Cobalt(II)-catalyzed regio- And stereoselective hydroarylation of alkynes with organoboronic acids

Article abstract of DOI:10.1002/chem.200801858

The series of cobalt (II)-catalyzed cross-coupling reactions of organoboronic acids with alkynes was investigated. The reaction provided a convenient method for the synthesis of highly substituted olefins by using less expensive cobalt complexes as catalysts under base-free conditioned. The scope of organoboronic acids 1 and alkynes 2 in the addition reaction under the standard reaction conditions was also analyzed. Based on the known metal-catalyzed couplings of organometallic reagents and alkynes, a possible reaction mechanism for the present hydroarylation reaction was proposed. These are the first cobalt-catalyzed addition reactions of organoboronic acids to alkynes. The unusual trans stereochemistry for the hydroarylation of substituted propargyl alcohol and amine was observed. The results showed that the organoboronic acid plays a dual role, acting both as a carbon nucleophile as well as proton source in the reaction.

Full text of DOI:10.1002/chem.200801858

DOI: 10.1002/chem.200801858
Cobalt(II)-Catalyzed Regio- and Stereoselective Hydroarylation of Alkynes
with Organoboronic Acids
Pao-Shun Lin, Masilamani Jeganmohan, and Chien-Hong Cheng*[a]
The transition-metal-catalyzed addition reactions of or-
ganometallic reagents to alkynes are a convenient route for
the synthesis of substituted olefins.[1] Organoboron, -silane,
-stannane, -magnesium, and -lithium reagents are commonly
employed as the transmetallating agents in this type of addi-
tion reaction;[1c,2] of these, organoboron reagents have
gained much attention because of their various advanta-
geous properties.[3] Palladium, nickel and rhodium com-
plexes are known to catalyze the addition of organoborons
yield (Table 1, entry 1). In addition, a small amount of ben-
zene, the protodeboronation product of 1a, was also ob-
served by GC–MS analysis. There was no biphenyl formed
in this reaction, which indicated that the cobalt(II) had not
been reduced.[8] This reaction is highly regio- and stereose-
lective, with the phenyl group of 1a adding to the n-C5H11-
substituted alkyne carbon to give exclusively the E stereo-
isomer. Note that this is the first report of a cobalt-catalyzed
addition reaction of an organoboronic acid with an alkyne.
To gain insight into this cobalt-catalyzed addition reac-
tion, the reaction between 1a and 2a was examined under
various conditions. No formation of product 3aa was ob-
ACTHNUTRGNEUNG
to alkynes. When palladium complexes[4] and [Ni(cod)2][5]
were used as the catalysts, various types of addition products
with different ratios of organoboron to alkyne were ob-
served. Simple 1:1 coupling of organoboronic acids with al-
kynes to give hydroarylation products were found when rho-
dium(I) complexes were used as the catalysts.[6] Although
the type of addition greatly depends on the nature of the
metal catalysts, all of these metal-catalyzed reactions of or-
ganoborons to alkynes gave addition products with syn ste-
reoselectivity. Our continuous interest in developing new re-
actions using less expensive and conveniently handled nickel
and cobalt complexes as catalysts prompted us to investigate
the addition of organoboronic acids to various p compo-
nents with cobalt complexes as the catalyst.[7] Herein, we
report a series of cobalt(II)-catalyzed, highly regio- and ste-
reoselective hydroarylations of alkynes using organoboronic
acids as reagents.
served if [Co
ACHTUNGTRENNUNG
action was then carried out in the presence of [CoACHTUNGTRENNUNG
and various phosphine ligands in CH3CN/THF (4:1) at 808C
for 12 h. The use of dppe (1 equiv with respect to the cobalt
complex) gave 3aa in quantitative 99% yield as determined
by the 1H NMR integration method. Note that under the
same reaction conditions in pure CH3CN, the hydroarylation
product 3aa was obtained in 81% yield, and in pure THF
the protodeboronation product of 1a was observed. The
presence of THF appears to increase the solubility of the ar-
ylboronic acid and dppe ligand, whereas the use of CH3CN
presumably facilitates the alkyne insertion and thus the for-
mation of 3aa. Use of bidentate bis(diphenylphosphino)me-
thane (dppm) and 1,3-bis(diphenylphosphino)propane
(dppp) afforded 3aa in 14 and 65% yield, respectively.[9]
Two other bidentate phosphine ligands, 1,4-bis(diphenyl-
phospheno)butane (dppb) and 1,1’-bis(diphenylphosphino)-
ferrocene (dppf), and the monodentate phosphane ligand
PPh3 were ineffective in the reaction. The cobalt(II) com-
When phenylboronic acid (1a) was treated with methyl
oct-2-ynoate (2a) in the presence of 5 mol% [CoACTHNUGTRENUNG(acac)2]/
dppe (acac=acetylacetonate, dppe=1,2-bis(diphenylphos-
phine)ethane) in CH3CN/THF (4:1) at 808C for 12 h, the
hydroarylation product 3aa was obtained in 93% isolated
plexes [CoACHTUNTRGNEUNG(OAc)2] and CoCl2 were also tested in the pres-
ence of dppe. The former gave product 3aa in 80% yield,
but the latter was inactive. Surprisingly, the hydroarylation
did not proceed by using Co(OH)2 in the presence of dppe
as the catalyst, but the reaction took place smoothly by the
addition of acacH into the system to afford 3aa in 95%
[a] Dr. P.-S. Lin, Dr. M. Jeganmohan, Prof. Dr. C.-H. Cheng
Department of Chemistry
National Tsing Hua University
Hsinchu 30013 (Taiwan)
Fax : (+886)3572-4698
yield.[9] The activity of the cobalt
ACTHUNTRGENN(GU III) complex, [CoACHTUNGTRENNUNG(acac)3],
E-mail: chcheng@mx.nthu.edu.tw
was also examined in the presence of one equivalent of
dppe. The reaction gave 3aa in 7% yield at 808C and 33%
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200801858.
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Chem. Eur. J. 2008, 14, 11296 – 11299

