Silver-catalyzed carbomagnesiation of terminal aryl and silyl alkynes and enynes in the presence of 1,2-dibromoethane

Article abstract of DOI:10.1039/b820521c

Regioselective carbomagnesiation of terminal alkynes and enynes with alkyl Grignard reagents has been achieved by the combined use of a silver catalyst and 1,2-dibromoethane. The Royal Society of Chemistry 2009.

Full text of DOI:10.1039/b820521c

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Silver-catalyzed carbomagnesiation of terminal aryl and silyl alkynes and
enynes in the presence of 1,2-dibromoethanew
Yuuki Fujii,a Jun Terao*b and Nobuaki Kambe*a
Received (in Cambridge, UK) 17th November 2008, Accepted 10th December 2008
First published as an Advance Article on the web 7th January 2009
DOI: 10.1039/b820521c
Regioselective carbomagnesiation of terminal alkynes and
enynes with alkyl Grignard reagents has been achieved by the
combined use of a silver catalyst and 1,2-dibromoethane.
Transition-metal catalyzed carbomagnesiation of carbon–
carbon multiple bonds is a useful and attractive method for
the preparation of Grignard reagents with concomitant con-
struction of the desired carbon skeletons via new carbon–carbon
bond formation.1 To date, addition of aryl,2 vinyl,3 allyl,4 and
primary-alkyl5 magnesium compounds toward carbon–carbon
unsaturated bonds has been accomplished by the aid of various
transition-metal catalysts. However, the use of secondary and
Scheme 1
Table 1 Silver-catalyzed carbomagnesiation of phenylacetylene with
tBu–MgCla
tertiary-alkyl Grignard reagents had so far been limited, mostly
to the reaction of activated alkynes or the ones having a
heteroatom directing group,6 until our discovery that Cu cata-
lyzes carbomagnesiation of unfunctionalized dienes and enynes
with secondary and tertiary alkyl Grignard reagents to give rise
to conjugated allyl or allenyl Grignard reagents (Scheme 1).7 If
the similar addition to alkynes proceeds, vinyl Grignard re-
agents can be formed. However, the Cu-catalyzed system was
not effective towards this transformation. Here, we disclose
silver catalyzed regioselective carbomagnesiation of terminal
alkynes with alkyl Grignard reagents in the presence of 1,2-
dibromoethane. This reaction can also be applied to enynes.
When the reaction of phenylacetylene (1.0 mmol) with
tBu–MgCl (1.6 mmol) was conducted in the presence of AgOTs
(0.05 mmol) in Et2O at ꢀ10 1C for 30 min and the reaction was
quenched by aqueous HCl, the hydroalkylation product 2a was
obtained in 28% yield (E : Z = 1 : 99) (Table 1, Entry 1).
Addition of PPh3 or P(p-C6H4Cl)3 increased the yield of 2a and
gave the by-product tBu–tBu in 4% yield (Entries 2 and 3). The
latter may be formed by reductive coupling of tert-alkyl silver
complex intermediates.8 This process reduces Ag(I) to Ag(0) and
may terminate the catalytic cycle. Hayashi and Nagano reported
that 1,2-dibromoethane acts as a reoxidizing reagent of Ag(0)
complex to Ag(I) in the silver catalyzed homo-coupling reaction
of alkyl Grignard reagents.9 We re-examined the reaction in the
presence of 1,2-dibromoethane (100 mol%) under the same
conditions as Entry 1–3 and found that the yields of 2a were
significantly improved as shown in Entries 4–6. The use of
Entry Catalyst
Additive
Yield (%)b E : Z
1
2
3
4
5
6
AgOTs
AgOTs + PPh3
None
None
AgOTs + P(p-C6H4Cl)3 None
28
59
58
1 : 99
2 : 98
3 : 97
2 : 98
6 : 94
4 : 96
2 : 98
1 : 99
1 : 99
8 : 92
AgOTs
BrCH2CH2Br 76
BrCH2CH2Br 79
AgOTs + P(p-C6H4Cl)3 BrCH2CH2Br 86
AgOTs + PPh3
7
(IMes)AgCl
(IMes)AgCl
(IMes)AgCl
(IMes)AgCl
BrCH2CH2Br 98 (88)
BrCH2CH2Br 88
ClCH2CH2Cl 34
8c
9
10
ICH2CH2I
17
a
Conditions: Ag catalyst (0.05 mmol), phenylacetylene (1.0 mmol),
t
b
additive (100 mol%), Bu–MgCl (1.6 mmol), ꢀ10 1C, 30 min. GC
c
yield. Isolated yield is in parentheses. 50 mol% additive was used.
