Catalytic asymmetric addition of arylboronic acids to N-Boc imines generated in?situ using C2-symmetric cationic N-heterocyclic carbenes (NHCs) Pd2+ diaquo complexes

Article abstract of DOI:10.1016/j.tet.2010.02.037

The catalytic asymmetric addition of arylboronic acids to N-Boc imines generated in situ from stable and easily prepared α-carbamoyl sulfones was realized by using chiral cationic C₂-symmetric N-heterocyclic carbene (NHC) Pd²⁺ diaquo

Full text of DOI:10.1016/j.tet.2010.02.037

Tetrahedron 66 (2010) 2619–2623
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Catalytic asymmetric addition of arylboronic acids to N-Boc imines generated
in situ using C2-symmetric cationic N-heterocyclic carbenes (NHCs) Pd2þ diaquo
complexes
*
Zhen Liu, Min Shi
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The catalytic asymmetric addition of arylboronic acids to N-Boc imines generated in situ from stable and
Received 28 December 2009
Received in revised form 5 February 2010
Accepted 5 February 2010
easily prepared a-carbamoyl sulfones was realized by using chiral cationic C2-symmetric N-heterocyclic
carbene (NHC) Pd2þ diaquo complexes 1a–c as the catalysts, producing the corresponding adducts in
good to high yields (up to 89%) and good to high enantioselectivities (up to 90% ee).
Ó 2010 Elsevier Ltd. All rights reserved.
Available online 11 February 2010
1. Introduction
hand, previously, we reported the catalytic enantioselective aryla-
tion of N-tosylarylimines with arylboronic acids using C2-sym-
Recently, N-heterocyclic carbenes (NHCs) have been widely used
as ancillary ligands in organometallic chemistry and catalysis since
they have several significant advantages over their phosphine
metric cationic N-heterocyclic carbenes (NHCs) Pd2þ diaquo
complexes, derived from 1,10-binaphthalenyl-2,20-diamine (BINAM)
or H8-BINAM, to afford the corresponding adducts in excellent
yields (up to 99%) and good to excellent enantioselectivities (up to
94% ee).3f,10 In this paper, we wish to report the extension on the
utilization of these chiral C2-symmetric cationic NHC–Pd2þ diaquo
complexes as the catalysts for the enantioselective arylation of
counterparts such as stronger
s-donor and weaker p-acceptor
properties than phosphine ligands and their air/moisture stabilities,
which make them to be handled easily and conveniently.1,2 Even
though the chiral NHC–metal complexes have been applied in some
catalytic asymmetric transformations1b,3 such as enolate arylation,4
N-Boc imines generated in situ similarly from a-carbamoyl sulfones
with arylboronic acids under mild conditions.
p
-allyl alkylation,5 and various ring-closing reactions with carbo-
palladation,6 the fully successful examples are still limited. Thus,
further exploration of novel catalytic asymmetric system using chiral
NHC–metal complexes is still highly desirable at the present stage.
The asymmetric addition of nucleophiles to tBuOC(O)-protected
imines (N-Boc imine) has provided a straightforward synthetic
approach to chiral amines because its precursor (Boc2O) is easily
available and N-protected group (N-Boc) can be cleaved under
several convenient acidic conditions (HCl or TFA).7 Thus far, al-
though asymmetric additions of nucleophiles such as arylboronic
acids to activated imine derivatives catalyzed by Rh complexes have
made great progress,8 the asymmetric addition of arylboronic acids
to N-Boc imines was missing until Ellman and co-workers first
reported on the Rh-catalyzed asymmetric addition of arylboronic
acids to N-Boc imines generated in situ from stable and easily
2. Results and discussion
2.1. Synthesis of chiral cationic C2-symmetric N-heterocyclic
carbene (NHC) Pd2D diaquo complexes 1a–c
As shown in Figure 1, a series of the chiral cationic NHC–Pd2þ
diaquo complexes 1a–c were designed and synthesized in a six-
step pathway starting from optically active 1,10-binaphthyl-2,20-
diamine (BINAM) or H8-BINAM according to our previously
reported procedure.3f,10
2.2. Catalytic enantioselective addition of arylboronic acids to
N-Boc imines generated in situ
prepared a-carbamoyl sulfones in the presence of Et3N and K2CO3,
affording a particularly efficient and straightforward synthetic
At first, we examined the catalytic ability of chiral NHC–Pd
catalyst 1a in the reactions of a-carbamoyl sulfone 2a (1.0 equiv)
method for the preparation of various chiral amines.9 On the other
with phenylboronic acid (2.0 equiv, the formation of the homo-
coupling products (Ar–Ar) of arylboronic acids was also observed
in this reaction) to develop the optimal conditions and the results of
these experiments are summarized in Table 1. 4 Å molecular sieves
* Corresponding author.
E-mail address: mshi@mail.sioc.ac.cn (M. Shi).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.02.037

2620
Z. Liu, M. Shi / Tetrahedron 66 (2010) 2619–2623
2+
2+
N Me
OH2
N R
N
N
N
OH2
OH2
Pd
Pd
N R
-
-
TfO
OH2
TfO
2
2
N
N Me
(R)-N-Me-NHC-Pd2+ 1a (R = Me)
(R)-H8-N-Me-NHC-Pd2+ 1c (R = Me)
(R)-N-Bn-NHC-Pd2+
(R = Bn)
1b
Figure 1. Chiral cationic NHC–Pd2þ diaquo complexes 1a–c.
