Rhodium-catalyzed asymmetric coupling reaction of allylic ethers with arylboronic acids

Article abstract of DOI:10.1021/ol3019902

An asymmetric allylic substitution of simple allylic ethers with arylboronic acids in the presence of a rhodium(I)/(R)-DTBM-SEGPHOS catalyst has been developed. The reactions proceeded smoothly at room temperature to give the corresponding branch products with excellent regioselectivities and good to excellent enantioselectivities.

Full text of DOI:10.1021/ol3019902

ORGANIC
LETTERS
2012
Vol. 14, No. 17
4502–4505
Rhodium-Catalyzed Asymmetric Coupling
Reaction of Allylic Ethers with Arylboronic
Acids
Hiroyoshi Kiuchi,† Dai Takahashi,† Kenji Funaki,† Tetsuo Sato,†,‡ and Shuichi Oi*,†,‡
Graduate School of Engineering, Department of Applied Chemistry and Environment
Conservation Research Institute, Tohoku University, 6-6-11 Aramaki-Aoba, Aoba-ku,
Sendai 980-8579, Japan
oishu@aporg.che.tohoku.ac.jp
Received July 18, 2012
ABSTRACT
An asymmetric allylic substitution of simple allylic ethers with arylboronic acids in the presence of a rhodium(I)/(R)-DTBM-SEGPHOS catalyst
has been developed. The reactions proceeded smoothly at room temperature to give the corresponding branch products with excellent
regioselectivities and good to excellent enantioselectivities.
A coupling reaction of alkenes with organoboron
reagents catalyzed by rhodium complexes has become
a promising method for CÀC bond formation.1 In
1997, Miyaura et al. reported the rhodium-catalyzed
1,4-addition of organoboronic acids to R,β-unsaturated
compounds,2 and an asymmetric 1,4-addition, catalyzed
by the rhodium(I)ÀBINAP system, was subsequently
developed by Hayashi and Miyaura et al.3 Hayashi et al.
clarified that these reactions proceeded via the addition of
the arylrhodium(I) species to the carbonÀcarbon double
bond of R,β-unsaturated compounds.4 Subsequently, the
arylrhodium(I) species have been found to react with
strained alkenes as well as electron-deficient alkenes.
Murakami et al. and Lautens et al. independently reported
the addition of arylboronic acids to oxanorbornenes,5
norbornenes,6 and allylic diol derivatives.7 These reac-
tions are thought to progress through the addition of
arylrhodium(I) species to the carbonÀcarbon double
bond, followed by β-elimination. The palladium- or rho-
dium-catalyzed allylic substitution of simple allylic acet-
ates or alcohols with arylboronic acids has also been
investigated.8,9 These reactions selectively gave linear
allylic arenes when the corresponding γ-substituted allylic
alcohols or esters were used, probably proceeding via
π-allyl complex intermediates (eq 1).
If the γ-substituted allylic alcohols or their derivatives
undergo addition of arylrhodium species followed by
β-oxy elimination, the reaction is expected to give branched
allylic arenes with chiral centers. Such transformations
† Graduate School of Engineering, Department of Applied Chemistry.
‡ Environment Conservation Research Institute.
(5) (a) Murakami, M.; Igawa, H. Chem. Commun. 2002, 390.
(b) Lautens, M.; Dockendorff, C.; Fagnou, K.; Malicki, A. Org. Lett.
2002, 4, 1311.
(1) For reviews, see: (a) Hayashi, T. Synlett 2001, 879. (b) Bolm, C.;
~
Hildebrand, J. P.; Muniz, K.; Hermanns, N. Angew. Chem., Int. Ed.
2001, 40, 3284. (c) Fagnou, K.; Lautens, M. Chem. Rev. 2003, 103, 169.
(d) Hayashi, T.; Yamasaki, K. Chem. Rev. 2003, 103, 2829. (e) Miura, T.;
Murakami, M. Chem. Commun. 2007, 217. (f) Christoffers, J.; Koripelly,
G.; Rosiak, A.; Rossle, M. Synthesis 2007, 1279. (g) Youn, S. W. Eur. J.
Org. Chem. 2009, 2597.
(2) Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics 1997, 16,
4229.
(3) Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.; Miyaura, N.
J. Am. Chem. Soc. 1998, 120, 5579.
(4) Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara., M. J. Am.
(6) (a) Miura, T; Murakami, M. Org. Lett. 2005, 7, 3339. (b) Menard,
F.; Lautens, M. Angew. Chem., Int. Ed. 2008, 47, 2085.
(7) (a) Menard, F.; Chapman, T. M.; Dockendorff, C.; Lautens, M.
Org. Lett. 2006, 8, 4569. (b) Miura, T.; Takahashi, Y.; Murakami, M.
Chem. Commun. 2007, 595. (c) Yu, B.; Menard, F.; Isono, N.; Lautens,
M. Synthesis 2009, 853.
(8) (a) Uozumi, Y.; Danjo, H.; Hayashi, T. J. Org. Chem. 1999, 64,
3384. (b) Bouyssi, D.; Gerusz, V.; Balme, G. Eur. J. Org. Chem. 2002,
2445. (c) Kayaki, Y.; Koda, T.; Ikariya, T. Eur. J. Org. Chem. 2004,
4989.
€
Chem. Soc. 2002, 124, 5052.
(9) Kabalka, G. W.; Dong, G.; Venkataiah, B. Org. Lett. 2003, 5, 893.
r
10.1021/ol3019902
Published on Web 08/17/2012
2012 American Chemical Society

