A palladium-catalyzed arylation of N-acyl-N,O-acetals with arylboronic reagents: Synthesis of diarylmethylamines protected by easily removable acyl group

Article abstract of DOI:10.1016/j.tet.2015.06.017

An efficient process was developed to synthesis diarylmethylamines protected by a readily removable acyl group using a palladium-catalyzed arylation of N-acyl-N,O-acetals with arylboronic reagents. The attractive features of this protocol are: the ease of

Full text of DOI:10.1016/j.tet.2015.06.017

Tetrahedron 71 (2015) 5337e5340
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A palladium-catalyzed arylation of N-acyl-N,O-acetals with
arylboronic reagents: synthesis of diarylmethylamines protected by
easily removable acyl group
*
Qian Chen , Chao Liu, Fang Guo, Liang Li
State Key Lab of Urban Water Resource and Environment (SKLUWRE) & Academy of Fundamental and Interdisciplinary Science,
Harbin Institute of Technology, Harbin, Heilongjiang 150080, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient process was developed to synthesis diarylmethylamines protected by a readily removable
acyl group using a palladium-catalyzed arylation of N-acyl-N,O-acetals with arylboronic reagents. The
attractive features of this protocol are: the ease of preparing substrate and the mild reaction condition
under an air atmosphere. Moderate enantioselectivity was observed in preliminary screening studies of
chiral ligands.
Received 6 February 2015
Received in revised form 1 June 2015
Accepted 3 June 2015
Available online 10 June 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Palladium-catalyzed
Arylation
N-Acyl-N,O-acetal
Arylboronic reagents
Diarylmethylamines
1. Introduction
asymmetric addition of arylboronic acids to ketimines, re-
spectively.8 Lautens reported that, trifluoromethylacetaldimines,
Diarylmethylamines are important structural motifs and po-
tential intermediates for some biologically significant pharmaceu-
ticals. Asymmetric addition of arylmetal reagents to C]N double
bonds of arylimines is a fundamentally important process that
represents one of the most straightforward ways to access chiral
diarylmethylamines in high yields and stereoselectivities.1 Among
them, Rh catalytic asymmetric addition of arylmetal reagents to C]
N double bonds of arylimines has been most extensively in-
vestigated.2 The early success of this type of arylation was reported
by Hayashi, and they realized the asymmetric addition of aryl-
stannane or aryltitannium reagents to N-sulfonylimines using
Rh(I)-MOP and BINAP system.3 In 2004, Tomioka demonstrated the
first example of adding arylboronic reagents to N-tosylarylimines
using a chiral Rh(I)-amidomonophosphane as catalyst, which
subsequently attracted considerable attentions.4,5
generated in situ from the corresponding N,O-acetals, undergo 1,2-
addition of arylboroxines under palladium(II) catalysis to generate
a variety of (trifluoromethyl)arylmethylamines with good to high
enantioselectivity.9
In another hand, the N-tosylarylimines shown a higher re-
activity in Rh and Pd catalytic arylation, however, the conditions
required for the reductive removal of a tosyl group from nitrogen,
such as costly samarium(II) iodide with HMPA in refluxing THF, are
incompatible with electron-accepting functional groups, e.g., car-
bonyl, nitro, and halogens. Therefore, a great deal of effort to access
chiral diarylmethylamines is to search substrates other than N-
tosylarylimines, in which the protective group of adducts can be
more easily removed. In this regard, the N-tert-butanesulfinyl
group,10 N,N-dimethylsulfamoyl,11 and the N-diphenylphosphinoyl
group can be cleaved under mild conditions that tolerate even
sensitive functionality.12 Curiously, although acyl groups are
broadly used for protection of an amino group, only few reports,
such as in situ generated N-Boc-imines and N-formylimines, feature
the use of the acyl imines as the substrate for this
transformation.13,14
Comparing with rhodium catalysis, the palladium-catalyzed
addition of arylboronic reagents to imines has fell behind and
become feasible only recently.6 Based on different chiral ligands,
such as bidentate N-heterocyclic carbene, bisphosphane, and
pyridine-oxazoline (Pyrox), several approaches have been de-
veloped for N-tosylarylimines.7 Zhang and Hayashi also reported
Herein, we report the first palladium-catalyzed arylation of N-
acyl-N,O-acetals with arylboronic reagents, thus representing
a practical synthesis of diaryl amines under an air atmosphere.