Table 1
Optimization of the reaction condition for catalytic enantioselective addition of arylboronic acids to N-Boc imines generated in situ using C2-symmetric cationic N-heterocyclic
carbene Pd2þ diaquo complexes 1a–c
SO2Ph
Ph
PhB(OH)2 (2 equiv), base (6 equiv), additive
*
BocHN
2a
BocHN
complex 1a, 4 A MS, solvent, 65 oC, 48 h
Me
Me
3a
Entry
Base
KOH
K2CO3
Et3N
Additivea
Solvent
Yield (%)b
ee (%)c
1
2
3
4
d
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
THF
<5
<5
<5
69
21
67
d
d
d
d
d
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
Cs2CO3
KOH
K3PO4$3H2O
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et2NH
Propylamine
DIPEA
DBU
86 (ꢁ)
82 (ꢁ)
68 (ꢁ)
72 (ꢁ)
d
5d
6e
7f
83
8g
9
<5
<5
<5
<5
17
20
<5
72
<5
<5
63
<5
<5
<5
d
10
11
12
13
14
15
16
17
18
19
20
21
d
d
72 (ꢁ)
84 (ꢁ)
d
84 (ꢁ)
d
DMAP
Et3N
Et3N
Et3N
Et3N
d
56 (ꢁ)
d
DMF
IPA
CH3CN
d
d
a
1.5 equiv of additive was added.
b
c
d
e
f
Isolated yields.
Determined by chiral HPLC.
4.0 equiv K2CO3 was added.
Complex 1b was used.
Complex 1c was used.
g
The counter anion of complex 1a was replaced with BFꢁ4 .
(240 mg for 0.15 mmol boronic acid) were added into this reaction
since N-Boc imines could be hydrolyzed by ambient moisture in the
reaction system. It was found that the reaction was sluggish
without the formation of the desired product 3a (Table 1, entries
1–3) if only base (KOH, K2CO3 or Et3N, 6.0 equiv) was used. Simi-
larly as that reported by Ellman, it was found that using Et3N
(1.5 equiv) as the additive and K2CO3 (6.0 equiv) as the base led to
the corresponding adduct 3a in 69% yield and 86% ee in dioxane at
65 ꢀC (Table 1, entry 4). The yield and the achieved ee value were
lower when 4.0 equiv of K2CO3 was used as the base under identical
conditions (Table 1, entry 5). On the basis of these tentatively op-
timized conditions, we next examined chiral NHC–Pd complexes 1b
and 1c in this reaction. We found that when chiral NHC–Pd com-
plex 1b was used as the catalyst, 3a was obtained in 67% yield and
68% ee (Table 1, entry 6), presumably due to that the sterically more
bulky Pd catalysts did not favor the catalytic process. In addition,
using chiral NHC–Pd complex 1c as the catalyst afforded 3a in 83%
yield and 72% ee under otherwise identical conditions. Poor con-
version was obtained when the counter anion of complex 1a was
replaced by BFꢁ4 (Table 1, entry 8). These results suggested that in
order to obtain superior ee value complex 1a is the best catalyst in
this asymmetric reaction, although higher yield of 3a could be re-
alized in the presence of chiral NHC–Pd complex 1c. The exami-
nation of various inorganic bases in combination with additive Et3N
as well as inorganic base K2CO3 in combination with many other
amine additives revealed that K2CO3 and Et3N are still the best
combination for this asymmetric addition reaction, which are very
similar as that of Ellman’s report (Table 1, entries 9–17). Moreover,
the examination of the solvent effect disclosed that dioxane is the
solvent of choice in the combination with K2CO3 (base) and Et3N

Z. Liu, M. Shi / Tetrahedron 66 (2010) 2619–2623
2621
Table 2
Catalytic asymmetric arylation of N-Boc Imines with phenylboronic acid
PhB(OH)2 (2 equiv), K2CO3 (6 equiv),
Ph
*
SO2Ph
Et3N (1.5 equiv), complex 1a
BocHN
R1
4 A MS, dioxane, 65 oC, 48 h
BocHN
R1
3
2
Entry
R1
Yield (%)a
ee (%)b
1
2
3
4
5
6
7
8
9
4-ClC6H4 (2b)
4-CF3C6H4 (2c)
4-FC6H4 (2d)
4-MeOC6H4 (2e)
3-ClC6H4 (2f)
3-MeC6H4 (2g)
3-MeOC6H4 (2h)
2-Thienyl (2i)
Cyclohexyl (2j)
75
83
89
52
87
71
88
84
<5
83 (S)c
87 (S)c
86 (þ)c
86 (S)c
73 (þ)
82 (ꢁ)
82 (þ)
84 (ꢁ)
d
a
Isolated yields.
b
c
Determined by chiral HPLC.