Table 1. Effects of Substrate Leaving Groupa
Table 2. Effects of Chiral Ligand in the Reaction of 1a with 2aa
3aa
4
yield
(%)b
ee
(%)b
yield
(%)b
entry
X
1
2
3
4
5
6
7
8c
4-CF3C6H4O
4-NO2C6H4O
PhO
1a
1b
1c
1d
1e
1f
22
25
14
11
0
77
64
48
40
À
<1
7
0
4-MeOC6H4O
HO
0
temp
time
(h)
yieldb
(%)
eeb
(%)
0
AcO
14
24
61
71
77
81
3
entry
chiral ligand
(R)-BINAP
(°C)
Cl
1g
1a
20
<1
1
2
3
4
5
6
7
8c
60
60
60
60
rt
20
20
20
20
20
20
20
1
61
71
63
71
4
81
85
82
90
82
83
78
92
4-CF3C6H4O
(R)-TolBINAP
a Reaction conditions: 1 (0.25 mmol), 2a (0.5 mmol), [RhCl(cod)]2
(5.0 mol % Rh), (R)-BINAP (5.5 mol %), KOH (0.25 mmol) in 1,
4-dioxane/H2O (5/1, 0.6 mL). b Yield and enantiomeric excess were
determined by GC analysis. c Reaction conditions: 1a (0.25 mmol), 2a
(1.0 mmol), [RhCl(nbd)]2 (5.0 mol % Rh), (R)-BINAP (7.5 mol %),
KOH (2.0 mmol) in 1,4-dioxane/H2O (5/1, 0.6 mL).
(S)-SEGPHOS
(R)-DTBM-SEGPHOS
(R)-BINAP
(R)-TolBINAP
rt
3
(S)-SEGPHOS
rt
5
(R)-DTBM-SEGPHOS
rt
75
a Reaction conditions: 1a (0.25 mmol), 2a (1.0 mmol), [RhCl(nbd)]2
(5.0 mol % Rh), chiral ligand (7.5 mol %), KOH (2.0 mmol) in 1,4-dioxane/
H2O (5/1, 0.6 mL). b Yield and enantiomeric excess were determined by GC
analysis. c (E)-1-Phenylbut-2-ene 4 was also obtained in 1% yield.
have the potential to be developed into asymmetric reac-
tions (eq 2).
Table 3. Rh-Catalyzed Asymmetric Coupling Reaction of
Allylic Ether 1 with 2aa
Here, we report that the regioselective and enantioselective
allylic substitution of simple allylic ethers with arylboronic
acids proceeded using chiral rhodium(I) complexes as cata-
lysts. The reactions provide optically active simple alkenes,
which are very useful sources of chiral compounds.
substrate 1
Initially, the effects of the allylic compound leaving
group on the rhodium-catalyzed asymmetric coupling re-
action of (E)-crotyl compounds 1aÀg with phenylboronic
acid 2a were investigated (Table 1). The substrate leaving
group is an important factor in the reactivity, regioselec-
tivity, and enantioselectivity of the reactions. When aryl
(E)-crotyl ethers 1aÀd were used as substrates, the reac-
tions proceeded regioselectively, giving the branched pro-
duct 3aa with moderate yields (Table 1, entries 1À4). Using
alcohol 1e did not result in a reaction (Table 1, entry 5).
Acetate 1f and chloride 1g gave isomeric linear product 4
and branched product 3aa (Table 1, entries 6 and 7). Using
(E)-crotyl 4-trifluoromethylphenyl ether 1a as the sub-
strate, further investigations into the catalyst, the amounts
of phenylboronic acid 2a, and the amount of ligand and
base used resulted in improvements in branched isomer
product yield
ee
entry
R1
R2
(E/Z)
3b
(%)
(%)e
1
2
3
4
5
Me
Et
H
H
H
(100/0) 1a
3aa
3ba
3ca
3aa
3ba
75c
84c
89d
82c
86c
92 (S)
(99/1)
(99/1)
1h
1i
85 (S)
n-Pr
H
85 (n.d.)f
89 (R)
87 (R)
Me (3/97)
Et (2/98)
1j
H
1k
a Reaction conditions: 1 (0.25 mmol), 2a (1.0 mmol), [RhCl(nbd)]2
(5.0 mol % Rh), (R)-DTBM-SEGPHOS (7.5 mol %), KOH (2.0 mmol)
in 1,4-dioxane/H2O (5/1, 0.6 mL) at rt for 1 h. b The yields of the linear
products 4 were below 1%. c GC yield. d Isolated yield. e Enantiomeric
excess values were determined by GC analysis. f The absolute config-
uration was not determined.
3aa yield and enantiomeric excess, to 61% yield and 81%
ee (Table 1, entry 8).
Org. Lett., Vol. 14, No. 17, 2012
4503

