Iron-catalyzed aryl- and alkenyllithiation of alkynes and its application to benzosilole synthesis

Article abstract of DOI:10.1039/c1cc11989c

Phenyl- and vinyllithiums having an alkyl substituent at their ortho- and cis-position, respectively, readily added to alkynes in the presence of 5 mol% of Fe(acac)₃. The reaction of o-(trimethylsilyl)phenyllithium with alkynes gave benzosilole

Full text of DOI:10.1039/c1cc11989c

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COMMUNICATION
Iron-catalyzed aryl- and alkenyllithiation of alkynes and its application
to benzosilole synthesisw
Eiji Shirakawa,* Seiji Masui, Rintaro Narui, Ryo Watabe, Daiji Ikeda and Tamio Hayashi*
Received 8th April 2011, Accepted 11th July 2011
DOI: 10.1039/c1cc11989c
Phenyl- and vinyllithiums having an alkyl substituent at their
ortho- and cis-position, respectively, readily added to alkynes in
the presence of 5 mol% of Fe(acac)3. The reaction of
o-(trimethylsilyl)phenyllithium with alkynes gave benzosiloles
through an addition–cyclization sequence.
Table 1 Aryllithiation of alkynes followed by methanolysisa
Carbometalation of internal alkynes gives trisubstituted vinyl-
metals, which are readily converted to tetrasubstituted alkenes
upon reaction with electrophiles.1 Several methods are available
for carbometalation of alkynes with arylmetals but relatively
harsh reaction conditions are required, in particular, in the
addition to dialkylacetylenes having no heteroatoms.2–4 Alkenyl-
metalation is even more difficult and no reports are available
for high-yielding alkenylmetalation of unfunctionalized
dialkylacetylenes.5 Here we report that phenyl- and vinyllithiums
having an alkyl substituent at the ortho- or cis-position,
respectively, add to alkynes including unfunctionalized dialkyl-
acetylenes under mild conditions in the presence of readily
available Fe(acac)3 as a catalyst without any other additives.6–7
The reaction of o-(trimethylsilyl)phenyllithiums with alkynes
leads to the one-pot synthesis of various benzosiloles,8 which
are known to have a wide application in optoelectronic area.9
The reaction of o-tolyllithium (1a: 2 equiv.) with 4-octyne (2m:
1 equiv.) in the presence of Fe(acac)3 (5 mol%) in Et2O at 30 1C
for 1.5 h followed by methanolysis of the resulting alkenyllithium
(3am) stereoselectively gave (E)-4-(o-tolyl)-4-octene (4am) in 84%
yield (entry 1 of Table 1).10 In contrast, no addition product was
obtained in the reaction of phenyllithium (1b) under the same
conditions (entry 2), showing a marked substituent effect at the
ortho position of phenyllithium. The catalyst system consisting of
Fe(acac)3/CuBr/PBu3, which is effective for arylmagnesiation of
dialkylacetylenes2a and aryllithiation of arylalkynes,6 also
catalyzed the addition of 1a but not that of 1b (entries 3 and 4).
Other metal complexes including those (Cr,2b Mn,3f Co,2c
Ni3d) reported to be effective for arylmetalation of arylacetylenes
and/or dialkylacetylenes did not catalyze the addition of
o-tolyllithium (1a) to alkyne 2m (entries 5–10). No reaction
took place in the absence of catalysts (entry 11).
Conv. Yield
(%)b (%)c
Entry R1
Catalyst (mol%)
1
Me (1a) Fe(acac)3 (5)
499 84
2
3
4
H (1b) Fe(acac)3 (5)
Me (1a) Fe(acac)3 (5)/CuBr (10)/PBu3 (40)
H (1b) Fe(acac)3 (5)/CuBr (10)/PBu3 (40)
o2
499
9
7
6
28
o2
73
o2
o2
o2
3
5
6
7
Me (1a) CrCl2 (5)/t-BuCO2H (6.7)
Me (1a) MnCl2 (5)
Me (1a) CoBr2 (5)
8
9
Me (1a) NiCl2(PPh3)2 (5)
Me (1a) CuBr (5)
22
o2
o2
o2
o2
o2
o2
o2
10
11
Me (1a) Pd(OAc)2 (5)
Me (1a) None
a
The reaction was carried out in Et2O (2.0 mL) under a nitrogen
atmosphere using an aryllithium (1: 0.80 mmol) and 4-octyne
(2m: 0.40 mmol) in the presence of a metal complex (0.020 mmol).
b
c
Conversion of 2m determined by GC and/or 1H NMR. Yield of
isolated product 4 based on 2m. Stereoselectivities Z 98%.
