A new method for the synthesis of acyltitanium complexes and their application to copper-mediated acylmetallation of carbon-carbon multiple bonds in aqueous media

Article abstract of DOI:10.1039/b503117f

Treatment of α,β-unsaturated carbonyl compounds or methyl propargyl ether with acylchlorobis(cyclopentadienyl)titanium in the presence of Methylamine and a copper salt in aqueous THF resulted in acylation of the carbon-carbon multiple bond, yielding the c

Full text of DOI:10.1039/b503117f

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C O M M U N I C A T I O N
A new method for the synthesis of acyltitanium complexes and their
application to copper-mediated acylmetallation of carbon–carbon
multiple bonds in aqueous media
Zhenfu Han, Takuma Fujioka, Shin-ichi Usugi, Hideki Yorimitsu, Hiroshi Shinokubo and
Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University,
Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto, 615-8510, Japan.
E-mail: oshima@orgrxn.mbox.media.kyoto-u.ac.jp; Fax: 81 75 383 2438; Tel: 81 75 383 2437
Received 2nd March 2005, Accepted 31st March 2005
First published as an Advance Article on the web 12th April 2005
Treatment of a,b-unsaturated carbonyl compounds or
methyl propargyl ether with acylchlorobis(cyclopenta-
dienyl)titanium in the presence of triethylamine and a
copper salt in aqueous THF resulted in acylation of the
carbon–carbon multiple bond, yielding the corresponding
1,4-diketones in good yields.
We turned our attention to the application of the acyltitanium
complexes to organic synthesis. Gratifyingly, we found that treat-
ment of methyl vinyl ketone (2.5 mmol) with 1a (0.50 mmol) in
the presence of triethylamine (1.0 mmol) and copper(I) cyanide
(0.50 mmol) in aqueous THF (THF–water 5 : 3) provided
the corresponding 1,4-diketone 2 quantitatively, based on 1a
(Scheme 2). It is worth noting that the absence of water, base, or
copper salt resulted in the formation of complex mixtures. The
reaction with ethyl propiolate furnished tricarbonyl compound
3 in excellent yield. Addition to ethyl 2-butynoate did not
produce any of the expected products. Allylic substitution of
allyl bromide proceeded smoothly to give allyl ketone 4.
Acylmetals are important reagents and are widely used in
organic synthesis.1 However, little attention has been paid to
the synthesis and reaction of acyltitanium compounds.2 In this
communication we report a facile method for the preparation
of acyltitanium compounds and their application to copper-
mediated 1,4-addition.
Titanocene dichloride (1.0 mmol) was treated with cy-
clopentylmagnesium chloride (1.5 mmol) in THF at 0 ◦C for
1 h to yield Cp2TiCl (Scheme 1).3 4-Methylbenzoyl chloride
=
(p-TolC( O)Cl, 1.0 mmol) was added to the mixture, and the
mixture was stirred at 25 ◦C for 24 h. The resulting precipitate
was filtered under air, washed with THF, and dried in vacuo to
yield 0.31 mmol of acylchlorobis(cyclopentadienyl)titanium 1a.
Possible unavoidable by-products include titanocene dichloride,
whichwas readily removed bythe above procedure. This complex
was stable under air for more than a few weeks. The complex
was identified by elemental analysis, 1H, 13C NMR, and IR
spectroscopy,4 and showed spectra similar to known g2-acyl
titanocene complexes.2g The bromide analogue of 1a formed
a single crystal suitable for X-ray crystallographic analysis,
revealing the structure of g2-acyl complex (Fig. 1). Other
complexes such as 1b and 1c were prepared in a similar manner.
Fortunately, the reaction tolerated a C(sp2)–I bond.
Scheme 2 Copper-mediated 1,4-addition and allylic substitution with
acyltitanium in aqueous media.
Interestingly, double acylation occurred in the reaction of
methyl propargyl ether (Table 1, entry 1) as well as propiolate,
although the reaction suffered from a lower yield. To improve
the yield of 5a, screening of reaction conditions was performed.
Other copper(I) salts did not result in any dramatic improvement
(entries 2–6). No 5a was obtained under catalysis by copper(II)
salts (entries 7 and 8). Intriguingly, both CuO and Cu2O
mediated the double acylation (entries 9 and 10). We finally
found that metallic copper powder purchased from Aldrich
