Enantiospecific Suzuki–Miyaura Coupling of Nonbenzylic α-(Acylamino)alkylboronic Acid Derivatives

Article abstract of DOI:10.1002/asia.201800536

Suzuki–Miyaura coupling of nonbenzylic α-(acylamino)alkylboron compounds with aryl halides is established. A Pd/PCy₂Ph catalyst promotes the reaction efficiently at 145 °C. The reaction of enantioenriched α-(acylamino)alkylboron compounds affords chiral 1-arylalkylamides in high enantiospecificity and inversion of configuration.

Full text of DOI:10.1002/asia.201800536

CHEMISTRY
AN ASIAN JOURNAL
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Accepted Article
Title: Enantiospecific Suzuki-Miyaura Coupling of Nonbenzylic α-
(Acylamino)alkylboronic Acid Derivatives
Authors: Toshimichi Ohmura, Kyoko Miwa, Tomotsugu Awano, and
Michinori Suginome
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To be cited as: Chem. Asian J. 10.1002/asia.201800536
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10.1002/asia.201800536
Chemistry - An Asian Journal
COMMUNICATION
Enantiospecific Suzuki-Miyaura Coupling of Nonbenzylic
α-(Acylamino)alkylboronic Acid Derivatives
Toshimichi Ohmura,*[a] Kyoko Miwa,[a] Tomotsugu Awano,[a] and Michinori Suginome*[a]
Abstract:
Suzuki-Miyaura
coupling
of
nonbenzylic
α-
Scheme 1. Enantioenriched α-Branched Alkylboron Compounds that Induce
Enantiospecific Suzuki-Miyaura Coupling with Inversion of Configuration
(acylamino)alkylboron compounds with aryl halides is established. A
Pd/PCy2Ph catalyst promotes the reaction efficiently at 145 °C. The
reaction of enantioenriched α-(acylamino)alkylboron compounds
affords chiral 1-arylalkylamides in high enantiospecificity and
inversion of configuration.
Enantioenriched α-(acylamino)alkylboronic acids and their
derivatives have received much attention due to their potential
]
bioactivities as analogues of α-amino acids.[4 More than 6,500
From both synthetic and mechanistic points of view,
interest in the stereochemical course of the cross-coupling of
chiral alkylboron compounds that contain boron-bound
enantioenriched α-(acylamino)alkylboronic acids have already
]
been reported in the literature.[5 Such structural diversity of α-
(acylamino)alkylboronic acids makes their utilization as
feedstock for asymmetric synthesis highly attractive. We have
reported previously on the palladium-catalyzed enantiospecific
]
stereogenic centers has been increasing.[
Over the past
1
decade, much effort has been devoted to improving catalysts
and reaction conditions to enable the enantiospecific Suzuki-
Miyaura coupling of various α-branched acyclic alkylboron
Suzuki-Miyaura
(acylamino)benzylboronic esters
diarylmethaneamine derivatives.[2] However, the reaction
conditions are not applicable to nonbenzylic α-
(acylamino)alkylboronates.
coupling
of
aryl
halides
with
α-
A
(Scheme 1) to afford
[
][ ]
3
compounds, 2 which had been considered much less reactive
than n-alkylboron and cycloalkylboron compounds. In addition to
the concern about the reaction efficiency, the stereochemical
course of the reaction, in conjunction with the enantiospecificity
(es), has been of great concern in the enantiospecific Suzuki-
Miyaura coupling. The stereochemical course has been
determined to depend on the structure of the alkylboron
compounds. In addition to stereoretentive cross-coupling
reactions, it has been reported that cross-coupling of α-
(acylamino)benzylboronates A,[2a,2b,3g] β-borylbutanamides B,[3b]
β,β-diborylpropanoate and amide C,[3c,3n] 2-borylbutanes D,[3j]
and 1,1-diborylhexane E[3h,3k] proceeds with stereochemical
inversion at the boron-bound stereogenic carbon centers
(Scheme 1). Taking advantage of enantiospecific Suzuki-
Miyaura coupling in asymmetric synthesis, it is highly desirable
to broaden the scope of alkylboron compounds through
improvement of the catalyst. A study of the stereochemical
course of the reaction would also lead to clarification of the
mechanism of the transmetalation process. To date, the
mechanism remains unclear, although it is involved in other
reactions of various transition metal catalysts.
