Cross-coupling reaction of thermally stable titanium(II)-alkyne complexes with aryl halides catalysed by a nickel complex

Article abstract of DOI:10.1039/b310565b

The first cross-coupling reaction of thermally stable titanium(II)-alkyne complexes with aryl iodides in the presence of a catalytic amount of Ni(cod)₂ is presented.

Full text of DOI:10.1039/b310565b

Cross-coupling reaction of thermally stable titanium(II)-alkyne complexes
with aryl halides catalysed by a nickel complex
Yasushi Obora, Hiroyuki Moriya, Makoto Tokunaga and Yasushi Tsuji*
Catalysis Research Center and Division of Chemistry, Graduate School of Science, Hokkaido University,
CREST, Japan Science and Technology Corporation (JST), Sapporo 060-0811, Japan.
E-mail: tsuji@cat.hokudai.ac.jp; Fax: +81(11)706-9156; Tel: +81(11)706-9155
Received (in Cambridge, UK) 2nd September 2003, Accepted 29th September 2003
First published as an Advance Article on the web 11th October 2003
The first cross-coupling reaction of thermally stable titaniu-
m(II)–alkyne complexes with aryl iodides in the presence of
a catalytic amount of Ni(cod)2 is presented.
Pr)4 in entry 1 (Table 1), 1 was not so stable and the yield of cis-
stilbene was less than 50%. Thus, the Ti(O-i-Pr)4–n-BuLi–
alkyne system is suitable for generation of the thermally stable
1. Various thermally stable Ti(II)–alkyne complexes (1b–f)
were successfully generated as evidenced by the excellent
yields of 2 after hydrolysis at 50 °C (entries 2–6, Table 1).
For further evaluation of the thermal stability of 1, the
allylation reaction of 1 with allylic bromides (3) at 50 °C was
carried out (eqn. 2, Table 2).
Alkyne–metal complexes prepared from low-valent early
transition metal compounds such as Ti(II), Zr(II), Nb(III), and
Ta(III) are very useful synthetic reagents since they are known to
2
function as 1,2-dicarboanionic olefins.1–4 Nonmetallocene (h -
alkyne)Ti(O-i-Pr)2 is an especially versatile synthetic reagent
and a wide variety of reactions have been explored by Sato and
coworkers.1,5 However, the Ti(II)–alkyne complexes thus
obtained are thermally unstable and can only be used below
230 °C.
On the other hand, much less attention has been paid to Ti
compounds as substrates in transition metal catalysed reac-
tions.6 It is well-known that the transition metal catalysed cross-
coupling reaction of organic halides with Mg, B, Sn, and Si
compounds is one of the most straightforward methods for C–C
bond formation.7 However, there is only one example of the
cross-coupling reaction using a Ti compounds, in which
thermally stable Ti(IV) compounds such as MeTi(O-i-Pr)3 and
PhTi(O-i-Pr)3 were employed as substrates.8
Quite recently, Eisch and coworkers reported that Ti(II)–
alkyne complexes prepared from alkynes and Bu2Ti(O-i-Pr)2
generated from Ti(O-i-Pr)4 and BuLi at 278 °C were thermally
stable at 25 °C.9 Their work prompted us to report our
independent finding that thermally stable Ti(II)–alkyne com-
plexes can be utilized as substrates in transition metal catalysed
reactions. In this communication, we report an unprecedented
transition metal catalysed cross-coupling reaction of Ti(II)–
alkyne complexes with aryl halides. The Ti(II) complexes were
stable even at 50 °C and Ni catalysed reaction afforded coupling
products in good yields.
(2)
In contrast to previous monoallylation reactions of 1 with 3 at
low temperature (250 °C, then warmed up to rt),10 the reaction
of 1a with allyl bromide (3a) at 50 °C afforded diallylation
product (4a) as a major product in high yield (99% yield and
90% selectivity, entry 1, Table 2). The allylation reactions with
crotyl bromide (3b) and methallyl bromide (3c) similarly gave
diallylation products as major product (entries 2 and 3, Table 2).
The higher reaction temperature (50 °C) would favor the
diallylation reaction.