COMMUNICATION
Table 1. Cobalt-catalyzed addition of organoboronic acids 1 to alkynes 2.[a]
yield when held at 908C for 24 h. Based on these studies,
we chose [CoACTHNUTRGNE(UNG acac)2] and dppe in a mixture of CH3CN/
THF (4:1) at 808C for 12 h as the standard conditions for
the coupling reactions (see Table 1).
Next, we examined the scope of organoboronic acids 1
and alkynes 2 in the addition reaction under the standard
reaction conditions. Both 1b and 1c efficiently underwent
hydroarylation with 2a to give products 3ba and 3ca in 96
and 91% yields, respectively (Table 1, entries 2 and 3). In
contrast, 2-methoxyphenylboronic acid was inactive. Under
similar reaction conditions, 1d, 1e, and 1 f also efficiently
coupled with 2a to provide the corresponding hydroaryla-
tion products 3da–fa in 94, 67, and 93% yields, respective-
ly (Table 1, entries 4–6). The particularly low yield of 3ea
(Table 1, entry 5) is probably attributed to the strong elec-
tron-withdrawing effect of the nitro group, leading to low
nucleophilicity of the 3-nitrophenyl moiety. Alkenylboron-
ic acids also worked well for the reaction. Thus, trans-2-
phenylvinylboronic acid (1g) reacted with 2a to afford the
substituted 1,3-diene product 3ga, both regio- and stereo-
selectively in 80% yield (Table 1, entry 7). Interestingly,
unlike 2-methoxyphenylboronic acid, the ortho-substituted
heteroaromatic boronic acid (1h) afforded the expected
product 3ha in 88% yield (Table 1, entry 8). In all of the
above cobalt-catalyzed reactions that involve 2a as the
alkyne substrate, the addition is regio- and stereoselective
to give only the cis-hydroarylation products. Under the re-
action conditions employed, a small amount of the proto-
deboronation products of the organoboronic acids were
produced, even when a 1:1 ratio of organoboronic acid and
alkyne was used.
In addition to 2a, compounds 2b and 2c also reacted
with 1 f to provide hydroarylation products 3 fb and 3 fc
(90 and 86% yield, respectively) with cis stereoselectivity.
The high regioselectivity of these reactions with alkynes
2a–c indicates that the addition belongs to a Michael-type
addition, with the aryl or styryl group adding to the b
carbon of the alkyne moiety. Surprisingly, unlike the reac-
tions using alkynes 2a–c, the hydroarylation of propargyl
alcohol 2d and propargyl carbamate 2e provided trans ad-
dition products 4 fd and 4 fe in 82 and 78% yields, respec-
tively after 24 h, in a highly regio- and stereoselective
manner. In contrast, compound 2 f afforded a 1:1 mixture
of the cis and trans addition products 3 ff and 4 ff in a 79%
combined yield. Shorter reaction times are necessary for
activated alkynes 2a–c and longer reaction times are re-
quired for propargyl alcohol 2d and propargyl carbamate
2e.
Entry 1
2
Product 3 or 4
Yield[b]
[%]
1
1a R1 =H
2a
3aa
93
R2 =n-C5H11
(99)[c]
R3 =CO2Me
2
3
4
5
6
1b R1 =4-OMe
1c R1 =3-OMe
1d R1 =3-CHO
1e R1 =3-NO2
1 f R1 =4-Br
2a
2a
2a
2a
2a
3ba
3ca
3da
3ea
3 fa
96
91
94
67
93
7
1g
2a
2a
3ga
80[d]
8
9
1h
1 f
3ha
3 fb
88[d]
90
2b
R2 =Ph
R3 =CO2Me
10
11
1 f
1 f
2c
3 fc
4 fd
86
R2 =Me
R3 =2-pyridine
2d
82[e]
R2 =CH2OH
R3 =Et
12
13
1 f
2e
4 fe
78[e]
R2 =CH2NHBoc R3 =4-(CO2Et)C6H4
R3 =p-CO2Et-
C6H4
1 f
2 f
3 ff/4 ff (1:1)
79
Based on the known metal-catalyzed couplings of organ-
ometallic reagents and alkynes, a possible reaction mecha-
nism for the present hydroarylation reaction has been pro-
posed (Scheme 1).[4,6] Transmetallation of an arylboronic
R2 =R3 =Et
[a] Unless otherwise stated, all reactions were carried out with organoboronic
acid 1 (2.0 mmol), alkyne 2 (1.0 mmol), [Co(acac)2] and dppe (5 mol%) in
CH3CN/THF (4:1; 2.0 mL) at 808C for 12 h. [b] Isolated yield. [c] Yield in pa-
renthesis was determined by the 1H NMR integration method with mesitylene
as an internal standard. [d] The reaction was carried out in CH3CN/THF
(3:1). [e] The reaction time was extended to 24 h.
AHCTUNGTRENNUNG
acid 1 with [CoACHTNUGRTNENUG(acac)2]/ACHUTNGTREN(NGUN dppe) gives an aryl cobalt(II) in-
termediate 5, together with acacH and HOBO.[10] Coordi-
native carbocobaltation of alkyne 2 with the cobalt–aryl
bond of 5 provides the cobalt–alkenyl intermediate 6. Pro-
tonolysis of intermediate 6 by acacH affords hydroaryla-
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11297

