Ruthenium-catalyzed oxidative heck reactions

Article abstract of DOI:10.1002/1521-3773(20020104)41:1<169::AID-ANIE169>3.0.CO;2-S

Aryl boronic acids can undergo a Heck-type reaction catalyzed by Ru^II in the presence of Cu^II, which serves as a reoxidant in each cycle (see scheme, step1).Compatibility with halide substituents offers attractive synthetic potential

Full text of DOI:10.1002/1521-3773(20020104)41:1<169::AID-ANIE169>3.0.CO;2-S

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provided the key to catalysis, since reversion from a Ru
complex to the halide together with a compatible method for
H
Ruthenium-Catalyzed Oxidative Heck
Reactions**
À
the formation of a Ru C bond would, in principle, complete
the cycle.
Edward J. Farrington, John M. Brown,*
C. F. J. Barnard, and E. Rowsell
In preliminary experiments it was established that the
reaction of 1a with PhSnBu3 or PhB(OH)2 occurred readily to
give 1c as a stable product.[7] This observation formed the
The coupling of organic electrophiles with alkenes is one of
the cornerstones of Pd complex catalysis. The basis of the
chemistry involved lies in early contributions by Mizoroki[1]
and Heck.[2] Many of Heck×s examples involve stoichiometric
reactions of organomercurials and other potential organic
nucleophiles in addition to Pd salts. Since then, but with a
notable recent exception (see below),[3] palladium complexes
have been used essentially exclusively in Heck catalysis.
Ruthenium complexes are readily accessible, but less
basis of
a successful stoichiometric reaction between
PhB(OH)2 and methyl propenoate, promoted by complex
1a in the presence of NEt3 under mild conditions. The use of
more than 2equivalents of Cu(OAc) 2 to reoxidize the
expected Ru H complex led to catalytic turnover; the
process was more efficient when PPh3 was omitted from the
initial Ru catalyst (Scheme 1).[8] Optimization experiments
[4]
À
widely utilized in the catalysis of C C coupling reactions.
A)
O
Faller and Chase demonstrated that complex 1b, prepared
from the dichloride 1a and PhMgBr, reacted with ethene and
2.5 mol% 4
O
Bu
2.5 equiv. Cu(OAc)2
O
Bu
+
O
PhB(OH)2
AgSbF6 to form styrene and the corresponding Ru
complex 2.[5] An intramolecular variant through insertion of
H
Ph
98% GC, 66% isolated
À
,
O
ethene into the Ru C bond of complex 3 was reported by
N
Pfeffer and co-workers.[6] These stoichiometric reactions
CH2Cl2, RT
+
O
B)
2.5 mol% 4
O
H
Bu
2.5 equiv. Cu(OAc)2
O
H
H
Bu
O
PhB(OH)2
+
Ph
D
Et3N, CH2Cl2, RT
Ru
Ru
H
D
X
Ph3P
Ph3P
X
21% D
80% D
49% isolated
Ph
Ru
Ru
O
O
O
O
1a X = Cl
1b X = Ph, Br
1c X = Ph, Cl
2
H
H
D
via
Ph
H
Bu
Bu
Ph
H
D
Scheme 1. Ruthenium-catalyzed Heck reactions: A) optimum conditions;
B) with stereospecifically labeled butyl propenoate.
demonstrated that other oxidizing agents (e.g. Me3NO,
Fremy×s salt) also promoted the reaction, but less effectively
than CuII. Significant improvements in the base component
were achieved by this approach: 3-quinuclidone gave the
highest turnover (Scheme 1A). The conditions were success-
fully applied with n-butyl propenoate and other ArB(OH)2
species (Arˆ p-CHO, OMe, OCF3).
Ru
Ru
Cl
NMe2
Cl
Cl
2
4
3
To compare the pathway with the more familiar Pd case, the
addition of PhB(OH)2 to butyl (Z)-3-D-propenoate[9] was
effected (Scheme 1B). The label was largely, but not com-
pletely, absent in the product. This is in accord with partial
stereoselectivity in the catalytic process, most probably
[*] E. J. Farrington, Dr. J. M. Brown
Dyson Perrins Laboratory
South Parks Rd. OXFORD OX1 3QY (UK)
Fax : (‡44)1865-275642
through stereospecific cis addition of Ru Ph[10] to the alkene
E-mail: bjm@herald.ox.ac.uk.