Table 4. Rh-Catalyzed Asymmetric Coupling Reaction of 1a
with Arylboronic Acids 2a
Scheme 1. Possible Mechanism
arylboronic acid 2
time product yield
ee
(%)e
entry
Ar
(h)
3b
(%)
1
2
3
4
5
6
7
8
9
Ph
2a
2b
2c
2d
2e
2f
1
1
3aa
3ab
3ac
3ad
3ae
3af
75c
87c
92 (S)
90 (S)
4-MeC6H4
3-MeC6H4
2-MeC6H4
4-MeOC6H4
4-BrC6H4
1
74c 92 (n.d.)f
45c 99 (n.d.)f
2d gave 3ad with excellent enantioselectivity (99% ee) but
in a slightly lower yield. The other 4-substituted phe-
nylboronic acids 2eÀg, which have either an electron-
donating or -withdrawing group, gave branched pro-
ducts 3aeÀ3af with moderate to good yields and high
enantioselectivities (Table 4, entries 5À7). Replacing
the phenyl group with a 1- or 2-naphthyl group gave
the products 3ag or 3ah with excellent enantioselectiv-
ities, but longer reaction times were required (Table 4,
entries 7 and 8). The coupling reaction of 1a with
6-methoxy-2-naphthylboronic acid (2i) gave the allylic
substituted product 3ai, which is a precursor of the
nonsteroidal anti-inflammatory drug naproxen, with a
63% yield and 91% ee (Table 4, entry 9).
The catalytic coupling reaction of allyl aryl ethers
with arylboronic acids may involve the carborhodation
of the carbonÀcarbon double bond, followed by β-alkoxy
elimination (eq 2), as proposed by Murakami et al. and
Lautens et al.5À7 A possible reaction mechanism is
shown in Scheme 1. A hydroxorhodium(I) species A is
initially generated by anion exchange of a chlororhodium-
(I) complex with potassium hydroxide. Subsequent trans-
metalation between A and the arylboronic acid 2 gives
an arylrhodium intermediate B. Enantioselective car-
borhodation gives intermediate C, and then β-aryloxy
elimination gives the coupling product 3 and generates
aryloxorhodium(I) species D. Anion exchange of D with
potassium hydroxide regenerates the initial species A.
The stereospecificity of the reaction (Table 3, entry 1 vs 4
and entry 2 vs 5) supports this additionÀelimination
mechanism. The bulky aryl groups on DTBM-SEGPHOS
would promote the β-aryloxy elimination and enhance the
enantioselectivity.
4
1
85d
71d
36d
64d
63d
92 (S)
92 (S)
>99 (S)
96 (S)
91 (S)
5
1-naphthyl
2-naphthyl
2g
2h
6
3ag
3ah
3ai
6
6-MeO-2-naphthyl 2i
20
a Reaction conditions: 1a (0.25 mmol), 2 (1.0 mmol), [RhCl(nbd)]2
(5.0 mol % Rh), (R)-DTBM-SEGPHOS (7.5 mol %), KOH (2.0 mmol)
in 1,4-dioxane/H2O (5/1, 0.6 mL) at room temperature. b The yields
of the linear products 4 were below 1%. c GC yield. d Isolated yield.
e Enantiomeric excess values were determined by GC analysis. f The
absolute configuration was not determined.