* Corresponding author. E-mail address: chenqian@hit.edu.cn (Q. Chen).
http://dx.doi.org/10.1016/j.tet.2015.06.017
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

5338
Q. Chen et al. / Tetrahedron 71 (2015) 5337e5340
2. Results and discussion
example, 3,5-dimethoxyphenyl and 2,6-dichlorophenyl, were suc-
cessfully obtained in moderate to high yields (52e84%) (Scheme 1,
2ie2l).
Considering the acyl imines are less stable, we chose N-acyl-O-
ethyl-N,O-acetals as a precursor of acyl imines. N-acyl-O-ethyl-N,O-
acetals can be prepared from aromatic aldehydes with a broad
range of amides mediated by Ti(OEt)4.15 To explore a new catalytic
system for this transformation, a model reaction using easily ac-
cessible phenylboronic acid or phenylboroxine and N-acyl-O-ethyl-
N,O-acetal 1a was investigated in detail by varying different pa-
rameters such as catalyst, ligand, base, and solvent to develop ap-
propriate reaction conditions (Table 1). At the outset, when Rh(I)
was used as catalysts, no reaction was observed in the presence of
base or not in dioxane (Table 1, entries 1 and 2). Then Pd(II) was
screened using 2,2-bipyridine (bpy) as ligand. No reaction was
observed without base, while ether exchange product was obtained
when K2CO3 was used as base in methanol (Table 1, entries 3 and
4).16 However, the reaction proceeded smoothly in 1,2-dichloro
ethane (DCE) (Table 1, entry 5). Lower reaction temperature, the
yield was improved a little (Table 1, entry 6). It should be note that,
air is essential to promote the transformation. No improvement
was founded under O2 atmosphere, while no reaction was detected
under N2 atmosphere (Table 1, entries 7 and 8). Lower yield was
observed when phenylboroxine was replaced by phenylboronic
acid (Table 1, entry 9). Pd(TFA)2 shown similar catalytic activity,
while PdCl2(CH3CN)2 could not catalyze the reaction (Table 1, en-
tries 10 and 11).
O
Ar2
Ar1
O
OEt
Ar1
Pd(OAc)2, bpy
DCE, 60°C, air
(Ar2BO)3
+
R
N
H
R
N
H
O
Ph
O
Ph
O
Ph
O
Ph
Ph
N
H
Ph
N
H
Ph
N
Ph
N
H
H
OMe
MeO
OMe
2c 71%
2b 66%
2d 83%
Ph
2e 68%
Cl
O
Ph
O
O
Ph
O
Ph
N
H
Ph
Cl
N
H
Ph
N
H
BnO
Ph
N
H
Cl
Cl
Cl
2h 63%
2i 59%
2g 65%
2f 49%
O
Ph
O
Ph
Cl
O
Ph
MeO
MeO
N
N
N
H
H
H
Cl
MeO
ClMeO
OMe
OMe
2l 52%
2k 84%
2j 53%
Scheme 1. Substrate scope. Reagents and conditions: N,O-acetals (0.3 mmol), ar-
ylboroxine (0.3 mmol), Pd(OAc)2 (0.015 mmol), bpy (0.018 mmol), DCE, 60 ꢀC, 18 h.
Next, the asymmetric version of this reaction was investigated.
