Oxidation and β-Alkylation of Alcohols Catalysed by Iridium(I) Complexes with Functionalised N-Heterocyclic Carbene Ligands

Article abstract of DOI:10.1002/chem.201502910

The borrowing hydrogen methodology allows for the use of alcohols as alkylating agents for C-C bond forming processes offering significant environmental benefits over traditional approaches. Iridium(I)-cyclooctadiene complexes having a NHC ligand with a O- or N-functionalised wingtip efficiently catalysed the oxidation and β-alkylation of secondary alcohols with primary alcohols in the presence of a base. The cationic complex [Ir(NCCH₃)(cod)(MeIm(2- methoxybenzyl))][BF₄] (cod=1,5-cyclooctadiene, MeIm=1-methylimidazolyl) having a rigid O-functionalised wingtip, shows the best catalyst performance in the dehydrogenation of benzyl alcohol in acetone, with an initial turnover frequency (TOF₀) of 1283 h^-1, and also in the β-alkylation of 2-propanol with butan-1-ol, which gives a conversion of 94 % in 10 h with a selectivity of 99 % for heptan-2-ol. We have investigated the full reaction mechanism including the dehydrogenation, the cross-aldol condensation and the hydrogenation step by DFT calculations. Interestingly, these studies revealed the participation of the iridium catalyst in the key step leading to the formation of the new C-C bond that involves the reaction of an O-bound enolate generated in the basic medium with the electrophilic aldehyde.

Full text of DOI:10.1002/chem.201502910

DOI: 10.1002/chem.201502910
Full Paper
&
Iridium Catalysis
Oxidation and b-Alkylation of Alcohols Catalysed by Iridium(I)
Complexes with Functionalised N-Heterocyclic Carbene Ligands
M. Victoria JimØnez,* Javier Fernµndez-Tornos, F. Javier Modrego, Jesffls J. PØrez-Torrente,*
and Luis A. Oro[a]
Abstract: The borrowing hydrogen methodology allows for
the use of alcohols as alkylating agents for CÀC bond form-
ing processes offering significant environmental benefits
over traditional approaches. Iridium(I)-cyclooctadiene com-
plexes having a NHC ligand with a O- or N-functionalised
wingtip efficiently catalysed the oxidation and b-alkylation
of secondary alcohols with primary alcohols in the presence
of a base. The cationic complex [Ir(NCCH3)(cod)(MeIm(2-
methoxybenzyl))][BF4] (cod=1,5-cyclooctadiene, MeIm=1-
methylimidazolyl) having a rigid O-functionalised wingtip,
shows the best catalyst performance in the dehydrogenation
of benzyl alcohol in acetone, with an initial turnover
frequency (TOF0) of 1283 hÀ1, and also in the b-alkylation of
2-propanol with butan-1-ol, which gives a conversion of
94% in 10 h with a selectivity of 99% for heptan-2-ol. We
have investigated the full reaction mechanism including
the dehydrogenation, the cross-aldol condensation and the
hydrogenation step by DFT calculations. Interestingly, these
studies revealed the participation of the iridium catalyst in
the key step leading to the formation of the new CÀC bond
that involves the reaction of an O-bound enolate generated
in the basic medium with the electrophilic aldehyde.
Introduction
Transition-metal-catalysed dehydrogenative oxidation of alco-
hols to synthetically valuable carbonyl compounds constitutes
a high atom-efficiency synthetic method alternative to the use
of stoichiometric oxidants. Dehydrogenation of alcohols
(Oppenauer-type oxidation) can be efficiently accomplished by
hydrogen-transfer catalysts if suitable hydrogen acceptors,
typically acetone or alkenes, are used.[1,2] On the other hand,
the oxidation of alcohols based on hydrogen transfer has also
been applied to the formation of CÀC and CÀN bonds through
the borrowing hydrogen methodology.
Scheme 1. Borrowing hydrogen strategy for CÀC and CÀN bond formation
reactions (cat-H2 denotes the formal abstraction of two hydrogen atoms by
the catalyst).