Herein, we describe an efficient new catalytic system for
the reaction of nonbenzylic α-(acylamino)alkylboron compounds
in Suzuki-Miyaura coupling with aryl halides (Scheme 2). The
coupling proceeds with inversion of stereochemistry at the
boron-bound stereogenic carbon center with high es.
t-Bu
O
Me
O
X–Ar
Pd cat
HN
HN
O
HN
R
or
Alkyl
B(pin)
Alkyl
BF3K
Alkyl
Ar
inversion
Scheme 2. This Work: Enantiospecific Suzuki-Miyaura Coupling of
Nonbenzylic α-(Acylamino)alkylboron Compounds with Inversion of
Configuration
Racemic 1-(acetylamino)-3-phenylpropylboronic ester 1a
was reacted with bromobenzene (2a) (Table 1). No coupling
reaction took place when the reaction was carried out in toluene
at 80 °C in the presence of Pd(dba)2 (5 mol %), XPhos (10
mol %), and K2CO3 (3 equiv) under reaction conditions identical
to those used for the coupling of benzylic boronates (entry 1).[2a]
We found that the reaction proceeded at elevated temperature
(135-145 °C) using m-xylene as a solvent, although yields of the
coupling product 3a were still low (11-15%, entries 3 and 4).
Among the bases examined, K2CO3 and CsF gave better yields
(entries 4-9). Phosphine ligands were then screened at 145 °C
using CsF as a base (entries 10-14). The product yield was
improved to 22% and 48% by CyJohnPhos and PCy2Ph,
respectively (entries 10 and 11), indicating that the
aryldicyclohexylphosphine with a less sterically hindered aryl
group is more effective. PCyPh2, PPh3, and PCy3 gave lower
yields than did PCy2Ph (entries 12-14). We finally established
reaction conditions using a small excess of 1a (1.2 equiv) to
obtain 3a in 81% isolated yield (entry 15).
R
O
Me
BF3K
O
B(dan)
HN
Ar
O
R
N
Y
BF3K
H
B(pin)
A
B
C (Y = O, NOMe)
10B(pin)
B(pin)
Me
R
BF3K
D (R = H or Ph)
E
[a]
Prof. Dr. T. Ohmura, K. Miwa, Dr. T. Awano, Prof. Dr. M. Suginome
Department of Synthetic Chemistry and Biological Chemistry,
Graduate School of Engineering, Kyoto University
Katsura, Nishikyo-ku, Kyoto 615-8510 (Japan)
E-mail: ohmura@sbchem.kyoto-u.ac.jp; suginome@sbchem.kyoto-
u.ac.jp
Supporting information for this article is given via a link at the end of
the document.