Determined by comparison of the sign of optical rotation to the literature values.5
(additive) if using NHC–Pd complex 1a as the catalyst and other
solvents such as tetrahydrofuran (THF), leading to the formation of
3a in 63% yield and 56% ee (Table 1, entry 18), dimethylformamide
(DMF), isopropyl alcohol (IPA), and CH3CN usually gave poorer re-
sults under the standard conditions (Table 1, entries 18–21).
Having established the optimal reaction conditions, the arylation
Encouraged by the above results, we next studied the asym-
metric addition reaction of a variety of arylboronic acids 4a–g with
-carbamoyl sulfone 2k under the standard conditions. The results
a
are summarized in Table 3. It was found that the corresponding
adducts 5 were produced in good to excellent yields (62–87%) and
good enantiomeric excesses (70–90%), whether they have electron-
donating or electron-withdrawing substituents on their benzene
rings (Table 3, entries 1–7).
Although the mechanism of this interesting asymmetric addi-
tion reaction has not been unequivocally established, a plausible
mechanism for this reaction has been shown in our previous
paper.3f A Pd hydroxo-complex might be the active species in this
asymmetric reaction.3f,11
of a variety of a-carbamoyl sulfones 2 having diverse substituents on
the benzene rings and [(benzenesulfonyl)cyclohexylmethyl]carbamic
acid tert-butyl ester 2j were evaluated for the reaction with
phenylboronic acid. The results are summarized in Table 2. The cor-
responding adducts 3 were obtained in high yields (up to 89%) and
good enantiomeric excesses (up to 86%) whether they have electron-
donating or electron-withdrawing substituents on the benzene rings
Table 3
Catalytic asymmetric arylation of N-Boc imine 2k with various arylboronic acids
R2B(OH)2 (2 equiv), K2CO3 (6 equiv),
R2
*
4
SO2Ph
1a
Et3N (1.5 equiv), complex
4 A MS, dioxane, 65 oC, 48 h
BocHN
Ph
BocHN
Ph
5
2k
Entry
R2
Yield (%)a
ee (%)b
1
2
3
4
5
6
7
4-ClC6H4 (4a)
4-CF3C6H4 (4b)
4-FC6H4 (4c)
4-MeOC6H4 (4d)
4-MeC6H4 (4e)
3-ClC6H4 (4f)
72
65
87
77
77
79
62
90 (R)c
88 (R)c
86 (ꢁ)
76 (R)c
70 (þ)
78 (ꢁ)
82 (ꢁ)
3-MeOC6H4 (4g)
a
Isolated yields.
b
c
Determined by chiral HPLC.
Determined by comparison of the sign of optical rotation to the literature values.5
(Table 2, entries 1–4). Furthermore, the position of substituents on
the benzene rings is also not restrictive for obtaining high enantio-
selectivities (Table 2, entries 1 and 5, and 4 and 7). It should be noted
that the asymmetric addition of phenylboronic acid to N-Boc 2-thi-
ophenyl carboxaldimine also proceeded smoothly, giving the corre-
sponding adduct 3i in 84% yield and 84% ee (Table 2, entry 8).
Unfortunately, the examination of the asymmetric addition of phe-
nylboronic acid to aliphatic substrate 2j failed to give the desired
product after 48 h (Table 2, entry 9). In addition, only a trace amount
of product was detected when the straightforward addition of phe-
nylboronic acid to the isolated pure N-Boc cyclohexyl imine was
carried out under the standard conditions.
3. Conclusion
In conclusion, we have successfully established an efficient cat-
alytic system for the enantioselective arylation of N-Boc imines
generated in situ with arylboronic acids using a series of novel chiral
C2-symmetric cationic NHC–Pd2þ diaquo complex catalysts using
K2CO3 as a base and Et3N as an additive under mild conditions. This
system provides easy access to chiral diarylmethylamides 3 or 5 in
good yields and good to high enantioselectivities. This interesting
asymmetric addition reaction also shows a broad substrate scope,
which enables the use of a variety of easily available
sulfones and arylboronic acids as the starting materials.
a-carbamoyl

2622
Z. Liu, M. Shi / Tetrahedron 66 (2010) 2619–2623
20
Development of other reactions using these NHC–Pd2þ diaquo
complex catalysts and probing the detailed mechanism are in
progress in our group.
product as a white solid (34.5 mg, 72%, 90% ee, [
a
]
ꢁ12.8 (c 0.4,
D
CHCl3), mp 124–125 ꢀC) or with N-Boc-
a
-(phenylsulfonyl)-4-chlor-
obenzylamine(57.3 mg, 0.15 mmol,1.0 equiv)and phenylboronicacid
(36.6 mg, 0.3 mmol, 2.0 equiv) to provide the product as a white solid
20
4. Experimental section
4.1. General methods
(35.5 mg, 75%, 83% ee, [
a
]
þ9.5 (c 0.7, CHCl3), mp 122–123 ꢀC). HPLC
D
(Daicel AD column, hexane/ethanol¼96:4, 1.0 mL/min, ¼222 nm):
l
tR¼10.7 min, 13.4 min. This is a known compound.9a 1H NMR (CDCl3,
400 MHz, TMS):
d 1.44 (9H, s), 5.12 (1H, m), 5.87 (1H, m), 7.17–7.22
Mp was obtained with a Yanagimoto micro melting point ap-
paratus and is uncorrected. Optical rotations were determined in
a solution of CHCl3 or CH2Cl2 at 20 ꢀC by using a Perkin–Elmer-241
(4H, m), 7.24–7.35 (5H, m). 13C NMR (CDCl3, 100 MHz, TMS):
d 28.3,
57.9, 80.0, 127.3, 127.6, 128.5, 128.71, 128.75, 133.1, 140.7, 141.5, 154.9.
