CHEMSUSCHEM
COMMUNICATIONS
DOI: 10.1002/cssc.201300815
Direct a-Alkylation of Ketones with Alcohols in Water
Guoqiang Xu,[a] Qiong Li,[a, b] Jiange Feng,[b] Qiang Liu,[a] Zuojun Zhang,[a] Xicheng Wang,[a]
Xiaoyun Zhang,[b] and Xindong Mu*[a]
The direct a-alkylation of ketones with alcohols has emerged
as a new green protocol to construct CÀC bonds with H2O as
the sole byproduct. In this work, a very simple and convenient
Pd/C catalytic system for the direct a-alkylation of ketones
with primary alcohols in pure water is developed. Based on
this catalytic system, aqueous mixtures of dilute acetone, 1-bu-
tanol, and ethanol (mimicking ABE fermentation products) can
be directly transformed into C5–C11 or longer-chain ketones
and alcohols, which are precursors to fuels.
which are primarily obtained from biomass feedstocks in the
form of dilute aqueous solutions, aqueous-phase processing
will exhibit additional advantage.[7] However, we are aware of
only very few reports concerning the aqueous-phase alkylation
of ketones with alcohols, and other related N-alkylations or C-
alkylations according to a similar reaction mechanism, so far.[8]
Usually the reaction is accomplished in organic solvents such
as toluene, xylene, or dioxane.
From a chemical equilibrium standpoint, it is easy to under-
stand that generally the presence of water has a negative
impact on a reaction with water as one of its products, let
alone when that water is used in solvent amounts. However,
we are interested in the development of novel catalytic trans-
formations that meet sustainable chemistry requirements, and
are pleased to report herein our exploration on the direct a-al-
kylation of ketones with alcohols in pure water.
The construction of new CÀC bonds is of fundamental impor-
tance in synthetic chemistry and other, related areas. Recently,
the direct a-alkylation of ketones with alcohols has emerged
as a new protocol.[1] Compared to the conventional method,
usually based on the reaction between alkyl halides and eno-
lates derived from ketones, this green alternative uses less
toxic and more easily available alcohols as the alkylating re-
agents and produces H2O as its sole byproduct. Several groups
have reported the use of homogeneous and heterogeneous
catalysts of Ru, Rh, Ir, Pd, and Ni in this process. For example,
RuCl3/PPh3, [Ir(cod)Cl]2/PPh3, and Pd/AlO(OH) have been suc-
cessfully applied in the alkylation of aromatic or aliphatic ke-
tones, and both activated (e.g., benzyl alcohol) and non-acti-
vated alcohols (e.g., 1-butanol) can be used as alkylating re-
agents.[2–4] Interestingly, this synthetic protocol was recently ef-
ficiently applied in the production of biofuel from acetone-1-
butanol-ethanol (ABE) fermentation products.[5] A critical step
in this novel route for the conversion of biomass into liquid
fuels is the construction of longer-carbon-chain components
(C5–C11 or higher) using the functionalities inherent in the start-
ing materials, which is just the aforementioned direct a-alkyla-
tion of acetone with 1-butanol and ethanol. On the other
hand, organic transformations in water are intriguing for green
and sustainable chemistry, and the unique properties of water
can lead to different reactivities and selectivities.[6] When con-
sidering the transformation of biomass derivatives such as ABE,
Generally, the direct a-alkylation of ketone is believed to be
initiated by the dehydrogenation of alcohol to afford the car-
bonyl intermediate (aldehyde or ketone), followed by aldol
condensation with the starting ketone to produce a,b-unsatu-
rated ketone and H2O, then followed by rehydrogenation
using the hydrogen generated in the first step to produce the
final, alkylated ketone. There is no need for additional oxidant
or reductant in this transformation, and therefore, the mecha-
nism is usually named as hydrogen auto-transfer or hydrogen-
borrowing mechanism.[1] Based on these findings, multifunc-
tional catalytic systems containing transition metals and bases
to promote the dehydrogenation/hydrogenation and aldol
condensation steps, respectively, were rationally surveyed.
Direct a-alkylation of acetophenone (1a) with 1-butanol (2a)
was chosen as model reaction, because a relatively simple dis-
tribution of products is more suitable for catalyst development
purposes (Scheme 1).
It is not surprising that some catalysts active in organic sol-
vents (e.g., RuCl3/PPh3-NaOH) are not apt for the aqueous-
phase reaction (Table 1, entry 1). A screening of different transi-
tion-metal catalysts revealed that the combination of RhCl3
and bipy (2, 2’-bipyridine) under basic conditions exhibits
some activity; however, its performance after optimizing base,
temperature, ligand, and other parameters was still inferior. Se-
lectivity to the desired alkylated product (1-phenyl-1-hexanone,
3a) was less than 30%, and considerable amounts of 1a were
reduced to 1-phenylethanol (4a) via transfer hydrogenation
with alcohol (entries 4–7, and Supporting Information,
Table S1). Additionally, the homogeneous transition-metal cata-
lysts precipitated under all circumstances examined. However,
to our delight, we found that Pd/C affords about 50% yield
and 80% selectivity to the expected alkylated ketone (entries 9
and 10), while Ru/C exhibits moderate selectivity (entry 8), and
[a] Dr. G. Xu, Q. Li, Q. Liu, Z. Zhang, Dr. X. Wang, Prof. Dr. X. Mu
CAS Key Laboratory of Bio-based Materials
Qingdao Institute of Bioenergy and Bioprocess Technology
Chinese Academy of Sciences
Qingdao, 266101 (PR China)
Fax: (+86)532-80662724
[b] Q. Li, J. Feng, Dr. X. Zhang
College of Science
China University of Petroleum, East China
Qingdao, 266555 (PR China)
Supporting Information for this article is available on the WWW under
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemSusChem 2014, 7, 105 – 109 105