Palladium-catalyzed addition of silyl-substituted chloroalkynes to terminal alkynes

Article abstract of DOI:10.1002/chem.201000865

Better together: A novel hybrid N-heterocyclic carbene (NHC) palladium complex, integrating a totally inorganic and polyanionic decatungstate unit, has been synthesized following a convergent strategy. The interplay of the Pd binding domains with the inorganic scaffold is instrumental in accessing multi-turnover catalysis in C-C crosscoupling and aromatic dehalogenation reactions under MW-assisted protocols (see scheme). (Figure Presented)

Full text of DOI:10.1002/chem.201000865

COMMUNICATION
DOI: 10.1002/chem.201000865
Palladium-Catalyzed Addition of Silyl-Substituted Chloroalkynes
to Terminal Alkynes
Tatsuya Wada,[a] Masayuki Iwasaki,[a, b] Azusa Kondoh,[a] Hideki Yorimitsu,*[a, b] and
Koichiro Oshima*[a]
The transition-metal-catalyzed addition of a carbon–halo-
gen s-bond to an alkyne is a very useful and attractive reac-
tion in organic synthesis because both a carbon–carbon
bond and a carbon–halogen bond are formed simultaneously
and atom-economically. The transformation can provide
structurally complex haloalkenes that can be further modi-
fied by carbon–carbon bond-forming reactions including
cross-coupling reactions. In spite of their usefulness, such
carbohalogenation reactions were mainly limited to the ad-
ditions of acid chlorides[1] and allyl halides.[2,3] Very recently,
Jiang and co-workers reported the first example of the addi-
tion of a carbon–halogen s-bond of a haloalkyne to an unac-
tivated alkyne.[4,5] They disclosed the palladium-catalyzed
addition of bromoalkynes to internal alkynes. Although a
variety of internal alkynes can participate in the reaction,
terminal alkynes are unsuitable. Moreover, addition of the
carbon–chlorine s-bond of chloroalkynes has not been re-
ported. Herein, we report the addition reaction of silyl-sub-
stituted chloroalkynes to terminal alkynes under palladium
catalysis to afford (Z)-1-chloro-1,3-enynes with perfect
regio- and stereoselectivity, which are useful building blocks
for the synthesis of highly functionalized enynes.[6]
alytic amounts of [Pd2ACTHNUGTERN(NUG dba)3] (dba=dibenzylideneacetone)
and triphenylphosphane in decalin at 1308C for 6 h afforded
the corresponding (Z)-1-chloro-1,3-enyne[7] 3aa in 46%
yield as determined by NMR spectroscopy. Nonpolar sol-
vents, such as decalin, cyclooctane, and xylene, were the sol-
vent of choice, and decalin gave the best result. Ethereal
solvents, such as di-n-butyl ether, and aprotic polar solvents,
such as DMF, decreased the yield. With respect to the cata-
lyst precursor, palladium (II) complexes, such as Pd
and [PdCl2A(MeCN)2] with triphenylphosphane (2 equiv rela-
tive to Pd), also showed catalytic activity and gave results
similar to those with [Pd2A(dba)3]. Interestingly, the method
ACHTUNGTRENNUNG(OAc)2
CTHUNGTRENNUNG
CTHUNGTRENNUNG
for the addition of phenylacetylene dramatically affected
the yield of 3aa. First, phenylacetylene was divided into two
portions, and the reaction was performed for 6 h, with addi-
tion of one portion at the beginning and the second portion
after 3 h, to provide 3aa in 62% yield (as determined by
NMR spectroscopy) and 60% yield of the isolated product
(Table 1, entry 1).[8] Second, slow addition of phenylacety-
lene over 3 h followed by heating for an additional 3 h was
also effective and gave 3aa in 55% yield by NMR spectros-
copy.[9] Further optimization including the screening of phos-
phane ligands, concentration, and additives, did not improve
the yield.[10]
Treatment of phenylacetylene (1a) with 4 equivalents of
(chloroethynyl)triisopropylsilane (2a) in the presence of cat-
Other haloalkynes were tested under the optimized reac-
tion conditions (Table 1, entries 1–4). In this reaction, the
silyl substituent on the haloalkynes was crucial. The reac-
tions of chloroalkynes that have a silyl group, such as the re-
actions of triisopropylsilyl-, triethylsilyl-, and tert-butyldime-
thylsilyl-substituted chloroalkynes 2a–2c with phenylacety-
lene, proceeded smoothly to afford the corresponding prod-
ucts in good yields (Table 1, entries 1–3). Whereas the reac-
tions of chloroalkynes derived from phenylacetylene or 1-
octyne provided complex mixtures with only trace amounts
of the corresponding adducts (<10%). A silyl-substituted
bromoalkyne 2d also underwent the addition reaction to
yield bromoalkene 3ad in moderate yield. However, the use
of an iodoalkyne did not result in any formation of the de-
sired adduct.
[a] T. Wada, M. Iwasaki, Dr. A. Kondoh, Prof. Dr. H. Yorimitsu,
Prof. Dr. K. Oshima
Department of Material Chemistry
Graduate School of Engineering, Kyoto University
Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510
Fax : (+81)75-383-2438
E-mail: oshima@orgrxn.mbox.media.kyoto-u.ac.jp
[b] M. Iwasaki, Prof. Dr. H. Yorimitsu
Present address
Department of Chemistry
Graduate School of Science, Kyoto University
Sakyo-ku, Kyoto 606-8502 (Japan)
Fax : (+81)75-753-3970
E-mail: yori@kuchem.kyoto-u.ac.jp
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201000865.
Chem. Eur. J. 2010, 16, 10671 – 10674
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10671