Since the Ti(II)–alkyne complexes (1) are thermally stable at
50 °C, 1 may be utilized as substrates even in a transition metal
Table 1 Hydrolysis of thermally stable Ti(II)–alkyne complexes (1)a
Thermally-stable Ti(II)–alkyne complexes (1) were success-
fully generated by slow addition of 2 equiv. of n-BuLi as a
reducing reagent (for the Ti(IV) to Ti(II) process) to a mixture of
Ti(O-i-Pr)4 and alkyne in THF at 278 °C followed by raising
the temperature to 50 °C (eqn. 1).
Yield of
Entry
R1
R2
2b (%)
1
2
3
4
5
6
Ph
Ph
1a
1b
1c
1d
1e
1f
99
97
92
90
95
95
p-CH3C6H4
Ph
Ph
n-Pr
(CH3)3Si
p-CH3C6H4
(CH3)Si
Me
n-Pr
(CH3)3Si
(1)
a Conditions: alkyne (0.50 mmol), Ti(O-i-Pr)4 (0.50 mmol), n-BuLi (1.0
mmol as 1.6 M hexane solution) and THF (3.0 mL) at 278 °C, then warmed
up to 50 °C. b GLC yields determined by the internal standard method.
Then, the THF solution of 1 was stirred for an additional hour
at 50 °C prior to further reaction. The formation of diph-
enylacetylene complex (1a) was verified by hydrolysis or
deuteriolysis of the reaction mixture affording cis-stilbene or
cis-stilbene-d2 ( > 98% D) in almost quantitative yield (entry 1,
Table 1). As for the reducing reagent, n-BuLi is appropriate to
stabilize the Ti(II)–alkyne complex at 50 °C. The use of s-BuLi
also works similarly as judged by the formation of cis-stilbene
in high yield (95%) after the hydrolysis. However, other
reducing reagents affect the thermal stability of 1 considerably:
1a prepared with i-PrMgBr or n-BuMgBr in lieu of n-BuLi was
not stable and afforded cis-stilbene in quite low yield ( ~ 20%)
after hydrolysis at 50 °C. As for a titanium compound, when
TiCl2(O-i-Pr)2 or Ti(O-t-Bu)4 was employed instead of Ti(O-i-
Table 2 Allylation of Ti(II)–alkyne complex (1a) with allylic bromides
(3)a
Yield (%)
(4 : 5)b
Entry
R3
R4
1
2
3
H
Me
H
H
H
Me
3a
3b
3c
99 (90c : 10c)
87 (77d : 23e)
77 (65c : 35e)
a Conditions: 1a (0.50 mmol), 3 (2.0 mmol) and THF (3.0 mL) at 50 °C for
24 h. b GLC yields determined by the internal standard method. c E : Z = 2
: 8. d E : Z = 1 : 9. e E : Z = 1 : 1.
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This journal is © The Royal Society of Chemistry 2003

catalysed reaction carried out above room temperature. Among
possible reactions, a cross-coupling reaction was chosen, and 1
was reacted with aryl iodide (6) in the presence of a nickel
catalyst (eqn. 3).
resonances were not consistent with the i-Pr carbons of i-PrOLi
(30.6 and 64.4 ppm) and Ti(O-i-Pr)4 (26.8 and 76.6 ppm) in the
same solvent and at the same concentration. This result might
2
suggest that 1 did not exist as a simple mixture of (h -
alkyne)Ti(O-i-Pr)2 and i-PrOLi, but was obtained as an ate-type
2
complex11 such as [(h -alkyne)Ti(O-i-Pr)4]22·2Li+, which
might cause the thermal stability of 1. Further study on the
structure and thermal stability of 1 is currently in progress.