C.-H. Cheng et al.
facile E–Z isomerization to intermediate 7 fd via a cobalt
carbene species 6’fd (Scheme 2a). The presence of the hy-
droxymethyl group in 7 fd stabilizes the cobalt intermediate
by forming a five-membered oxametallocycle (8 fd). The
latter becomes the major cobalt intermediate among 6–8 fd
in the catalytic solution, and is protonated to give the ob-
served trans-hydroarylation product 4 fd stereoselectively. A
similar explanation can be applied to the hydroarylation of
alkyne 2e to give 4 fe. For the carbocobaltation of 3-hexyne,
facile E–Z isomerization of intermediates 6 ff and 7 ff also
occurs (Scheme 2b). In the absence of a chelating heteroa-
tom, protonation of the two intermediates leads to a 1:1
mixture of E and Z isomers 3 ff and 4 ff, respectively. On
the other hand, intermediate 6 fa from the carbocobaltation
of 2a does not form the metal carbene species 6’fa due to
the electron-withdrawing property of the ester group
(Scheme 2c). Thus, no E–Z isomerization occurs and only
the cis-hydroarylation product 3 fa was obtained. The analo-
gous regio- and cis-stereoselective hydroarylation of 2c is at-
tributed to the coordination of the pyridyl group to the
metal center during the carbocobaltation of the alkyne.[6b]
In the reaction, the organoboronic acid appears to play a
dual role, acting as both a transmetallating agent and a
proton source.[4g,12] The dual role of the organoboronic acid
is illustrated by the treatment of phenylboroxine or 9a with
Scheme 1. Proposed mechanism for the coupling of organoboronic acids
1 and alkynes 2.
tion product 3 and regenerates the active cobalt(II) species
for further catalytic cycles. A competitive pathway through
protonolysis of the cobalt(II)–aryl bond in species 5 by
acacH leads to the observed protodeboronation product,
ArH, of arylboronic acid 1. This accounts for the require-
ment of extra arylboronic acid (2 equiv) for this reaction.
The hydroarylation of alkynes with
a -CH2OH or
-CH2NH(Boc) group show unusual selectivity for trans addi-
N
2a in the presence of the [CoACTHUNGRETNNU(G acac)2]/dppe system, which
tion.[11] This stereoselectivity has not been reported so far in
the metal-catalyzed hydroarylation of alkynes with arylbor-
onic acids,[5,6] and may be explained based on the proposed
process illustrated in Scheme 2. It is likely that intermediate
6 fd, obtained from the carbocobaltation of 2d, undergoes
did not give the hydroarylation product. However, treating
phenylboroxine with D2O (3 equiv) to provide PhB(OD)2
(1a-D), followed by treatment with 2a in the presence of
the [CoACHTUNTGRNE(UNG acac)2]/dppe system gave the deuterated coupling
product 3aa-D in 90% isolated yield, in which approximate-
ly 50% of the vinyl protons were deuterated based on
1H NMR spectroscopy results (Scheme 3).[6a,12]
Scheme 3. Illustrating the dual role of the organoboronic acid, which acts
as both a transmetallating agent and a proton source.
In conclusion, we have demonstrated a series of co-
balt(II)-catalyzed cross-coupling reactions of organoboronic
acids with alkynes. The reaction provides a convenient
method for the synthesis of highly substituted olefins by
using less expensive cobalt complexes as catalysts under
base-free conditions. In addition, these are the first cobalt-
catalyzed addition reactions of organoboronic acids to al-
kynes. An unusual trans stereochemistry for the hydroaryla-
tion of substituted propargyl alcohol and amine was ob-
Scheme 2. Proposed key pathways for the observed stereochemistry of
the hydroarylation of various alkynes.
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Chem. Eur. J. 2008, 14, 11296 – 11299