À
Dr. C. F. J. Barnard, Dr. E. Rowsell
Johnson Matthey Technology Centre
followed by some randomization (Ru keto-enol equili-
bria?)[11] prior to stereospecific Ru-H/D cis elimination.
Electrospray mass spectrometry revealed intermediates in
the catalytic cycle, best observed with 4-BrC6H4B(OH)2 in a
CH3CN matrix (Scheme 2). Before the addition of the alkene,
three monomeric complexes 5a c and one dimeric cationic
complex 5d can be characterized on the basis of the typical
Blount×s Court, Sonning Common, Reading RG4 9NH (UK)
[**] We thank the EPSRC for CASE support (to EJF) with Johnson
Matthey, who also provided the Ru salts. Dr. R. T. Aplin was very
helpful in acquiring electrospray mass spectra.
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
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CO2Bu
CO2Bu
B(OH)2
a
Cl
Cl
+
Ru
Ru
Ru
b
(NCMe)n
X
X
Br
Br
MeO2C
5a n = 0; 393 amu
5b n = 1; 434 amu
5c n = 2; 475 amu
5d 699 amu
Scheme 3. Ru-catalyzed reactions of haloaryl boronic acids. Reagents and
conditions: a) boronic acid (0.4 mmol), [Ru(p-cymene)Cl2]2 (6.2mg,
0.02mmol), Cu(OAc) 2 (201 mg, 1 mmol), quinuclidin-3-one (126 mg,
1 mmol), and butyl propenoate (155 mg, 1.2mmol), toluene, 24 h, room
temperature, X ˆ m-Cl (77%), X ˆ p-Cl (93%), X ˆ p-Br (63%),[13] X ˆ
m-Br (96%), X ˆ m-I (76%), X ˆ p-I (77%); b) butyl p-iodocinnamate
(50 mg, 0.15 mmol), tris(o-tolyl)phosphane (4.56 mg, 0.015 mmol),
Pd2(dba)3 (7.8 mg, 0.0076 mmol), methyl propenoate (65 mg, 0.76 mmol),
triethylamine (76 mg, 0.76 mmol), DMF, 24 h, room temperature, 10
(90%); dba ˆ trans,trans-dibenzylideneacetone, DMF ˆ N,N-dimethyl-
formamide. For product characterization, see Supporting Information.
a)
b)
4
NCMe
NCMe
Ru
MeCN
Ru
À
Br
demonstrate the generality of the selective C B activation
and transfer. Good yields are maintained over a range of
boronic acids substituted with Cl, Br, or I. In one case, a
+
MeO2C
Br
CO2Me
À
tandem Pd- and Ru-catalyzed coupling reaction in which C B
À
6b 561 amu
is activated first, followed by C X, gave the unsymmetrical
6a 520 amu
phenylene-bis-propenoate 10.[14]
Scheme 2. Cationic species observed by electrospray mass spectrometry
recorded on a Micromass BioQ II-ZS at a cone voltage of ‡20 V, Ru-102,
Br-81, Cl-35 ion specified. Reagents and conditions: a) [Ru(p-cymene)Cl2]2
(3.26 Â 10À5 mol), p-bromobenzeneboronic acid (3.26 Â 10À5 mol), NEt3
(3.26 Â 10À5 mol), MeCN (20 mL), 30 min, room temperature; b) same
conditions as (a), but allowed to stand with a tenfold excess of methyl
propenoate for 15 h at À208C before assay.
In related work, it was demonstrated that aryl stannanes,[15]
aryl silanols,[16]and aryl boronic acids[17] can be coupled with
electrophilic alkenes under Pd(OAc)2 catalysis (5 10 mol%).
In the first two cases CuII is present as a reoxidant. In the last
case, the authors favor, but do not prove, an oxidative addition
of ArB(OH)2 as the initial step; the reaction works only in
AcOH. Very recently, Lautens and co-workers observed the
coupling of styrenes with an excess of functionally diverse
boronic acids in aqueous solution, to form E stilbenes in the
absence of a formal oxidant.[3] The relationship of these
procedures to ours is intriguing, but as yet unclear.
