Ligand-controlled cross-dimerization and -trimerization of alkynes under nickel catalysis

Article abstract of DOI:10.1002/adsc.200800399

The cross-dimerization of diphenylacetylene with trimethylsilylacetylene via C-H bond cleavage in the presence of a catalytic amount of bis(cyclooctadiene)nickel [Ni(cod)₂] together with a pyridine-based ligand efficiently proceeds to give the corresponding enyne compound with good yield. In contrast, their 1:2 cross-trimerization leading to a dienyne derivative takes place selectively using a triarylphosphine ligand. The regioselective cross-dimerization of some unsymmetrical internal arylalkynes with terminal silylacetylenes is also accomplished using the pyridine ligand.

Full text of DOI:10.1002/adsc.200800399

FULL PAPERS
DOI: 10.1002/adsc.200800399
Ligand-Controlled Cross-Dimerization and -Trimerization of
Alkynes under Nickel Catalysis
Naoto Matsuyama,a Hayato Tsurugi,a Tetsuya Satoh,a and Masahiro Miuraa,*
a
Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
Fax : (+81)-6-6879-7360; e-mail: miura@chem.eng.osaka-u.ac.jp
Received: June 26, 2008; Revised: August 9, 2008; Published online: September 24, 2008
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800399.
Abstract: The cross-dimerization of diphenylacety- ylphosphine ligand. The regioselective cross-dimer-
À
lene with trimethylsilylacetylene via C H bond
cleavage in the presence of a catalytic amount of with terminal silylacetylenes is also accomplished
A
bis(cyclooctadiene)nickel [Ni(cod)2] together with a using the pyridine ligand.
U
pyridine-based ligand efficiently proceeds to give the
corresponding enyne compound with good yield. In
contrast, their 1:2 cross-trimerization leading to a di- Keywords: alkynes; cross-dimerization; cross-trimeri-
enyne derivative takes place selectively using a triar- zation; ligand effects; nickel
Introduction
ACHTREUNG
AHCTREUNG
[6]
A
alysis are of genuine synthetic utility in preparing p- catalysts, respectively. Thus, the selective linear trime-
conjugated compounds such as enynes which are ver- rization leading to dienynes is a relatively more diffi-
satile building blocks in organic synthesis.[1] Thus, the cult, but also interesting, target in constructing p-con-
homo-dimerization of terminal alkynes as a straight- jugated systems.[7] In the course of our study of regio-
forward and practical method leading to enynes has and stereoselective alkyne cross-couplings using sil-
been extensively studied to selectively synthesize one
A
À
of the three possible (E)-, (Z)-, and geminal-enyne C(sp) H bond cleavage using Ni, since such reactions
isomers. In contrast, the selective cross-dimerization with this metal have been less explored.[5,9] It has
of two different alkynes is, in general, difficult due to been found that the combination of Ni
the fact that the formation of cross- and homo-dimer- with a pyridine-based ligand such as 4-(N,N-dimethyl-
ized regio- and stereoisomers is possible and, thus, amino)pyridine effectively catalyzes the cross-dimeri-
has been a major challenge.[2–6] Among the early lead- zation of diphenylacetylene with trimethylsilylacety-
ing examples is the palladium-catalyzed reaction with lene. In contrast, the 1:2 cross-trimerization of the
(cod)2 together
AHCTREUNG
AHCTREUNG
internal alkynes having an electron-withdrawing substrates takes place selectively using a triarylphos-
group as acetylene acceptors.[2] Such reactions have phine ligand in place of the pyridine. The regioselec-
also been achieved by using other transition metal tive cross-dimerization of a number of unsymmetrical
catalysts including Ru, Rh, and Ir.[3] Recently, some internal arylalkynes with terminal silylacetylenes has
selective cross-dimerization reactions of terminal sil- also been achieved using the pyridine ligand. These
ylacetylenes as acetylene donors with unactivated in- new findings are reported herein.