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10.1002/asia.201800536
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COMMUNICATION
Table 1. Screening of Reaction Conditions[a]
Table 2. Suzuki-Miyaura Coupling of α-(Acetylamino)alkylboronic Esters 1[a]
Me
Me
Pd(dba)2 (5 mol %)
PCy2Ph (10 mol %)
Pd(dba)2 (5 mol %)
ligand (10 mol %)
HN
O
O
HN
O
O
NHAc
Ph
NHAc
Ar
+
+
X
Ar
Br Ph
R
B
Ph
B
base (3 equiv)
m-xylene
80-145 °C, 12 h
Ph
CsF (3 equiv)
m-xylene
145 °C, 12 h
R
O
O
1
(1.2 equiv)
3
2 (X = Br)
4 (X = Cl)
rac-1a
ligand
2a (1.2 equiv)
3a
entry
1[c]
2[c]
3
base
temp/°C
80
% yield[b]
entry
R
X, Ar
% yield[b]
74 (3b)
89 (3c)
83 (3d)
78 (3a)
71 (3e)
65 (3f)
XPhos
XPhos
XPhos
XPhos
XPhos
XPhos
XPhos
XPhos
XPhos
CyJohnPhos
PCy2Ph
PCyPh2
PPh3
K2CO3
K2CO3
K2CO3
K2CO3
KF
0
1
2
3
4
5
6
7
8
Ph(CH2)2 (1a)
Ph(CH2)2 (1a)
Ph(CH2)2 (1a)
Ph(CH2)2 (1a)
Ph(CH2)2 (1a)
Ph(CH2)2 (1a)
n-C8H17 (1b)
Br, 4-MeOC6H4 (2b)
Br, 4-CF3C6H4 (2c)
Br, 2-MeC6H4 (2d)
Cl, Ph (4a)
110
135
145
145
145
145
145
145
145
145
145
145
145
145
0
11
4
15
5
0
Cl, 4-MeO2CC6H4 (4b)
Cl, 1-naphthyl (4c)
Br, Ph (2a)
6
K3PO4
KOH
Cs2CO3
CsF
4
7
4
84 (3g)
80 (3h)
8
5
(CH3)2CHCH2 (1c)
Br, Ph (2a)
9
17
[a] Pd(dba)2 (0.0050 mmol), PCy2Ph (0.010 mmol), CsF (0.30 mmol), 1 (0.12
mmol), and 2 or 4 (0.10 mmol) were reacted in m-xylene (0.4 mL) at 145 °C
for 12 h. [b] Isolated yield based on 2 or 4.
10
11
12
13
14
15[d]
CsF
22
CsF
48
We then focused on the stereochemical course of the
reaction (Table 3). Under the conditions established above, a
reaction of enantioenriched (S)-1a (90% ee) with 2a afforded 3a
in 82% yield with 24% ee (27% es, entry 1). The absolute
CsF
46
CsF
29
configuration of the major enantiomer was assigned as S,[6
]
PCy3
CsF
40
indicating that the C–C bond formation proceeded with inversion
of configuration at the boron-bound carbon atom. This
stereochemical course is in accord with that observed for α-
aminobenzylboronate in our previous work. The es of the
reaction of (S)-1a was improved to 71% when the reaction was
carried out with phenol (2.5 equiv) as an additive,[2b] although the
chemical yield decreased (42%, entry 2).[7] Boron reagents (S)-5,
(S)-7, and (S)-9a bearing propionyl, benzoyl, and pivaloyl groups
on the nitrogen atoms, respectively, reacted with 2a efficiently to
afford 6, 8, and 10a in 70-76% yields with es values of 42–95%
(entries 3–5).[6] These results indicate that es is strongly
dependent on the structure of the acyl group. Here, the highest
es was realized with the sterically demanding pivaloyl group
(95% es, entry 5).
PCy2Ph
CsF
83[e] (81)[f]
[a] Pd(dba)2 (0.0050 mmol), a ligand (0.010 mmol), a base (0.30 mmol), 1a
(0.10 mmol), and 2a (0.12 mmol) were reacted in m-xylene (0.4 mL) for 12 h
at the temperature indicated. [b] GC yield based on 1a. [c] In toluene instead
of m-xylene. [d] 1a (0.12 mmol) and 2a 0.10 mmol) were reacted. [e] GC
yield based on 2a. [f] Isolated yield based on 2a. XPhos: 2-
(dicyclohexylphosphino)-2’,4’,6’-triisopropylbiphenyl.
(dicyclohexylphosphino)biphenyl.