isotope distributions in the parent molecular ion. In the
presence of methyl propenoate, the same set of monomeric
ions are observed together with two distinct new halide-free
species, corresponding to monoalkene complexes with one or
two coordinated acetonitrile ligands. The simplest represen-
tation in which these preserve an 18e configuration at the
ruthenium center is as the aryl and alkyl complexes 6a before,
and 6b after the expected migration step; ring slippage is an
alternative possibility.[12] The nature of propenoate binding
The synthetic potential of the ruthenium Heck reaction is
being actively investigated further.[18]
Experimental Section
+
Butyl (E)-3-bromocinnamate: 3-bromobenzeneboronic acid (81 mg,
CH2
0.4 mmol), [Ru(p-cymene)Cl2]2 (6.2mg, 0.02mmol), Cu(OAc) (201 mg,
2
1 mmol), and 3-quinuclidinone (126 mg, 1 mmol) were combined in a dry
Schlenk tube, which was sealed and placed under vacuum for 30 min. The
Schlenk tube was flushed with argon, and butyl propenoate (155 mg,
1.2mmol) and freshly distilled toluene (10 mL) were added through a
syringe. The reaction mixture was stirred for 24 h at ambient temperature.
The volatile components were removed in vacuo, and the product was
purified by flash column chromatography on silica gel (diethyl ether) to
give butyl (E)-3-bromocinnamate (112mg, 96%). M.p. 36 8C; 1H NMR
(500 MHz, CDCl3): d ˆ 0.96 (3H, t, J ˆ 7.3 Hz ; CH3), 1.44 (2H, m; CH2),
1.70 (2H, m; CH2), 4.22 (2H, t, J ˆ 6.7 Hz; OCH2), 6.46 (1H, d, J ˆ 16 Hz;
H1), 7.26 (1H, dd, J ˆ 8 Hz and 7.95 Hz; H5'), 7.46 (1H, d, J ˆ 8 Hz; H4'),
7.52(1H, d, J ˆ 7.95 Hz; H6'), 7.61 (1H, d, J ˆ 16 Hz; H3), 7.68 (1H, s; H2');
13C NMR (125.8 MHz, CDCl3): d ˆ 13.6 (CH3), 19.1 (CH2), 30.6 (CH2), 64.5
(OCH2), 119.7 (C2), 122.9, 126.5, 130.3, 130.6, 132.9, 136.4, (C1', C2', C3',
CO2tBu
tBuO2C
Ru
7
CH2
CO2tBu
CO2tBu
ButO2C
Br
ButO2C
9
8
was explored through the use of methylene malonate 7, which
gave rise to a strong acetonitrile-free molecular ion 8 for the
coordinated alkene complex, under conditions in which the
parent malonate 9 remains passive.
The inertness of the aryl bromide residue towards ruthe-
nium (i.e. dominance of nucleophilic attack by the boronic
acid) indicated valuable synthetic potential. Several haloaryl
boronic acids were subjected to our best conditions of
catalytic turnover, with n-butyl propenoate as the alkene
component. The results are recorded in Scheme 3, and
C4', C5', C6'), 142.7 (C3) 166.5 (C1); IR (Nujol): nÄmax ˆ 2920.9, 1727.3
À1
ˆ
ˆ
(C O), 1641.7 cm (C C); HR-MS: calcd for C13H16O2Br: 283.0335,
found: 283.0335; MS (atmospheric pressure chemical ionisation; APCI ‡ ):
m/z (%): 284 [MH ‡ ], 226 [M À Bu].
Coupling of butyl (Z)-3-D-propenoate: Benzeneboronic acid (10 mg, 8.2 Â
10À5 mol), [Ru(p-cymene)Cl2]2 (1.25 mg, 4.1 Â 10À7 mol), and Cu(OAc)2
(40.9 mg, 0.21mmol) were combined in a vial, and THF (0.9 mL) and
170
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triethylamine (0.1 mL) were added. Butyl (Z)-3-D-propenoate was added
through a syringe. The vial was sealed, and the reaction mixture was stirred
at ambient temperature for 17 h. The solvent was removed in vacuo, and
the product was purified by filtration through a short plug of silica gel
(diethyl ether) to afford butyl (E)-cinnamate (8.2mg, 49%). B.p. 280
2848C; 1H NMR (500 MHz, CDCl3): d ˆ 0.99 (3H, t, J ˆ 7.3 Hz ; CH3), 1.43
(2H, m; CH2), 1.72(2H, m; CH 2), 4.23 (2H, t, J ˆ 6.7 Hz; OCH2), 6.48 (1H,
d, J ˆ 16 Hz; H2), 7.40 (3H, m; ArH), 7.53 (2H, m; ArH), 7.77 (1H, d, J ˆ
16 Hz; H3); 13C NMR (125.8 MHz, CDCl3): d ˆ 13.6 (CH3), 19.1 (CH2),
30.6 (CH2), 64.3 (OCH2), 118.2 (C2), 127.9, 128.7, 130.1, 134.3, (Ar-C), 144.4
(C3), 167.0 (C1); UV/Vis: nÄmax (MeOH) ˆ 276 nm (e ˆ 22000); MS (CI ‡ ):
Enantiopure Double-Helical Alkynyl
Cyclophanes
De Lie An, Takehiko Nakano, Akihiro Orita, and
Junzo Otera*
Chiral p-conjugated molecules have been the subject of
extensive investigation from the standpoints of structural
chemistry and material science.[1] Double-helical molecules, in
particular, are of great interest on account of their unique
structural features as well as potential applications in optics
and electronics. Several twisted alkynyl cyclophanes have
been reported, but, unfortunately, they were obtained as
racemates.[2, 3] To the best of our knowledge, only one
nonracemic double-helical molecule has been prepared.
