Angewandte
Chemie
DOI: 10.1002/anie.200804757
Synthetic Methods
Catalyzed Dehydrogenative Coupling of Primary Alcohols with Water,
Methanol, or Amines**
Theo Zweifel, Jean-Valꢀre Naubron, and Hansjꢁrg Grꢂtzmacher*
Fossil resources (petroleum, natural gas, coal) are widely used
for the production of basic organic chemicals.[1] This increas-
ingly limited feedstock is at the end of the process in which
CO2 is reduced to hydrocarbons by photosynthesis and
subsequent biological and slow geochemical processes [Eq.1].
(cooperative ligand).[6] However, the reaction requires ele-
vated temperatures (> 1008C) to achieve high yields of the
products (> 90%). We report herein an alternative approach
which allows the chemoselective, homogeneously catalyzed
DHC of primary alcohols with water, methanol, or amines to
give carboxylic acids, methyl esters, or amides, respectively.
The products are organic chemicals of key importance and are
produced under very mild reaction conditions. The reaction
can be performed such that the requisite hydrogen acceptor A
is quantitatively regenerated with hydrogen peroxide, H2O2,
in a second catalytic reaction. Hence the net reaction is
[Eq.2]:
n CO2þn H2Oþhn ! ðCHOHÞnþn O2 ! ðCH2Þnþ1=n O2
ð1Þ
Carbonyl compounds (aldehydes, ketones, carboxylic
acids and their derivatives) which are an economically
highly important class of organic chemicals, are mostly
produced from this oxygen-poor feedstock by oxygenation
(oxidation) or carbonylation reactions. For both reaction
types a wide range of rather efficient catalysts have been
developed.[2] Fossil resources need to be replaced by renew-
able ones which are ideally neutral in CO2 consumption/
production.[3] Plant biomass, containing compounds with a
relatively high oxygen content (sugars and other polyalco-
hols), is a rapidly renewable feedstock and uses sun light as an
energy source for its formation. New catalysts and catalytic
systems are needed to convert this biomass into fine-
chemicals. Milstein et al. recently reported a RuII complex
having a “dearomatized” aminomethyl phosphinomethyl
pyridine as a pincer ligand (Scheme 1), which allowed the
dehydrogenative coupling (DHC) of primary alcohols to give
symmetrical esters[4] and of alcohols and amines to give
amides (Scheme 1).[5] In this highly chemoselective reaction, a
hydrogen acceptor is not needed and the ligand plays an
active role in the hydrogen abstraction and liberation process
RCH2OHþR1XHþ2 H2O2 ! RCOðXR1Þþ4 H2O
ð2Þ
Recently we described the synthesis of the rhodium(I)/
diolefin amido complex [Rh(trop2N)(PPh3)] (2) (trop2N =
bis(5-H-dibenzo[a,d]cyclohepten-5-yl)-amide). The structure
of this compound strongly deviates from the expected planar
form of a tetra-coordinated ML4 complex (M = d8 metal
center, L = 2 electron donor ligand) with a 16 valence
electron configuration. Instead a saw-horse-type structure is
created by the combination of two p-acceptor olefinic binding
sites, and an amido and phosphane s-donor groups each
placed in a trans-position. As a result, the amido function is
Lewis basic (the highest occupied orbital (HOMO) is
localized on the N center) and the adjacent rhodium center
is Lewis acidic (the lowest unoccupied orbital (LUMO) is
localized on the metal center) (Figure 1). Because of this
special electronic situation, 2 easily cleaves H2 heterolytically
ꢀ
across the Rh N bond and is a catalyst for the hydrogenation
[7]
=
of unsaturated compounds R2C X (X = O, NR’). Further-
more, complex 2 catalyzes the transfer hydrogenation of
ketones and activated olefins, using ethanol as a (renewable)
hydrogen source, with high efficiency.[8] Calculations indi-
cated that in this reaction amido complex 2 not only serves as
catalyst for dehydrogenation of ethanol to acetaldehyde, but
also catalyzes the irreversible coupling of this aldehyde with
another equivalent of ethanol to give ethylacetate.
Scheme 1. Dehydrogenative coupling promoted by the Milstein cata-
lyst. No hydrogen acceptor is required.
The unprecedented activity of a catalyst for this type of
reaction led us to investigate the possibility of using 1 as a
catalyst for the DHC of primary hydroxy groups in com-
pounds 4–14 with water, methanol, or amines to furnish
carboxylic acids, methyl esters, or amides, respectively.
Because the amido complex 2 is air-sensitive, it was generated
in situ using an alkoxide or hydroxide base and the stable
[*] Dipl.-Chem. T. Zweifel, Dr. J.-V. Naubron, Prof. Dr. H. Grꢀtzmacher
Department of Chemistry and Applied Biology
ETH-Hꢁnggerberg, CH-8093 Zurich, Switzerland
E-mail: gruetzmacher@inorg.chem.ethz.ch
ꢀ
[Rh(trop2NH)(PPh3)]+ (CF3SO3 ) (1). A simplified catalytic
[**] This work was supported by the Swiss National Science Foundation
(SNF) and the ETH Zurich
cycle is shown in Scheme 2. We chose cyclohexanone
(cHexO) as the hydrogen acceptor A because a) it has a
high heat of hydrogenation (18.4 kcalmolꢀ1 versus 16.6 kcal
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2009, 48, 559 –563
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
559