Next, the reaction of 1a with phenylboronic acid 2a was
performed using various chiral ligands (Table 2). The
reaction using (R)-TolBINAP or (S)-SEGPHOS, instead
of (R)-BINAP, gave 3aa with a better yield and ee (Table 2,
entries 1À3), and (R)-DTBM-SEGPHOS gave a still high-
er yield and ee (Table 2, entry 4). The reaction proceeded
smoothly even at room temperature using (R)-DTBM-
SEGPHOS as the ligand, giving 3aa at 75% yield and 92%
ee after 1 h (Table 2, entry 8). However, the reactions were
considerably slower using (R)-BINAP, (R)-TolBINAP,
and (S)-SEGPHOS (Table 2, entries 5À7).
Under the optimized reaction conditions, using (R)-
DTBM-SEGPHOS as the ligand, we examined the reac-
tions of γ-substituted allylic ethers 1hÀk with phenylboro-
nic acid 2a. The results are summarized in Table 3.
Regardless of the substrate steric hindrance and geo-
metrical isomerism, in all cases, the reaction provided the
branched products 3aaÀ3ca with excellent regioselectiv-
ities and good yields and enantioselectivities (Table 3,
entries 2À5). The reactions also proceeded stereospecifi-
cally: (E)-substrates 1a and 1h gave (S)-products (Table 3,
entries 1 and 2), and (Z)-substrates 1j and 1k gave
(R)-products (Table 3, entries 4 and 5).
Then, we investigated the scope of arylboronic acid in
the reaction with 1a. The results are summarized in Table 4.
Using p- or m-tolylboronic acids 2b and 2c gave the
corresponding products 3ab and 3ac with good yields
and high enantioselectivities, as in the case of 2a (Table 4,
entries 1À3). The reaction with bulky o-tolylboronic acid
In summary, we have developed a regio- and enantio-
selective allylic substitution of simple allylic ethers
with arylboronic acids using a rhodium(I)/(R)-DTBM-
SEGPHOS catalyst system. The reactions proceeded in
high yields with excellent regioselectivities, under very
mild conditions, to give optically active simple alkenes.
Further studies are in progress to expand the scope
and investigate the mechanistic details of this reaction
system.
4504
Org. Lett., Vol. 14, No. 17, 2012

Acknowledgment. This work was supported in part by a
Grant-in-Aid for Scientific Research on Innovative Areas
“Molecular Activation Directed toward Straightforward
Synthesis” from MEXT, Japan and by a commissioned
project conducted by New Energy and Industrial Technol-
ogy Development Organization (NEDO).
Supporting Information Available. Experimental pro-
cedures and characterization data for substrates and
products. This material is available free of charge via
the Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 17, 2012
4505