4.2.3. [Phenyl-(4-trifluoromethylphenyl)methyl]carbamic acid tert-
butyl ester. The general procedure was followed with N-Boc-a-
MC polarimeter; [a .
]D-values are given in units of 10ꢁ1 deg cm2 gꢁ1
Infrared spectra were measured on a spectrometer. Unless noted,
1H NMR spectra were recorded for solution in CDCl3 with tetra-
methylsilane (TMS) as internal standard; 19F NMR spectra were
recorded at 376 MHz for a solution in CDCl3 with CFCl3 as the ex-
ternal reference. J-values are in hertz (Hz). Mass spectra were
recorded with a HP-5989 instrument and HRMS was measured by
a Finnigan MAþ mass spectrometer. Organic solvents used were
dried by standard methods when necessary. Commercially
obtained reagents were used without further purification. All
reactions were monitored by TLC with Huanghai 60F254 silica gel
coated plates. Flash column chromatography was carried out using
300–400 mesh silica gel at increased pressure. All reactions were
performed under argon using standard Schlenk techniques. The
optical purities of adducts were determined by HPLC analysis using
a chiral stationary phase column (column, Daicel Co. Chiralcel AD
and OD) and the absolute configuration of the major enantiomer
was assigned according to the sign of the specific rotation.
C2-Symmetric cationic N-heterocyclic carbenes (NHCs) Pd2þ
diaquo complexes 1a–c were prepared according to our previously
reported procedure.3f,10
(phenylsulfonyl)benzylamine (52.1 mg, 0.15 mmol, 1.0 equiv) and
4-(trifluoromethyl)phenylboronic acid (57.0 mg, 0.3 mmol, 2.0 equiv)
20
to provide the product as a white solid (34.1 mg, 65%, 88% ee, [a]
D
ꢁ54 (c 0.15, CHCl3), mp 124–125 ꢀC) or with N-Boc-
a
-(phenyl-
0.15 mmol,
sulfonyl)-4-(trifluoromethyl)benzylamine
(62.3 mg,
1.0 equiv) and phenylboronic acid (36.6 mg, 0.3 mmol, 2.0 equiv) to
20
provide the product as a white solid (44 mg, 83%, 87% ee, [
a
]
þ33.4
D
(c 0.75, CHCl3), mp 125–126 ꢀC). HPLC (Daicel AD column,
hexane/iPrOH¼95:5, 0.7 mL/min,
l
¼214 nm): tR¼13.2 min, 14.3 min.
This is a known compound.9a 1H NMR (CDCl3, 400 MHz, TMS):
d
1.44
(9H, s), 5.17 (1H, m), 5.95 (1H, m), 7.20–7.22 (2H, m), 7.26–7.35 (3H,
m), 7.38–7.40 (2H, m), 7.58 (2H, d, J¼8.0 Hz). 19F NMR (CDCl3,
376 MHz, CFCl3):
d
ꢁ65.43. 13C NMR (CDCl3, 100 MHz, TMS):
d 28.3,
58.2, 80.2, 124.1 (q, J¼270.8 Hz), 125.5 (q, J¼36 Hz), 127.3, 127.4, 127.8,
128.9, 141.1, 146.1, 154.9.
4.2.4. [(4-Fluorophenyl)phenylmethyl]carbamic
ester. The general procedure was followed with N-Boc-
acid
tert-butyl
-(phenyl-
a
sulfonyl)benzylamine (52.1 mg, 0.15 mmol, 1.0 equiv) and 4-fluoro-
phenylboronic acid (42.0 mg, 0.3 mmol, 2.0 equiv) to provide the
20
product as a white solid (47.7 mg, 87%, 86% ee, [
a
]
ꢁ12.9 (c 1.0,
D
4.2. General procedure for the enantioselective addition of
arylboronic acids to N-Boc imines generated in situ
CHCl3), mp 117–118 ꢀC) or with N-Boc-
a
-(phenylsulfonyl)-4-fluo-
robenzylamine (54.8 mg, 0.15 mmol, 1.0 equiv) and phenylboronic
acid (36.6 mg, 0.3 mmol, 2.0 equiv) to provide the product as a white
20
In a dried Schlenk tube, catalyst (0.0075 mmol), 4 Å molecular
solid (48.9 mg, 89%, 86% ee, [
a
]
þ10.1 (c 1.0, CHCl3), mp 118–119 ꢀC).