First, we screened some nitrogen-containing and diphosphine li-
gands instead of the bpy as shown in Table 2. We initially employed
the easily available pyridine-oxazoline (Pyrox) and bisoxazoline as
ligands. We were disappointed that no reaction was observed when
using the Pyrox (L1) and bisoxazolines (L2 and L3) instead of the
bpy, the started material was recovered and some decomposed
compounds were detected (Table 2, entries 1e3). Phosphinoox-
azoline ligand, L4, was also not a good ligand for the present re-
action (Table 2, entry 4). When using the R-Binap instead of the bpy,
the reaction proceeded smoothly, giving the protected diary-
lmethylamine in 80% yield, but the enantioselectivity was marginal
(Table 2, entry 5). Subsequently, we speculated that the position of
a substituent on the phenyl ring of acetals could have a positive
influence on the enantioselectivity. In fact, the enantioselectivity
was improved to 12% by introducing a chloride atom to the ortho-
position of benzene in acetal (Table 2, entry 6). The
Table 1
Optimization of the reaction conditions
O
Ph
O
OEt
Catalyst
Ligand
Ph
N
H
Ph
N
H
+
(PhBO)3
solvent
NO2
NO2
2a
1a
Entry Cat. (mol %)
Ligand
(mol %)
Solvent
T (ꢀC) Time Yielda
(h)
(%)
1b
2
[RhCl(C2H4)2]2 (1.5) dppe (3) Dioxane-H2O 80
10
10
15
15
12
12
12
12
12
12
12
d
d
d
d
70
79
d
75
37
78
d
[RhCl(C2H4)2]2 (1.5) dppe (3) Dioxane
80
80
80
80
60
60
60
60
60
60
3c,d
4
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(TFA)2 (5)
PdCl2(CH3CN)2 (5)
bpy (6)
bpy (6)
bpy (6)
bpy (6)
bpy (6)
bpy (6)
bpy (6)
bpy (6)
bpy (6)
MeOH
MeOH
DCE
DCE
DCE
DCE
DCE
DCE
DCE
5
6
7e
8f
9g
10
11
Table 2
Asymmetric arylation of N-acyl-N,O-acetala
a
Isolated yield.
3 equiv PhB(OH)2 and 1 equiv KOH was used.
2 equiv K2CO3 was used.
Ether exchange product was obtained (see notes 16).
Under N2.
Under O2.
b
c
d
e
f
Entry
Ar1
Ligand(mol %)
Yield(%)b
Ee(%)c
1
2
3
4
5
6
7
8
9
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
2-ClC6H4
2-MeOC6H4
4-MeOC6H4
2-BnOC6H4
L1
L2
L3
L4
d
d
d
d
80
52
57
43
18
d
d
d
d
1
12
37
1
g
3 equiv PhB(OH)2 was used.
R-Binap (6)
R-Binap (6)
R-Binap (6)
R-Binap (6)
R-Binap (6)
Having identified optimized reaction conditions (Table 1, entry 6),
we next evaluated the substrate scope of the palladium-catalyzed
arylation. As shown in Scheme 1, the nature of the substituent on
the phenyl ring of the N,O-acetals had very little effect on the re-
activity. N,O-acetals, in which aryl groups having electron-donating
andewithdrawing substituted groups, for example, 2-
30
a
Reaction conditions: N,O-acetals (0.3 mmol), arylboroxine (0.3 mmol), Pd(OAc)2
(0.015 mmol), chiral ligand (0.018 mmol), DCE, 60 ꢀC, 18 h.
b
Isolated yield.
methoxyphenyl,
3-methoxyphenyl,
4-methoxyphenyl,
4-
c
Determined by HPLC using chiral Daicel column with hexane-i-PrOH as solvent.