ternal and terminal alkynes have been disclosed.[4] On
the other hand, formation of linear cross-trimerization
products in a 1:2 or 2:1 manner together with 1:1 Results and Discussion
cross-dimerization products has been reported in
some reactions such as those of 1-phenylsulfonyl-1- When diphenylacetylene (1a) (0.25 mmol) was treated
propyne with phenylacetylene or propargyl alcohol, with trimethylsilylacetylene (2a) (0.75 mmol) in the
diphenylacetylene with silylacetylenes, and tert-butyl- presence of Ni(cod)2 (2.5 mol%) in pyridine at 1008C,
G
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Ligand-Controlled Cross-Dimerization and -Trimerization of Alkynes
FULL PAPERS
the 1:1 cross-dimerization product 3aa was formed in CF3C6H4)3 was most effective for the trimerization,
94% yield with an E/Z ratio of 94:6 together with a giving an 83% yield of 4aa along with only a small
small amount of the 1:2 cross-trimerization product amount of 3aa. The use of bidentate phosphines, dppb
4aa with 1Z,3E-configuration (Table 1, entry 1). The and Xantphos, resulted in high selectivity for 3aa with
reaction in toluene with use of 4-(dimethylamino)pyr- the E-configuration, albeit the yield was moderate to
idine (DMAP) (30 mol%) as ligand proceeded effi- low (entries 8 and 9). The reaction of 1a with tert-bu-
ciently at 508C to allow the selective formation of 3aa tyldimethylsilylacetylene (2b) in place of 2a in the
(entry 2), whereas the conversion of 1a was very low presence of Ni(cod)2 with DMAP or P(4-CF3C6H4)3
G
(less than 5%) in the absence of DMAP. A bidentate selectively gave the corresponding enyne 3ab or dien-
nitrogen ligand, 2,2’-bipyridine, was far less effective yne 4ab in good yields (entries 10 and 11). It should
(entry 3). In contrast to the nitrogen-based ligand be mentioned that the formation of a mixture of 3ab
DMAP, the use of triarylphosphines (2.5 mol%) sig- and 4ab in a ratio of ca. 1:3 from 1a and 2b using Ni-
nificantly promoted the formation of cross-trimer 4aa
C
ligands as in the case using 2a. The use of a further
Table 1. Nickel-catalyzed reaction of diphenylacetylene (1a) bulky terminal alkyne, triisopropylsilylacetylene (2c)
with silylacetylenes 2a–c.[a]
in the presence of P(4-CF3C6H4)3 resulted in a consid-
erable increase in the ratio of enyne 3ac to dienyne
4ac (entry 13), while 3ac was exclusively formed on
using DMAP (entry 12). We also examined the reac-
tions of 1a with phenylacetylene and tert-butylacety-
lene under the conditions used for entries 2 and 7.
With use of these terminal alkynes in the presence of
DMAP as ligand, formation of the expected 1:1 cross-
dimerization products was detected by GC-MS, but
the yields were only around 25%. The reactions using
P(4-CF3C6H4)3 were not successful, giving complex
mixtures.
Next, we carried out the co-dimerization reactions
of 3-phenyl-2-propyn-1-ol (5a) and its derivatives 5b–
e with silylacetylene 2b for the sake of comparison
with our previous study using a rhodium catalyst; we
reported that the reactions of propargyl alcohols 5a,
5c, and 5e with 2b using [Rh(OH)(cod)]2/dppb as cat-
N
alyst proceed regio- and stereoselectively to give the
corresponding enynes 6ab, 6cb, and 6eb.[4c] While the
reaction of 5a with 2a in the presence of Ni(cod)2/
E
DMAP was sluggish (Table 2, entry 1), the enyne 6ab
was selectively formed using Xantphos as ligand
(entry 2). This regioselectivity is in harmony with the
rhodium catalysis[4c,d] as well as the related palladium-
catalyzed reactions.[2c] The co-dimerization of methyl
ether 5b with 2b proceeded using 2,6-lutidine as well
as DMAP and Xantphos as ligands (entries 3–5). In-
terestingly, the product regioselectivity was highly de-
[a]
[b]
Reaction
conditions:
[Ni
G
N
0.00625:0.00625:0.25:0.75 (in mmol) in toluene (2.5 mL) pendent on the identity of ligands; the pyridine li-
under N2.
