)methanol (Table 2,
entry 5): Light yellow oil; 1H NMR δ 7.92 (s, 1H), 7.81ꢀ7.77 (m, 2H),
7.46 (d, J = 7.8 Hz, 1H), 7.19 (d, J = 7.8 Hz, 1H), 6.27 (s, 1H), 2.67 (d, J =
3.6 Hz, 1H); 13C NMR δ 145.8, 140.3, 133.9, 130.5 (q, J = 33.5 Hz, 1C),
130.3, 129.2, 128.8, 128.3 (q, J = 30.6 Hz), 127.8, 123.5 (q, J = 272.7 Hz),
123.2 (q, J = 272.7 Hz), 123.0 (q, J = 3.9 Hz), 70.0; 19F NMR δ ꢀ58.9,
ꢀ63.7 ppm; IR 3325(br), 1491(s), 1345(m), 1300(s), 1124(s); HR-MS
(-ESI) calcd for C16H10ClF6O3 [M + HCOO]ꢀ 399.0228, found
399.0231.
7.55 (t, J = 7.2 Hz, 1H), 7.31 (d, J = 7.8 Hz, 1H), 7.17 (d, J = 7.8 Hz, 1H),
6.88 (d, J = 8.4 Hz, 1H), 6.37 (s, 1H), 3.80 (s, 3H); 13C NMR δ 170.5,
163.4, 149.7, 134.2, 129.3, 128.8, 128.3, 125.9, 125.5, 122.9, 114.3, 82.7,
55.3, 21.1.
General Procedure for CuCl/Bipyridine-Catalyzed Addi-
tion Reactions of Arylboroxines with r,β-Unsaturated Ke-
tones. To a vial containing R,β-unsaturated ketone (0.25 mmol),
arylboroxine (0.168 mmol), base (NaOAc, 0.75 mmol), and CuCl/
bipyridine (0.025 mmol/0.05 mmol) was added o-xylene (1.0 mL). After
the mixture was stirred at 135 °C for 6ꢀ8 h, the reaction was quenched
by 4 N HCl (2 mL) aqueous solution. The mixture was extracted with
CH2Cl2 (3 ꢁ 15 mL). The organic layers were combined. After
evaporation of the organic solvents, the residue was subjected to column
chromatography [silica gel, ethyl acetate/hexane (v/v = 1:20) as eluent]
to afford the products.
(4-Nitrophenyl)(phenyl)methanol11c (Table 2, entry 6): 1H NMR δ
8.19 (d, J = 7.2 Hz, 2H), 7.57 (d, J = 8.4 Hz, 2H), 7.38ꢀ7.30 (m, 5H),
5.92 (d, J = 3.0 Hz, 1H), 2.40 (d, J = 3.0 Hz, 1H); 13C NMR δ 150.7,
147.2, 142.7, 129.0, 128.4, 127.0, 126.7, 123.7, 75.5.
4-(Hydroxyphenylmethyl)benzonitrile11a (Table 2, entry 7): 1H
NMR δ 7.58 (d, J = 8.4 Hz, 2H), 7.48 (t, J = 8.4 Hz, 2H), 7.35ꢀ7.28
(m, 5H), 5.75 (d, J = 3.0 Hz, 1H), 2.70 (d, J = 3.6 Hz, 1H); 13C NMR δ
148.8, 142.7, 132.2, 128.8, 128.2, 126.9, 126.6, 118.8, 110.9, 75.5.
(4-Chlorophenyl)(phenyl)methanol11c (Table 2, entry 8): 1H NMR δ
7.33ꢀ7.30 (m, 4H), 7.28ꢀ7.25 (m, 5H), 5.74 (d, J = 2.4 Hz, 1H), 2.49
(d, J = 2.4 Hz, 1H); 13C NMR δ 143.3, 142.1, 133.2, 128.6, 128.5, 127.8,
127.7, 126.5, 75.5.