Table 2 illustrates the scope of the present carbolithiation of
alkynes. Pentyl and isopropyl groups substituted at the ortho-
position of phenyllithium also promoted the carbolithiation of
4-octyne (2m) to give the corresponding addition products in
high yields (entries 1 and 2). Introduction of an electron-donating
group into the para-position of o-tolyllithium did not affect the
reaction but an electron-withdrawing group lowered the yield
(entries 3 and 4). Phenyllithiums having a methoxy, tert-butyl or
phenyl group at the ortho-position did not add to 4-octyne under
the same conditions. As well as dialkylacetylenes, aryl(alkyl)- and
diarylacetylenes underwent the addition of 1a (entries 5–7). In the
aryllithiation of alkyl(phenyl)acetylenes 2n and 2o, lithium was
attached predominantly to the carbon having the aryl group. The
o-tolyl group of 1a selectively attacked the less hindered carbon
of dissymmetrical dialkylacetylene 2q (entry 8). Trimethylvinyl-
lithium (5a), which has a structure similar to 1a, added to
7-tetradecyne (2r) in a high yield (entry 9). It should be noted
that the alkenyllithiation does not take place with dimethyl-
vinyllithiums lacking a substituent at the cis- or a-position.
Department of Chemistry, Graduate School of Science,
Kyoto University, Kyoto, 606-8502, Japan.
E-mail: shirakawa@kuchem.kyoto-u.ac.jp
w Electronic supplementary information (ESI) available: Experimental
procedure and spectral data. See DOI: 10.1039/c1cc11989c
c
9714 Chem. Commun., 2011, 47, 9714–9716
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Table 2 Aryl- and alkenyllithiation of alkynes followed by metha-
nolysisa
Entry R2–Li (1 or 5) R3, R4 in 2
T/1C Time/h Yield (%)b
Scheme 1 Stoichiometric reactions of FeCl3.
1
Pr, Pr (2m)
30
30
2
4
86
2
3
4
5
6
7
Pr, Pr (2m)
Pr, Pr (2m)
Pr, Pr (2m)
Bu, Ph (2n)
Me, Ph (2o)
Ph, Ph (2p)
89
83
55
84c
80
79
30 19
30
ꢀ20
ꢀ20
ꢀ20
6
Scheme 2 A plausible catalytic cycle.
5.5
1
of 1b gives tetraarylferrate 70, which does not accept coordination
of alkyne 2 (Scheme 2). In contrast, the reaction with 6 equiv. of
1b gives triarylferrate 7, which accepts coordination and
insertion of 2, leading to 3. In the case of 1a, its bulkiness
unstabilizes tetraarylferrate 70 and thus relevant triarylferrate
7 (or a less ligated ferrate) readily adds to 2. After the addition,
8 possibly accepts attack of 1 to be converted to 80, from
which the most bulky alkenyl group eliminates to give 3 and
regenerate 7.
2.5
8
Bu, t-Bu (2q)
Hex, Hex (2r)
Hex, Hex (2r)
30 15
80
81
85
9
0
0
1.5
1.5
The carbolithiation products can be readily transformed
into tetrasubstituted alkenes. For example, 3am was treated
with benzaldehyde to give the corresponding allylic alcohol in
78% yield (Scheme 3). The bromination product was obtained
upon reaction with 1,2-dibromoethane.