A more plausible mechanism would be a PdII-based mech-
anism (Scheme 1), which is similar to the mechanism of hal-
oallylation of alkynes.[2] In this mechanism, an active chloro-
Table 1. Palladium-catalyzed addition of silyl-substituted haloalkynes to
terminal alkynes.[a]
Entry
1
R
2
[Si]
X
3
Yield [%][b]
1
2
3
4
1a Ph
1a Ph
1a Ph
1a Ph
2a iPr3
2b tBuMe2Si Cl
2c Et3Si
2d Et3Si
Cl
3aa 60
3ab 71
3ac 74
Cl
Br 3ad 38
5
6
7
8
1b p-MeO-C6H4 2c Et3Si
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
3bc 69
3cc 63
3dc 66
3ec 34
1c p-CF3-C6H4
1d p-Cl-C6H4
1e o-Me-C6H4
2c Et3Si
2c Et3Si
2c Et3Si
2c Et3Si
2c Et3Si
2c Et3Si
2c Et3Si
2c Et3Si
9
1 f
1g cC6H11
1h AcO(CH2)9
(CH2)8
HO(CH2)9
nC10H21
3 fc
65
10
11
12
13
3gc 56
3hc 64
ACHTUNGTRENNUNG
1i
1j
Ac
N
3ic
3jc
59
62
ACHTUNGTRENNUNG
[a] Conditions:
1
(0.25 mmolꢁ2),
2
(2.0 mmol),
[Pd2ACTHUNGTRENNU(G dba)3]
Scheme 1. A plausible mechanism.
(0.0063 mmol), PPh3 (0.013 mmol), decalin (4.0 mL). [b] Yield of the iso-
lated product.
palladium(II) complex participates in syn-chloropalladation
of a terminal alkyne to provide a 2-chloro-1-alkenylpalladi-
um species. Insertion of a haloalkyne followed by anti-b-
chloride elimination[13] affords the adduct and regenerates
the initial palladium(II) complex.
As shown in Scheme 2, the amount of chloroalkyne is
quite important. As the amount of 2c increases, the yield of
3ac was improved. In all the reactions, phenylacetylene was
Next, the scope of terminal alkynes was investigated
(Table 1, entries 5–13). Electron-rich and electron-deficient
arylacetylenes underwent the reaction to yield the products
in good yields (Table 1, entries 5–7). The steric hindrance of
1e decreased the yield (Table 1, entry 8). Aliphatic alkynes
also participated in this reaction. The reactions of primary
and secondary alkyl-substituted alkynes occurred to provide
the corresponding products in good yields (Table 1, entries 9
and 10). However, tert-butylacetylene was converted into
the product in very low yield due to its bulkiness. A variety
of functional groups including ester, keto, and hydroxy
groups, were tolerated under the reaction conditions
(Table 1, entries 11–13). Even a chloro group on the ben-
zene ring of terminal alkynes remained intact (Table 1,
entry 7). Attempted reactions of internal alkynes, instead of
terminal alkynes, resulted in no conversion.
Scheme 2. The effect of varying the amount of chloroalkyne: 2c
(1 equiv)!3ac (30%) (with 0.21 equiv of 2c recovered); 2c (2 equiv)!
3ac (48%) (with 0.32 equiv of 2c recovered); 2c (3 equiv)!3ac (58%)
(with 0.42 equiv of 2c recovered); 2c (4 equiv)!3ac (74%).
The reaction mechanism of this haloalkynylation is not
clear at this stage. One of the possible pathways is a Pd0/PdII
mechanism initiated by oxidative addition of a haloalkyne
to Pd0, which is related to the transition-metal-catalyzed ad-
dition of acid chlorides to alkynes.[1] The oxidative addition
affords (alkynyl)chloropalladium(II). Syn-chloropallada-
tion[2] or alkynylpalladation[11] of a terminal alkyne followed
by reductive elimination provides the product and regener-
ates the initial Pd0 complex. However, the stoichiometric re-
action of phenylacetylene with (tert-butyldimethylsilylethy-
completely consumed and the trimers of phenylacetylene
were observed. These results imply that the insertion of the
chloroalkyne (Scheme 1) would compete with that of phe-
nylacetylene. Further investigation is required to evaluate