(3)
Ni(cod)2 showed the highest catalytic activity and cross-
coupling products (7a and 8a) were afforded in 81% total yield
from 1a and 4-iodobenzotrifluoride (6a) at 50 °C with 5 mol%
of the nickel complex (entry 1, Table 3).† Other nickel or
palladium catalyst precursors such as Ni(acac)2, Pd(OAc)2, and
Pd(PPh3)4 only showed poor catalytic activity. The catalyst
loading slightly affected the reaction: iodobenzene (6b) af-
forded the products in 60, 65, and 75% yields with 10, 40, and
100 mol% of Ni(cod)2, (entries 2–4, Table 3). 3-Iodobenzotri-
fluoride (6c) and 1-fluoro-4-iodobenzene (6d) afforded the
corresponding products in moderate yields (entries 5 and 6). As
for aryl halides, iodides gave the best results, whereas the
corresponding bromides, chlorides, and triflates afforded low
yields ( < 10%). Other Ti(II) complexes of di-p-tolylacetylene
(1b), 4-octyne (1e), and 3-hexyne (1g) also provided the
corresponding coupling products in moderate to high yields
(entries 7–9, Table 3).
Notes and references
† A mixture of diphenylacetylene (89 mg, 0.50 mmol), Ti(O-i-Pr)4 (115 mg,
0.50 mmol) and THF (3.0 mL) was placed with a magnetic stirring bar in a
20 mL round-bottomed flask under an argon flow. The mixture was cooled
to 278 °C and n-BuLi (1.0 mmol, 1.6 M solution in hexane) was added
dropwise over 5 min. Then, the reaction mixture was slowly warmed to 50
°C over 1 h and stirred at the same temperature for an additional hour. To
this solution, 6a (544 mg, 2.0 mmol) and Ni(cod)2 (7 mg, 0.025 mmol) were
added and the reaction mixture was stirred at 50 °C for 24 h. After the
reaction, the whole mixture was passed through a short silica gel column to
afford a clear yellow solution. GLC and GC-MS analyses of the reaction
mixture showed the formation of the cross-coupling products (7a and 8a)12
in 81% yield. Isolation of the cross-coupling products for NMR analysis
was carried out by column chromatography (silica gel with hexane/CH2Cl2,
95/5).
1 F. Sato and H. Urabe, in Titanium and Zirconium in Organic Synthesis,
ed. I. Marek, Wiley-VCH, Weinheim, 2002, p. 319; F. Sato, H. Urabe
and S. Okamoto, Chem. Rev., 2000, 100, 2835.
2 O. G. Kulinkovich and A. de Meijere, Chem. Rev., 2000, 100, 2789; J.
J. Eisch, J. Organomet. Chem., 2001, 617–618, 148; J. J. Eisch, J. N.
Gitua, P. O. Otieno and X. Shi, J. Organomet. Chem., 2001, 624,
229.
3 S. L. Buchwald and R. B. Nielsen, Chem. Rev., 1988, 88, 1047; E.
Negishi and T. Takahashi, Acc. Chem Res., 1994, 27, 124; E. Negishi
and T. Takahashi, Bull. Chem. Soc. Jpn., 1988, 71, 755; A. Ohff, S.
Pulst, C. Lefeber, N. Peulecke, P. Arndt, V. V. Burlakov and U.
Rosenthal, Synlett, 1996, 118.
Although all attempts to isolate or fully characterize 1 were
unsuccessful, we measured the 13C NMR spectrum of 1a in
THF-d8 (0.3 M). In the aliphatic region of the spectrum, two
peaks at 28.4 and 72.6 ppm were assignable to methyl and
methine carbons of the i-Pr group, respectively. These two
Table 3 Nickel-complex catalysed cross-coupling reaction of Ti(II)–alkyne
complexes (1) with aryl iodides (6)a
4 Y. Kataoka, J. Miyai, K. Oshima, K. Takai and K. Utimoto, J. Org.
Chem., 1992, 57, 1973; J. B. Hartung Jr. and S. F. Pedersen, J. Am.
Chem. Soc., 1989, 111, 5468; J. R. Strickler, M. A. Bruck, P. A. Wexler
and D. E. Wigley, Organometallics, 1990, 9, 266.
5 K. Harada, H. Urabe and F. Sato, Tetrahedron Lett., 1995, 36, 3203.
6 For Ti compounds as substrates in a transition metal catalysed reaction,
see: Y. Tsuji and T. Ishii, J. Organomet. Chem., 1992, 425, 41; S.
Fleming, J. Kabbara, K. Nickisch, H. Neh and J. Westermann,
Tetrahedron Lett., 1994, 35, 6075; M. Arai, B. H. Lipshutz and E.
