The palladium-catalyzed addition of organoboronic acids to alkynes

Article abstract of DOI:10.1002/anie.200390214

No base is necessary: Excellent yields are produced on addition of organoboronic acids to alkynes under mild reaction conditions when palladium compounds are used as catalysts (see scheme). Unlike the Suzuki-type cross-coupling reaction, the current reaction occurs in an acidic medium.

Full text of DOI:10.1002/anie.200390214

Angewandte
Chemie
Palladium-Catalyzed Addition
The Palladium-Catalyzed Addition of
Organoboronic Acids to Alkynes**
Chang Ho Oh,* Hyung Hoon Jung, Ki Seong Kim, and
Nakjoong Kim
Palladium-catalyzed cross-coupling of organoboronic acids
with organic halides or their equivalents has long been the
subject of intensive work in the area of transition-metal
chemistry.[1] The Suzuki reaction is now one of the most
[*] Prof. Dr. C. H. Oh, H. H. Jung, K. S. Kim, N. Kim
Department of Chemistry
Hanyang University
Sungdong-Gu, Seoul 131-791 (Korea)
Fax: (+82)2-2299-0762
E-mail: changho@hanyang.ac.kr
[**] We wish to acknowledge the financial support of KOSEF (2001-1-
123-001-5) andthe Center for Molecular Design andSynthesis
(CMDS, R11-1999-05601).
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Table 1: Pd-catalyzed hydroalkylation of alkynes 1 with organoboronic acids 2.[a]
general reactions used to synthesize
stereodefined alka-
biaryls,[2]
Entry
Alkyne
RB(OH)2
T [8C]
t [h]
Products
Yield [%]
dienes,[3] and trienes.[4] Since a vari-
ety of organoboron compounds
have now become readily available,
much attention has been devoted to
develop a new aspect of organo-
boron chemistry.
Miyaura and co-workers report-
ed the rhodium-catalyzed 1,4-con-
jugated addition of organoboronic
acids to a,b-unsaturated ketones
through a sequence of boron–rho-
dium transmetalation reactions.[5] 13
The use of the chiral binap–rhodi-
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1b
1b
1c
1c
1d
1d
1e
1e
1 f
2i
2j
2k
2l
2m
2n
2o
2i
2l
2i
2l
2i
2l
2i
2l
2i
2l
2i
2l
2i
2l
80
70
70
40
60
70
70
60
60
80
80
50
60
60
80
80
80
80
80
80
80
10
4
5
12
6
12
12
2
3ai
3aj
3ak
3al
3am
3an
3ao
3bi
3bl
3ci
3cl
3di
3dl
3ei
3el
3 fi
3 fl
93
96
65
88
83
83
92
90
88
91
75
85
78
99
89
94
9
3
10
11
12
12
12
15
5
48
24
6
4
8
8
4
14
15
16
17
18
19
20
21
um (binap = 2,2’-bis(diphenylphos-
phanyl)-1,1’-binaphthyl)
catalyst
1 f
72
enabled asymmetric additions of
organoboronic acids to aldehydes,[6]
N-sulfonyl imines,[7] a,b-unsaturat-
ed enones,[8] and a,b-unsaturated
esters to be achieved.[9] The rhodi-
um-catalyzed additions of aryl bor-
onic acids to unactivated alkenes
and alkynes were also accomplish-
ed.[10] The well-accepted catalytic
1g
1g
1h
1h
3gi, 4gi
3gl, 4gl
3hi, 4hi
3hl, 4hl
80 (4:1)[b]
85 (3:1)[b]
84 (4:1)[b]
78 (1:1)[b]
4
[a] The reaction was carriedout with 1 andorganoboronic acid 2 (1.2 equiv) in 1.0 mL of 1,4-dioxane in
the presence of 3 mol% of [Pd(PPh3)4] andacetic acid(0.10–0.15 equiv). [b] The combinedyields and
isomeric ratios were determined by 1H NMR spectral analysis.
cycle for the hydroarylation of unactivated alkynes involves
the addition of aryl–rhodium intermediates (Ar-Rh-L),
formed by oxidative addition of the rhodium catalyst to the
ArB(OH)2 species, to the p bond of the substrate.[11] Similar
hydroarylations have also been attained by nickel-catalyzed
additions of aryl magnesium or aryl zinc reagents to alkynes
or by titanium-catalyzed hydrozincations of alkynes.[12] Here
we report the first example of palladium-catalyzed hydro-
arylations of alkynes with organoboronic acids and a mech-
anistic interpretation based on a isotope-labeling study.
The palladium-catalyzed additions of a series of organo-
boronic acids (2i–2o) to various alkynes (1a–1h) were
tained (entry 1) when a mixture of 1a, 2i (1.2 equiv), acetic
acid (0.10–0.15 equiv), and [Pd(PPh3)4] (3 mol% relative to
1a) in 1,4-dioxane was heated at 808C for 10 h. The reaction
took place very slowly (several days), even in the absence of
an acid additive.