Remarkably, the borrowing hydrogen approach is a tandem
process that produces the in situ formation of alkenes or
imines through nucleophilic addition to electrophilic carbonyl
compounds derived from alcohols by hydrogen-transfer oxida-
tion. These are redox-neutral processes because the temporary
removal of hydrogen by the transition-metal catalyst is
followed by the delivery to the unsaturated products leading
to the formation of new CÀC and CÀN bonds by means of hy-
drogen-transfer reactions (Scheme 1). The search for efficient
hydrogen-borrowing catalysts[3] is very stimulating as these
tandem strategies provide easy access to a wide range of
highly valuable organic molecules while introducing environ-
mental benefit with water as the only reaction byproduct. In
this context, the borrowing hydrogen methodology applied to
the b-alkylation of secondary alcohols with primary alcohols
involves the formation of CÀC bonds by the activation of two
alcohols in one reaction sequence (hydrogen autotransfer
reactions).[4] Related CÀC bond-forming processes based on
the activation of alcohols by using the borrowing hydrogen
methodology are, for example, the a-alkylation of carbonyl
compounds and related compounds,[5] the alkylation of active
methylene compounds involving Knoevenagel-type transfor-
mations[6] or the condensation of primary alcohols (Guerbet
condensation).[7] In addition, other processes based on the de-
hydrogenative coupling of alcohols have also been reported.[8]
[a] Dr. M. V. JimØnez, Dr. J. Fernµndez-Tornos, Dr. F. J. Modrego,
Prof. J. J. PØrez-Torrente, Prof. L. A. Oro
Departamento de Química Inorgµnica
Instituto de Síntesis Química y Catµlisis HomogØnea-ISQCH
Universidad de Zaragoza-CSIC
C/Pedro Cerbuna, 50009-Zaragoza (Spain)
E-mail: vjimenez@unizar.es
perez@unizar.es
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201502910.
Chem. Eur. J. 2015, 21, 17877 – 17889
17877
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
N-Heterocyclic carbenes (NHCs) have attracted increasing
attention as ligands for homogeneous catalysis. NHCs have
proven to be efficient ancillary ligands because of their strong
coordination ability that imparts to the metal complexes an
adequate balance between stability and activity. In addition,
their remarkable tuneable character allows for the control of
the sterically and electronic properties of the metal centre.[9]
The easy access to a variety of NHC ligands from imidazolium
salts[10] in combination with well-established methodologies for
coordination, has led to the preparation of a range of transi-
tion-metal complexes with different geometries and potential
catalytic applications.[11] Iridium– and ruthenium–NHC well-de-
fined transition-metal complexes have found application in the
catalytic oxidation of alcohols through dehydrogenation and
hydrogen-transfer processes, as well as in catalytic bond-form-
ing reactions based on the borrowing hydrogen methodology.
The outstanding catalytic activity of the complex [Cp*IrCl2]2
(Cp*=h5-C5Me5) in this type of processes[12] has led to the de-
velopment of new Cp*IrIII–NHC catalyst precursors. Thus, modi-
fied Cp*–IrIII catalyst systems having pentamethylcyclopenta-
dienyl-thetered NHC ligands,[13] bidentate pyrimidine-,[14]
hydroxy-, ether- and alkoxide-functionalised[15] NHC ligands for
the transfer hydrogenation, the b-alkylation of secondary
alcohols with primary alcohols, and the N-alkylation of amines
with primary alcohols have been recently reported.
fer hydrogenation of several unsaturated substrates, such as
ketones, aldehydes, a,b-unsaturated ketones and imines in 2-
propanol/KOH medium.[16] Interestingly, given the reversible
nature of many hydrogen-transfer processes, the oxidation of
alcohols to carbonyl compounds might be also performed by
hydrogen-transfer catalysts helped by suitable hydrogen ac-
ceptors. We have observed that the donor function and flexi-
bility of the backbone in the NHC ligands strongly influence
the catalytic activity in the transfer hydrogenation. Thus, a set
of catalysts has been chosen in order to explore their
performance in an Oppenauer-type alcohol oxidation and
related secondary alcohol b-alkylation reactions by using the
borrowing hydrogen methodology.