1,3,3-Triphenylpropan-1-one11c (Table 3, entry 1): 1H NMR δ 7.92
(d, J = 6.6 Hz, 2H), 7.51 (t, J = 6.6 Hz, 1H), 7.40 (d, J = 7.2 Hz, 2H),
7.26ꢀ7.25 (m, 8H), 7.17ꢀ7.14 (m, 2H), 4.83 (t, J = 7.2 Hz, 1H), 3.72
(d, J = 7.2 Hz, 2H); 13C NMR δ 197.9, 144.1, 137.0, 133.0, 128.5, 128.4,
128.0, 127.8, 126.3, 45.9, 44.7.
1,3-Diphenyl-3-p-tolylpropan-1-one11c (Table 3, entry 2): 1H NMR
δ 7.93 (d, J = 7.2 Hz, 2H), 7.54 (t, J = 6.6 Hz, 1H), 7.43 (t, J = 7.8 Hz,
2H), 7.26 (t, J = 4.8 Hz, 2H), 7.17ꢀ7.15 (m, 3H), 7.07 (d, J = 7.8 Hz,
Phenyl(p-tolyl)methanol11c (Table 2, entry 9): 1H NMR δ 7.34 (d, J =
7.2 Hz, 2H), 7.30 (t, J = 7.8 Hz, 2H), 7.24ꢀ7.22 (m, 3H), 7.12 (d, J = 7.8
Hz, 2H), 5.75 (s, 1H), 2.36 (br, 1H), 2.31 (s, 3H); 13C NMR δ 143.9,
140.9, 137.2, 129.1, 128.4, 127.4, 126.5, 126.4, 76.0, 21.1.
2H), 4.79 (t, J = 7.2 Hz, 1H), 3.72 (d, J = 7.8 Hz, 2H), 2.28 (s, 3H); 13
C
Di(p-tolyl)methanol11c (Table 2, entry 10): 1H NMR δ 7.22 (d, J =
7.2 Hz, 4H), 7.11 (d, J = 7.8 Hz, 4H), 5.72 (s, 1H), 2.31 (s, 6H), 2.27 (s,
1H); 13C NMR δ 141.1, 137.0, 129.1, 126.4, 75.8, 21.0.
NMR δ 198.0, 144.4, 141.1, 137.1, 135.9, 133.0, 129.2, 128.6, 128.5,
128.0, 127.8, 127.6, 126.3, 45.5, 44.8, 21.0.
1,3-Diphenyl-3-o-tolylpropan-1-one11a (Table 3, entry 3): 1H NMR
δ 7.92 (d, J = 7.8 Hz, 2H), 7.53 (t, J = 7.8 Hz, 1H), 7.42 (t, J = 7.8 Hz,
2H), 7.25 (t, J = 8.4 Hz, 2H), 7.23ꢀ7.20 (m, 3H), 7.17ꢀ7.09 (m, 4H),
5.02 (t, J = 7.2 Hz, 1H), 3.71 (m, 2H), 2.32 (s, 3H); 13C NMR δ 198.0,
Phenyl(o-tolyl)methanol11c (Table 2, entry 11): 1H NMR δ 7.50 (d,
J = 7.8 Hz, 1H), 7.31ꢀ7.30 (4 m, H), 7.27ꢀ7.22 (m, 2H), 7.19 (t, J =
7.8 Hz, 1H), 7.13 (d, J = 7.2 Hz, 1H), 5.98 (d, J = 3.6 Hz, 1H), 2.23
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NOTE
143.7, 141.8, 137.0, 136.4, 133.0, 130.7, 128.6, 128.4, 128.0, 127.9, 126.3,
126.2, 126.0, 45.0, 41.8, 19.9.
N-Tosyl-(4-chlorophenyl)phenylmethylamine17d (Table 4, entry 9):
1H NMR δ 7.54 (d, J = 8.4 Hz, 2H), 7.20ꢀ7.19 (m, 3H), 7.17ꢀ7.12 (m,
4H), 7.06ꢀ7.04 (m, 4H), 5.53 (d, J = 7.2 Hz, 1H), 5.41 (d, J = 7.2 Hz,
1H), 2.38 (s, 3H); 13C NMR δ 143.4, 140.0, 139.0, 137.2, 133.4, 129.4,
128.8, 128.7, 128.6, 127.8, 127.2, 127.1, 60.7, 21.5.