Both 3,5-dimethylphenylboronic acid (2j) and 4-
(hydroxymethyl)phenylboronic acid (2k) added to the alkyne
1a under the optimal conditions to give the hydroarylation
products 3aj and 3ak in yields of 96 and 65%, respectively
(entries 2 and 3). In addition, trans-1-hexenylboronic acid
(2l), trans-2-phenylvinylboronic acid (2m), trans-2-(4-chloro-
phenyl)vinylboronic acid (2n), and 2-benzofuranylboronic
examined (Scheme 1, Table 1). The reaction of 5-hexyn-1-ol acid (2o) added to the alkyne 1a to give the corresponding
(1a) with phenylboronic acid (2i) was first examined in a
variety of solvents (such as 1,4-dioxane, THF, and toluene) in
the presence of a catalytic amount of formic or acetic acid.
The optimal yield of 5-phenyl-5-hexen-1-ol (3ai) was ob-
dienes 3al, 3am, 3an, and 3ao in yields of 88, 83, 83, and 92%,
respectively (entries 4–7). Next, the palladium-catalyzed
addition of organoboronic acids to various terminal alkynes
was tested. As expected, both aryl and alkenylboronic acids 2i
and 2l added to the alkynes 1b–d to give the corresponding
products 3bi, 3bl, 3ci, 3cl, 3di, and 3dl, respectively, in
excellent yields (entries 8–13). Two internal alkynes, 4-octyne
(1e) and 2-butyne-1,4-diol (1 f), also underwent hydroaryl-
ation with organoboronic acids (2i and 2l) in excellent yields,
although 4-octyne (1e) required a relatively long reaction
time for completion (entries 14–17). Finally, the two alkynes
1g and 1h conjugated with electron-withdrawing groups were
treated with boronic acids (2i and 2l) under the same
conditions. As expected, the reactions were very facile but
gave a mixture of regioisomers of the addition products 3 and
4.
R1
R
R2
R1
R2
R
RB(OH)2 (2, 1.2 equiv)
[Pd(PPh3)4] (3 mol%), H+
R1
R2
+
1
3
4
R1 =
R2 =
H
H
H
R =
2i: C6
1a: (CH2)4OH
1b: (CH2)4OBn
1c: C6H5
H5
2j: 3,5-(CH3)2C6H3
2k: 4-(CH2OH)C6H4
2l: n-C4H9CH=CH2
2m: C6H5CH=CH2
1d:
H
CH2
E
E
nPr
1e: nPr
2n: 4-ClC6H4CH=CH2
2o:
CH2OH
COOEt
COOEt
1f: CH2OH
1g: nBu
1h: C6H5
To gain more insight into the mechanism of the present
reaction the reaction of alkyne 1a with phenylboronic acid
was conducted using deuterated acetic acid (DOAc;
Scheme 2). Only 40% of the deteurium-incorporated product
O
Scheme 1.
806
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Chemie
(acacH = acetylacetone),[17] [Pd(OR)L2] (R = H, Me, Ac),
R1
Ph
H
R1
Ph
D(H)
H
a
c
R1
H
and [Pt(OR)(S)L2] (R = H, Me; S = solvent) under neutral
conditions. The reductive elimination of the intermediate II
would form the desired products (3 and 4) and the eliminated
Pd0 species.
+
1a
D(H)
[D](E)-3ai
[D](Z)-3ai
(Z:E = 3:1)
b
The presence of a mineral base has been generally
believed to be fundamental for the success of the Suzuki-
type cross-coupling. The present study shows importantly that
the alkenylpalladium intermediates I could be smoothly
cross-coupled with organoboronic acids even in acidic media.
It is noteworthy that no base is involved in the catalytic cycle.
In conclusion, we have shown for the first time that
palladium compounds can catalyze the addition of organo-
boronic acids to alkynes. The ready availability of alkynes and
organoboronic acids combined with the excellent chemical
yields and mild reaction conditions of this process suggest that
the present reaction should find wide application in organic
synthesis.
R1
D(H)
[D1]1a
(50% D)
only [D](E)-3ai
a) 3 mol% [Pd(PPh3)4], 3 equiv DOAc, 1.2 equiv 2i, 1,4-dioxane, 80 °C, 5 h.
b) 3 mol% [Pd(PPh3)4], 3 equiv DOAc, 1,4-dioxane, 80 °C, 2 h.
c) 3 mol% [Pd(PPh3)4], 3 mol% HOAc, 1.2 equiv 2i, 1,4-dioxane, 80 °C, 5 h.
Scheme 2.
[D]3ai was isolated in a Z:E ratio of 3:1 as evident by
1H NMR analysis when 3.0 equivalents of deuterated acetic
acid were used. This result indicated that there was some
stereochemical scrambling or deuterium exchange between
the alkyne-H and AcOD prior to the addition of D-Pd-OAc
to the triple bond.[13] In fact, the 50% deuterated alkyne
[D1]1a was obtained when alkyne 1a was exposed to similar
conditions in the absence of phenyboronic acid. When the
reaction of the 50% deuterated alkyne [D1]1a with 2i was
examined in the presence of a catalytic amount of acetic acid,
[D1](E)-3ai was obtained exclusively without any loss of
deuterium.[14]
Received: August 29, 2002
Revised: November 5, 2002 [Z50062]
[1] a) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457; b) A.