10
11
12
a
Pr, Pr (2m)
Bu, Ph (2n)
0
2
1
83
The trimethylsilyl group is effective as an ortho substituent
that promotes the aryllithiation, where the addition was found
to be followed by cyclization through nucleophilic substitution
at the silicon atom, giving directly benzosiloles.12 Thus, the
reaction of o-(trimethylsilyl)phenyllithium (10a: 1.6 equiv.)
with 4-octyne (2m: 1 equiv.) in Et2O at 30 1C for 2.5 h gave
1,1-dimethyl-2,3-dipropyl-1-silaindene (11am) in 92% yield
(entry 1 of Table 3). Various benzosiloles were synthesized
by this addition–cyclization sequence. Arylalkynes reacted
with 10a at a lower temperature to give the corresponding
benzosiloles with high regioselectivities (entries 2–4). Conjugated
diyne 2s underwent regioselective addition at one of the two
triple bonds (entry 5). The yield of a silole was high with
fluoro-substituted aryllithium 10b (entry 6). Compounds 13
ꢀ20
81d
The reaction was carried out in Et2O (4.0 mL) under a nitrogen
atmosphere using an organolithium (1 or 5: 1.6 mmol) and an alkyne
b
(2: 0.80 mmol) in the presence of Fe(acac)3 (0.040 mmol). Yield of
isolated product 4 or 6 based on 2. Unless otherwise noted, an isomer
c
was produced with Z 97% selectivity. (E)-2-(2-methylphenyl)-1-
phenyl-1-hexene
(Z)-2-(2-methylphenyl)-1-phenyl-1-hexene
(4an) : (E)-1-(2-methylphenyl)-2-phenyl-1-hexene:
d
= 90 : 8 : 2. 6cn : regio-
isomer = 94 : 6.
The efficient alkenyllithiation was also observed with cyclic
trisubstituted vinyllithiums 5b and 5c (entries 10–12).
Treatment of FeCl3 (0.40 mmol) with phenyllithium
(1b: 10 equiv.) at ꢀ20 1C for 1 h followed by the reaction of
4-octyne (2m: 1 equiv.) at 30 1C for 2 h, after methanolysis,
gave only a trace amount of 4bm with a low conversion of 2m
(Scheme 1). Reduction of the amount of 1b to 6 equiv.
increased the yield of 4bm and conversion of 2m to 9% and
27%. On the other hand, the same reaction using 10 equiv. of
o-tolyllithium (1a) gave 4am in 88% yield. The result is
rationally understood by the following consideration based
on the report that the reaction of FeCl3 with an excess amount
of 1b gives Li4[Ph4Fe].11 The reaction of FeCl3 with 10 equiv.
Scheme 3 Reaction of aryllithiation product 3am with electrophiles.
Chem. Commun., 2011, 47, 9714–9716 9715
c
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Table 3 Benzosilole synthesis through aryllithiation–cyclizationa
Engl., 1997, 36, 93–95; (f) H. Yorimitsu, J. Tang, K. Okada,
H. Shinokubo and K. Oshima, Chem. Lett., 1998, 11–12.
4 For examples of carbometalation of dialkylacetylenes having no
heteroatoms using organometals other than arylmetals, see:
E. Shirakawa, K. Yamasaki, H. Yoshida and T. Hiyama, J. Am.
Chem. Soc., 1999, 121, 10221–10222; M. Suginome, M. Shirakura
and A. Yamamoto, J. Am. Chem. Soc., 2006, 128, 14438–14439.
5 Alkenylmetalations of functionalized alkynes have been reported. For
intramolecular alkenyllithiation of silylalkynes, see: G. Wu, F. E.
Cederbaum and E. Negishi, Tetrahedron Lett., 1990, 31, 493–496. For
vinylmagnesiation of propargylic alcohols, see: P. Forgione and
A. G. Fallis, Tetrahedron Lett., 2000, 41, 11–15; P. Forgione,
P. D. Wilson and A. G. Fallis, Tetrahedron Lett., 2000, 41, 17–20. For
decarbonylative alkenylstannylation of propargylic esters, see:
Y. Nakao, J. Satoh, E. Shirakawa and T. Hiyama, Angew. Chem.,
Int. Ed., 2006, 45, 2271–2274. For alkenylmagnesiation of o-hydroxy-
methylphenylacetylenes, see: K. Murakami, H. Ohmiya, H. Yorimitsu
and K. Oshima, Chem. Lett., 2007, 1066–1067.
6 We have reported iron-catalyzed alkyllithiation of arylalkynes. In
the paper, we have also disclosed that Fe(acac)3/CuBr/PBu3 as a
catalyst is effective for the addition of PhLi to PhCRCMe.
