TiCl4-Zn induced reductive acylation of ketones with acylsilanes

Article abstract of DOI:10.1246/cl.2002.44

Acylsilanes were found to react with ketones in the presence of a low-valent titanium reagent generated from titanium(IV) chloride and zinc, giving the corresponding reductive acylated compounds.

Full text of DOI:10.1246/cl.2002.44

44
Chemistry Letters 2002
TiCl4-Zn Induced Reductive Acylation of Ketones with Acylsilanes
Hidehiro Sakurai, Yuka Imamoto, and Toshikazu Hiraoꢀ
Department of Applied Chemistry, Faculty of Engineering, Osaka University, Yamada-oka, Suita, Osaka 565-0871
(Received October 22, 2001; CL-011035)
Acylsilanes were found to react with ketones in the presence
reagents did not promote any coupling reactions (entries 1 and 2),
whereas the benzyl phenyl ketone (2a) was obtained with Ticl4.
The yield was increased to 38% in the presence of 4 molar
amounts of metallic zinc in DME as shown in entry 5.
Benzylsilane 3a was also isolated in 19% yield. It should be
noted that a trace amount of alkenic product via McMurry
of a low-valent titanium reagent generated from titanium(IV)
chloride and zinc, giving the corresponding reductive acylated
compounds.
reaction, which is a major product of Furstner’s conditions,12 was
Since the discovery by Mukaiyama,1 Tyrlik,2 and McMurry,3
one- and/or two-electron reduction of carbonyl compounds
induced by a low-valent titanium have provided a variety of
important organic transformations such as symmetrical 1,2-diol
formation (pinacol coupling) and alkene formation (McMurry
coupling).4 Recent reports from our laboratory have demon-
strated highly diastereoselective pinacol coupling reactions using
a catalytic amount of titanium or vanadium complex with
chlorosilane and co-reductant metal such as Zn, Al, etc.5{7
Acylsilane is a stable main group-metal acyl compound and
exhibits characteristic reactivities.8 Because of its high energy
level of n orbital, electrochemical behavior of acylsilanes has
been extensively studied.9;10 However, only few synthetic
applications have been investigated involving one- and/or two-
electron reduction of acylsilanes. As for the reductive self-
coupling reactions, the following two examples have been
reported. Metallic ytterbium promotes the double Peterson
reaction of aroylsilane, giving the alkyne.11 On the other hand,
the reaction with low-valent titanium reagents affords a mixture
of several products derived from McMurry, Brook, or Peterson
reactions.12 Such a complicated reaction process might prevent
further application. In this paper we report that low-valent
titanium generated by TiCl4 and Zn induces a reductive
(deoxygenative) acylation of ketones with acylsilanes.
¨
detected under these conditions.
A possible pathway to 2a is shown in Scheme 1. One-electron
or further reduction of 1a occurs to produce the pinacol coupling
intermediate A. Peterson elimination of A affords the metal
enolate C, which is then converted to the ketone 2a after
hydrolysis. If successive reduction process occurs predominantly
and the thus-formed dianion equivalent B possesses enough
nucleophilicity to other carbonyl compounds, reductive (deox-
ygenative) acylation can be developed. Since the reduction
potential of acylsilanes usually ranges between those of
aldehydes and ketones, the cross-coupling reaction with ketones
was next examined.13
First, self-coupling of 4-methoxybenzoyltrimethylsilane (1a)
was attempted using a low-valent vanadium or titanium
compound under an argon atmosphere (Table 1). Vanadium
Table 1. Self-coupling reaction of 1a
Scheme 1.
The reaction conditions were optimized with acetophenone
employed (Table 2). As shown in entry 1, TiCl4 þ 2Zn/DME
gave thedesired cross-coupling product 4a, accompanied with the
self-coupling product 2a in 36% and 7% yields, respectively.
Since the reaction temperature did not influence the yield
drastically (entry 2), the following entries were carried out at
room temperature. Titanium compounds were screened to find
that TiCl4 gave the best result (entries 2–5). Solvent effect was
also studied (entries 6–8) to show that DME is a suitable solvent.
It is noteworthy that no coupling product 4a but self-coupling
product 2a was obtained using THF as a solvent. Addition of
Me3SiCl did not improve the yield. Finally, the yield of 2a was
increased to 51% when 2 molar amounts of acetophenone were
Copyright Ó 2002 The Chemical Society of Japan