The iridium(I) complexes containing hemilabile O- and N-
donor-functionalised NHC ligands were synthesised by using
the free NHC ligands generated in situ by deprotonation of
the functionalised imidazolium salts[16,20] by the methoxo li-
gands in the dinuclear complex [{Ir(m-OMe)(cod)}2]. This syn-
thetic route provides access to the neutral mononuclear com-
plexes [IrX(cod)(MeIm\Z)] (1–4, X=Cl or Br, \Z=2-methox-
yethyl, 2-methoxybenzyl, pyridin-2-ylmethyl and 3-dimethyla-
minopropyl; MeIm=1-methylimidazolyl) having uncoordinated
O- and N-donor functions with different backbone flexibility.
The cationic complexes [Ir(NCCH3)(cod)(MeIm\Z)]BF4 (5 and 6,
\Z=2-methoxyethyl and 2-methoxybenzyl) containing O-func-
tionalised NHC ligands have uncoordinated methoxy frag-
ments due to the coordination of a labile acetonitrile ligand. In
contrast, the cationic complexes having N-functionalised NHC
ligands, that is, [Ir(cod)(MeIm\Z)]BF4 (7 and 8, \Z=pyridin-2-
ylmethyl and 3-dimethylaminopropyl) feature NHC ligands,
which are k2-C,N coordinated (Scheme 2).
Our current interest is focused on the synthesis and catalytic
applications of transition-metal complexes containing hetero-
ditopic ligands of a hemilabile character. We have recently
reported the high catalytic performance of (cod)–IrI (cod=1,5-
cyclooctadiene)-based catalyst having hemilabile O- and N-
donor-functionalised NHC ligands in transfer hydrogenation.[16]
We have found an interesting relationship between the donor
function, the flexibility of the backbone and the length of the
linker in the NHC ligands with the catalytic activity in transfer-
hydrogenation catalysis. In particular, the catalyst precursors
based on O-donor-functionalised NHC ligands were found to
be much more active than the corresponding N-functionalised
ligands.[14,17,18]
The aim of this work is to assess the catalytic activity of se-
lected iridium(I) catalyst precursors having a heteroditopic
NHC ligand, but devoid of a cyclopendadienyl ligand, in the b-
alkylation of secondary alcohols with primary alcohols. In view
of the lack of mechanistic studies on this hydrogen autotrans-
fer process,[19] the reaction mechanism has been investigated
by DFT calculations. Remarkably, these studies have revealed
the key role of the transition-metal catalyst not only in the
dehydrogenation and hydrogenation steps but also in the
cross-condensation step leading to the formation of the new
CÀC bond.
Scheme 2. Neutral and cationic iridium(I) complexes with functionalised
NHC ligands.
Results and Discussion
The b-alkylation of secondary alcohols with primary alcohols
is a tandem reaction in which both alcohols are converted into
carbonyl compounds by the temporary removal of hydrogen.
For this reason, the iridium catalysts have been tested in the
oxidation of primary and secondary alcohols with the aim
Catalysts
We have recently reported on the catalytic activity of a series
of neutral and cationic iridium(I) complexes based on hemila-
bile O-donor- and N-donor-functionalised NHC ligands in trans-
Chem. Eur. J. 2015, 21, 17877 – 17889
www.chemeurj.org
17878
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
of establishing the optimal hydrogen-borrowing reaction
conditions.
Table 1. Catalytic dehydrogenation and hydrogen-transfer oxidation of
benzyl alcohol and 1-phenylethanol.[a]
Oppenauer-type oxidation catalysis
Entry
R
Base
Time
[h]
A[b]
Yield [%]/
TOF0 [hÀ1
]
[c]
The neutral complex [IrBr(cod)(MeIm(2-methoxybenzyl))](2)
and the cationic [Ir(NCCH3)(cod)(MeIm(2-methoxybenzyl))][BF4]
(6) iridium complexes featuring a methoxy-functionalised NHC
ligand with a rigid wingtip were found to be the most active
catalysts in the transfer hydrogenation of ketones.[16] Thus,
both complexes have been tested as catalyst precursors for
the dehydrogenation of primary and secondary alcohols (Op-
penauer-type oxidation). The oxidation of benzyl alcohol and
1-phenylethanol to benzaldehyde and acetophenone, respec-
tively, were chosen as model reactions to optimise the reaction
conditions and to establish the basis for their application in
hydrogen-borrowing reactions. The catalytic reactions were
performed in toluene at 110 8C by using different inorganic
and organic bases. Standard catalyst loadings of 1 mol% with
a catalyst/substrate/base ratio of 1:100:100 were routinely
used. The conversion attained after 24 h or the reaction time
to get conversions over 90% (determined by GC by using me-
sitylene as internal standard) by using compound 2 as catalyst
precursor, and the turnover frequencies (TOF0s) calculated at
initial time are shown in Table 1.