(IMes)AgCl (IMes = 1,3-dimesitylimidazol-2-ylidene)10 as a
catalyst afforded 2a in 98% GC yield (Entry 7). The product
was obtained in pure form in 88% yield by silica gel column
chromatography. When the amount of 1,2-dibromoethane was
reduced to 50 mol%, the yield of 2a decreased to 88% yield
(Entry 8). 1,2-Dichloroethane and 1,2-diiodoethane were less
efficient than 1,2-dibromoethane, and formed 2a in 34% and
17% yields, respectively (Entries 9 and 10).
a Department of Applied Chemistry Graduate School of Engineering,
Osaka University, Yamadaoka 2-1, Suita, Osaka 565-0871, Japan.
E-mail: kambe@chem.eng.osaka-u.ac.jp; Fax: +81-6-6879-7390;
Tel: +81-6-6879-7388
Results of the present silver catalyzed carbomagnesiation
using other substrates are shown in Table 2. The present
carbomagnesiation was applicable to p-, m- and o-methyl sub-
stituted phenylacetylene under the conditions of the
(IMes)AgCl–Br(CH2)2Br catalytic system (condition A)
(Table 2, Entries 1–3). Methoxy and trifluoromethyl groups
b Department of Energy and Hydrocarbon Chemistry, Graduate
School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
E-mail: terao@scl.kyoto-u.ac.jp; Fax: +81-75-383-2516;
Tel: +81-75-383-2514
w Electronic supplementary information (ESI) available: Experimental
procedures and 1H and 13C NMR spectra. See DOI: 10.1039/b820521c
ꢁc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 1115–1117 | 1115

View Article Online
Table 2 Silver-catalyzed carbomagnesiation of terminal alkynes
Yield
Conditiona Product (%)b
Entry R
R0–MgX
E : Z
1
2
3
4
5
6
7
8
4-MeC6H4 tBu–MgCl
3-MeC6H4 tBu–MgCl
2-MeC6H4 tBu–MgCl
4-MeOC6H4 tBu–MgCl
4-CF3C6H4 tBu–MgCl
A
A
A
A
A
A
A
B
2b
2c
2d
2e
2f
2g
2h
2h
2i
2j
2j
2k
2l
88 (80) 2 : 98
90 (83) 2 : 98
91 (81) 7 : 93
(70)
(81)
(65)
2 : 98
1 : 99
3 : 97
3-Thienyl
Ph
tBu–MgCl
sBu–MgCl
sBu–MgCl
Scheme 2
59 (43) 12 : 88
81 (68) 14 : 86
83 (71) 20 : 80
64 (49) 42 : 58
73 (58) 43 : 57
89 (73) 42 : 58
Ph
Ph
Ph
Ph
Ph
PhMe2Si
9
cHex–MgCl B
10
11
12
13
nBu–MgCl
nBu–MgCl
A
C
nOct–MgBr C
tBu–MgCl
C
(66)
8 : 92
a
Condition A: (IMes)AgCl (5 mol%), phenylacetylene (1.0 mmol),
1,2-dibromoethane (100 mol%), R0–MgX (1.6 mmol), ꢀ10 1C, 30 min;
B: AgOTs (5 mol%), P(p-C6H4Cl)3 (5 mol%), phenylacetylene
(1.0 mmol), 1,2-dibromoethane (200 mol%), R0–MgX (1.6 mmol),
ꢀ10 1C, 30 min; C: (IMes)AgCl (5 mol%), phenylacetylene
(1.0 mmol), 1,2-dibromoethane (200 mol%), R0–MgX (2.0 mmol),
b
ꢀ10 1C, 3 h. GC yield. Isolated yield is in parentheses.