CyJohnPhos:
2-
The optimized reaction conditions were applied to the
coupling of α-(acetylamino)alkylboronic esters with aryl
1
bromides 2 or aryl chlorides 4 (Table 2). The reaction of 1a with
electron-rich 4-bromoanisole (2b) and electron-deficient 1-
bromo-4-(trifluoromethyl)benzene (2c) afforded 3b and 3c in
74% and 89% yields, respectively (entries 1 and 2). Sterically
demanding 2-bromotoluene (2d) also afforded 3d in 83% yield
(entry 3). These results indicated that the electronic and steric
differences of aryl bromides have little effect on the coupling.
Aryl chlorides 4a, 4b, and 4c afforded the coupling products 3a,
3e, and 3f in 65-78% yields under the identical conditions
(entries 4-6). 1-Aminoalkylboronic esters 1b and 1c reacted with
2a to afford the coupling products 3g and 3h in 84% and 80%
yields, respectively (entries 7 and 8).
Table 3. Effect of Acyl Groups on Stereochemical Course of the Coupling[a]
R
Pd(dba)2 (5 mol %)
O
PCy2Ph (10 mol %)
HN
O
O
+
Br Ph
HN
R
Ph
B
CsF (3 equiv)
m-xylene
Ph
Ph
O
145 °C, 12 h
(S)-3a, 6, 8, 10a
(S)-1a, 5, 7, 9a
2a
(1.2 equiv)
entry
boronic ester
% yield[b]
82 (3a)
42 (3a)
% ee[c] % es[d] config
1
1a (R = Me, 90% ee)
1a (R = Me, 90% ee)
24
64
27
71
inv
inv
2[e]
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10.1002/asia.201800536
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100. [e] (R)-9 was used. [f] (R)-10 was formed.
3
4
5
5 (R = Et, 97% ee)
7 (R = Ph, 96% ee)
9a (R = t-Bu, 91% ee)
75 (6)
41
66
86
42
69
95
inv
inv
inv
As demonstrated in Table 3, the acyl groups on the nitrogen
atom play an important role in chirality transfer through the
cross-coupling reaction. We then turned our attention to
controlling the stereospecificity through the structure of the boryl
group. A trifluoroborate salt (R)-11 (95% ee), prepared from (R)-
1a with KHF2 in MeOH, was subjected to coupling with 2a (Table
5). Although the coupling did not proceed at all under the
conditions identical to those used for the coupling of 1a (entry 1),
the desired reaction took place when using water as an additive;
i.e., the coupling product 3a was obtained in moderate yield
(entry 2). It is noteworthy that a significant improvement in es
(85%) was achieved compared with the corresponding acetyl-
protected boronic ester 1a (27% es, entry 1, Table 3). Further
improvements in the chemical yield and es were achieved by
using K2CO3 as a base; i.e., 3a was obtained in 78% yield with
90% es (entry 4). Stereochemical inversion was confirmed.
Electronically and sterically different aryl bromides 2b-d were
then subjected to coupling with (R)-11 under the modified
conditions (entries 5–7). As observed in the coupling of
enantioenriched 9a (entries 1-3, Table 4), no significant
electronic and steric effects of aryl bromides were observed in
the es of the coupling, and 3b-d were obtained in 67-90% yields
with 83-89% es.
76 (8)
70 (10a)
[a] Pd(dba)2 (0.0050 mmol), PCy2Ph (0.010 mmol), CsF (0.30 mmol), an
organoboron compound (0.12 mmol), and 2a (0.10 mmol) were reacted in
m-xylene (0.4 mL) for 12 h at 145 °C. [b] Isolated yield based on 2a. [c]
Determined by HPLC or SFC with a chiral stationary phase column. [d] % es
= (product ee/starting material ee) x 100. [e] PhOH (2.5 equiv) was added.
Stereospecific
coupling
of
enantioenriched
α-(pivaloylamino)alkylboronic esters 9 was carried out (Table 4).