chlorophenyl, and 2-chlorophenyl groups were smoothly con-
verted into protected diarylmethylamines, giving the correspond-
ing 2 in good to high yields (49e83%) (Scheme 1, 2be2h). More
over, the aryl of acyl in N,O-acetals can be variable. Thus, the desired
protected diarylmethylamines, in which aryl groups of acyl having
electron-donating andewithdrawing substituted groups, for
O
O
N
O
N
O
N
O
O
t-Bu
N
N
N
N
PPh2
L4
Bn
Bn
L1
L2
L3

Q. Chen et al. / Tetrahedron 71 (2015) 5337e5340
5339
enantioselectivity was further improved to 37% when acetal bear-
ing 2-methoxyphenyl was used as substrate (Table 2, entry 7). The
acetal with 4-methoxyphenyl gave a racemic product (Table 2,
entry 8). Lower reactivity and lower enantioselectivity was ob-
served when the methyl of 2-methoxyl benzene in acetal was
replaced by benzyl (Table 2, entry 7 vs entry 9). Future focus will be
paid to improve the enantioselectivity of this transformation.
In conclusion, we developed a palladium-catalyzed arylation of
N-acyl-N,O-acetals with arylboronic reagents to yield diary-
lmethylamines protected by a readily removable acyl group. The
ease of preparing substrate and the mild reaction condition make
this transformation attractive and representing a practical syn-
thesis of diaryl amines under an air atmosphere. Preliminary
screening studies of chiral ligands indicated the possibility of the
asymmetric version of the present reaction. Further studies are
underway at screening other ligands and/or designing novel chiral
ligand for this reaction.
1H), 3.82 (s, 3H). 13C NMR (101 MHz, CDCl3)
d
166.4, 159.0, 141.7,
134.3, 133.7, 131.7, 128.9, 128.5, 127.4, 127.0, 114.2, 56.9, 55.3. IR(KBr)
3303, 1635, 1528, 698. HRMS-ESI (m/z): [MþH]þ calcd for
C
21H19NO2 318.1494, found 318.1494.
Compound 2e: Yield 68%, white solid, mp 123e125 ꢀC. 1H NMR
(400 MHz, CDCl3)
d
7.95e7.73 (m, 2H), 7.53 (d, J¼7.4 Hz, 1H), 7.47 (t,
J¼7.5 Hz, 2H), 7.41e7.23 (m, 5H), 7.07e6.79 (m, 3H), 6.69 (d,
J¼7.6 Hz,1H), 6.45 (d, J¼7.8 Hz,1H), 3.80 (s, 3H). 13C NMR (100 MHz,
CDCl3)
d 166.5, 159.9, 143.1, 141.4, 134.3, 131.7, 129.8, 128.7, 127.6,
127.1, 119.8, 113.6, 112.7, 57.4, 55.2. IR(KBr) 3306, 1635, 1526, 699.
HRMS-ESI (m/z):[MþH]þ calcd for C21H19NO2 318.1494, found
318.1494.
Compound 2f: Yield 49%, white solid, mp 179e182 ꢀC. 1H NMR
(400 MHz, CDCl3) d 7.76e7.57 (m, 3H), 7.50e7.43 (m, 2H), 7.41e7.23
(m, 10H), 7.16 (dd, J¼7.2, 2.1 Hz, 2H), 7.05 (dd, J¼13.6, 7.5 Hz, 2H),
6.62 (d, J¼9.0 Hz, 1H), 5.01 (m, 2H). 13C NMR (100 MHz, CDCl3)
d
166.1, 156.3, 141.9, 136.3, 134.5, 131.3, 130.2, 129.1, 128.4, 127.9,
126.9, 126.6, 121.4, 112.4, 70.2, 55.4. IR(KBr) 3340, 1634, 1519, 750.
HRMS-ESI (m/z): [MþH]þ calcd for C27H23NO2 394.1807, found
394.1808.