Scheme 3
It has been known that alkyl silver ate complexes are formed
from silver(I) complexes and alkyl lithium or Grignard
reagents.11 To confirm whether silver ate complexes rather
than neutral complexes are active species toward terminal
acetylenes in the present reaction, we carried out the reactions
on the aryl ring did not significantly affect the yield of the
products (Entries 4–5). Thienyl alkyne also underwent carbo-
magnesiation giving rise to the corresponding alkene in 65%
s
isolated yield (Entry 6). Bu–MgCl also added to phenylacety-
lene to give 2h in 59% yield under the same conditions (Entry 7).
Combined use of AgOTs (5 mol%) and P(p-C6H4Cl)3 (5 mol%)
was more suitable for sec-butylmagnesiation than (IMes)AgCl
and gave 2h in 81% yield (Entry 8, condition B). Under identical
t
using stoichiometric amounts of (IMes)AgCl, Bu–MgCl, and
phenylacetylene. As shown in Scheme 4, desired product 2a
was obtained in 40% yield. The use of 2.0 equiv. of tBu–MgCl,
which may generate alkyl silver ate complexes, gave a similar
result. These results may indicate that alkyl silver ate com-
plexes do not play an important role in the present reaction.
To examine the reactivities of the alkyl Grignard reagents in
this catalytic system, we performed the following competitive
experiments: an Et2O solution of (IMes)AgCl, phenylacetylene,
and 1,2-dibromoethane was added to a mixture of equimolar
c
conditions, Hex–MgCl also smoothly underwent carbomagne-
siation to afford 2i in 83% yield (Entry 9). Primary-alkyl
Grignard reagents also gave hydroalkylated product 2j and 2k
in moderate to good yields when the reaction was conducted for
3 h in the presence of a large amount of 1,2-dibromoethane
(Entries 10–12, condition C). No reaction took place with
methyl, benzyl or phenyl Grignard reagents. As for the alkynes,
dimethylphenylsilyl alkyne gave 2l in 66% isolated yield
(entry 13). Aliphatic alkynes and internal alkynes, however, did
not undergo carbomagnesiation under the conditions examined.
Vinyl Grignard reagents formed by the present carbo-
magnesiation can be trapped with various electrophiles
(Scheme 2). For example, quenching of 1a with D2O gave
deuterated product 3a in 94% yield (97% d). Electrophilic trap-
ping of 1a with CO2, benzaldehyde, and chlorophenylsilane
afforded 3b, 3c, and 3d in 88%, 81%, and 74% yields, respectively.
A plausible reaction mechanism is outlined in Scheme 3.
The reaction of silver complex with alkyl Grignard reagent
forms an alkyl silver complex 4.11 Then, 4 reacts with a
terminal alkyne to afford vinyl silver complex 5 which under-
goes transmetallation with alkyl Grignard reagents to give
vinyl Grignard reagents 1 and regenerate 4.
t
s
n
amounts of Bu–MgCl, Bu–MgCl, and Bu–MgCl. Quenching
the reaction with H2O afforded hydroalkylation products 2a, 2h
and 2j in 59%, 8%, and o1% yields, respectively (Scheme 5).
Preferred formation of the products having a highly branched
butyl group may suggest that the addition of alkyl silver com-
plexes toward phenylacetylene proceeds via a radical mechanism.
Scheme 4
ꢁc
This journal is The Royal Society of Chemistry 2009
1116 | Chem. Commun., 2009, 1115–1117

View Article Online
Notes and references
1 (a) Organomagnesium Methods in Organic Synthesis, ed.
B. J. Wakefield, Academic Press Inc, San Diego, 1995;
(b) U. M. Dzhemilev and A. G. Ibragimov, Russ. Chem. Rev.,
2005, 74, 807; (c) The Chemistry of Organomagnesium Chemistry,
ed. Z. Rappoport and I. Marek, John Wiley & Sons, Chichester,
2008.