1
H
H
H
H
H
Cs2CO3
Cs2CO3
KOH
NaOMe
KOtBu
24
24
24
24
24
–
–
–
–
–
68/283
46/109
45/97
42/79
69/289
2[d]
3
4
5
6
H
H
Cs2CO3
Cs2CO3
24
24
95/349
94/337
7[d]
8
H
Cs2CO3
12
92/560
9[e]
10
H
KOH
8
92/894
55/182
CH3
Cs2CO3
24
–
11
12
CH3
CH3
Cs2CO3
Cs2CO3
24
17
92/318
91/411
13
CH3
Cs2CO3
12
95/573
The catalytic systems with Cs2CO3 or KOtBu are much more
efficient for the dehydrogenation of benzyl alcohol than those
based on NaOMe or KOH providing up to 70% conversion in
24 h (Table 1, entries 1–5). However, the widely used and less
hygroscopic Cs2CO3 was selected as base. The temperature has
a strong influence on the catalyst performance and a sharp de-
crease in the catalytic activity was observed when the temper-
ature was lowered from 110 to 808C (Table 1, entries 1 and 2).
The presence of hydrogen acceptors, such as 3,3-dimethyl-1-
butene or benzylideneacetophenone, in an equimolecular
amount with the alcohol displaces the equilibrium to the pro-
duction of benzaldehyde almost quantitatively with initial
TOF0s of 349–360 hÀ1 (Table 1, entries 6–8). The good conver-
sions attained in the presence of a hydrogen acceptor allow
shorter reaction times and milder reaction conditions (Table 1,
entry 8). Interestingly, the oxidation of benzyl alcohol in ace-
tone as solvent at 408C for 8 h by using KOH as base gave
a conversion of 92% with the highest initial TOF0 of 894 hÀ1
(Table 1, entry 9). Catalyst 2 was also efficient in the dehydro-
genation of 1-phenylethanol by using Cs2CO3 as base showing
similar catalytic activities (Table 1, entries 10–13).
[a] Reaction conditions: catalyst (0.03 mmol, 1 mol%), catalyst/benzylic al-
cohol/base ratio of 1:100:100, in toluene (0.3 mL) at 110 8C. [b] Hydrogen
acceptor (3 mmol). [c] Determined by GC analysis by using mesitylene as
internal standard. Initial turnover frequency (mol of product per mol of
catalyst per hour) determined at initial time, 60 s. [d] T=808C. [e] Ace-
tone as solvent, T=408C.
Most of the reported studies on transition-metal-catalysed
hydrogen-transfer oxidation reactions of alcohols have mainly
been performed on secondary alcohols[21] and relatively few ex-
amples of the oxidation of primary alcohols affording alde-
hydes have been described.[22] Interestingly, the dinuclear IrIII
complex [Cp*IrCl2]2 has revealed to be an efficient catalyst for
the oxidation of both primary and secondary benzylic alcohols,
which contrast with the inactivity of the dinuclear complex
[Ir(m-Cl(cod)]2.[12,23] In particular, a conversion of 86% in the oxi-
dation of benzyl alcohol in acetone as solvent at room temper-
ature was attained with [Cp*IrCl2]2 after 6 h. On the other
hand, related iridium(III) complexes bearing amino-functional-
ised Cp* or NHC ligands are much more efficient catalyst pre-
cursors in the Oppenauer-type oxidation of alcohols, reaching
an average TOF of 242 in the oxidation of 1-phenylethanol
without any base additive.[23a] Certainly, the electronic and
steric properties of the Cp* and NHC ligands in combination
with the basic properties of the substituent account for the
high catalytic activities.[23]
The related cationic iridium complex [Ir(cod)(NCCH3)-
(MeIm(2-methoxybenzyl))][BF4] (6), which showed a higher cat-
alytic activity in the transfer hydrogenation of cyclohexanone,
has also shown to be an efficient catalyst for the dehydrogena-
tion of benzyl alcohol, exhibiting comparable catalytic activities
to those attained with compound 2 under the same experi-
mental conditions. However, complex 6 showed better per-
formance than complex 2 in the hydrogen-transfer oxidation
of benzyl alcohol in acetone by using KOH as base providing
a conversion of 91% in 6 h with an initial TOF0 of 1283 hÀ1.