The reaction of (S)-9a (98% ee) with electron-rich 2b and
electron-deficient 2c afforded 10b and 10c with 98% and 95%
es, respectively. This indicated that the electronic effect of aryl
bromides does not play
a key role in control of the
stereochemical course of the reaction (entries 1 and 2). High es
was also achieved in the coupling with sterically demanding 2d
(94% es, entry 3). Chlorobenzene (4a) gave a similar es to that
of 2a in the coupling (95% es, entry 4). 1-Aminononan-1-
ylboronic acid derivative (R)-9b (92% ee) and 1-amino-3-
methylbutan-1-ylboronic acid derivative (R)-9c (90% ee) reacted
with 2a to afford products with 99% and 97% es, respectively
(entries 5 and 6). In contrast, the es dropped to 73% in the
reaction of (amino)cyclohexylmethylboronic acid derivative (R)-
9d.
Table
5.
Enantiospecific
Suzuki-Miyaura
Coupling
of
α-
(Acetylamino)alkyltrifluoroborate 11[a]
Table
4.
Enantiospecific
Suzuki-Miyaura
Coupling
of
α-
(Pivaloylamino)alkylboronates 9[a]
O
Pd(dba)2 (5 mol %)
PCy2Ph (10 mol %)
NHAc
Ar
t-Bu
HN
Me
Pd(dba)2 (5 mol %)
PCy2Ph (10 mol %)
+
Br Ar
Ph
HN
O
O
Ph
BF3K
base (3 equiv)
H2O (0 or 39 equiv)
m-xylene
NHPiv
Ar
+
X
Ar
(R)-11
2
(R)-3
R
B
CsF (3 equiv)
m-xylene
R
95% ee
O
145 °C, 12 h
(1.2 equiv)
145 °C, 6-12 h
(S)-9 (1.2 equiv)
2 (X = Br)
4 (X = Cl)
(S)-10
entry Ar
base
additive
-
% yield[b]
% ee[c]% es[d]
time/h % yield[b] % ee[c]% es[d]
1
2
3
4
5
6
7
Ph (2a)
Ph (2a)
CsF
0 (3a)
-
-
entry
1
R
X, Ar
CsF
H2O
-
44 (3a)
30 (3a)
78 (3a)
67 (3b)
89 (3c)
72 (3d)
80
78
85
84
83
79
85
82
90
89
88
83
Ph(CH2)2
(9a, 98% ee)
Br, 4-MeOC6H4 (2b) 12
65 (10b) 96
73 (10c) 93
70 (10d) 92
58 (10a) 87
83 (10e)[f] 91
85 (10f)[f] 88
35 (10g)[f] 65
98
95
94
96
99
97
73
Ph (2a)
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Ph(CH2)2
(9a, 98% ee)
2
Br, 4-CF3C6H4 (2c)
Br, 2-MeC6H4 (2d)
Cl, Ph (4a)
8
Ph (2a)
H2O
H2O
H2O
H2O
4-MeOC6H4 (2b)
4-CF3C6H4 (2c)
2-MeC6H4 (2d)
Ph(CH2)2
(9a, 98% ee)
3
6
Ph(CH2)2
(9a, 91% ee)
4
12
12
12
12
n-C8H17
(9b, 92% ee)
5[e]
6[e]
7[e]
Br, Ph (2a)
[a] Pd(dba)2 (0.0050 mmol), PCy2Ph (0.010 mmol), a base (0.30 mmol), H2O
(0 or 70 µL), (R)-11 (0.12 mmol), and 2 (0.10 mmol) were reacted in m-
xylene (0.5 mL) at 145 °C. [b] Isolated yield based on 2. [c] Determined by
SFC with a chiral stationary phase column. [d] % es = (product ee/starting
material ee) x 100.