Chemistry Letters 2002
Table 2. The reaction of 1a with acetophenone
45
yield (entries 3, 5, and 6), suggesting the nucleophilicity of the
dianion equivalent, generated from acylsilane, influences the
reaction course.
As described above, reductive cross-coupling of acylsilanes
with ketones can be induced by TiCl4 and Zn in DME, giving the
reductive acylation products. The similar product has been
reported in the reaction of dianion of benzophenone with
acylsilane, which serves as a dianion accepter.15 On the other
hand, the present reaction demonstrated that acylsilanes possess a
unique reactivity as dianion donors.
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science, and Technology, Japan. H. S. thanks the financial
support from NOVARTIS Foundation (Japan) for the promotion
of science.
Dedicated to Prof. Teruaki Mukaiyama on the occasion of his
75th birthday.
References and Notes
1
T. Mukaiyama, T. Sato, and J. Hanna, Chem. Lett., 1973, 1041; For
recent reports; T. Mukaiyama, N. Yoshimura, K. Igarashi, and A.
Kagayama, Tetrahedron, 57, 2499 (2001), and references cited therein.
S. Tyrlik and I. Wolochowicz, Bull. Soc. Chim. Fr., 1973, 2147.
J. E. McMurry and P. Fleming, J. Am. Chem. Soc., 96, 4708 (1974).
For general reviews; G. M. Robertson, in ‘‘Comprehensive Organic
Synthesis,’’ ed. by B. M. Trost and I. Fleming, Pergamon Press, Oxford
2
3
4
used as shown in entry 10.
(1991), Vol. 3, p 563; A. Furstner and B. Bogdanovic, Angew. Chem.,
¨
Int. Ed. Engl., 35, 2442 (1996).
Table 3 shows the representative results of the reaction of
acylsilanes with various ketones.14 Reductively acylated com-
pounds 4 were yielded as a major product starting from both
aromatic and aliphatic ketones. When excess amounts of ketone
were used, 4 was obtained as a sole product (entry 4). The more
electron-donating acylsilane was allowed to produce 4 in a better
5
Cat. Cp2TiCl2 or Cp2VCl2/R3SiCl/Zn system for aliphatic aldehydes
and aromatic aldimines; a) T. Hirao, T. Hasegawa, Y. Muguruma, and I.
Ikeda, J. Org. Chem., 61, 366 (1996). b) T. Hirao, M. Asahara, Y.
Muguruma, and A. Ogawa, J. Org. Chem., 63, 2812 (1998). c) T. Hirao,
B. Hatano, M. Asahara, Y. Muguruma, and A. Ogawa, Tetrahedron
Lett., 39, 5247 (1998). d) B. Hatano, A. Ogawa, and T. Hirao, J. Org.
Chem., 63, 9421 (1998).
6
7
8
9
Cat. VOCl3/Me3SiCl/Al system for aromatic aldehydes; T. Hirao, B.
Hatano, Y. Imamoto, and A. Ogawa, J. Org. Chem., 64, 7665 (1999).
Cat. VOCl3 or TiCl4/Ac2O or AcCl/Zn system for aromatic aldehydes;
T. Hirao, H. Takeuchi, A. Ogawa, and H. Sakurai, Synlett, 2000, 1658.
Reviews; a) A. G. Brook, Acc. Chem. Res., 7, 77 (1974). b) P. C. B.
Page, S. S. Klair, and S. Rosenthal, Chem. Soc. Rev., 19, 147 (1990).
For electrochemical oxidation, see, J. Yoshida, M. Itoh, S. Matsunaga,
and S. Irie, J. Org. Chem., 57, 4877 (1992).
Table 3. The reaction of 1 with ketones
10 For electrochemical reduction, see, a) K. Mochida, S. Okui, K.
Ichikawa, O. Kanakubo, T. Tsuchiya, and K. Yamamoto, Chem. Lett.,
1986, 805. b) K. Mochida and K. Yamamoto, Bull. Chem. Soc. Jpn., 61,
2933 (1988).
11 Y. Taniguchi, N. Fujii, Y. Makioka, K. Takaki, and Y. Fujiwara, Chem.
Lett., 1993, 1165.
12 A. Furstner, G. Seidel, B. Gabor, C. Kopiske, C. Kruger, and R. Mynott,
¨
Tetrahedron, 51, 8875 (1995).
¨
13 In the reaction with aldehydes, reduction of aldehydes proceeded
predominantly, giving the pinacol coupling products.
14 Typical procedure: To a mixture of TiCl4 (57 mg, 0.3 mmol) and zinc
powder (78.5 mg, 1.2 mmol) in DME (5 mL) was added a ketone
(0.6 mmol) then an acylsilane (0.3 mmol) at room temperature under an
argon atmosphere. After stirring for 20 h, the reaction was quenched
with ether (10 mL) and HCl aq (1 M, 10 mL). The organic layer was
separated and then washed with saturated aqueous NaHCO3 (10 mL),
water (10 mL ꢁ 2), and brine (10 mL), dried over Na2SO4, and
concentrated in vacuo. The crude product was purified by silica-gel
column chromatography, giving the coupling product 4.
15 Y. Taniguchi, A. Nagafuji, Y. Makioka, K. Takaki, and Y. Fujiwara,
Tetahedron Lett., 35, 6897 (1994).