2 (a) H. Yorimitsu, J. Tang, K. Okada, H. Shinokubo and
K. Oshima, Chem. Lett., 1998, 11; (b) M. Xie and X. Huang,
Synlett, 2003, 477; (c) K. Itami, T. Kamei and J. Yoshida, J. Am.
Chem. Soc., 2003, 125, 14670; (d) M. Xie, L. Liu, J. Wang and
S. Wang, J. Organomet. Chem., 2005, 690, 4058; (e) E. Shirakawa,
T. Yamagami, T. Kimura, S. Yamaguchi and T. Hayashi, J. Am.
Chem. Soc., 2005, 127, 17164; (f) S. Simaan, A. Masarwa, P. Bertus
and I. Marek, Angew. Chem., Int. Ed., 2006, 45, 3963;
(g) T. Yamagami, R. Shintani, E. Shirakawa and T. Hayashi,
Org. Lett., 2007, 9, 1045; (h) K. Murakami, H. Ohmiya,
H. Yorimitsu and K. Oshima, Org. Lett., 2007, 9, 1569.
Scheme 5
It is known that alkyl silver complexes add to enyne deriva-
tives to give allenyl silver complexes.11a,12 We then applied the
present carbomagnesiation to enynes. The reaction of hexyl
substituted enyne 6a with tBu–MgCl under condition A
followed by hydrolysis gave a mixture of 7a and 7b in 64%
and 26% yields, respectively (Scheme 6). This result indicates
the formation of propargyl and/or allenyl Grignard reagents
8.13 When 8 was trapped with cyclopentanone, 9a was obtained
regioselectively in 85% yield as a single isomer (Table 3, Entry
1). The use of sBu–MgCl also afforded the corresponding
coupling product 9b in 81% yield (Entry 2). On the other hand,
carbomagnesiation using nBu–MgCl failed to give 9c (Entry 3).
Phenyl and silyl substituted enyne 6b and 6c underwent carbo-
magnesiation and successive electrophilic trapping afforded
coupling products 9d and 9e in good yields (Entries 4–5).
In conclusion, regioselective carbomagnesiation of terminal
alkynes with various alkyl Grignard reagents was found to
proceed using silver catalysts, such as (IMes)AgCl or AgOTs,
in the presence of 1,2-dibromoethane as a reoxidizing reagent.
Vinyl Grignard reagents generated by the present method were
successfully trapped with various electrophiles. This catalytic
system could also be applicable to the regioselective carbo-
magnesiation of enynes.
3 K. Murakami, H. Ohmiya, H. Yorimitsu and K. Oshima, Chem.
Lett., 2007, 1066.
4 (a) S. Akutagawa and S. Otsuka, J. Am. Chem. Soc., 1975, 97,
6870; (b) K. Okada, K. Oshima and K. Utimoto, J. Am. Chem.
Soc., 1996, 118, 6076; (c) J. Tang, K. Okada, H. Shinokubo and
K. Oshima, Tetrahedron, 1997, 53, 5061; (d) T. Nishikawa,
H. Shinokubo and K. Oshima, Org. Lett., 2003, 5, 4623.
5 (a) J. G. Duboudin and B. Jousseaume, J. Organomet. Chem.,
1972, 44, C1; (b) B. B. Snider, M. Karras and R. S. E. Conn, J. Am.