4,4-Diphenylbutan-2-one11e (Table 3, entry 4): 1H NMR δ 7.27 (t,
J = 7.8 Hz, 4H), 7.24 (d, J = 7.2 Hz, 4H), 7.17 (t, J = 7.2 Hz, 2H), 4.59 (t,
J = 7.2 Hz, 1H), 3.18 (d, J = 7.8 Hz, 2H), 2.08 (s, 3H); 13C NMR δ 206.9,
143.8, 128.6, 127.7, 126.4, 49.7, 46.0, 30.6.
4-Phenyl-4-p-tolylbutan-2-one11e (Table 3, entry 5): 1H NMR δ 7.25
(t, J = 7.2 Hz, 2H), 7.21 (d, J = 7.2 Hz, 2H), 7.16 (t, J = 7.2 Hz, 1H),
7.11ꢀ7.07 (m, 4H), 4.54 (t, J = 7.2 Hz, 1H), 3.15 (d, J = 7.2 Hz, 2H),
2.28 (s, 3H), 2.06 (s, 3H); 13C NMR δ 206.9, 144.0 140.7, 135.9, 129.2,
128.5, 127.5, 127.4, 126.3, 49.7, 45.6, 30.6, 20.9.
’ ASSOCIATED CONTENT
S
Supporting Information. NMR spectra of CuCl/bipyr-
b
idine-catalyzed addition reaction products. This material is
available free of charge via the Internet at http://pubs.acs.org.
4-(4-Methoxyphenyl)-4-phenylbutan-2-one11e (Table 3, entry 6):
1H NMR δ 7.26 (t, J = 7.2 Hz, 4H), 7.21ꢀ7.19 (m, 2H), 7.16 (t, J =
7.2 Hz, 2H), 7.13 (d, J = 7.2 Hz, 2H), 6.81 (d, J = 7.2 Hz, 2H), 4.53 (t, J =
7.2 Hz, 1H), 3.75 (s, 3H,), 3.14 (d, J = 7.8 Hz, 2H), 2.06 (s, 3H); 13C
NMR δ 207.0, 158.0, 144.2, 135.9, 128.6, 128.5, 127.5, 126.3, 113.9,
55.1, 49.8, 45.2, 30.6.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: qiaosheng.hu@csi.cuny.edu.
4-Phenyl-4-o-tolylbutan-2-one11e (Table 3, entry 7): 1H NMR δ
7.25ꢀ7.22 (m, 3H), 7.19ꢀ7.09 (m, 6H), 4.78 (t, J = 7.2 Hz, 1H), 3.14 (d,
J = 7.2 Hz, 2H), 2.29 (s, 3H), 2.06 (s, 3H); 13C NMR δ 206.9, 143.4, 141.5,
136.3, 130.7, 128.4, 127.9, 126.40, 126.2 (2C), 126.0, 50.0, 41.9, 30.6, 19.8.
4-Phenyloctan-2-one11c (Table 3, entry 8): 1H NMR δ 7.28 (t, J = 7.8
Hz, 2H), 7.20ꢀ7.16 (m, 3H), 3.10 (m, 1H), 2.75ꢀ2.67 (m, 2H), 2.01 (s,
3H), 1.65ꢀ1.52 (m, 2H), 1.31ꢀ1.18 (m, 2H), 1.17ꢀ1.05 (m, 2H), 0.82
(t, J = 7.2 Hz, 3H); 13C NMR δ 208.0, 144.6, 128.4, 127.4, 126.3, 50.9,
41.3, 36.2, 30.6, 29.5, 25.6, 22.6, 13.9.
’ ACKNOWLEDGMENT
We gratefully thank the NSF (CHE0719311) for funding.
Partial support from PSCꢀCUNY Research Award Programs is
also acknowledged. We thank the Frontier Scientific for its
generous gifts of arylboronic acids.