D
HPLC (Daicel AD column, hexane/iPrOH¼95:5, 0.7 mL/min,
sieves (240 mg), arylboronic acids (0.3 mmol), N-Boc-
sulfonyl)arylamine (0.15 mmol), K2CO3 (0.9 mmol), triethylamine
(31.2 L, 0.225 mmol) were dissolved in 1,4-dioxane (2 mL) under
a-(phenyl-
l
¼214 nm): tR¼10.3 min, 11.6 min. IR (KBr)
n 3371, 2925, 2854, 1686,
1509, 1235, 1173, 1043, 846, 696 cmꢁ1
TMS): 1.43 (9H, s), 5.19 (1H, m), 5.88 (1H, m), 6.96–7.02 (2H, m),
;
1H NMR (CDCl3, 400 MHz,
m
argon atmosphere. The solution was stirred at 65 ꢀC. After the
reaction was completed (monitored by TLC plates), the solvent was
removed under vacuum and the residue was purified by flash
column chromatography on silica gel eluted with ethyl acetate:-
petroleum ether (1:20, v/v) to afford the products.
d
7.18–7.24 (4H, m), 7.24–7.27 (1H, m), 7.29–7.34 (2H, m); 19F NMR
(CDCl3, 376 MHz, CFCl3):
d
ꢁ115.4; 13C NMR (CDCl3, 100 MHz, TMS):
d
28.3, 57.8, 79.9, 115.3 (d, J¼22.0 Hz), 127.2, 127.4, 128.6, 128.7, 128.8,
137.9 (d, J¼3.0 Hz), 141.8, 154.9, 161.9 (d, J¼244.3 Hz). MS (ESI) m/e
324 (Mþþ23, 10.3); HRMS (ESI) calcd for C18H20FNO2Naþ requires
324.1376. Found 324.1370.
4.2.1. (Phenyl-p-tolylmethyl)carbamic acid tert-butyl ester. The
general procedure was followed with N-Boc-a-(phenyl-
sulfonyl)benzylamine (52.1 mg, 0.15 mmol, 1.0 equiv) and 4-
4.2.5. [(4-Methoxyphenyl)phenylmethyl]carbamic acid tert-butyl
methylphenylboronic acid (40.8 mg, 0.3 mmol, 2.0 equiv) to provide
ester. The general procedure was followed with N-Boc-a-(phenyl-
sulfonyl)benzylamine (52.1 mg, 0.15 mmol, 1.0 equiv) and 4-
20
the product as a white solid (32.6 mg, 77%, 70% ee, [
CHCl3), mp 129–130 ꢀC) or with N-Boc-
a
]
þ16.8 (c 0.7,
D
a
-(phenylsulfonyl)-4-
methoxyphenylboronic acid (45.6 mg, 0.3 mmol, 2.0 equiv) to provide
20
methylbenzylamine (54.2 mg, 0.15 mmol, 1.0 equiv) and phenyl-
boronic acid (36.6 mg, 0.3 mmol, 2.0 equiv) to provide the product
the product as a white solid (36.3 mg, 77%, 76% ee, [
a
]
þ15.2 (c 0.75,
D
CHCl3), mp 98–99 ꢀC) or with N-Boc-
a-(phenylsulfonyl)-4-methox-
20
as a white solid (29.1 mg, 69%, 86% ee, [
a]
ꢁ14.1 (c 0.95, CHCl3), mp
ybenzylamine (56.6 mg, 0.15 mmol, 1.0 equiv) and phenylboronic acid
D
130–131 ꢀC). HPLC (Daicel AD column, hexane/ethanol¼96:4,
(36.6 mg, 0.3 mmol, 2.0 equiv) to provide the product as a white solid
20
1.0 mL/min,
l
¼222 nm): tR¼9.0 min, 10.8 min. This is a known
(24.5 mg, 52%, 86% ee, [
a
]
ꢁ12.6 (c 0.5, CHCl3), mp 101–102 ꢀC). HPLC
D
compound.9a 1H NMR (CDCl3, 400 MHz, TMS):
(3H, s), 5.14 (1H, m), 5.87 (1H, m), 7.12 (4H, m), 7.23–7.25 (3H, m),
7.29–7.33 (2H, m); 13C NMR (CDCl3,100 MHz, TMS):
21.1, 28.4, 58.1,
d
1.44 (9H, s), 2.32
(Daicel AD column, hexane/ethanol¼96:4, 1.0 mL/min, ¼222 nm):
l
tR¼11.7 min, 18.7 min. This is a known compound.9a 1H NMR (CDCl3,
d
400 MHz, TMS): d 1.43 (9H, s), 3.78 (3H, s), 5.12 (1H, m), 5.86 (1H, m),
79.7, 127.12, 127.13, 127.2, 128.5, 129.3, 137.0, 139.2, 142.3, 155.0.
6.84 (2H, d, J¼8.4 Hz), 7.15 (2H, d, J¼8.4 Hz), 7.23–7.25 (3H, m), 7.30–
7.33 (2H, m). 13C NMR (CDCl3, 100 MHz, TMS):
d
28.3, 55.2, 57.8, 79.7,
4.2.2. [(4-Chlorophenyl)-phenylmethyl]carbamic acid tert-butyl
113.9, 127.1, 127.2, 128.4, 128.5, 134.3, 142.3, 155.0, 158.8.
ester. The general procedure was followed with N-Boc-a-(phenyl-
sulfonyl)benzylamine (52.1 mg, 0.15 mmol, 1.0 equiv) and 4-chlor-
ophenylboronic acid (46.9 mg, 0.3 mmol, 2.0 equiv) to provide the
4.2.6. [(3-Chlorophenyl)phenylmethyl]carbamic acid tert-butyl es-
ter. The general procedure was followed with N-Boc-a-

Z. Liu, M. Shi / Tetrahedron 66 (2010) 2619–2623
2623
(phenylsulfonyl)benzylamine (52.1 mg, 0.15 mmol, 1.0 equiv) and
3-chlorophenylboronic acid (46.9 mg, 0.3 mmol, 2.0 equiv) to pro-
Supplementary data
20
vide the product as awhite solid (37.8 mg, 79%, 78% ee, [
a
]
D
ꢁ29.0 (c
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2010.02.037.
