Selective cine substitution of 1-arylethenyl acetates with arylboron reagents and a diene/rhodium catalyst

Article abstract of DOI:10.1002/anie.201002745

When the crowd says Bo: A carbon-carbon bond is selectively formed at the β position of 1- arylethenyl acetate when the alkenyl substrate is reacted with arylboronic acids in the presence of a cycloocta-1,5-diene/rhodium catalyst. The choice of the ligand is crucial for the unusual cine substitution. Copyright

Full text of DOI:10.1002/anie.201002745

Communications
DOI: 10.1002/anie.201002745
cine Substitution
Selective cine Substitution of 1-Arylethenyl Acetates with Arylboron
Reagents and a Diene/Rhodium Catalyst**
Jung-Yi Yu, Ryosuke Shimizu, and Ryoichi Kuwano*
Nucleophilic substitution is a fundamental reaction in organic
synthesis. In the reaction, the nucleophile normally attacks on
the carbon atom bonded to a leaving group. However, the
attack sometimes occurs at the adjacent position and forms a
cine-substitution product.[1] Most of the reported cine substi-
tutions have been observed in the reactions of electrophilic
aromatic compounds with nucleophiles.[2] The unusual regio-
selectivity has been rare in the reaction of alkenyl electro-
philes. Only alkenyl sulfones,[3] tosylates,[4,5] and phos-
phates[5,6] were known to react with organometals on the b-
carbon atoms of the leaving group through transition-metal
catalysis.[7] Recently, we reported that a phosphine/rhodium
complex promoted the coupling of 1-phenylethenyl acetate
with an arylboronic acid to exclusively produce the ipso-
substitution product, 1,1-diarylethene [Eq. (1)].[8,9] During
the course of the study, the cine substitution was observed
when the reaction was conducted in the absence of the
phosphine ligand. Herein, we report a rhodium-catalyzed
cine substitution of alkenyl acetates with arylboronic acids
[Eq. (2)]. The unusual regiochemistry was caused by the
chelation of a diene ligand to the rhodium catalyst.
Table 1: Optimization of the rhodium catalyst for cine substitution of
1-phenylethenyl acetate (1a) with phenylboronic acid (2a).[a]
Entry
[Rh]
Additive[b]
Yield of Yield of
3a [%][c] 4a [%][c]
1
2
[{RhCl(cod)}2]
[{RhCl(cod)}2]
dppb (5)
<1
26
14
4
–
3
4
5
6
7
8
9
10
11
12
[{RhCl(nbd)}2]
–
–
–
<1
<1
<1
18
38
<1
42
80
62
19
3
3
<1
1
4
[{RhCl(coe)2}2]
[{RhCl(C2H4)2}2]
[{RhCl(C2H4)2]2]
[Rh(cod)2]BF4
[Rh(nbd)2]SbF6
[{Rh(OAc)(cod)}2]
[{Rh(OAc)(cod)}2]
[{Rh(OAc)(cod)}2]
cod (10)
–
–
–
5
8
tAmOH (100)
iPr2NH (100)
13
5
[{Rh(OAc)(cod)}2] cod (10), tAmOH (100)
69
(75)[d]
71
(6)[d]
5
13
[{Rh(OAc)(cod)}2] cod (10), iPr2NH (100)
(85)[d]
8
(5)[d]
14[e] [{Rh(OAc)(cod)}2] cod (10), iPr2NH (100)
<1
[a] Reactions were conducted in toluene (1.0 mL) for 3 h. The ratio of 1a
(0.20 mmol)/2a/K3PO4/[Rh] was 100:150:300:5.0. [b] The amount of
each additive (mol% to 1a) was indicated in parentheses. [c] GC yield
(average of two runs). [d] GC yields after 24 h are indicated in the
parentheses. [e] The reaction was conducted without K3PO4. dppb=1,4-
bis(diphenylphosphino)butane, cod=cycloocta-1,5-diene, nbd=nor-
borna-2,5-diene, coe=cyclooctene, tAm=1,1-dimethylpropyl.