’ REFERENCES
4-p-Tolyloctan-2-one11c (Table 3, entry 9): 1H NMR δ 7.09 (d, J = 8.4
Hz, 2H), 7.05 (d, J = 7.8 Hz, 2H), 3.07ꢀ3.05 (m, 1H), 2.72ꢀ2.67 (m,
2H), 2.30 (s, 3H), 2.00 (s, 3H), 1.61ꢀ1.51 (m, 2H), 1.28ꢀ1.20 (m, 2H),
1.16ꢀ1.07 (m, 2H), 0.82 (t, J = 7.2 Hz, 3H); 13C NMR δ 208.2, 141.5,
135.7, 129.1, 127.3, 51.1, 40.9, 36.2, 30.6, 29.6, 22.6, 21.0, 13.9.
General Procedure for CuCl/Bipyridine-Catalyzed Addi-
tion Reactions of Arylboroxines with N-Tosyl Aldimine. To a
10 mL pressure vial containing N-tosyl aldimine (0.25 mmol), arylbor-
oxine (0.168 mmol), base (NaOAC, 0.75 mmol), and CuCl/bipyridine
(0.025 mmol/0.05 mmol) was added toluene/4-chlorotoluene (total
1.0 mL, 1:1 ratio). The vial was then sealed with a rubber septum and
placed in the microwave reactor. After the mixture in the sealed vial was
irradiated by microwave at 180 °C for 30 min, the reaction was quenched
by adding 4 N HCl (2 mL) aqueous solution. The mixture was extracted
with CH2Cl2 (3 ꢁ 15 mL). The organic layers were combined. After
evaporation of the organic solvents, the residue was subjected to column
chromatography [silica gel, ethyl acetate/hexane (v/v = 1:20) as eluent]
to afford the products.
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N-Tosyldiphenylmethylamine17c (Table 4, entry 4): 1H NMR δ 7.56
(d, J = 8.4 Hz, 2H), 7.21ꢀ7.09 (m, 12H), 5.57 (d, J = 7.8 Hz, 1H), 5.18
(d, J = 7.2 Hz, 1H), 2.37 (s, 3H); 13C NMR δ 143.2, 140.5, 137.3, 129.3,
128.5, 127.5, 127.3, 127.2, 61.3, 21.5.
N-Tosylphenyl-(p-tolyl)methylamine17d (Table 4, entries 5 and 8):
1H NMR δ 7.56 (d, J = 8.4 Hz, 2H), 7.21ꢀ7.20 (m, 3H), 7.14ꢀ7.10 (m,
4H), 7.02ꢀ6.96 (m, 4H), 5.52 (d, J = 7.8 Hz, 1H), 5.10 (d, J = 7.2 Hz,
1H), 2.38 (s, 3H), 2.28 (s, 3H); 13C NMR δ 143.2, 140.5, 137.3, 129.3,
128.5, 127.5, 127.3, 127.2, 61.3, 21.5, 21.0.
N-Tosylphenyl-(o-tolyl)methylamine17d (Table 4, entry 6): 1H NMR
δ 7.55 (d, J = 7.8 Hz, 2H), 7.21ꢀ7.19 (m, 3H), 7.13ꢀ7.10 (m, 4H),
7.06ꢀ7.05 (m, 4H), 5.80 (d, J = 7.2 Hz, 1H), 5.10 (d, J = 6.6 Hz, 1H),
2.37 (s, 3H), 2.16 (s, 3H); 13C NMR δ 143.2, 140.0, 138.2, 137.4, 135.5,
130.6, 129.3, 128.5, 127.6, 127.5, 127.2, 127.1, 126.1, 58.1, 21.5, 19.3.
N-Tosyl-(4-methoxyphenyl)-phenylmethylamine17d (Table 4, entry 7):
1H NMR δ 7.56 (d, J = 7.8 Hz, 2H), 7.22ꢀ7.17 (m, 3H), 7.14ꢀ7.10 (m,
4H), 7.00 (d, J = 8.4 Hz, 2H), 6.73 (d, J = 8.4 Hz, 2H), 5.52 (d, J = 6.6 Hz,
1H), 5.09 (d, J = 7.2 Hz, 1H), 3.75 (s, 3H), 2.38 (s, 3H); 13C NMR δ160.0,
143.1, 140.7, 137.4, 132.7, 129.3, 128.6, 128.5, 127.4, 127.3, 127.2, 60.8,
55.2, 21.5.
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