Chem. Soc., 1978, 100, 4624; (c) A. Alexakis, G. Cahiez and
J. F. Normant, J. Organomet. Chem., 1979, 177, 293;
(d) U. M. Dzhemilev and O. S. Vostrikova, J. Organomet. Chem.,
1985, 285, 43; (e) A. H. Hoveyda and Z. Xu, J. Am. Chem. Soc.,
1991, 113, 5079; (f) T. Takahashi, T. Seki, Y. Nitto, M. Saburi,
C. J. Rousset and E. Negishi, J. Am. Chem. Soc., 1991, 113, 6266;
(g) L. Bell, R. J. Whitby, R. V. H. Jones and M. C. H. Standen,
Tetrahedron Lett., 1996, 37, 7139; (h) R. Fischer, D. Walther,
P. Gebhardt and H. Gorls, Organometallics, 2000, 19, 2532;
¨
(i) U. M. Dzhemilev, V. A. D’yakonov, L. O. Khafizova and
A. G. Ibragimov, Tetrahedron, 2004, 60, 1287; (j) D. Zhang and
J. M. Ready, J. Am. Chem. Soc., 2006, 128, 15050.
6 (a) It has been reported that the Ni-catalyzed carbomagnesiations
afford a mixture of carbo- and hydromagnesiation products:
J. G. Duboudin, B. Jousseaume and A. Saux, J. Organomet.
Chem., 1978, 162, 209; Cu-catalyzed carbomagnesiations see:
(b) J. G. Duboudin, B. Jousseaume and A. Saux, J. Organomet.
Chem., 1979, 168, 1; (c) H. Chechik-Lankin, S. Livshin and
I. Marek, Synlett, 2005, 2098; (d) G. H. Fang, Z. J. Yan. J. Yang
and M. Z. Deng, Synthesis, 2006, 1148; (e) H. Yasui, H. Yorimitsu
and K. Oshima, Chem. Lett., 2007, 32; Mn-catalyzed carbomag-
nesiation see: (f) S. Nishimae, R. Inoue, H. Shinokubo and
K. Oshima, Chem. Lett., 1998, 785.
7 H. Todo, J. Terao, H. Watanabe, H. Kuniyasu and N. Kambe,
Chem. Commun., 2008, 1332.
8 (a) J. H. Gardner and P. Borgstrom, J. Am. Chem. Soc., 1929, 51,
3375; (b) M. Tamura and J. K. Kochi, J. Am. Chem. Soc., 1971, 93,
1483; (c) M. Tamura and J. K. Kochi, Synthesis, 1971, 303;
(d) M. Tamura and J. K. Kochi, Bull. Chem. Soc. Jpn., 1972, 45,
1120; (e) G. M. Whitesides, D. E. Bergbreiter and P. E. Kendall,
J. Am. Chem. Soc., 1974, 96, 2806; (f) G. M. Whitesides and
F. D. Gutowski, J. Org. Chem., 1976, 41, 2882.
Scheme 6
Table 3 Silver-catalyzed carbomagnesiation of enynes
9 T. Nagano and T. Hayashi, Chem. Lett., 2005, 34, 1152.
10 T. Ramnial, C. D. Abernethy, M. D. Spicer, I. D. McKenzie,
I. D. Gay and J. A. C. Clyburne, Inorg. Chem., 2003, 42, 1391.
11 (a) H. Westmijze, H. Kleijn and P. Vermeer, J. Organomet. Chem.,
1979, 172, 377; (b) D. E. Bergbreiter and T. J. Lynch, J. Org.
Chem., 1981, 46, 727.
12 (a) H. Kleijn, H. Westmijze, J. Meijer and P. Vermeer, J. Organomet.
Chem., 1980, 192, 275; (b) H. Westmijze, H. Kleijn, H. J. T. Bos and
P. Vermeer, J. Organomet. Chem., 1980, 199, 293; (c) H. Kleijn,
H. Westmijze, J. Meijer and P. Vermeer, J. Organomet. Chem., 1981,
206, 257; (d) M. Tigchelaar, J. Meijer, H. Kleijn, H. J. T. Bos and
P. Vermeer, J. Organomet. Chem., 1981, 221, 117; (e) H. Westmijze,
H. Kleijn and P. Vermeer, J. Organomet. Chem., 1982, 234, 117.
13 K. V. Baker, J. M. Brown, N. Hughes, A. J. Skarnulis and
A. Sexton, J. Org. Chem., 1991, 56, 698.
Entry
Enyne
Time
30 min
3 h
3 h
30 min
30 min
R0
Yield (%)
n
1
2
3
4
5
6a (R = Hex)
6a
6a
6b (R = Ph)
6c (R = TMS)
tBu
sBu
nBu
tBu
tBu
9a; 85
9b; 81
9c; o1
9d; 87
9e; 85
ꢁc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 1115–1117 | 1117