bisphosphine (Table 1, entry 2). When the cod ligand was
replaced by norborna-2,5-diene,[10] cyclooctene, or ethylene,
no formation of the cine-substitution product, stilbene (3a),
was observed (Table 1, entries 3–5). These observations
suggest that the coordination of cod to rhodium is crucial
for the cine substitution. Indeed, [{RhCl(ethylene)2}2] prefer-
entially catalyzed the cine-substitution reaction in the pres-
ence of cod (Table 1, entry 6).[11] As compared to the diene
ligand, the anionic ligand or counteranion on the rhodium
atom did not affect the regioselectivity (Table 1, entries 7 and
9). The yield of 3a improved remarkably by the addition of
tert-amyl alcohol or diisopropylamine (Table 1, entries 10 and
11).[12] The addition of cod brought about further enhance-
ment of the production of 3a when diisopropylamine was
chosen as the additive (Table 1, entry 13). Furthermore,
potassium phosphate was indispensable for successful cine
substitution (Table 1, entry 14). The catalyst loading could be
reduced to 3 mol% under the optimized conditions (Table 2,
entry 1). The cine-substitution product 3a was isolated in
75% yield.
In our previous study,[8] the reaction of 1-phenylethenyl
acetate (1a) with phenylboronic acid (2a) was attempted in
the presence of a [{RhCl(cod)}2]/dppb catalyst, which pro-
duced the typical cross-coupling product 4a exclusively
(Table 1, entry 1). To our surprise, the cine substitution
proceeded selectively in the absence of the bidentate
[*] Dr. J.-Y. Yu, R. Shimizu, Prof. Dr. R. Kuwano
Department of Chemistry, Graduate School of Sciences, Kyushu
University
6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan)
Fax: (+81)92-642-2572
E-mail: rkuwano@chem.kyushu-univ.jp
Homepage: http://www.scc.kyushu-u.ac.jp/Yuki/maine.html
[**] This work was partly supported by KAKENHI (No. 19020051) and by
a Grant-in-Aid for the Global COE Program, “Science for Future
Molecular Systems” from MEXT.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201002745.
6396
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Chemie
Table 2: Reactions of 1a with organoboron compounds 2 or 2’.[a]
phenone,[13] but the undesirable reaction was successfully
suppressed by using ethylene glycol ester 2’ in the place of 2.
Steric hindrance from the ortho substituent of 2i would be
favorable for the cine substitution (Table 2, entry 9). As with
2i, 1-naphthylboronic ester 2j’ afforded 3j in high yield with
no ipso substitution (Table 2, entry 10). However, the use of
more-congested substrate 2k’ resulted in disturbing the
cine substitution, giving 4k preferentially (Table 2, entry 11).
The regioselectivity of the reaction of 1 with 2 was
strongly influenced by both the electronic and steric proper-
ties of the substituent on the aromatic ring of 1 (Table 3). The
electron-deficient substrate 1b was converted into the desired
stilbene 3 f with complete regioselectivity (Table 3, entry 1),
whilst the electron-donating methoxy group of 1c induced the
undesired ipso-substitution (Table 3, entry 2). The reaction of
1d, which has the methoxy substituent at the meta-position,
afforded comparable regioselectivity to that of 1a (Table 3,
entry 3). The ortho substituent in 1e hampered the cine sub-
stitution (Table 3, entry 4). The ratio of 3 to 4 in the reactions
of 1c and 1d was raised by using 2i as the nucleophilic
substrate (Table 3, entries 5 and 6). These observations
Entry
Substrate 2 or 2’
t
[h]
3/4[b]
Product 3
Yield
[%][c]
1
2
3
4
48 93:7
75
70
67
81
24 94:6
24 83:17
48 90:10[d]
5
72 85:15
71
Table 3: Reaction of 1-arylethenyl acetates 1 with 2a or 2i.[a]
6
72 89:11
72 93:7
68
71
73
96
85
24[e]
Entry
1
Substrate 1
2
t
[h]
3/4[b]
Product 3
Yield
[%][c]
7
2a 48 >99:1
91
8
72 92:8
2
3
4
2a 48
2a 48
2a 48
64:36
85:15
57:43
45
69
39
9
24 >99:1
48 >99:1
72 43:57
10
11
[a] Reactions were conducted in toluene (2.0 mL). The ratio of
5
6
7
1c
1d
1e
2i 24
95:5
90
73
30
1
(0.5 mmol)/2/K3PO4/iPr2NH/[{Rh(OAc)(cod)}2]/cod
was
100:150:300:100:1.5:6.0. [b] Determined by the 1H NMR analysis of
the reaction mixture. [c] Yield of isolated 3. [d] Determined by GC
analysis. [e] Compound 4k was isolated in 58% yield.