these and other hypotheses including a PdII/PdIV mecha-
nism.[4]
Finally, the utility of the chloroalkynylation products was
demonstrated by an array of palladium-catalyzed cross-cou-
pling reactions (Scheme 3). The choice of phosphane ligand
was quite important for the transformations (Scheme 4).
Suzuki–Miyaura coupling of 3aa with arylboronic acid[14]
proceeded by using L1[15] as the ligand to yield 4 quantita-
tively (Scheme 3a). Product 4 is amenable to further trans-
formations. For instance, desilylation under mild conditions
followed by Sonogashira coupling[16] afforded 5 in good
yield (Scheme 3b). The adduct 3aa also underwent Suzuki–
nyl)chlorobis(triphenylphosphine)palladium[12] afforded
a
complex mixture containing the trimer of phenylacetylene,
1,3,5- and 1,2,4-triphenylbenzene [Eq. (1)]. The Pd0/PdII
mechanism is thus unlikely.
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Pd-Catalyzed Addition of Chloroalkynes to Terminal Alkynes
COMMUNICATION
Experimental Section
Typical procedure: [Pd2ACTHNUTRGNEUNG(dba)3] (5.7 mg, 0.0063 mmol) and triphenylphos-
phane (3.3 mg, 0.013 mmol) were placed in a 20 mL reaction flask under
argon. Decalin (1.0 mL) was added, and the mixture was stirred for
15 min. Phenylacetylene (1a, 0.026 g, 0.25 mmol), (chloroethynyl)triethyl-
silane (2c, 0.35 g, 2.0 mmol), and decalin (2.0 mL) were sequentially
added, and the resulting mixture was heated at 1308C for 3 h. After
which time the mixture was cooled to ambient temperature and a solu-
tion of phenylacetylene (0.026 g, 0.25 mmol) in decalin (1.0 mL) was
added. The reaction mixture was then stirred at 1308C for an additional
3 h. After which the mixture was cooled to room temperature and the re-
action was quenched with water. The product was extracted with ethyl
acetate three times. The combined organic layers were dried over anhy-
drous sodium sulfate and concentrated in vacuo. Purification on silica gel
(eluted with hexane) provided 3aa (0.10 g, 0.37 mmol) in 74% yield as a
yellow oil.
Acknowledgements
This work was supported by Grants-in-Aid for Scientific Research, COE
research, and Global COE Research from the JSPS. M.I. and A.K. ac-
knowledge the JSPS for financial support.
Keywords: addition reactions
palladium · synthetic methods
·
alkynes
·
enynes
·
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Scheme 4. Useful ligands in the transformation of 3aa.
Miyaura coupling with alkenylboronic acid and Sonogashira
coupling with 1-octyne by using L2[17] as the ligand to pro-
vide 1,3-dien-5-yne 6 and 3-en-1,5-diyne 7, respectively, in
high yields (Scheme 3c and d).
In conclusion, we have developed the addition reaction of
the carbon–chlorine s-bond of chloroalkynes to terminal al-
kynes under palladium catalysis. The products, 1-chloro-1,3-
enynes, are demonstrated to be useful building blocks for
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Chem. Eur. J. 2010, 16, 10671 – 10674
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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[8] See the Experimental Section for the detailed experimental proce-
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[9] When 1a was added in two portions or slowly, the amount of un-
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Received: April 7, 2010
Published online: August 5, 2010
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Chem. Eur. J. 2010, 16, 10671 – 10674