(CH3)2CHCH2
(9c, 90% ee)
Br, Ph (2a)
cyclo-C6H11
(9d, 90% ee)
The observed configuration inversion is assumed to be the
consequence of stereoinvertive transmetallation (Scheme 3A),
as we proposed previously for the coupling of α-
Br, Ph (2a)
[a] Pd(dba)2 (0.0050 mmol), PCy2Ph (0.010 mmol), CsF (0.30 mmol), (S)-9
(0.12 mmol), and 2 or 4 (0.10 mmol) were reacted in m-xylene (0.4 mL) at
145 °C. [b] Isolated yield based on 2 or 4. [c] Determined by SFC with a
chiral stationary phase column. [d] % es = (product ee/starting material ee) x
(acylamino)benzylboronates.[2]
Transmetallation
to
form
alkylpalladium intermediates takes place through an open
transition state TS1 because intramolecular coordination of the
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10.1002/asia.201800536
Chemistry - An Asian Journal
COMMUNICATION
carbonyl group to the boron atom blocks the approach of the
palladium to the boron-bound carbon atom, which should be
involved in stereoretentive transmetallation (TS2). The N-
Pivaloyl derivative resulted in higher es than the N-acetyl, N-
propionyl, and N-benzoyl analogues (Table 3), because the
steric bulkiness of the pivaloyl group makes the coordinated
conformation I more favorable than the open conformation II. In
the reaction of trifluoroborate 11, carbonyl-coordinated I’ is
formed through partial hydrolysis of the borate, which promotes
the coupling with inversion of configuration (Scheme 3B). Even
the sterically less bulky acetyl derivative gave high es, because
the coordination of the carbonyl group to the more acidic boron
atom in I' is stronger than that in I (Z = OR).
JP26288048 for Scientific Research (B) (TO), and JP15H05811
for Scientific Research on Innovative Areas in Precisely
Designed Catalysts with Customized Scaffolding (MS). TO also
expresses his appreciation for the support by The Nikko
Memorial Agency.
Keywords: Asymmetric synthesis • Cross-coupling •
Organoboron compounds • Stereospecific reaction • Synthetic
methods
[1]
[2]
[3]
For reviews, see: a) A. H. Cherney, N. T. Kadunce, S. E. Reisman,
Chem. Rev. 2015, 115, 9587–9652; b) C.-Y. Wang, J. Derosa, M. R.
Biscoe, Chem. Sci. 2015, 6, 5105–5113; c) D. Leonori, V. K. Aggarwal,
Angew. Chem. Int. Ed. 2015, 54, 1082–1096; d) J. P. G. Rygus, C. M.
Crudden, J. Am. Chem. Soc. 2017, 139, 18124–18137.
A
R
R
a) T. Ohmura, T. Awano, M. Suginome, J. Am. Chem. Soc. 2010, 132,
13191–13193; b) T. Awano, T. Ohmura, M. Suginome, J. Am. Chem.
Soc. 2011, 133, 20738–20741; For Suzuki-Miyaura coupling of racemic
α-(acetylamino)benzylboronates, see: c) T. Ohmura, T. Awano, M.
Suginome, Chem. Lett. 2009, 38, 664-665.
L(Ar)Pd
base
Y
N
C
O
HN
O
Z
Y
inversion
L(Ar)Pd
B
Z
alkyl
B
H
Z
Z
alkyl
TS1
I
a) D. Imao, B. W. Glasspoole, V. S. Laberge, C. M. Crudden, J. Am.
Chem. Soc. 2009, 131, 5024–5025; b) D. L. Sandrock, L. Jean-Gérard,
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Chem. Soc. 2011, 133, 4758–4761; e) G. A. Molander, S. R.
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Jeon, J. Yun, Angew. Chem. Int. Ed. 2013, 52, 3989–3992; g) K. Hong,
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Matthew, B. W. Glasspoole, P. Eisenberger, C. M. Crudden, J. Am.
