Mizoroki-Heck type reaction of organoboron reagents with alkenes and alkynes. A Pd(II)-catalyzed pathway with Cu(OAc)2 as an oxidant

Article abstract of DOI:10.1021/ol016529y

Formula presented In contrast to the Pd(0)-catalyzed mechanism by Uemura, Mizoroki-Heck type reaction of boronic acids is found to proceed under a Pd(II)-mediated pathway using a catalytic amount of Pd(OAc)₂ in the presence of Cu(OAc)₂ as an oxidant. Treatment of a variety of alkenes with boronic acids, boronates, and sodium tetraphenylborate furnishes β-arylated and alkenylated products in good to excellent yields. The reactions with norbornene, norbornadiene, and diphenylacetylene are also performed to give 1:2 or 2:1 coupling products.

Full text of DOI:10.1021/ol016529y

ORGANIC
LETTERS
2001
Vol. 3, No. 21
3313-3316
Mizoroki−Heck Type Reaction of
Organoboron Reagents with Alkenes
and Alkynes. A Pd(II)-Catalyzed Pathway
with Cu(OAc)2 as an Oxidant
Xiaoli Du, Masahiro Suguro, Kazunori Hirabayashi, and Atsunori Mori*
Chemical Resources Laboratory, Tokyo Institute of Technology, Nagatsuta,
Yokohama 226-8503, Japan
Takashi Nishikata, Nobuhito Hagiwara, Kentaro Kawata, Takeaki Okeda,
Hui Feng Wang, Keigo Fugami, and Masanori Kosugi*
Department of Chemistry, Faculty of Engineering, Gunma UniVersity, Kiryu,
Gunma 376-8515, Japan
amori@res.titech.ac.jp
Received August 3, 2001
ABSTRACT
In contrast to the Pd(0)-catalyzed mechanism by Uemura, Mizoroki−Heck type reaction of boronic acids is found to proceed under a Pd(II)-
mediated pathway using a catalytic amount of Pd(OAc)2 in the presence of Cu(OAc)2 as an oxidant. Treatment of a variety of alkenes with
boronic acids, boronates, and sodium tetraphenylborate furnishes â-arylated and alkenylated products in good to excellent yields. The reactions
with norbornene, norbornadiene, and diphenylacetylene are also performed to give 1:2 or 2:1 coupling products.
In addition to the conventional Mizoroki-Heck (MH)
reaction of unsaturated compounds with organic halides as
an electrophile,1,2 the related reactions with several nucleo-
philic organometallic reagents such as silanols3 and orga-
nostannanes4 have also attracted much attention recently. In
contrast to MH reaction catalyzed by Pd(0) as shown in eq
1 of Scheme 1, organometallic reagent-mediated MH-type
reactions usually require stoichiometric Pd(II) or a catalytic
amount of Pd(II) in the presence of an appropriate oxidant.
This is the case with the reaction of silanol and trialkyltin
(eq 2). This is because the reaction involves transmetalation
between the reagents and Pd(II) species to form the orga-
nopalladium complex like A as a key step. On the other hand,
the MH-type reaction of boronic acid was shown by Uemura
Scheme 1
* E-mail for second corresponding author: kosugi@chem.gunma-u.ac.jp.
(1) (a) Mizoroki, T.; Mori, K.; Ozaki, A. Bull. Chem. Soc. Jpn. 1971,
44, 581. (b) Heck, R. F.; Nolley, J. P., Jr. J. Org. Chem. 1972, 37, 2320.
(2) For reviews, see: (a) Heck, R. F. Org. React. 1982, 27, 345. (b)
Tsuji, J. Palladium Reagents and Catalysts; InnoVations in Organic
Synthesis; Wiley: Chichester, 1996.
(3) (a) Hirabayashi, K.; Nishihara, Y.; Mori, A.; Hiyama, T. Tetrahedron
Lett. 1998, 39, 7893. (b) Hirabayashi, K.; Kondo, T.; Toriyama, F.;
Nishihara, Y.; Mori, A. Bull. Chem. Soc. Jpn. 2000, 73, 749. (c) Hirabayashi,
K.; Ando, J.; Kawashima, J.; Nishihara, Y.; Mori, A.; Hiyama, T. Bull.
Chem. Soc. Jpn. 2000, 73, 1409.
(4) (a) Oda, H.; Morishita, M.; Fugami, K.; Sano, H.; Kosugi, M. Chem.
Lett. 1996, 811. (b) Fugami, K.; Hagiwara, S.; Oda, H.; Kosugi, M. Synlett
1998, 477. (c) Hirabayashi, K.; Ando, J.; Nishihara, Y.; Mori, A.; Hiyama,
T. Synlett 1999, 99. See also: (d) Heck, R. F. J. Am. Chem. Soc. 1968, 90,
5518. (e) Heck, R. F. J. Am. Chem. Soc. 1969, 91, 6707.
10.1021/ol016529y CCC: $20.00 © 2001 American Chemical Society
Published on Web 09/20/2001