Cobalt(II)-Catalyzed Hydroarylation Reactions
COMMUNICATION
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ACHTUNGTRENNUNG[CoACHTUNGTRENNUNG(acac)2]/dppe, but becomes very slow if [CoCAHTNUGTRNEUN(GN acac)3]/dppe
is used as the catalyst. The organoboronic acid plays a dual
role, acting both as a carbon nucleophile as well as a proton
source in the reaction.
Experimental Section
General procedure for the addition reaction of 1 with 2: A sealed tube
containing [CoACHTUNGTRENNUNG(acac)2]/dppe (1 equiv dppe to [CoACHTUNTGERN(NUGN acac)2]; 0.050 mmol,
5.0 mol%) and arylboronic acid 1 (2.00 mmol) was evacuated and purged
with nitrogen gas three times. Freshly distilled CH3CN (1.6 mL), THF
(0.4 mL), and alkyne 2 (1.00 mmol) were added to the system. The dark-
red reaction mixture was stirred at 808C for 12 h. The mixture was then
filtered through a short Celite and silicagel pad and was thoroughly
washed with dichloromethane. The filtrate was concentrated, and the res-
idue was purified on a silicagel column using hexane/ethyl acetate as the
eluent to afford the desired addition product 3.
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Acknowledgements
We thank the National Science Council of Republic of China (NSC 96-
2113-M-007-020-MY3) for support of this research.
Keywords: alkynes
·
cobalt
·
cross-coupling
·
hydroarylation · organoboronic acids
[9] In the presence of Co(OH)2 and HacacR, R=Me, CF3, Ph, tBu, the
addition product 3aa was obtained in 95, 99, 82, and 43% yield, re-
spectively (808C for 24 h).
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Received: September 9, 2008
Published online: November 27, 2008
Chem. Eur. J. 2008, 14, 11296 – 11299
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www.chemeurj.org
11299