Suzuki, J. Organomet. Chem. 1999, 576, 147.
[2] a) T. Hayashi, S. Niizuma, T. Kamikawa, N. Suzuki, Y. Uozumi,J.
Am. Chem. Soc. 1995, 117, 9101; b) T. Kamikawa, T. Hayashi,
Tetrahedron 1999, 55, 3455.
A proposed mechanism based on the deuterium-labeling
study is shown in Scheme 3. The syn addition of the H-Pd-
OAc species into the triple bond would form the alkenylpal-
[3] a) M. J. Burk, J. G. Allen, W. F. Kiesman, J. Am. Chem. Soc.
1998, 120, 657; b) N. HØnaff, A. Whiting, J. Chem. Soc. Perkin
Trans. 1 2000, 395.
[4] a) W. R. Roush, K. J. Moriarty, B. B. Brown, Tetrahedron Lett.
1990, 31, 6509; b) J. Uenishi, R. Kawahama, O. Yonemitsu, J.
Tsuji, J. Org. Chem. 1996, 61, 5716.
Pd0
HOAc
R1
R
R2
H-Pd-OAc
R1
R2
[5] M. Sakai, H. Hayashi, N. Miyaura, Organometallics 1997, 16,
4229.
+
1
3 + 4
[6] a) M. Sakai, M. Ueda, N. Miyaura, Angew. Chem. 1998, 110,
3475; Angew. Chem. Int. Ed. 1998, 37, 3279; b) M. Ueda, N.
Miyaura, J. Org. Chem. 2000, 65, 4450.
[7] M. Ueda, N. Miyaura, J. Organomet. Chem. 2000, 595, 31.
[8] a) T. Hayashi, T. Senda, Y. Takaya, M. Ogasawara,J. Am. Chem.
Soc. 1999, 121, 11591; b) Y. Takaya, M. Ogasawara, T. Hayashi,
Tetrahedron Lett. 1998, 39, 8479; c) Y. Takaya, M. Ogasawara, T.
Hayashi, M. Sakai, N. Miyaura, J. Am. Chem. Soc. 1998, 120,
5579.
R1
R2
+ AcOH
R1
AcOPd
R2
Pd
I
II
R
O B OH
RB(OH)2
5
2
Scheme 3.
[9] S. Sakuma, M. Sakai, R. Itooka, N. Miyaura, J. Org. Chem. 2000,
65, 5951.
[10] a) K. Oguma, M. Miura, T. Satoh, M. Nomura,J. Am. Chem. Soc.
2000, 122, 10464; b) M. Lautens, A. Roy, K. Fukuoka, K.
Fagnou, B. Martin-Matute, J. Am. Chem. Soc. 2001, 123, 5358;
c) M. Lautens, M. Yoshida, Org. Lett. 2002, 4, 123.
[11] T. Hayashi, K. Inoue, N. Taniguchi, M. Ogasawara,J. Am. Chem.
Soc. 2001, 123, 9918.
[12] a) For a review on the Ni-catalyzed addition, see I. N. Houpis, J.
Lee, Tetrahedron 2000, 56, 817; b) for a review on the organozinc
reagents, see P. Knochel, J. J. Almena Perea, P. Jones, Tetrahe-
dron 1998, 54, 8275; c) for a review on the organotitanium
reagents, see F. Sato, H. Urabe, S. Okamoto, Chem. Rev. 2000,
100, 2835.
ladium intermediate I. The reaction was complete even in the
presence of a catalytic amount of the acid, which suggests that
a proton source for the hydropalladation reaction could be
the organoboronic acid. The organic group can transfer from
the metal–boron species to the metal–palladium species to
form the intermediates (II) containing two organic ligands in
the coordination sphere of the palladium center, acetic acid,
and a boric acid derivative such as metaboric acid. It has been
well-documented that the high oxophilicity of the boron
center and the electron richness of palladium(0) and plati-
num(0) complexes would induce transmetalation, whereby
organic groups on the boron atom readily transfer to
[13] B. M. Trost, D. L. Romero, F. Rise, J. Am. Chem. Soc. 1994, 116,
4268.
1
[14] Some representative H signals were observed at d = 5.25 ppm
Pd(OAc)2,[15]
[h3-C3H5PdOAc]2,[16]
[h3-C3H5Pd(acac)]
for H1, d = 5.04 ppm for H2, and the 13C NMR signal for the
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Communications
terminal olefinic carbon atom was observed at d = 111.89 ppm (t,
J = 24 Hz) in the NMR spectra.
[15] H. A. Dieck, R. F. Heck, J. Org. Chem. 1975, 40, 1083.
[16] N. Miyaura, K. Yamada, H. Suginome, A. Suzuki, J. Am. Chem.
Soc. 1985, 107, 972.
[17] A. Suzuki in Metal-Catalyzed Cross-Coupling Reactions (Eds.: F.
Diederich, P. J. Stang), VCH, Weinheim, 1988; p. 49.
808
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