0.45, CHCl3), mp 101–102 ꢀC) or with N-Boc-
a-(phenylsulfonyl)-3-
chlorobenzylamine (57.3 mg, 0.15 mmol, 1.0 equiv) and phenyl-
boronic acid (36.6 mg, 0.3 mmol, 2.0 equiv) to provide the product
20
as a white solid (41.6 mg, 87%, 73% ee, [
a
]
D
þ13.5 (c 0.5, CHCl3),
mp 103–104 ꢀC). HPLC (Daicel OD column, hexane/iPrOH¼98:2,
References and notes
0.7 mL/min,
l
¼230 nm): tR¼11.9 min, 13.2 min. This is a known
1. (a) Bourisou, D.; Guerret, O.; Gabbai, F. P.; Bertrand, G. Chem. Rev. 2000, 100,
39–92; (b) Herrmann, W. A. Angew. Chem., Int. Ed. 2002, 41, 1290–1309; (c)
Hillier, A. C.; Grasa, G. A.; Viciu, M. S.; Lee, H. M.; Yang, C.; Nolan, S. P. J. Orga-
nomet. Chem. 2002, 653, 69–82; (d) Clavier, H.; Nolan, S. P. Annu. Rep. Prog.
Chem., Sect. B 2007, 103, 193–222; (e) Glorius, F.; Stahl, S. S.; Nolan, S. P.; Peris,
E.; Bellemin-Laponnaz, S.; Louie, J.; Ritter, T. Top. Organomet. Chem. 2007, 21,
1–218; (f) Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G. Angew. Chem., Int. Ed.
2007, 46, 2768–2813; (g) Radiusa, U.; Bickelhaupt, F. M. Coord. Chem. Rev. 2009,
253, 678–686.
compound.9a 1H NMR (CDCl3, 400 MHz, TMS):
(1H, m), 5.87 (1H, m), 7.13–7.14 (1H, m), 7.20–7.29 (6H, m), 7.31–7.35
(2H, m). 13C NMR (CDCl3, 100 MHz, TMS):
28.3, 58.1, 80.1, 125.3,
d 1.44 (9H, s), 5.14
d
127.2, 127.3, 127.5, 127.7, 128.8, 129.8, 134.5, 141.3, 144.2, 154.9.
4.2.7. [(3-Methoxyphenyl)phenylmethyl]carbamic acid tert-butyl es-
ter. The general procedure was followed with N-Boc-a-(phenyl-
2. (a) Scholl, M.; Dong, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953–956; (b)
Choi, T.-L.; Grubbs, R. H. Angew. Chem., Int. Ed. 2003, 42, 1743–1746; (c) Navarro,
O.; Kelly, R. A., III; Nolan, S. P. J. Am. Chem. Soc. 2003, 125, 16194–16195; (d)
Marion, N.; Navarro, O.; Mei, J.; Stevens, E. D.; Scott, N. M.; Nolan, S. P. J. Am.
Chem. Soc. 2006, 128, 4101–4111; (e) Navarro, O.; Marion, N.; Mei, J.; Nolan, S. P.
Chem.dEur. J. 2006, 12, 5142–5148; (f) Albrecht, M.; Crabtree, R. H.; Mata, J.;
Peris, E. Chem. Commun. 2002, 32–33; (g) Albrecht, M.; Miecznikowski, J. R.;
Samuel, A.; Faller, J. W.; Crabtree, R. H. Organometallics 2002, 21, 3596–3604.
3. (a) Gade, L. H.; Cesar, V.; Bellemin-Laponnaz, S. Angew. Chem., Int. Ed. 2004, 43,
1014–1017; (b) Van Veldhuizen, J. J.; Garber, S. B.; Kingsbury, J. S.; Hoveyda, A.
H. J. Am. Chem. Soc. 2002, 124, 4954–4955; (c) Van Veldhuizen, J. J.; Gillingham,
D. G.; Garber, S. B.; Kataoka, O.; Hoveyda, A. H. J. Am. Chem. Soc. 2003, 125,
12502–12508; (d) Larsen, A. O.; Leu, W.; Oberhuber, C. N.; Campbell, J. E.;
Hoveyda, A. H. J. Am. Chem. Soc. 2004, 126, 11130–11131; (e) Mandai, H.; Mandai,
K.; Snapper, M. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2008, 130, 17961–17969; (f)
Ma, G. N.; Zhang, T.; Shi, M. Org. Lett. 2009, 11, 875–878; (g) Lowry, R. J.; Veige,
M. K.; Cle´ment, O.; Abboud, K. A.; Ghiviriga, I.; Veige, A. S. Organometallics 2008,
27, 5184–5195; (h) Lee, K.-S.; Brown, M. K.; Hird, A. W.; Hoveyda, A. H. J. Am.