2i 24 >99:1
The optimized catalyst system allowed a variety of
arylboronic acids to react with alkenyl acetate 1a, thus
selectively yielding the desired cine-substitution products 3
(Table 2). The production of 3 was scarcely affected by the
electronic property of the para or meta substituent on the
aromatic ring of 2 (Table 2, entries 2–8). Electron-deficient
arylboronic acids caused the decomposition of 1a to aceto-
2i 72
66:34
[a] Reactions were conducted in toluene (2.0 mL). The ratio of
1(0.5 mmol)/2/K3PO4/iPr2NH/[{Rh(OAc)(cod)}2]/cod
was
100:150:300:100:1.5:6.0. [b] Determined by 1H NMR analysis of the
reaction mixture. [c] Yield of isolated 3.
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À
suggest that the regiochemistry was controlled by the steric
successive re-insertion of the carbon carbon double bond to
hindrance of R2 as well as by the electronic property of R1.
To investigate the mechanism of the catalytic cine sub-
stitution, we attempted the reaction using the deuterium-
labeled substrate [D2]-1a (> 99% D) (Scheme 1). The reac-
the (hydrido)rhodium in D with reverse direction generates
the intermediate E, which yields the cine-substitution product
3 through b-oxygen elimination. The undesired ipso-substi-
tution might proceed through the insertion of 1 into the
À
carbon rhodium bond in B with opposite regiochemistry,
thus leading to the formation of F. Alternatively, the side-
product 4 might be formed through a typical cross-coupling
mechanism.[8,16]
In summary, the selective cine substitution of 1-aryl
ethenyl acetates 1 with arylboronic acids 2 was found to
proceed in the presence of a cod-ligated rhodium catalyst. The
chelation of the diene to rhodium is crucial for the unusual
regiochemistry. The catalytic reaction reported here is the
first successful cine substitution of alkenyl acetates.
Scheme 1. Deuterium-labeled experiments.
Received: May 6, 2010
Revised: June 7, 2010
Published online: July 22, 2010
tion of [D2]-1a with phenylboronic acid 2a afforded the cine-
substitution product [D2]-3a with 63% deuteration at its
alkene moiety. When the reaction was stopped after 3 hours,
91% of [D2]-1a had been consumed and the alkene moiety of
the recovered starting material retained 60% deuteration.[14]
This observation indicates that the incorporation of a hydro-
gen atom into the cine-substitution product was partly caused
by the deuterium–hydrogen exchange, which took place
before the catalytic cycle of the cine substitution. Further-
more, [D2]-3 f (43% Da, 80% Db) was obtained from the
reaction of 2 f with [D2]-1a, in which one of the deuterium
atoms at the b position migrated onto the a position during
the catalytic process. The results of these deuterium-labeled
experiments suggest that the 1-arylethenyl esters 1 undergo
the cine substitution through the pathway as shown in
Scheme 2. The diene-ligated (acetato)rhodium(I) A reacts
Keywords: acetates · boranes · homogeneous catalysis ·
.
olefination · rhodium
´
´
[1] For a review, see: J. Suwinski, K. Swierczek, Tetrahedron 2001,
57, 1639.
[2] For recent examples, see: a) C. Enguehard, H. Allouchi, A.
Gueiffier, S. L. Buchwald, J. Org. Chem. 2003, 68, 5614; b) W.
Kleist, S. S. Prꢀckl, M. Drees, K. Kꢀhler, L. Djakovitch, J. Mol.
Catal. A 2009, 303, 15.
[3] K. Yoshida, T. Hayashi, J. Am. Chem. Soc. 2003, 125, 2872.
[4] M. E. Limmert, A. H. Roy, J. F. Hartwig, J. Org. Chem. 2005, 70,
9364.
[5] A. L. Hansen, J.-P. Ebran, T. M. Gøgsig, T. Skrydstrup, J. Org.
Chem. 2007, 72, 6464.
[6] a) A. T. Lindhardt, T. M. Gøgsig, T. Skrydstrup, J. Org. Chem.
2009, 74, 135; b) A. L. Hansen, J.-P. Ebran, M. Ahlquist, P.-O.
Norrby, T. Skrydstrup, Angew. Chem. 2006, 118, 3427; Angew.