gands afforded unexpectedly and preferably 7bb,
while 6bb was selectively formed in the case of Xant-
phos. The reactions of 5c–e with 2b using 2,6-lutidine
as ligand also showed unusual regioselectivity to give
7cb, 7db, and 7eb selectively (entries 6, 8, 10). The use
of Xantphos in the reaction of 5c unexpectedly led
not to 6cb, but to 7cb with almost complete E-selec-
tivity (entry 7). The bidentate ligand was, however,
not effective for the reactions of 5d and 5e (entries 9
and 11).
GC yield based on the amount of 1a used. Value in pa-
rentheses indicates isolated yield.
Pyridine (2.5 mL) was used as solvent.
E/Z ratio of 3a, determined by GC or H NMR.
DMAP [4-(N,N-dimethylamino)pyridine, 0.0375 mmol]
was used.
bpy=2,2’-bipyridine.
dppb=Ph2P(CH2)4PPh2.
Xantphos=4,5-bis(diphenylphosphino)-9,9-dimethylxan-
[c]
[d]
[e]
1
[f]
[g]
[h]
A
thene.
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Naoto Matsuyama et al.
FULL PAPERS
Table 2. Cross-dimerization of arylalkynes 5a–e with silyl-
The reactions of some symmetrical internal alkynes
including 4-octyne, 2-butyne-1,4-diol, 1,4-dimethoxy-
2-butyne, and dimethyl acetylenedicarboxylate with
A
2a were also examined using Ni(cod)2/DMAP. Among
U
the alkynes, 1,4-dimethoxy-2-butyne (5f) smoothly re-
acted with 2a to give the corresponding enyne 8fa
with a good yield (Scheme 1), although the reactions
of the other internal alkynes did not proceed. The
alkyne 5f was also coupled with silylacetylenes 2b and
2c. The reaction of 5f with 2a using Xantphos as
ligand also tookplace stereoselectively, albeit the
yield of 8fa (35%) was moderate.
Scheme 1. Reaction of 1,4-dimethoxy-2-butyne (5f) with si-
[a]
lylacetylenes 2a–c. Reaction conditions:
[Ni
ACHTREUNG
[b]
A
ACHTREUNG
AHCTREUNG
Since the selective 1:2 cross-trimerization of al-
kynes such as that of 1a with 2a is an attractive,
straightforward way to construct a p-conjugated dien-
yne system, the reactions of a number of diarylacety-
lenes with 2a were examined under the conditions
used for entry 7 in Table 1 using P(4-CF3C6H4)3 as
ligand. As depicted in Scheme 2, the diarylacetylenes
[a]
[b]
Reaction conditions: [Ni(cod)2]:[2b]:[5]=0.0125:0.75:0.25
(in mmol) in toluene (2.5 mL) under N2. Si=SiMe2Bu-t
(2b).
A
Isolated yield based on the amount of 5 used. Product
1
ratio was determined by H NMR. Unless the E/Z ratio
is noted, E>98%.
[c]
[d]
[e]
[f]
30 mol% of ligand was used.
5 mol% of ligand was used.
2,6-Lutidine (0.1 mL) was used.
Toluene (1.4 mL) was used.
Less than 10% yield.
[g]
[h]
[i]
Scheme 2. Reaction of diarylacetylenes 1b–e with silylacety-
lene 2a to give dienynes 4. Reaction conditions:
Complex mixture.
No reaction.
