Rhodium-catalyzed (E)-selective cross-dimerization of terminal alkynes

Article abstract of DOI:10.1039/b804573a

Cross-dimerization of various terminal alkynes with different bulky terminal alkynes such as triisopropylsilylacetylene and 1-trimethylsilyloxy-1,1- diphenyl-2-propyne efficiently proceeds in the presence of a rhodium catalyst system to produce the corresponding (E)-enynes with high regio- and stereoselectivity. The Royal Society of Chemistry.

Full text of DOI:10.1039/b804573a

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Rhodium-catalyzed (E)-selective cross-dimerization of terminal alkynesw
Takashi Katagiri, Hayato Tsurugi, Tetsuya Satoh and Masahiro Miura*
Received (in Cambridge, UK) 17th March 2008, Accepted 8th April 2008
First published as an Advance Article on the web 7th May 2008
DOI: 10.1039/b804573a
Cross-dimerization of various terminal alkynes with different
bulky terminal alkynes such as triisopropylsilylacetylene and
1-trimethylsilyloxy-1,1-diphenyl-2-propyne efficiently proceeds
in the presence of a rhodium catalyst system to produce the
corresponding (E)-enynes with high regio- and stereoselectivity.
Scheme
Transition-metal catalyst.
1 Cross-dimerization of terminal alkynes. TM-cat. =
Alkyne coupling reactions by transition-metal catalysis are of
genuine synthetic utility in preparing p-conjugated four car-
bon compounds such as enynes which are versatile building
blocks in organic synthesis.1 Thus, the dimerization of term-
inal alkynes as a straightforward and practical method leading
to enynes has been extensively studied to selectively synthesize
one of the three possible (E)-, (Z)- and gem-enyne isomers
(gem = geminal). In contrast, the selective cross-dimerization
of two different alkynes is, in general, difficult due to the fact
that the formation of cross- and homo-dimerized regio- and
stereoisomers is possible, and thus, a major challenge.2–8
Among the early leading examples is the palladium-catalyzed
reaction of internal alkynes having an electron-withdrawing
group as acetylene acceptors.2 Such reactions have also been
achieved by using other transition-metal catalysts.3 Recently,
some selective cross-dimerization reactions of terminal silyl-
acetylenes as acetylene donors with unactivated internal and
even terminal alkynes have been disclosed.4–6 However, the
examples for the selective cross-dimerization of terminal
alkynes are still very limited (Scheme 1). Katayama and
Ozawa described that in the presence of a vinylidene–ruthe-
nium complex, terminal arylacetylenes react with terminal
silylacetylenes to selectively afford the corresponding (Z)-
enynes.4 In contrast, Tsukada and Inoue reported that a
dinuclear palladium complex catalyzes the reaction of a
number of terminal alkynes with triisopropylsilylacetylene to
selectively give gem-enynes.6,7 As for the selective cross-(E)-
enyne synthesis, only a single example, that is the reaction of
phenylacetylene with 1-pentyne catalyzed by a rhodium com-
plex bearing a PNP-pincer ligand, was described by Ozerov
and co-workers.8 In the course of our study of alkyne coupling
reactions,5a,9 we have found that various terminal alkynes
couple with bulky terminal alkynes such as triisopropylsilyla-
cetylene (1) and 1-trimethylsilyloxy-1,1-diphenyl-2-propyne