3. Experimental section
3.1. General information
Compound 2g: Yield 65%, white solid, mp 144e147 ꢀC. 1H NMR
(400 MHz, CDCl3)
d
7.88e7.80 (m, 2H), 7.55 (t, J¼7.3 Hz, 1H), 7.48
Commercial reagents were purchased and used without further
purification. Dioxane was distilled from LiAlH4 under nitrogen. DCE
and CH3OH were distilled over CaH2 under nitrogen. HRMS were
obtained from Agilent 6520 Q-TOF LC/MS. 1H and 13C NMR data was
acquired on a Bruker AV-400 MHz spectrometer. N-acyl-N,O-acetals
were prepared according to a literature procedure.15
(t, J¼7.5 Hz, 2H), 7.43e7.23 (m, 8H), 6.64 (d, J¼7.7 Hz, 1H), 6.44 (d,
J¼7.6 Hz, 1H). 13C NMR (100 MHz, CDCl3)
d 166.5, 140.0, 134.0,
131.9, 128.8, 127.9, 127.6, 127.0, 57.0. IR(KBr) 3256, 1635, 1535, 696.
HRMS-ESI(m/z):[MþH]þ calcd for C20H16ClNO 322.0999, found
322.0996.
Compound 2h: Yield 63%, white solid, mp 162e164 ꢀC. 1H NMR
(400 MHz, CDCl3)
d
7.93e7.78 (m, 2H), 7.54 (d, J¼7.3 Hz, 1H),
3.2. General procedure for synthesis of diarylmethylamines 2
7.51e7.41 (m, 4H), 7.40e7.25 (m, 6H), 6.87 (d, J¼7.5 Hz, 1H), 6.75 (d,
J¼7.7 Hz, 1H). 13C NMR (100 MHz, CDCl3)
d 166.4, 140.0, 138.5, 134.1,
In 25 mL flask, palladium acetate (0.015 mmol, 5 mol %) and li-
gand (0.018 mmol, 6 mol %) were dissolved in 2 mL DCE and the
yellow solution was stirred 15 min at room temperature. The N,O-
acetal (0.30 mmol, 1 equiv) and the aryl boroxine (0.30 mmol,
1 equiv) were then added as a solid. The mixture was stirred at
60 ꢀC under air. After the indicated amount of time, the reaction
was cooled to room temperature. After dilution with CH2Cl2, the
mixture was washed with saturated NaHCO3 and brine, and then
dried over Na2SO4. Then the solvent was evaporated to dryness
under vacuum. The resulting residue was purified by silica gel
column chromatography to afford the desired product.
131.8, 130.4, 129.1, 128.7, 127.7, 127.4, 127.1, 55.6. IR(KBr) 3301,2925,
1638, 1536, 751. HRMS-ESI (m/z): [MþH]þ calcd for C20H16ClNO
322.0999, found 322.0997.
Compound 2i: Yield 59%, white solid, mp 159e161 ꢀC. 1H NMR
(400 MHz, CDCl3)
d 7.44e7.32 (m, 9H), 7.32e7.25 (m, 2H), 6.49 (d,
J¼7.8 Hz, 1H), 6.31 (d, J¼7.3 Hz, 1H). 13C NMR (100 MHz, CDCl3)
d
163.7, 140.3, 139.2, 135.6, 133.5, 132.4, 130.8, 128.9, 128.1, 127.7,
57.0. IR(KBr) 3201, 1646, 1536, 697. HRMS-ESI(m/z):[MþH]þ calcd
for C20H14Cl3NO 390.0219, found 390.0222.
Compound 2j: Yield 53%, white solid, mp 189e192 ꢀC. 1H NMR
(400 MHz, CDCl3)
d 7.44e7.10 (m, 9H), 7.04e6.88 (m, 2H), 6.83 (d,
Compound 2a: Yield 79%, white solid, mp 159e162 ꢀC. 1H NMR
J¼8.0 Hz,1H), 6.65 (d, J¼8.7 Hz,1H), 3.72 (s, 3H). 13C NMR (100 MHz,
(400 MHz, CDCl3)
d
8.24 (d, J¼8.7 Hz, 2H), 7.85 (d, J¼7.3 Hz, 2H),
CDCl3) d 171.5, 146.6, 133.7, 128.0, 127.2, 122.1, 115.4, 83.4, 61.5.