(99.999% purity) enhanced the efficiency of the reaction (entry
11). Copper powders from other companies such as Wako Pure
Chemical were also effective, although the yields were lower.
Triethylamine proved to be the base of choice after intensive
screening (entries 16–25). The amounts of water, triethylamine,
and copper were varied until no further improvement could be
obtained.
Scheme 1 Synthesis of acyltitanium complexes.
Under the optimized conditions (entry 11 in Table 1), the
double acylation of various alkynes were surveyed (Table 2).
Propargyl alcohol underwent acylation to provide 5b in 42%
yield (entry 1), whereas its silyl ether resisted acylation (entry 2).
Aliphatic as well as aromatic acetylenes reacted to yield the
corresponding 1,4-diketones (entries 3–5). Ethyl ethynyl ether
Fig. 1 ORTEP diagram of the bromide analogue of 1a.5 Hydrogen
atoms are omitted for clarity.
1 6 2 2
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 6 2 2 – 1 6 2 3
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
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Table 1 Double acylation of methyl propargyl ether
Entry “Cu”
Base
Yield of 5a (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
CuCN
CuI
CuBr
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
56
42
52
54
56
57
0
Scheme 4 A possible mechanism for the reaction of unactivated
alkynes.
CuCl
7. The g1-complex would transfer the acyl moiety more readily
to copper. The resulting copper reagent 8 would seem to be
able to resist hydrolysis, and effects acylcupration to yield the
vinylic copper compound 9, which would be readily hydrolyzed.6
Further addition of an acyl moiety would afford doubly acylated
products.
This work was supported by Grants-in-Aid for Scientific
Research and COE Research from the Ministry of Education,
Culture, Sports, Science and Technology, Government of Japan.
We thank Professor Masaki Shimizu (Department of Material
Chemistry, Kyoto University) for generous help with the X-ray
crystallographic analysis. Z.H. acknowledges JSPS for financial
support.
CuOAc
CuSPh
Cu(OAc)2
Cu(OTf)2
CuO
0
57
39
73
51
68
66
58
66
18
6
CuO2
Cu (Aldrich)a
Cu (Aldrich, nanosize)b Et3N
Cu (Wako)c
Cu (Kanto)d
Cu (Merck)e
Cu (Aldrich)
Cu (Aldrich)
Cu (Aldrich)
Cu (Aldrich)
Cu (Aldrich)
Cu (Aldrich)
Cu (Aldrich)
Cu (Aldrich)
Cu (Aldrich)
Cu (Aldrich)
Et3N
Et3N
Et3N
Et2NH
PrNH2
NH3
Pyridine
Imidazole
DBU
0
0
14
References
1-Methylpiperidine 49
iPr2NEt
DMAP
K2CO3
60
31
39
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Table 2 Double acylation of alkynes
Entry
R
Product
Yield (%)
1
2
3
4
5
CH2OH
5b
5c
5d
5e
5f
42
CH2OSitBuMe2
Ph
trace
28
3 H. A. Martin and F. Jellinek, J. Organomet. Chem., 1968, 12, 149.
p-MeOC6H4
37
43
1
4 Spectral data for 1a: IR 1566 cm−1; H NMR (d/ppm, CDCl3) 2.54
nC6H13
(s, 3H), 5.84 (s, 10H), 7.49 (d, J = 8.1 Hz, 2H), 7.80 (d, J = 8.1 Hz,
2H); 13C NMR (d/ppm, CDCl3) 22.44, 110.40, 130.17, 130.43, 130.78,
147.16, 282.23.
underwent monoacylation to afford 6 regioselectively in good
yield (Scheme 3).
5 Crystal data for the bromide analogue of 1a: formula, C18H17BrOTi
¯
˚
(FW = 377.13), orange blocks, triclinic, P1, a = 7.7237(7) A, b =
◦
◦
˚
˚
9.8885(9) A, c◦ = 11.0929(10) A, a = 81.444(2) , b = 70.937(2) ,
3
˚
c = 89.529(2) , V = 791.12(12) A , Z = 2, T = 293 K; no. of
reflections measured: 4848, observed: 3431 (I > 2.00r(I)), R1 =
0.0335 (I > 2.00r(I)), wR2 = 0.0892 (I > 2.00r(I)), R1 = 0.0417 (all
data), wR2 = 0.0926 (all data). CCDC reference number 265208. See
http://www.rsc.org/suppdata/ob/b5/b503117f/ for crystallographic
data in CIF or other electronic format.
Scheme 3 Addition to ethyl ethynyl ether.
6 (a) D. Seyferth and R. C. Hui, J. Am. Chem. Soc., 1985, 107, 4551;
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477; (d) T. Tsuda, M. Miwa and T. Saegusa, J. Org. Chem., 1986, 44,
3734; (e) N.-S. Li, S. Yu and G. W. Kabalka, Organometallics, 1999,
18, 1811.
The exact mechanism of the acylation reaction, especially the
roles of water and triethylamine, is not clear at this stage. As
outlined in Scheme 4, a combination of triethylamine and water
could transform 1a to a putative g1-acyltitanium complex such as
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 1 6 2 2 – 1 6 2 3
1 6 2 3