Namely, a cyclophane was synthesized by connecting a (‡)-
2,15-diethynyl[6]helicene auxiliary with ortho-phenylene
bridges.[4] However, this synthesis was rather lengthy, and
only one enantiomer was obtained. Moreover, in the key
coupling of the helicene with an o-diiodobenzene unit, the
target molecule was obtained in less than 3% yield. We report
here on a rational synthesis and full characterization of
double-helical alkynyl cyclophanes 1 of both enantiopure
forms.[5]
The synthetic route is shown in Scheme 1. Separately (R)-
and (S)-2,2'-diformyl-1,1'-binaphthyl (2)[6] underwent car-
bon carbon coupling, and the resulting diethynyl compound
3 was converted to the monosilylethynyl derivative 4.
Exposure of this compound to an aryl iodide with the
diethyltriazene function 5 afforded 6. The triazene derivatives
6 were transformed into iodides 7 or desilylated to give 8.[7]
Sonogashira coupling[8] of 7 with 8 furnished 9. After
conversion of 9 to 11 via 10 through successive functional
group transformations, intramolecular Sonogashira coupling
provided the desired cyclophanes 1 in enantiopure form
(Table 1). These compounds formed white needlelike crystals
upon recrystallization, but none of them were suitable for
X-ray analyses. Then, we prepared racemic 1b by mixing
equimolar amounts of (R,P)- and (S,M)-1b. Recrystallization
of this mixture from CH2Cl2/hexane furnished crystals con-
ducive to X-ray crystallographic analysis.[9]
‡
m/z (%): 205 [MH ].
Received: August 10, 2001 [Z17712]
[1] T. Mizoroki, K. Mori, A. Ozaki, Bull. Chem. Soc. Jpn. 1971, 44, 581.
[2] R. F. Heck, J. Am. Chem. Soc. 1968, 90, 5518 5526; R. F. Heck, Acc.
Chem. Res. 1979, 12, 146 151; R. F. Heck, Org. React. 1982, 27, 345
391, and references therein.
[3] M. Lautens, A. Roy, K. Fukuoka, K. Fagnou, B. Martin-Matute, J. Am.
Chem. Soc. 2001, 123, 5358 5359.
À
[4] Notably, the C H activation discovered by Murai: S. Murai, F.
Kakiuchi, S. Sekine, Y. Tanaka, A. Kamatani, M. Sonoda, N. Chatani,
Nature 1993, 366, 529 531; F. Kakiuchi, S. Sekine, Y. Tanaka, A.
Kamatani, M. Sonoda, N. Chatani, S. Murai, Bull. Chem. Soc. Jpn.
1995, 68, 62 83; S. Busch, W. Leitner, Adv. Synth. Catal. 2001, 343,
192 195; for an intramolecular variant, see: H. Weissman, X. P. Song,
D. Milstein, J. Am. Chem. Soc. 2001, 123, 337 338; for Ru cyclo-
isomerizations, see: Y. Yamamoto, Y.-i. Nakagai, N. Ohkoshi, K. Itoh,
J. Am. Chem. Soc. 2001, 123, 6372 6380; for a general review, see:
B. M. Trost, F. D. Toste, A. B. Pinkerton, Chem. Rev. 2001, 101, 2067
2096.
