FULL PAPER
DOI: 10.1002/cjoc.201200524
An Efficient α-Alkylation of Aromatic Ketones with Primary
Alcohols Catalyzed by [Cp*IrCl ] without Solvent
2
2
a
a,c
a
a,c
Li, Jian (李剑)
Zhang, Weixing (张卫星)
Wang, Feng (王锋)
Jiang, Min (江敏)
,a
,a,b
Dong, Xiaochun* (董肖椿)
Zhao, Weili* (赵伟利)
a
School of Pharmacy, Fudan University, Shanghai 201203, China
b
Key Laboratory for Special Functional Materials of the Ministry of Education, Henan University,
Kaifeng, Henan 475004, China
c
Roche Pharma Research and Early Development China, Shanghai 201203, China
Aromatic ketones are directly alkylated at α position with primary alcohols at 110 ℃ in the presence of
catalytic amount of KOH and [Cp*IrCl ] (Cp*=pentamethylcyclopentadienyl) catalyst. The reaction is carried out
2
2
in the absence of any solvent or additive, which generates only water as the byproduct in theory. It is very efficient
and generally completed in 10 min in good isolated yields. The reaction is believed to undergo successive hydrogen
transfer and cross aldol condensation processes.
Keywords carbon-carbon σ-bond formation, iridium catalyzed hydrogen transfer, α-alkylation of ketones, aldol
condensation, solvent-free
Introduction
cohol in toluene through oxidation-alkylation-reduction
[
16]
processes.
Mechanistic study pursued suggests that
One of the challenges for chemists nowadays is to
develop efficient, selective, high yielding, environmen-
tally benign, and sustainable processes.
base induced α-alkylation of ketone was a key proc-
[16]
ess.
relatively long reaction time (normally over 4 h). Re-
cently we have reported a green reaction of [Cp*IrCl
The above reported methods normally require
[
1,2]
α-Alkylation
of enolates of ketones with electrophilic alkylating
agents for a C—C bond formation has been known as
one of the most fundamental reactions in organic chem-
2 2
]
[17]
catalyzed alkylation of amines with alcohols. We are
interested in the green reaction of α-alkylation of ketone
with alcohols. Herein we report an efficient α-alkylation
of aromatic ketones with primary alcohols catalyzed by
[
3]
istry. However, the disadvantages of this protocol are
the usage of organic solvent and formation of
stoichiometric undesirable salt. Recently transition
metal-catalyzed α-alkylation of ketone through borrow-
ing hydrogen mechanism attracted much attention as an
[
2 2
Cp*IrCl ] in the presence of catalytic amount of base
without solvent.
[
4-8]
efficient, clean and atom-economic protocol.
process allows convenient introduction of an alkyl
Such a
Results and Discussion
group to the α position of ketones with water as
For the model reaction, acetophenone (1) and
n-butanol (2) were selected as the reaction partners for
solventless reaction. The various screened conditions
are collected in Table 1. Without base, no reaction took
place when 1 (1 mmol) and 2 (1.5 mmol) were heated at
110 ℃ in the presence of [Cp*IrCl ] (0.01 mmol)
(Entry 1, Table 1). In a stark contrast, in the presence of
KOH (1 mmol), complete conversion of 1 was reached
in 10 min at 110 ℃ and 1-phenylhexan-1-one (3) was
obtained in 51% GC yield with minor amount (19%) of
1-phenyhexan-1-ol (4) as the side product (Entry 2, Ta-
ble 1). With 0.6 equiv. of base, higher yield of desired
product was obtained with concomitant reduced amount
of the side product (Entry 3, Table 1). The optimum
co-product. Cho et al. reported RuCl (PPh ) catalyzed
2 3 3
α-alkylation of ketone with primary alcohols through
aldol condensation, followed by hydrogenation to gen-
[
9-13]
erate α-alkylated alcohols.
They also demonstrated
that by adding 1-dodecene as hydrogen acceptor,
2
2
[10]
α-alkylated ketone was obtained as major product.
Yus et al. reported RuCl (DMSO) efficiently catalyzed
α-alkylation of ketone with alcohol in dioxane in the
2
4
[
14]
presence of stoichiometric amount of base. Ishii et al.
developed a [Ir(cod)Cl] /PPh /KOH catalytic system
which catalyzed α-alkylation of ketone with primary
2
3
[15]
alcohols without solvent. Yamaguchi et al. reported
the [Cp*IrCl catalyzed β-alkylation of secondary al-
2 2
]
*
E-mail: xcdong@shmu.edu.cn, zhaoweili@fudan.edu.cn; Tel.: 0086-021-51980123 (X. Dong), Tel./Fax: 0086-021-51980111 (W. Zhao).
Received May 28, 2012; accepted July 4, 2012; published online XXXX, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201200524 or from the author.
Chin. J. Chem. 2012, XX, 1—4
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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