[Ni
A
0.00625:0.00625:0.25:0.75 (in mmol).
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Ligand-Controlled Cross-Dimerization and -Trimerization of Alkynes
FULL PAPERS
having electron-donating 1b,c and -withdrawing sub- derstand the observed ligand effects on regioselectivi-
stituents 1d as well as bis(2-thienyl)acetylene (1e) ef- ty in the insertion steps. Also, participation of an alte-
fectively reacted with 2a to produce 1:2 cross-trimers native mechanism that involves a nickelacycle as in-
4ba–4ea with good isolated yields. Treatment of the termediate, especially for the cross-trimerization,
unsymmetrical acetylene 5b with 2a under the same cannot be excluded.
conditions, however, gave a complex mixture contain-
ing trimerized products, which was confirmed by GC-
MS.
The silyl groups in compounds 4 may be expected
Conclusions
to undergo certain desilylative transformation reac- We have described remarkable ligand effects on the
tions. As an example, the terminal silyl moiety of 4aa nickel-catalyzed cross-oligomerization of alkynes. The
was selectively substituted by desilylative Sonogashira cross-dimer of diphenylacetylene and trimethylsilyl-
coupling[10] with iodobenzene to afford 1,2,6-triphen- acetylene is selectively formed in the presence of
yl-4-trimethylsilyl-(1Z,3E)-1,3-hexadien-5-yne (9) in Ni(cod)2/DMAP, while their 1:2 cross-trimerization
G
72% yield. The subsequent protodesilylation by treat- takes place with use of P(4-CF3C6H4)3 as ligand in
ment with Bu4NF also proceeded to form of 1,2,6-tri- place of DMAP. The cross-dimerization of internal ar-
phenyl-1,3-hexa-5-yne (10) (Scheme 3). It is worth ylalkynes having an oxygen function at the propargyl
noting that compound 10 was previously used as a position in place of diphenylacetylene also proceeds
substrate for electrocyclization after partial hydroge- effectively to give the corresponding enynes with un-
nation.[11]
usual regioselectivity in some cases.
Experimental Section
General Remarks
1H and 13C NMR spectra were measured at 400 MHz and
100 MHz, respectively, for CDCl3 solutions. The configura-
tions of the products were determined with the aid of NOE,
HMBC, and HMQC measurements. MS data were obtained
in the EI mode unless otherwise noted. GC analysis was car-
ried out using a silicon OV-17 column (i.d. 2.6 mm”1.5 m)
or a CBP-1 capillary column (i.d. 0.5 mm”25 m). GC-MS
analysis was carried out using a CBP-1 capillary column (i.d.
0.25 mm”25 m).
Diarylacetylenes 1b–1e were prepared by the Sonogashira
coupling of trimethylsilylacetylene (2a) with aryl iodides ac-
cording to the published method.[10]
The following experimental procedures may be regarded
as typical in methodology and scale. Other product data are
given in the Supporting Information.
Scheme 3. Sonogashira coupling and desilylation of 4aa.
[a]
Reaction
conditions:
[4aa]:[Pd]:
G
N
0.25:0.015:0.25:1.5 (in mmol) in o-xylene-H2O (1.0 mL, 95:5
v/v), 1008C, 9 h. [b] 10 (0.25 mmol), 08C, 30 min.