Nakamura, Tetrahedron, 1992, 48, 5709; A. N. Kasatkin, A. N. Kulak,
G. A. Tolstikov and S. I. Lomakina, Izv. Akad. Nauk, Ser. Khim., 1988,
2159; A. N. Kasatkin, A. N. Kulak and G. A. Tolstikov, Izv. Akad. Nauk,
Ser. Khim., 1987, 391.
7 J. Tsuji, Palladium Reagents and Catalysts, Wiley, Chichester, 1995; P.
J. Harrington, in Comprehensive Organometallic Chemistry II, eds. E.
W. Abel, F. G. A. Stone and G. Wilkinson, Pergamon, Oxford, 1995,
vol. 12, p. 797; B. M. Trost, Acc. Chem. Res., 1996, 29, 355 and
references cited therein.
8 J.-W. Han, N. Tokunaga and T. Hayashi, Synlett, 2002, 871.
9 J. J. Eisch and J. N. Gitua, Organometallics, 2003, 22, 24.
10 Y. Takayama, Y. Gao and F. Sato, Angew. Chem., Int. Ed. Engl., 1997,
36, 851.
Entry
R ( = R1 = R2)
Ar
Yield (%) (7 : 8)b,c
1
Ph (1a)
1a
1a
1a
1a
1a
p-CH3C6H4 (1b)
n-Pr (1e)
Et (1g)
p-CF3C6H4 (6a)
Ph (6b)
6b
81 (74d : 26e) (7a : 8a)
60 (65 : 35) (7b : 8b)
65 (55 : 45) (7b : 8b)
75 (40 : 60) (7b : 8b)
2f
3g
4h
5
6b
m-CF3C6H4 (6c) 55 (89i : 11e) (7c : 8c)
6
7
8
9
p-FC6H4 (6d)
40 (90e : 10e) (7d : 8d)
72 (79d : 21e) (7e : 8e)
48 (84i : 16e) (7f : 8f)
41 (93d : 7e) (7g : 8g)
6a
6a
6d
a Conditions: 1 (0.50 mmol), 6 (2.0 mmol), Ni(cod)2 (0.025 mmol, 5 mol%),
and THF (3.0 mL) at 50 °C for 24 h. b GLC yields determined by the internal
standard method. c In addition to the coupling products, 3,6-dihydro-
2,2,4-trimethyl-5,6-diphenyl-2H-pyran was obtained (5–20%) in entries
1–6: 1H NMR (CDCl3) d 1.42 (s, 3H), 1.48 (s, 3H), 1.60 (s, 3H), 1.93 (d, J
= 15 Hz, 1H), 2.56 (d, J = 16 Hz, 1H), 5.25 (s, 1H), 6.76 (d, J = 4 Hz, 2H),
7.08–7.18 (m, 8 H); 13C NMR (CDCl3) d 21.2 (CH3), 23.6 (CH3), 30.9
(CH3), 42.4 (CH2), 71.4 (C), 78.1 (CH), 126.1 (CH), 126.6 (CH), 127.2
(CH), 127.6 (CH), 127.8 (CH), 128.3 (CH), 129.4 (CH), 133.6 (C), 139.3
(C), 141.3 (C); HRMS (EI) calc. for C20H22O: m/z 278.1671. Found: m/z
278.1666. Anal. calc. for C20H22O: C, 86.29; H, 7.97. Found: C, 85.99, H,
7.88%. d E : Z = 4 : 6. e E : Z = 1 : 1. f Ni(cod)2 (0.050 mmol, 10 mol%).
11 M. T. Reetz, R. Steinbach, J. Westermann, R. Peter and B. Wenderoth,
Chem. Ber., 1985, 118, 1421; M. J. Hampden-Smith, D. S. Williams and
A. L. Rheingold, Inorg. Chem., 1990, 29, 4076.
12 M.-J. Wu, L.-M. Wei, C.-F. Lin, S.-P. Leou and L.-L. Wei, Tetrahedron,
2001, 57, 7839.
g Ni(cod)2 (0.20 mmol, 40 mol%). h Ni(cod)2 (0.50 mmol, 100 mol%). i
: Z = 3 : 7.
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