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Am. Chem. Soc. 2014, 136, 6534–6537; j) L. Li, S. Zhao, A. Joshi-
Pangu, M. Diane, M. R. Biscoe, J. Am. Chem. Soc. 2014, 136, 14027–
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Am. Chem. Soc. 2014, 136, 17918–17921; l) G. L. Hoang, Z.-D. Yang,
S. M. Smith, R. Pal, J. L. Miska, D. E. Rérez, L. S. W. Pelter, X. C.
Zeng, J. M. Takacs, Org. Lett. 2015, 17, 940–943; m) T. P. Blaisdell, J.
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Hoang, J. M. Takacs, Chem. Sci. 2017, 8, 4511–4516.
O
O
NH
C
L(Ar)Pd
base
Y
R
R
NH
Z
Z
retention
B
H
Z
B
alkyl
alkyl
L(Ar)Pd
Y
Z
II
TS2
B
Me
base
H2O
O
HN
O
Me
NH
BF3K
inversion
TS1
Z
B
F
I' (Z = F or OH)
alkyl
alkyl
11
Scheme 3. Mechanistic Considerations
In conclusion, we have established suitable reaction
conditions for the Suzuki-Miyaura coupling of nonbenzylic
α-(acylamino)alkylboronic esters. Use of Pd/PCy2Ph catalyst at
145 °C was found to be essential for the efficient coupling. The
coupling proceeded with stereochemical inversion at the boron-
bound carbon center with high stereospecificity. Further
investigations into applicable organoboron reagents in the
stereospecific Suzuki-Miyaura coupling are currently underway
in our laboratory.
[4]
For reviews, see: a) W. Yang, X. Gao, B. Wang, In Boronic Acids ed. D.
G. Hall, Wiley-VCH, Weinheim, 2005, p 481–512; b) R. Smoum, A.
Rubinstein, V. M. Dembitsky, M. Srebnik, Chem. Rev. 2012, 112,
4156–4220; c) P. Andrés, G. Ballano, M. I. Calaza, C. Cativiela, Chem.
Soc. Rev. 2016, 45, 2291–2307.
[5]
[6]
A result of searching SciFinder with “R–CH(NHCOR’)–B(OH)2 having R
configuration”.
Absolute configuration of the major enantiomer of 3a, 6, 8, and 10a
were assigned to be S by comparison with specific rotation of authentic
samples.
[7]
To check the possibility of stereoretentive coupling,[2b] the reaction of 1a
with 2a was carried out in the presence of Zr(Oi-Pr)4•i-PrOH (0.5 equiv)
under the conditions demonstrated in Table 3. However, the additive
completely suppressed the coupling reaction and no 3a was formed at
all.
Acknowledgements
This work was supported by JSPS KAKENHI Grant Numbers
JP23655082 for Challenging Exploratory Research (TO),
This article is protected by copyright. All rights reserved.

10.1002/asia.201800536
Chemistry - An Asian Journal
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
T. Ohmura,* K. Miwa, T. Awano, M.
Suginome*
X–Ar (X = Br or Cl)
Pd(dba)2 (5 mol %)
R = Piv
B = B(pin)
R = Ac
B = BF3K
R
R
PCy2Ph (10 mol %)
HN
HN
up to 99% es up to 90% es
inversion inversion
Page No. – Page No.
CsF or K2CO3/H2O
m-xylene
Alkyl
B
Alkyl
Ar
Enantiospecific Suzuki-Miyaura
Coupling of Nonbenzylic
α-(Acylamino)alkylboronic Acid
Derivatives
145 °C, 6-12 h
Inside-out: Suzuki-Miyaura coupling of nonbenzylic α-(acylamino)alkylboron
compounds with aryl halides is established. A Pd/PCy2Ph catalyst promotes the
reaction efficiently at 145 °C. The reaction of enantioenriched α-
(acylamino)alkylboron compounds gives chiral 1-arylalkylamides in high
enantiosepecificity with inversion of configuration.
This article is protected by copyright. All rights reserved.