Chem. Soc. 2006, 128, 7182–7184; (i) He, M.; Beahm, B. J.; Bode, J. W. Org. Lett.
2008, 10, 3817–3820; (j) Bittermann, A.; Baskakov, D.; Herrmann, W. A. Or-
ganometallics 2009, 28, 5107–5111; (k) Neumann, E.; Pfaltz, A. Organometallics
2005, 24, 2008–2011.
sulfonyl)benzylamine (52.1 mg, 0.15 mmol, 1.0 equiv) and
3-methoxyphenylboronic acid (45.6 mg, 0.3 mmol, 2.0 equiv) to
20
provide the product as a white solid (29.0 mg, 62%, 82% ee, [a]
D
ꢁ3.3 (c 0.5, CHCl3), mp 79–80 ꢀC) or with N-Boc-
a-(phenyl-
sulfonyl)-3-methoxybenzylamine (56.6 mg, 0.15 mmol, 1.0 equiv)
and phenylboronic acid (36.6 mg, 0.3 mmol, 2.0 equiv) to provide
20
the product as a white solid (41.3 mg, 88%, 82% ee, [
a]
þ1.6 (c 1.15,
D
CHCl3), mp 77–78 ꢀC). HPLC (Daicel AD column, hexane/
ethanol¼98:2, 1.0 mL/min, ¼222 nm): tR¼22.3 min, 26.1 min. IR
(KBr) 2955, 2925, 2854, 1704, 1490, 1462, 1260, 1166, 1020, 764,
698 cmꢁ1; 1H NMR (CDCl3, 400 MHz, TMS):
1.44 (9H, s), 3.76 (3H,
s), 5.16 (1H, m), 5.87 (1H, m), 6.78–6.84 (3H, m), 7.21–7.26 (4H, m),
7.29–7.33 (2H, m). 13C NMR (CDCl3, 100 MHz, TMS):
28.3, 55.2,
l
n
d
d
58.4, 79.8, 112.5, 113.1, 119.5, 127.2, 127.3, 128.6, 129.6, 141.9, 143.7,
155.0, 159.8. MS (EI) m/e 313 (Mþ, 1.90); HRMS (EI) calcd for
C19H23NO3 requires 313.1678. Found 313.1681.
4. (a) Glorius, F.; Altenhoff, G.; Goddard, R.; Lehmann, C. Chem. Commun. 2002,
2704–2705; (b) Lee, S.; Hartwig, J. F. J. Org. Chem. 2001, 66, 3402–3415; (c)
Arao, T.; Kondo, K.; Aoyama, T. Tetrahedron Lett. 2006, 47, 1417–1420; (d)
Bertogg, A.; Camponovo, F.; Togni, A. Eur. J. Inorg. Chem. 2005, 347–356; (e)
Bonnet, L. G.; Douthwaite, R. E.; Hodgson, R. Organometallics 2003, 22,
4384–4386.
5. (a) Bonnet, L. G.; Douthwaite, R. E.; Kariuki, B. M. Organometallics 2003, 22,
4187–4189; (b) Flahaut, A.; Baltaze, J. P.; Roland, S.; Mangeney, P. J. Organomet.
Chem. 2006, 691, 3498–3508.
6. (a) Sato, Y.; Imakuni, N.; Mori, M. Adv. Synth. Catal. 2003, 345, 488–491; (b) Sato,
Y.; Imakuni, N.; Hirose, T.; Wakamatsu, H.; Mori, M. J. Organomet. Chem. 2003,
687, 392–402.
7. (a) Greene, T. W.; Wuts, P. G. Protective Groups in Organic Synthesis; John
Wiley & Sons: NY, 1999, pp 518–525; (b) The use of a-carbamoyl sulfones for
4.2.8. (Phenylthiophen-2-yl-methyl)carbamic acid tert-butyl es-
ter. The general procedure was followed with N-Boc-
sulfonyl)- -(thiophen-2-yl)-methylamine (53.0 mg, 0.15 mmol,
1.0 equiv) and phenylboronic acid (36.6 mg, 0.3 mmol, 2.0 equiv) to
a-(phenyl-
a
20
provide the product as a white solid (36.3 mg, 84%, 84% ee, [
a
]
ꢁ3.4
D
(c 0.91, CHCl3), mp 135–136 ꢀC). HPLC (Daicel AD column,
hexane/iPrOH¼95:5, 0.7 mL/min,
l
¼214 nm): tR¼19.7 min, 21.3 min.
This is a known compound.9a 1H NMR (CDCl3, 400 MHz, TMS):
d
1.44
(9H, s), 5.27 (1H, m), 6.11 (1H, m), 6.79 (1H, d, J¼3.2 Hz), 6.91 (1H, dd,
J¼3.2, 4.8 Hz), 7.20–7.22 (1H, m), 7.27–7.37 (5H, m). 13C NMR (CDCl3,
the in situ generation of N-Boc imines Petrini, M. Chem. Rev. 2005, 105,
3949–3977.