(4) in the presence of a selected rhodium–phosphine catalyst
system to produce the corresponding (E)-enyne compounds
with high regio- and stereoselectivity.10
In an initial attempt, the reaction of 1-octyne (2a) with the
silylacetylene 1 (1 equiv.) was carried out in the presence of
[RhCl(cod)]2 (3 mol% Rh) and PPh3 (P/Rh = 2) in refluxing
toluene (entry 1 in Table 1). After 8 h, a mixture of the
corresponding (E)-, (Z)- and gem-enynes 3a was formed in a
ratio of 33 : 41 : 67 and a total yield of 42%. Use of PnBu3 as
ligand in place of PPh3 was found to accelerate the reaction to
produce 3a in 97% yield within 3 h, favorably affording the
(E)-isomer with 83% selectivity (entry 2). It is often observed
in various transition-metal catalyzed reactions that bispho-
sphine ligands having large bite angles enhance stereoselectiv-
ity. Thus, we next examined dppb, dCypb and Xantphos (see
Table 1 for abbreviations). The ligands dppb and dCypb
unexpectedly gave comparable amounts of (E)- and gem-
isomers (entries 4 and 5). However, Xantphos showed a
Table 1 Cross-dimerization of 1-octyne (2a) with triisopropylsilyl-
acetylene (1)a
Entry
X
Ligand
Solventb Time/h Yieldc (%) (E/Z/gem)c
1
2
3
4
5
6
7
Cl
Cl
Cl
Cl
Cl
Cl
Cl
PPh3
PnBu3
T
T
X
T
T
T
X
X
X
X
8
3
3
6
6
6
3
6
6
8
42 (33/tr./67)
97 (83/7/10)
99 (85/4/11)
8 (50/tr./50)
67 (58/4/38)
21 (80/13/7)
74 (91/4/5)
PnBu3
dppbd
dCypbe
Xantphosf
Xantphos
8
OH Xantphos
17 (25/50/25)
83 (92/3/5)
9
I
I
Xantphos
Xantphos
10g
97 (90)h (95/2/3)
a
Reaction conditions: 1 (0.5 mmol), 2a (0.5 mmol), [Rh(X)(cod)]2
(0.0075 mmol), ligand (0.03 or 0.015 mmol, P/Rh = 2), in refluxing
b
solvent (5 mL) under N2. T = toluene, X = o-xylene. Total yield
c
Department of Applied Chemistry, Faculty of Engineering, Osaka
University, Suita, Osaka 565-0871, Japan.
E-mail: miura@chem.eng.osaka-u.ac.jp
w Electronic supplementary information (ESI) available: Experimental
procedures and characterization data for all new compounds. See
DOI: 10.1039/b804573a
d
and ratio of E : Z : gem were determined by GC analysis. dppb =
e
Ph2P(CH2)4PPh2. dCypb = Cy2P(CH2)4PCy2 (Cy = cyclohexyl).
f
Xantphos
0.6 mmol of 2a was used. Isolated yield.
=
4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene.
h
g
ꢀc
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Table 2 Cross-dimerization of various terminal alkynes 2 with
triisopropylsilylacetylene (1)a
Entry
2
Time/h
Product,
yieldb (%) (E/Z/gem)c
Scheme 2 Cross-dimerization of terminal alkynes 2a, e, f, l with 4.
Reaction conditions: 4 (0.5 mmol), 2 (0.6 mmol), [RhI(cod)]2 (0.0075
mmol), Xantphos (0.015 mmol), in refluxing o-xylene (5 mL) under N2
for 3–12 h.
1
2
6
6
3b, 76 (92/4/4)
3c, 63 (99/tr./tr.)
3d
4d
3
3
3d, 58 (96/3/1)
3e, 60 (94/3/3)
Scheme 3 Reaction of diyne 9 with alkyne 4. Reaction conditions: 4
(0.5 mmol), 9 (1.0 mmol), [RhI(cod)]2 (0.0075 mmol), Xantphos
(0.015 mmol), in refluxing o-xylene (5 mL) under N2 for 8 h.
5
6
3
6
3f, 85 (96/1/3)
3g, 57 (94/tr./6)
dimerization is slow.11 The initially formed silylalkynyl-
(hydroido)rhodium intermediate is considered to undergo
insertion of 2. The subsequent reductive elimination may
afford enynes 3. The regioselective insertion of 2 is responsible
for high E-selectivity.
7
3
3
3h, 70 (99/tr./tr.)