7.63e7.44 (m, 5H), 7.44e7.34 (m, 3H), 7.30 (s, 1H), 6.70 (d, J¼7.0 Hz,
IR(KBr) 3296, 1650, 1529, 1248, 747. HRMS-ESI(m/z):[MþH]þ calcd
for C21H17Cl2NO2 386.0715, found 386.0718.
1H), 6.51 (d, J¼7.1 Hz, 1H). 13C NMR (100 MHz, CDCl3)
d 159.1, 138.8,
135.6, 128.7, 127.6, 127.1, 126.5, 123.2, 119.7, 107.2, 106.7, 101.2, 69.1,
32.5. IR(KBr) 3307, 1633, 1517, 1349, 696. HRMS-ESI (m/z): [MþH]þ
calcd for C20H16N2O3 333.1239, found 333.1245.
Compound 2k: Yield 84%, white solid, mp 175e177 ꢀC. 1H NMR
(400 MHz, CDCl3)
d
7.49e7.16 (m, 8H), 6.95 (d, J¼2.2 Hz, 2H),
6.70e6.57 (m, 2H), 6.40 (d, J¼7.6 Hz, 1H), 3.84 (s, 6H). 13C NMR
Compound 2b: Yield 66%, white solid, mp 170e171 ꢀC. 1H NMR
(100 MHz, CDCl3) d 166.3, 161.0, 140.9, 139.9, 136.2, 133.4, 129.0,
(400 MHz, CDCl3)
d
7.94e7.78 (m, 2H), 7.54 (t, J¼7.4 Hz, 1H), 7.47 (t,
127.9, 127.5, 105.1, 103.6, 57.0, 55.6. IR(KBr) 3280, 1591, 1527, 1248,
1151, 761. HRMS-ESI(m/z):[MþH]þ calcd for C22H20ClNO3 382.1210,
found 382.1216.
J¼7.4 Hz, 2H), 7.42e7.26 (m, 5H), 7.20 (q, J¼8.2 Hz, 4H), 6.66 (d,
J¼7.6 Hz,1H), 6.44 (d, J¼7.7 Hz,1H), 2.37 (s, 3H). 13C NMR (100 MHz,
CDCl3)
d
166.4, 141.6, 138.6, 137.3, 134.3, 131.7, 129.5, 128.7, 127.7,
Compound 2l: Yield 52%, white solid, mp 232e234 ꢀC. 1H NMR
127.0, 57.2, 21.1. IR(KBr) 3307, 1638, 1522, 703. HRMS-ESI (m/z):
(400 MHz, CDCl3) d 7.42e7.16 (m, 7H), 7.08e6.85 (m, 4H), 6.61 (dd,
[MþH]þ calcd for C21H19NO 302.1545, found 302.1549.
J¼4.9 and 2.6 Hz, 2H), 3.85 (s, 6H), 3.81 (s, 3H). 13C NMR (100 MHz,
Compound 2c: Yield 71%, white solid, mp 151e153 ꢀC. 1H NMR
CDCl3) d 166.2, 160.9, 157.3, 141.7, 137.0, 129.7, 129.0, 128.3, 127.0,
(400 MHz, CDCl3)
d
7.96e7.75 (m, 2H), 7.60e7.43 (m, 4H), 7.42e7.20
126.7, 121.1, 111.7, 105.1, 103.4, 55.6, 54.9. IR(KBr) 3253, 1595, 1156,
748. HRMS-ESI (m/z): [MþH]þ calcd for C23H23NO4 378.1705, found
378.1694.