to proceed under Pd(0)-catalyzed conditions (eq 3).5 In this
reaction, oxidatiVe addition of the carbon-boron bond to
Pd(0) to give B is shown to be the initial step of the catalytic
cycle. We have been interested in studying the difference of
such organometalloids. Here we report our recent findings
on organoboron-mediated catalytic MH-type reaction, which
can be performed also via a Pd(II)-catalyzed pathway in an
aprotic polar solvent such as DMF using copper(II) acetate
as an inexpensive oxidant.
65% yield after stirring for only 3 h. Use of a slightly excess
amount (1.2 equiv) of phenylboronic acid improved the yield
to 84%.
As summarized in Table 1, we examined the MH-type
reaction of phenylboronic acid (1) with various alkenes. The
reactions proceeded smoothly to afford the corresponding
phenylated products in reasonable yields. In addition to
alkenes bearing an electron-withdrawing substituent (2a-
d), allyl phenyl ether (2e) and styrene (2f) also affected the
reaction. All the alkenes examined except acrylonitrile (2d)
afforded the products with E-configuration, exclusively. The
reaction with 1,2-disubstituted alkenes such as ethyl crotonate
(2g) and ethyl fumarate (2h) also proceeded stereoselectively.
Although these reactions required a higher reaction temper-
ature than those of Pd(0)-catalyzed reactions (rt, 1 d),5a
boronic acid was much more reactive than silanols and aryltin
reagents.
The reaction of phenylboronic acid (1, 1 mmol) with butyl
acrylate (2a, 1 mmol) was carried out as shown in Scheme
2 under the similar conditions as for silanol or tin using 10
Scheme 2
Table 2 shows the reaction of various boron reagents with
butyl acrylate. Use of boronic acids 4-8 that possess an
electron-withdrawing or -donating substituent on the aromatic
ring was found to be equally effective irrespective of the
electronic effect. Sodium tetraphenylborate (9) also under-
went the arylation in a good yield.6 Moreover, the reaction
of alkenylpinacolboranes 10 instead of the corresponding
boronic acids was also effective to give the corresponding
dienoates in notably good yields.5a Thus, the boronic esters
mol % of Pd(OAc)2, 2.0 equiv of Cu(OAc)2, and 3.0 equiv
of LiOAc in DMF (7.5 mL) at 100 °C.3c In contrast to the
reactions of silanols and tin reagents, which required a
reaction period of 24 h to result in a reasonable yield, the
product, butyl 3-phenyl-2-propenoate (3a), was obtained in
Table 1. MH-Type Reaction of PhB(OH)2 with Various
Alkenesa
Table 2. MH-Type Reaction of Organolboron Reagents 4-10
with Butyl Acrylate (2a)a
a The reaction was performed under the same conditions as those in Table
1 unless otherwise noted. b The ratio of 2a/9 was 2.2, and the reaction was
carried out in the absence of LiOAc. The yield was estimated on the basis
of the mol amount of 9. c The reaction of 10a (0.5 mmol) was carried out
with 2a (0.6 mmol) in DMF (2 mL) at 75 °C for 4.3 h in the absence of
LiOAc. d The reaction was carried out using 3 mol % of PdCl2(PhCN)2
and 2.0 equiv of Cu(OAc)2 in DMF (2 mL) at 82 °C for 5.3 h in the absence
of LiOAc.
a The reaction was carried out using 5 mol % of Pd(OAc)2, alkene 2
(0.2 mmol), and 1 (0.24 mmol) in the presence of Cu(OAc)2 (0.4 nnol) and
LiOAc (0.6 mmol) in DMF (1.5 mL) at 100 °C for 4 h.
3314
Org. Lett., Vol. 3, No. 21, 2001