3i, 61 (99/tr./1)
8d
Based on the above consideration, we examined the bulky
alkyne 4 as a candidate of acetylene donor, whose masking
group is readily removable as well as triisopropylsilyl group in
1.5b The results for the reactions of 2a, e, f, l with 4 are shown in
Scheme 2. As expected, high (E)-selectivity more than 98% was
obtained in each case. It is worth noting that 1,6-heptadiyne 9
reacted with 4 in a 2 : 1 manner to afford compound 10
(Scheme 3). The reaction is considered to proceed through initial
cyclodimerization of 9 followed by co-dimerization with 4.
In summary, the selective formation of (E)-enyne in the
cross-dimerization of two different terminal alkynes can be
achieved by employing bulky terminal alkynes as acetylene
donors in the presence of a suitable rhodium-bisphosphine
catalyst system.12 This straightforward method is expected to
be employed effectively for preparing various synthetically
useful enyne compounds because of its high functional group
tolerability as well as stereoselectivity.
9
6
3
3j, 68 (89/4/7)
10
3k, 56 (99/tr./1)
a
Reaction conditions: 1 (0.5 mmol), 2 (0.6 mmol), [RhI(cod)]2 (0.0075
mmol), Xantphos (0.015 mmol), in refluxing o-xylene (5 mL) under
N2. Isolated yield. Ratio of E/Z/gem determined by 1H NMR.
b
c
d
Reaction in refluxing toluene.
relatively high (E)-selectivity (entry 6), albeit the yield of 3a
was low. The reaction was enhanced in refluxing o-xylene
(entry 7). It was also observed that use of [RhI(cod)]2 in place
of [RhCl(cod)]2 improves the yield of 3a (entry 9). Finally, use
of a slightly excess amount of 2a (1.2 equiv.) allowed 97%
yield of 3a and 95% (E)-selectivity (entry 10).
This work was supported by Grants-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science, and Technology, Japan. We thank Ms Y. Miyaji of
Osaka University for the measurement of NMR spectra.
Table 2 summarizes the results for the cross-dimerization
reactions of various terminal alkynes 2b–k with the silyl-
acetylene 1 in the presence of [RhI(cod)]2/Xantphos in
o-xylene or toluene. As is shown, good product yield and high
(E)-selectivity were generally obtained. Various functional
groups involving cyano, ester, hydroxyl and amino groups
were tolerable in this reaction. However, using simple propar-
gyl alcohol and ethyl propiolate did not give any expected
products.
Notes and references
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S. Sakaguchi and Y. Ishii, Adv. Synth. Catal., 2005, 347, 872. Rh:
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dimerization seem to be the high reactivity and bulkiness of
the silylacetylene 1. Thus, it may act as an effective acetylene
donor via initial C(sp)–H bond cleavage and the rate of its self-
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12. Rhodium-catalyzed reaction of triisopropylsilylacetylene (1) with
1-octyne (2a) (entry 10 in Table 1): A mixture of [RhI(cod)]2
(0.0075 mmol, 5.1 mg), Xantphos (0.015 mmol, 8.7 mg), 1 (0.50
mmol, 91 mg), 2a (0.60 mmol, 66 mg) and 1-methylnaphthalene
(ca. 50 mg) as internal standard in o-xylene (5 mL) was refluxed
for 8 h with stirring under N2, and then the solvent was evaporated
to dryness. The residue was purified by silica gel column chroma-
tography using hexane as eluent to afford 3a as an oil (131 mg,
90% yield). 1H NMR (400 MHz, CDCl3) d 0.89 (t, J = 7.0 Hz,
3H), 1.08 (m, 21H), 1.19–1.44 (m, 8H), 2.10 (ddt, 4J = 1.5 Hz, J =
7.7 Hz, J = 7.0 Hz, 2H), 5.52 (dt, 4J = 1.5 Hz, J = 15.8 Hz, 1H),
6.20 (dt, J = 15.8 Hz, J = 7.0 Hz, 1H). 13C NMR (100 MHz,
CDCl3) d 11.34, 14.06, 18.62, 22.57, 28.59, 28.85, 31.66, 33.09,
88.52, 106.10, 109.84, 145.85. HRMS (EI) m/z calc. for C19H36Si:
292.2586 (M+), found: 292.2590.
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¨
¨
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Chem. Commun., 2008, 3405–3407 | 3407