Chem. Int. Ed. 2006, 45, 3349; c) J.-P. Ebran, A. L. Hansen, T. M.
Gøgsig, T. Skrydstrup, J. Am. Chem. Soc. 2007, 129, 6931.
[7] For the electrophilic cine substitution of alkenylmetal substrates
with aryl halides using
a palladium catalyst, see: a) J. C.
Anderson, S. Anguille, R. Bailey, Chem. Commun. 2002, 2018;
b) E. Fillion, N. J. Taylor, J. Am. Chem. Soc. 2003, 125, 12700.
[8] J.-Y. Yu, R. Kuwano, Angew. Chem. 2009, 121, 7353; Angew.
Chem. Int. Ed. 2009, 48, 7217.
[9] Separately, Kwong et al. reported the rhodium-catalyzed cross-
coupling of vinyl acetate promptly after our report (see Ref. [8]):
H. W. Lee, F. Y. Kwong, Synlett 2009, 3151.
Scheme 2. A possible pathway of the catalytic cine substitution.
[10] In general, compared to cod, the nbd ligand tightly binds to a
transition metal with a small bite angle. The properties of nbd
may be disadvantageous for the b-hydride elimination from C to
afford the intermediate D in Scheme 2; a) J. L. Butikofer, E. W.
Kalberer, W. C. Schuster, D. M. Roddick, Acta Crystallogr. Sect.
C 2004, 60, m353; b) H.-J. Drexler, S. Zhang, A. Sun, A.
Spannenberg, A. Arrieta, A. Preetz, D. Heller, Tetrahedron:
Asymmetry 2004, 15, 2139.
[11] a) T. Hayashi, K. Ueyama, N. Tokunaga, K. Yoshida, J. Am.
Chem. Soc. 2003, 125, 11508; b) C. Defieber, J.-F. Paquin, S.
Serna, E. M. Carreira, Org. Lett. 2004, 6, 3873.
[12] The additives, tert-amyl alcohol and diisopropylamine, may
activate 2a through the interaction between the lone pair of the
additives and the boron atom of 2a. Alternatively, the additives
may assist 2a to dissolve in toluene.
with organoboron 2 to form (aryl)rhodium B. The trans-
metalation might take precedence over the oxidative addition
of 1 to A, because the coordination of cod to the rhodium
center accelerates the formation of B.[15] The syn addition of B
to alkenyl acetate 1 takes place, and then forms (alkyl)rho-
dium C preferentially. The regiochemistry in the addition
would be governed synergistically by the electronic property
of R1 and the steric repulsion between R1 and R2. Electron-
withdrawing R1 is advantageous to the selective formation of
C, because it enhances the electrophilicity of the b-carbon
atom in 1. The b-hydride elimination from C and the
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Chemie
[13] The uses of the electron-deficient arylboronic acids, 2d, 2e, and
2 f, instead of their corresponding arylboronate, afforded the
cine-substitution products 3d, 3e, and 3 f in 25%, 21%, and 19%
yield, respectively. The use of electron-deficient arylboronic acid
2g did not afford any cine-substitution product (3g).
[14] The reaction produced [D2]-3a and [D2]-4a in a 92:8 molar ratio.
The cine-substitution product (67% D) was isolated in 70%
yield.
[15] The kinetic studies of the rhodium-catalyzed 1,4-addition of
phenylboronic acid to the enone indicated that the reaction
between (hydroxo)rhodium(I) and the organoboron compound
is the rate-determining step in the catalytic reaction and that the
use of a diene ligand in place of bisphosphine causes the
acceleration of the transmetalation step. See: a) A. Kina, H.
Iwamura, T. Hayashi, J. Am. Chem. Soc. 2006, 128, 3904; b) A.
Kina, Y. Yasuhara, T. Nishimura, H. Iwamura, T. Hayashi,
Chem. Asian J. 2006, 1, 707; c) W.-L. Duan, H. Iwamura, R.
Shintani, T. Hayashi, J. Am. Chem. Soc. 2007, 129, 2130.
[16] In our previous report (see Ref. [8]), we concluded that the ipso-
substitution proceeded through the oxidative addition of vinyl
acetate to bis(phosphine)-chelated rhodium(I). The chelation of
the bis(phosphine) would be advantageous to the oxidative
addition because it would increase the electron density on the
rhodium.
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