were found to be available for the alkenylmetal-based MH-
type reaction without hydrolysis of the boronate moiety.
Employment of substrates that generate an intermediate
not amenable to â-hydride elimination results in remarkable
1:2 condensation reactions. Indeed, the reaction with nor-
bornene (11) induced double arylation as shown in Scheme
3.4b,7 In this reaction, chloroacetone was found to be an
smoothly underwent the double alkenylation. These results
are generally better than their tin counterparts.4b Moreover,
alkenylboron-based protocol is advantageous because the
reagents are much more readily accessible in stereoselective
fashion in comparison to the corresponding tributyltin
reagents. We assume that the reaction pathway is rationalized
as follows: alkenylpalladation to norbornene would form
an intermediary palladium adduct through syn-addition as
proposed in the usual MH-type reaction. However, the rigid
bicyclo[2.2.1] structure would circumvent conformational
rotation leading to the syn-periplaner orientation of Pd-C-
C-H unit that facilitates the â-hydride elimination. Thus,
subsequent transmetalation with the second alkenylboronate
10 to the palladated intermediate followed by reductive
elimination would afford the double alkenylated product.
On the other hand, B-(2-phenylethenyl)pinacolborane (10a)
reacted with diphenylacetylene (16a) and dimethyl acety-
lenedicarboxylate (16b) to give 5-(benzylidene)-1,2,3,4-
tetraphenyl-1,3-cyclopentadiene (17a) and 5-(benzylidene)-
1,2,3,4-tetrakis(methoxycarbonyl)-1,3-cyclopentadiene (17b),
the 1:2 condensation products of the boron reagent and
alkynes (Scheme 5). These products are potentially interest-
Scheme 3
effective oxidant, whereas none of the copper(II) salts
examined gave good results. The doubly arylated product
12 was obtained in 34% yield accompanied by 59% of
biphenyl, while the corresponding organotin-mediated reac-
tion gave much better yields of diarylated norbornane
derivatives.4b
Scheme 5
The reaction of alkenylboronic esters 10 with norbornene
(11) and norbornadiene (13) gave much better results
(Scheme 4). When the reactions of B-(2-phenylethenyl)-
Scheme 4
ing precursors of densely substituted cyclopentadienyl
ligands.8,9 The reaction is assumed to proceed via alkenylpal-
ladation giving an intermediate I. Insertion of the second
alkyne molecule gives II.10 Then, intramolecular carbopal-
ladation becomes feasible, leading to III, and subsequent
dehydropalladation produces 17. Neither double alkenylated
products nor any noncyclized alkyne oligomers were obtained
at all.
pinacolborane (10a) were carried out with 1.5 mol % of
PdCl2(PhCN)2 in the presence of 1.0 equiv of chloroacetone
and 1.0 equiv of potassium carbonate in THF (6.0 mL), 2,3-
bis[(E)-2-phenylethenyl]norbornane (14a) and 5,6-bis[(E)-
2-phenylethenyl]norbornene (15a) were obtained as single
isomers in 72% and 90% yields, respectively.4a,b Some other
alkenylboronates 10b-d with a different R group also
In summary, we have shown that the Mizoroki-Heck type
reaction of several organoboron reagents occurs in aprotic
(8) (a) Wu, G.; Rheingold, A. L.; Geib, S. J.; Heck, R. F. Organometallics
1987, 6, 1941. (b) Silverberg, L. J.; Wu, G.; Rheingold, A. L.; Heck, R. F.
J. Organomet. Chem. 1991, 409, 411 and references therein. (c) Yagyu,
T.; Osakada, K.; Brookhart, M. Organometallics 2000, 19, 2125 and
references therein. (d) Takahashi, T.; Seki, S.; Kotora, M. Jpn. Kokai Tokkyo
Koho JP 08301792 A2 19 Nov 1996 Heisei; Chem. Abstr. 1997, 126, 89089.
(9) Bailey, P. M.; Mann, B. E.; Brown, I. D.; Maitlis, P. M. J. Chem.
Soc., Chem. Commun. 1976, 238.
(10) (a) A related reaction catalyzed by Pd(0) is reported to proceed via
a formation of palladacyclopentadiene intermediate: Shirakawa, E.; Yoshida,
H.; Nakao, Y.; Hiyama, T. J. Am. Chem. Soc. 1999, 121, 4290. (b) A fulvene
formation via nickelacyclopentadiene: Iyoda, M.; Mizusuna, A.; Oda, M.
Chem. Lett. 1988, 149.
(5) (a) Cho, C. S.; Uemura, S. J. Organomet. Chem. 1994, 465, 85. (b)
Rhodium-catalyzed MH-type reaction of boronic acid: Lautens, M.; Roy,
Ame´lie, Fukuoka, K.; Fagnou, K.; Mart´ın-Matute, B. J. Am. Chem. Soc.
2001, 123, 5358. See also: (c) Dieck, H. A.; Heck, R. F. J. Org. Chem.
1975, 40, 1083. (d) Karabelas, K.; Hallberg, A. J. Org. Chem. 1988, 53,
4909.
(6) The reaction using NaBPh4 with AgOAc in acetic acid was also shown
by Uemura: Cho, C. S.; Itotani, K.; Uemura, S. J. Organomet. Chem. 1993,
443, 253.
(7) Rossi, B.; Carpita, A.; Bigelli, C. Tetrahedron Lett. 1985, 26, 523.
Org. Lett., Vol. 3, No. 21, 2001
3315

polar solvents with various alkenes and alkynes in good to
excellent yields. MH-type reaction of organoboron reagents
were revealed to proceed via both Pd(0)-5a and Pd(II)-
catalyzed pathways. Such divergent characteristics have not
been observed in the MH-type reactions with related silicon
or tin.
Acknowledgment. This work was partially supported by
a Grant-in-Aid for Scientific Research (no. 13650915) from
Japan Society for the Promotion of Science.
OL016529Y
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Org. Lett., Vol. 3, No. 21, 2001