(m, 6H), 7.13e6.79 (m, 2H), 6.65 (d, J¼8.8 Hz, 1H), 3.82 (s, 3H). 13
C
NMR (100 MHz, CDCl3) d 166.4, 157.3, 141.8, 134.7, 131.5, 129.7, 129.1,
128.6, 128.3, 127.0, 126.7, 121.1, 111.7, 55.6, 54.8. IR(KBr) 3315, 1630,
1533, 697. HRMS-ESI(m/z):[MþH]þ calcd for C21H19NO2 318.1494,
found 318.1496.
3.3. General procedure for asymmetric synthesis of diary-
lmethylamines 2
Compound 2d: Yield 83%, white solid, mp 180e181 ꢀC. 1H NMR
(400 MHz, CDCl3)
d
7.94e7.76 (m, 2H), 7.60e7.42 (m, 3H), 7.41e7.18
These were synthesized in an exactly analogous manner to ra-
(m, 6H), 7.01e6.81 (m, 2H), 6.67 (d, J¼7.4 Hz, 1H), 6.43 (d, J¼7.7 Hz,
cemic compounds 2 but using R-BINAP as ligand.

5340
Q. Chen et al. / Tetrahedron 71 (2015) 5337e5340
20
Compound (þ)-2a: Yield 80%, white solid, mp 160e162 ꢀC. [
a]
D
3. (a) Hayashi, T.; Ishigetani, M. J. Am. Chem. Soc. 2000, 122, 976; (b) Hayashi, T.;
Ishigetani, M. Tetrahedron 2001, 57, 2589; (c) Hayashi, T.; Kawai, M.; Tokunaga,
N. Angew. Chem., Int. Ed. 2004, 43, 6125.
4. Kuriyama, M.; Soeta, T.; Hao, X. Y.; Chen, Q.; Tomioka, K. J. Am. Chem. Soc. 2004,
126, 8128.
5. (a) Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani, R.; Hayashi, T.
J. Am. Chem. Soc. 2004, 126, 13584; (b) Otomaru, Y.; Tokunaga, N.; Shintani, R.;
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Q. J. Am. Chem. Soc. 2007, 129, 5336; (d) Duan, H.-F.; Jia, Y.-X.; Wang, L.-X.; Zhou,
Q.-L. Org. Lett. 2006, 8, 2567; (e) Yang, H.-Y.; Xu, M.-H. Chem. Commun. 2010,
9223; (f) Shao, C.; Yu, H.-J.; Wu, N.-Y.; Feng, C.-G.; Lin, G.-Q. Org. Lett. 2010, 12,
3820; (g) Shintani, R.; Narui, R.; Tsutsumi, Y.; Hayashi, S.; Hayashi, T. Chem.
Commun. 2011, 6123; (h) Cui, Z.; Yu, H.-J.; Yang, R.-F.; Gao, W.-Y.; Feng, C.-G.;
Lin, G.-Q. J. Am. Chem. Soc. 2011, 133, 12394.
þ0.3 (c 0.1 CHCl3), 1% ee (OJ-H, hexane-i-PrOH/9:1, 0.5 mL/min,
254 nm, 8.1 and 9.7 min for major and minor).
20
Compound (þ)-2c: Yield 57%, white solid, mp 150e152 ꢀC. [
a]
D
þ15.0 (c 0.1 CHCl3), 37% ee (OJ-H, hexane-i-PrOH/49:1, 0.5 mL/min,
254 nm, 27.9 and 22.3 min for major and minor).
20
Compound (þ)-2d: Yield 43%, white solid, mp 179e181 ꢀC. [
a]
D
þ0.2 (c 0.1 CHCl3), 1% ee (OD-H, hexane-i-PrOH/19:1, 0.5 mL/min,
254 nm, 50.8 and 37.1 min for major and minor).
20
Compound (þ)-2f: Yield 18%, white solid, mp 179e182 ꢀC. [
a]
D
þ8.2 (c 0.1 CHCl3), 30% ee (OD-H, hexane-i-PrOH/19:1, 0.5 mL/min,
6. Dai, H.; Lu, X. Org. Lett. 2007, 9, 3077.
254 nm, 33.8 and 24.7 min for major and minor).