However, the Fe/Cu system is not applicable to dialkylacetylenes
(cf. entry 4 of Table 1). E. Shirakawa, D. Ikeda, T. Ozawa,
S. Watanabe and T. Hayashi, Chem. Commun., 2009, 1885–1887.
7 There have been several reports on iron-catalyzed carbometalation of
alkynes. For alkyllithiation of alkynes having a hereroatom, see:
M. Hojo, Y. Murakami, H. Aihara, R. Sakuragi, Y. Baba and
A. Hosomi, Angew. Chem., Int. Ed., 2001, 40, 621–623. For alkyl-
magnesiation of alkynes having a heteroatom, see: D. Zhang and J. M.
Ready, J. Am. Chem. Soc., 2006, 128, 15050–15051. For arylmagnesiation
of arylalkynes, see: T. Yamagami, R. Shintani, E. Shirakawa and
T. Hayashi, Org. Lett., 2007, 9, 1045–1048 See also ref. 2a.
T/
1C
Time/ Yield Isomer
h
(%)b ratioc
Entry R5 in 10 R3, R4 in 2
1
2
3
4
5
6
H (10a) Pr, Pr (2m)
H (10a) Me, Ph (2o)
H (10a) Bu, Ph (2n)
H (10a) Ph, Ph (2p)
30 2.5
2
92
91
87
93
73
95
—
ꢀ20
97 : 3
94 : 6
—
499 : 1
499 : 1
ꢀ20 2.5
ꢀ20 2.5
H (10a) Bu, 1-hexynyl (2s) ꢀ20
2
F (10b)
Me, Ph (2o)
ꢀ20 1.5
a
The reaction was carried out in Et2O (2.0 mL) under a nitrogen
atmosphere using an o-(trimethylsilyl)phenyllithium (10: 0.64 mmol)
and an alkyne (2: 0.40 mmol) in the presence of Fe(acac)3 (0.020 mmol).
c
Yield of isolated product 11 based on 2. 11 : regioisomer concerning
b
alkyne 2.
8 Synthesis of benzosiloles through an addition–cyclization sequence is
accomplished by rhodium-catalyzed reaction of o-(trimethylsilyl)-
phenylboronic acids with alkynes. M. Tobisu, M. Onoe, Y. Kita and
N. Chatani, J. Am. Chem. Soc., 2009, 131, 7506–7507. For examples of
other benzosilole synthesis, see: M. D. Rausch and L. P. Klemann,
J. Am. Chem. Soc., 1967, 89, 5732–5733; Y. Ura, Y. Li, F.-Y. Tsai,
K. Nakajima, M. Kotora and T. Takahashi, Heterocycles, 2000, 52,
1171–1189; S. Yamaguchi, C. Xu, H. Yamada and A. Wakamiya,
J. Organomet. Chem., 2005, 690, 5365–5377; T. Matsuda,
Y. Yamaguchi and M. Murakami, Synlett, 2008, 561–564;
T. Matsuda, S. Kadowaki, Y. Yamaguchi and M. Murakami, Chem.
Commun., 2008, 2744–2746; L. Ilies, Y. Sato, C. Mitsui, H. Tsuji and
E. Nakamura, Chem.–Asian J., 2010, 5, 1376–1381.
Scheme 4 Synthesis of compounds having two or three benzosilole
units linked by a benzene ring.
having two or three benzosilole units with conjugation through a
benzene ring were obtained in high yields by the reaction of
polyynes 12 (Scheme 4).
9 For reviews on properties of siloles, see: S. Yamaguchi and K. Tamao,
J. Chem. Soc., Dalton Trans., 1998, 3693–3702; J. Dubac, A. Laporterie
and G. Manuel, Chem. Rev., 1990, 90, 215–263; M. Hissler, P. W. Dyer
´
and R. Reau, Coord. Chem. Rev., 2003, 244, 1–44; J. Chen and Y. Cao,
Macromol. Rapid Commun., 2007, 28, 1714–1742.
This work has been supported financially in part by a Grant-in-
Aid for Scientific Research (No. 22605005) from Ministry of
Education, Culture, Sports, Science and Technology, Japan.
10 Use of FeCl3 (Z99.99% trace metals basis, Aldrich Co., product
number 451649) instead of Fe(acac)3 scored a similar yield (79%). For
the facility of handling, we used Fe(acac)3 for further examination.