[5] J. W. Faller, K. J. Chase, Organometallics 1995, 14, 1592 1600.
[6] V. Ritleng, J. P. Sutter, M. Pfeffer, C. Sirlin, Chem. Commun.
2000,129 130.
[7] The X-ray structure of complex 1c has been determined: A. R.
Cowley, E. J. Farrington, Acta Crystallogr. Sect. E, submitted.
[8] A referee has suggested that the Cu(OAc)2 may activate the aryl
boronic acid directly, on the basis of reported Cu-catalyzed nucleo-
philic substitutions: P. S. Herradura, K. A. Pendola, R. K. Guy, Org.
Lett. 2000, 2, 2019 2022; we have observed a reaction between
PhB(OH)2 and complex 4 at a rate commensurate with the observed
turnover, thus trapping the initially formed intermediate by addition
of PPh3 to form 1c. In the presence of the acetate analogue of complex
4 (5 mol%), the reaction between PhB(OH)2 and Cu(OAc)2 yields
PhOAc as the only characterized organic product in 61% yield; see:
P. Y. S. Lam, G. Vincent, C. G. Clark, S. Deudon, P. K. Jadhav,
Tetrahedron Lett. 2001, 42, 3415 3418.
[9] R. K. Hill, G. R. Newkome, J. Org. Chem., 1969, 34, 740 741.
[10] In the case of Pd, this is assumed on the basis of the overall
As is evident from the ORTEP view depicted in Figure 1,
the cyclophane skeleton is twisted, resulting in the double-
À
stereochemical course of catalysis to be a syn addition of Pd R and
À
then a syn elimination of Pd H; R. F. Heck, J. Am. Chem. Soc. 1969,
ꢀ
helical motif. The C C bonds are slightly deformed from
91, 6707 6715; H. A. Dieck, R. F. Heck, J. Am. Chem. Soc. 1974, 96,
1133 1136.
linearity. Notably, the two binaphthyl groups differ signifi-
cantly in the dihedral angle defined by the naphthalene planes
(688 and 788, respectively). The space-filling model (Figure 2)
indicates that the symmetrical structure places the inside
hydrogen atoms of the phenylene rings very close to each
other. The resulting ring strain is passed on unsymmetrically
into the binaphthyl termini in the crystal.
[11] M. Ikeda, S. El-Bialy, T. Yakura, Heterocycles 1999, 51, 1957 1970.
[12] M. A. Bennett, Z. Lu, X. Wang, M. Bown, D. C. R. Hockless, J. Am.
Chem. Soc. 1998, 120, 10409 10415.
[13] M. Miura, H. Hashimoto, K. Itoh, M. Nomura J. Chem. Soc. Perkin
Trans. 1 1990, 2207 11.
[14] For tandem Heck reactions of dihalobenzenes, see, for example: J. E.
Plevyak, J. E. Dickerson, R. F. Heck, J. Org. Chem. 1979, 44, 4078 4083.
[15] K. Hirabayashi, J. Ando, Y. Nishihara, A. Mori, T. Hiyama, Synlett
1999, 99 101; K. Hirabayashi, J. Ando, J. Kawashima, Y. Nishihara,
A. Mori, T. Hiyama, Bull. Chem. Soc. Jpn. 2000, 73, 1409 1417.
[16] K. Hirabayashi, Y. Nishihara, A. Mori, T. Hiyama, Tetrahedron Lett.
1998, 39, 7893 7896.
1
In contrast to the solid-state molecular structure, H and
13C NMR spectra of 1 (Table 1) are compatible with a single
[*] Prof. Dr. J. Otera, Dr. D. L. An, T. Nakano, Dr. A. Orita
Department of Applied Chemistry, Okayama University of Science
Ridai-cho, Okayama 700-0005 (Japan)
[17] C. S. Cho, S. Uemura, J. Organomet. Chem. 1994, 465, 85 92.
[18] An oxidative palladium-catalyzed Heck reaction of boronates has
been reported; X. L. Du, M. Suguro, K. Hirabayashi, A. Mori, T.
Nishikata, N. Hagiwara, K. Kawata, T. Okeda, H. F. Wang, K. Fugami,
M. Kosugi, Org. Lett. 2001, 3, 3313 3316.
Fax : (‡81)-86-256-4292
E-mail: otera@high.ous.ac.jp
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1433-7851/02/4101-0171 $ 17.50+.50/0
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