100 MHz, TMS):
d 28.3, 54.4, 80.0, 125.0, 125.4, 126.8, 126.9, 127.7,
128.6, 141.7, 146.4, 154.7.
8. (a) Kuriyama, M.; Soeta, T.; Hao, X.; Chen, Q.; Tomioka, K. J. Am. Chem. Soc. 2004,
126, 8128–8129; (b) Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.;
Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584–13585; (c) Otomaru,
Y.; Tokunaga, N.; Shintani, R.; Hayashi, T. Org. Lett. 2005, 7, 307–310; (d) Weix,
D. J.; Shi, Y.; Ellman, J. A. J. Am. Chem. Soc. 2005, 127, 1092–1093; (e) Jagt, R. B. C.;
Toullec, P. Y.; Geerdink, D.; de Vries, J. G.; Feringa, B. L.; Minnaard, A. J. Angew.
Chem., Int. Ed. 2006, 45, 2789–2791; (f) Duan, H. F.; Jia, Y. X.; Wang, L. X.; Zhou,
Q. L. Org. Lett. 2006, 8, 2567–2569; (g) Wang, Z. Q.; Feng, C. G.; Xu, M. H.; Lin, G.
Q. J. Am. Chem. Soc. 2007, 129, 5336–5337; (h) Marelli, C.; Monti, C.; Gennari, C.;
Piarulli, U. Synlett 2007, 2213–2216; (i) Vilaivan, T.; Bhanthumnavin, W.; Sri-
tana-Anant, Y. Curr. Org. Chem. 2005, 9, 1315–1392; (j) Rudolph, J.; Bolm, C.;
Norrby, P.-O. J. Am. Chem. Soc. 2005, 127, 1548–1552 For original papers in the
addition of arylboronic acid to imines; (k) Please also see Ueda, M.; Miyaura, N.
J. Organomet. Chem. 2000, 595, 31–35; (l) Ueda, M.; Saito, A.; Miyaura, N. Synlett
2000, 1637–1639.
4.2.9. (Phenyl-m-tolylmethyl)carbamic acid tert-butyl ester. The
general procedure was followed with N-Boc-a-(phenylsulfonyl)-3-
methylbenzylamine (54.2 mg, 0.15 mmol, 1.0 equiv) and phenyl-
boronic acid (36.6 mg, 0.3 mmol, 2.0 equiv) to provide the product as
20
a white solid (31.8 mg, 71%, 82% ee, [
a
]
ꢁ5.4 (c 0.75, CHCl3), mp 99–
D
100 ꢀC). HPLC (Daicel AD column, hexane/ethanol¼98:2,1.0 mL/min,
l
¼222 nm): tR¼8.8 min, 10.3 min. This is a known compound.9a 1
H
NMR (CDCl3, 400 MHz, TMS): d 1.44 (9H, s), 2.32 (3H, s), 5.13 (1H, m),
5.86 (1H, m), 7.02–7.07 (3H, m), 7.18–7.26 (4H, m), 7.30–7.34 (2H, m).
13C NMR (CDCl3, 100 MHz, TMS):
d
21.5, 28.4, 58.4, 79.7, 124.2,127.15,
9. (a) Nakagawa, H.; Rech, J. C.; Sindelar, R. W.; Ellman, J. A. Org. Lett. 2007, 9,
5155–5157; (b) For Rh(I)-catalyzed asymmetric addition of N-Dpp aryl imines
(Dpp¼diphenylphosphinoyl) with arylboronic acids, see: Weix, D. J.; Shi, Y.;
Ellman, J. A. J. Am. Chem. Soc. 2005, 127, 1092–1093.
127.24, 128.0, 128.1, 128.5, 128.6, 138.3, 142.0, 142.2, 155.0.
Acknowledgements
10. For the papers of our group on the chiral NHC–Pd(II) complexes, see: (a) Chen,
T.; Jiang, J. J.; Xu, Q.; Shi, M. Org. Lett. 2007, 9, 865–868; (b) Zhang, T.; Shi, M.
Chem.dEur. J. 2008, 14, 3759–3764; (c) Liu, L. J.; Wang, F. J.; Shi, M. Eur. J. Inorg.
Chem. 2009, 13, 1723–1728 Selected papers of Pd(II)-catalyzed asymmetric
addition of N-tosyl aryl imines with arylboronic acids: (d) He, P.; Lu, Y.; Hu, Q. S.
Tetrahedron Lett. 2007, 48, 5283–5288; (e) Zhang, Q.; Chen, J.; Wu, M.; Cheng, J.;
Qin, C.; Su, W.; Ding, J. Synlett 2008, 935–939.
We thank the Shanghai Municipal Committee of Science and
Technology (06XD14005, 08dj1400100-2), National Basic Research
Program of China (973)-2010CB833302, and the National Natural
Science Foundation of China for financial support (20872162,
20672127, 20821002, and 20732008) and also thank Mr. Jie Sun for
X-ray diffraction.
11. For directly observed transmetalation from boron to rhodium, see: Zhao, P.;
Incarvito, D. C.; Hartwig, J. F. J. Am. Chem. Soc. 2007, 129, 1876–1877.