Notes and references
1 For reviews, see: P. Knochel, Comprehensive Organic Synthesis, ed.
B. M. Trost, I. Fleming and M. F. Semmelhack, Pergamon Press,
New York, 1991, vol. 4, pp. 865–911; I. Marek, N. Chinkov and
D. Banon-Tenne, Metal-Catalyzed Cross-Coupling Reactions, ed.
A. de Meijere and F. Diederich, Wiley-VCH, Weinheim, 2nd edn,
2004, pp. 395–478. For a review including synthesis of tetrasubstituted
alkenes through carbometalation of alkynes, see: A. B. Flynn and
W. W. Ogilvie, Chem. Rev., 2007, 107, 4698–4745. For a review on
carbolithiation, see: A.-M. L. Hogan and D. F. O’Shea, Chem.
Commun., 2008, 3839–3851.
2 For examples of arylmetalation of dialkylacetylenes having no
heteroatoms, see: (a) E. Shirakawa, T. Yamagami, T. Kimura,
S. Yamaguchi and T. Hayashi, J. Am. Chem. Soc., 2005, 127,
17164–17165; (b) K. Murakami, H. Ohmiya, H. Yorimitsu and
K. Oshima, Org. Lett., 2007, 9, 1569–1571; (c) K. Murakami,
H. Yorimitsu and K. Oshima, Org. Lett., 2009, 11, 2373–2375.
3 For arylmetalation of arylalkynes, see: (a) J. J. Eisch and W. C. Kaska,
J. Am. Chem. Soc., 1966, 88, 2976–2983; (b) J. J. Eisch, R. Amtmann
and M. W. Foxton, J. Organomet. Chem., 1969, 16, P55–P59;
(c) J. J. Eisch and R. Amtmann, J. Org. Chem., 1972, 37, 3410–3415;
(d) J. G. Duboudin and B. Jousseaume, J. Organomet. Chem., 1978, 162,
11 Furstner and coworkers have recently reported in relation to the
¨
mechanism of iron-catalyzed cross-coupling reaction that treatment of
FeCl3 with a large excess of phenyllithium (1b) in Et2O gives [Ph4Fe]-
[Li(OEt )] . A. Furstner, H. Krause and C. W. Lehmann, Angew.
¨
Chem., Int. Ed., 2006, 45, 440–444; A. Furstner, R. Martin,
2
4
¨
H. Krause, G. Seidel, R. Goddard and C. W. Lehmann, J. Am. Chem.
Soc., 2008, 130, 8773–8787; B. D. Sherry and A. Furstner, Acc. Chem.
¨
Res., 2008, 41, 1500–1511. See also: T. A. Bazhenova,
R. M. Lobkovskaya, R. P. Shibaeva, A. E. Shilov, A. K. Shilova,
M. Gruselle, G. Leny and B. Tchoubar, J. Organomet. Chem., 1983, 244,
265–272. GC analysis in our hands showed that the reaction of FeCl3
(0.40 mmol) with Ar–Li (1a: 10 equiv. or 1b: 10 or 6 equiv.) gave Ar–Ar
in 0.54–0.68 mmol, which roughly corresponds to reduction of Fe(III) to
Fe(0). Generation of Ar–Ar was completed within 20 min in each case.
12 For examples of silole ring formation through nucleophilic sub-
stitution on a silicon atom by C(sp2)–Li with Me as a leaving
group, where pentaorganosilicates are considered to be intermedi-
ates, see: Z. Wang, H. Fang and Z. Xi, Tetrahedron Lett., 2005, 46,
499–501; P. F. Hudrlik, D. Dai and A. M. Hudrlik, J. Organomet.
Chem., 2006, 691, 1257–1264; Z. Xi, Bull. Chem. Soc. Jpn., 2007,
80, 1021–1032; N. Yu, C. Wang, F. Zhao, L. Liu, W.-X. Zhang
and Z. Xi, Chem.–Eur. J., 2008, 14, 5670–5679.
209–222; (e) T. Studemann and P. Knochel, Angew. Chem., Int. Ed.
¨
c
9716 Chem. Commun., 2011, 47, 9714–9716
This journal is The Royal Society of Chemistry 2011