As for the first step of the nickel-catalyzed reac-
À
tions of terminal silylacetylenes via C(sp) H bond
Nickel-Catalyzed Cross-Dimerization of Diphenyl-
acetylene (1a) with Trimethylsilylacetylene (2a)
(Table 1, entry 2)
cleavage, oxidative addition of the acetylenes to
nickel(0) species to give (R3SiCC)(H)Ni(II) com-
plexes is usually postulated.[5,9] It may be reasonable
to consider that the subsequent insertion of the inter-
nal acetylene or successive double insertion of inter-
A mixture of Ni
A
0.05M toluene solution), DMAP (0.0375 mmol, 4.5 mg), 1a
À
À
nal and terminal acetylenes to the Ni C or Ni H (0.25 mmol, 45 mg), 2a (0.75 mmol, 74 mg), and hexamethyl-
benzene (ca. 50 mg) as internal standard in toluene (2.5 mL)
was stirred in a Schlenktube at 50 8C for 9 h under an N2 at-
mosphere. The solvent was evaporated, and then the residue
was purified by column chromatography on silica gel using
hexane as eluent to afford 3aa as a white solid; yield:
bonds of the key intermediates and reductive elimina-
tion afford enynes and dienynes. It was confirmed
that enyne 3aa did not react with 2a under the condi-
tions used for entry 7 in Table 1. This suggests that a
stepwise route to 4 through 3 does not participate.
The striking effects of pyridine- or phosphine-based
ligands on the selectivity of di- and trimerizations
could be caused by the different ease of reductive
elimination after the first insertion. However, further
1
57.5 mg (82%). The H and 13C NMR spectra matched with
those reported previously.[8c] The E/Z ratio of 3aa estimated
1
by H NMR was 88:12. Recrystallization with hexane gave
1
(E)-3aa; mp 878C; H NMR: d=0.24 (s, 9H), 7.04–7.07 (m,
2H), 7.10 (s, 1H), 7.14–7.16 (m, 3H), 7.26–7.30 (m, 3H),
studies are required to establish this as well as to un- 7.36–7.38 (m, 2H); 13C NMR: d=À0.01, 94.46, 107.60,
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Naoto Matsuyama et al.
FULL PAPERS
124.19, 127.66, 127.80, 128.08, 128.40, 129.08, 129.33, 135.99,
137.33, 137.36; HR-MS: m/z= 276.1338, calcd. for C19H20Si:
276.1334; anal. calcd. for C19H20Si: C 82.55, H 7.29; found:
C 82.52, H 7.31.
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Nickel-Catalyzed 1:2 Cross-Trimerization of Diphen-
ylacetylene (1a) with Trimethylsilylacetylene (2a)
(entry 7 in Table 1)
A mixture of Ni(cod)2 (0.00625 mmol, 1.70 mg=0.125 mL of
N
0.05M toluene solution), (4-CF3C6H4)3P (0.00625 mmol,
2.9 mg), 1a (0.25 mmol, 45 mg), 2a (0.75 mmol, 74 mg), and
hexamethylbenzene (ca. 50 mg) as internal standard in tolu-
ene (2.5 mL) was stirred in a Schlenktube at 50 8C for 3 h
under N2 atmosphere. The solvent was evaporated, and then
the residue was purified by column chromatography on
silica gel using hexane as eluent to afford 4aa as a white
solid; yield: 72 mg (82%); mp 908C (from methanol);
1H NMR: d=0.05 (s, 9H), 0.20 (s, 9H), 6.62 (s, 1H), 6.93–
6.96 (m, 2H), 7.08–7.10 (m, 3H), 7.22–7.24 (m, 2H), 7.26 (s,
1H), 7.32–7.33 (m, 3H); 13C NMR: d=À1.92, 0.10, 104.47,
109.04, 125.11, 127.19, 127.47, 127.92, 128.53, 129.69 (over-
lapped), 133.46, 136.72, 139.59, 140.90, 147.64; HR-MS:
m/z=374.1884, calcd. for C24H30Si2: 374.1886; anal. calcd.
for C24H30Si2: C 76.94, H 8.07; found: C 76.72, H 8.02.
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Acknowledgements
[7] GaCl3-catalyzed linear trimerization: Y. Kido, M. Ya-
This work was partly supported by a Grant-in-Aid from the
Ministry of Education, Culture, Sports, Science, and Technol-
ogy, Japan. We thank Ms. Y. Miyaji of Osaka University for
the measurement of NMR spectra.
maguchi, J. Org. Chem. 1998, 63, 8086.
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