7. (a) Ma, G.-N.; Zhang, T.; Shi, M. Org. Lett. 2009, 11, 875; (b) Yu, A.; Wu, Y.; Cheng,
B.; Wei, K.; Li, J. Adv. Synth. Catal. 2009, 351, 767; (c) Dai, H.; Lu, X. Tetrahedron
Lett. 2009, 50, 3478; (d) Marques, C. S.; Burke, A. J. Eur. J. Org. Chem. 2010, 1639.
8. (a) Yang, G.; Zhang, W. Angew. Chem., Int. Ed. 2013, 52, 7540; (b) Jiang, C.; Lu, Y.;
Hayashi, T. Angew. Chem., Int. Ed. 2014, 53, 9936.
20
Compound (þ)-2h: Yield 52%, white solid, mp 161e163 ꢀC. [
a]
D
þ16.7 (c 0.1 CHCl3), 12% ee (OJ-H, hexane-i-PrOH/99:1, 0.3 mL/min,
254 nm, 44.3 and 52.6 min for major and minor).
9. Johnson, T.; Lautens, M. Org. Lett. 2013, 15, 4043.
10. Weix, D. J.; Shi, Y.; Ellman, J. A. J. Am. Chem. Soc. 2005, 127, 1092.
11. (a) Jagt, R. B. C.; Toullec, P. Y.; Geerdink, D.; de Vries, J. G.; Feringa, B. L.; Min-
naard, A. J. Angew. Chem., Int. Ed. 2006, 45, 2789; (b) Cao, Z.; Du, H. Org. Lett.
2010, 12, 2602.
12. (a) Trincado, M.; Ellman, J. A. Angew. Chem., Int. Ed. 2008, 47, 5623; (b) Hao, X.;
Kuriyama, M.; Chen, Q.; Yamamoto, Y.; Yamada, K.; Tomioka, K. Org. Lett. 2009,
11, 4470.
Acknowledgements
We are grateful for the financial support of SKLUWRE
(No.2014TS04), ‘the Fundamental Research Funds for the Central
Universities’ (Grant No. HIT. IBRSEM.A.201404), the Natural Science
Foundation of China (NSFC No. 20902015).
13. Bishop, J. A.; Lou, S.; Schaus, S. E. Angew. Chem., Int. Ed. 2009, 48, 4337.
€
14. (a) Hermanns, N.; Dahmen, S.; Bolm, C.; Brase, S. Angew. Chem., Int. Ed. 2002, 41,
2692; (b) Nakagawa, H.; Rech, J. C.; Sindelar, R. W.; Ellman, J. A. Org. Lett. 2007,
9, 5155.
Supplementary data
15. Li, M.; Luo, B.; Liu, Q.; Hu, Y.; Ganesan, A.; Huan, P. Org. Lett. 2014, 16, 10.
16. The structure of ether exchange product is assigned as follow based on 1H NMR.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2015.06.017.
O
OMe
References and notes
Ph
N
H
NO2
1. Schmidt, F.; Stemmler, R. T.; Rudolph, J.; Bolm, C. Chem. Soc. Rev. 2006, 35, 454.
2. (a) Fagnou, K.; Lautens, M. Chem. Rev. 2003, 103, 169; (b) Hayashi, T.; Yamasaki,
K. Chem. Rev. 2003, 103, 2829; (c) Tian, P.; Dong, H.-Q.; Lin, G.-Q. ACS Catal. 2012,
2, 95.
1H NMR. (400 MHz, CDCl3)
J¼8.8Hz, 2H), 7.58e7.56 (m,1H), 7.48e7.46(m, 2H), 6.52e6.50 (br, 2H), 3.59(s, 3H).
d
8.23 (d, J¼8.8 Hz, 2H), 7.82 (d, J¼7.2 Hz, 2H), 7.69 (d,