The oxidation of 1-phenylethanol to acetophenone catalysed
by [Ir(NCCH3)(cod)(MeIm(2-methoxybenzyl))][BF4] (6) was moni-
1
tored by H NMR spectroscopy ([D6]acetone at 408C). The reac-
tion prolife obtained from a catalytic test at a catalyst loading
Chem. Eur. J. 2015, 21, 17877 – 17889
www.chemeurj.org
17879
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Figure 1. Time dependence of the catalytic hydrogen-transfer oxidation of 1-
phenylethanol catalysed by complex 6 (10 mol%). The reaction was per-
formed in [D6]acetone at 408C by using Cs2CO3 as base (catalyst/1-phenyle-
thanol/base ratio of 1:10:10).
of 10 mol% by using a catalyst/1-phenylethanol/Cs2CO3 ratio
of 1:10:10 is shown in Figure 1. As can be observed, no appar-
ent induction period was detected and quantitative conversion
was attained within 2 h. In general, the reaction profile resem-
bles those obtained for the ketone reduction by transfer hy-
drogenation catalysed by complex 6,[16] and in consequence,
a pseudo-first-order kinetic behaviour can be inferred. The par-
tially deuterated 2-propanol formed by reduction of the hydro-
gen acceptor (i.e., [D6]acetone) was observed at d=1.17 ppm.
Interestingly, when the oxidation reaction was performed in
[D8]toluene at 110 8C without any hydrogen acceptor,
molecular hydrogen was detected at d=4.19 ppm.[24,25]
Scheme 3. Proposed mechanism for the Oppenauer-type oxidation of
benzyl alcohol catalysed by complex 2.
acceptor, alcoholysis produces gaseous H2 and the regenera-
tion of the iridium alkoxo species (outer cycle in Scheme 3).
However, in the presence of a suitable hydrogen acceptor,
such as acetone, the insertion into the IrÀH bond followed by
alkoxide exchange proceeds to regenerate the iridium alkoxo
species with release of 2-propanol, the reduced form of the
acceptor (main cycle in Scheme 3).
It has been proposed that key intermediates in the Oppena-
uer-type oxidation of alcohols are metal–alkoxide species that
evolve to iridium–hydrides[12a] or ruthenium–hydrides[26] as
active species. In this regard, it is worth mentioning that this
transformation is also a key step in the redox isomerisation of
allylic alcohols and the racemisation of secondary alcohols cat-
alysed by ruthenium cyclopentadienyl complexes.[27] In fact, we
have identified by NMR spectroscopy and mass spectrometry
the relevant alkoxo intermediates [Ir(OR)(cod)(MeIm\Z)] and
the unsaturated hydride species [IrH(cod)(MeIm\Z)] (\Z=2-
methoxybenzyl) involved in the transfer hydrogenation of un-
saturated substrates in 2-propanol/KOH catalysed by iridium(I)
complexes having hemilabile O- and N- donor-functionalised
NHC ligands.[16a] Interestingly, DFT calculations have allowed to
identify an interaction between the b-H atom on the alkoxo
ligand and the methoxy fragment of the NHC ligand, which re-
sults in a net destabilisation of the alkoxo intermediate, there-
by facilitating the b-H elimination step, leading to the hydride
intermediate.[16a] Thus, considering the reversibility of both hy-
drogen-transfer processes it is likely that the Oppenauer-type
oxidation of alcohols proceeds through the closely related
mechanism shown in Scheme 3.
b-Alkylation of alcohols catalysed by iridium complexes
with O/N-donor-functionalised NHC ligands
The b-alkylation of secondary alcohols with primary alcohols is
a tandem reaction[28] that proceeds through successive hydro-
gen-transfer oxidation of the secondary and primary alcohols
(borrowing hydrogen) to give a ketone and an aldehyde, re-
spectively, followed by cross-aldol condensation mediated
by base to afford a a, b-unsaturated ketone (and water),
which is reduced by transfer hydrogenation to the b-alkylated
alcohol (Scheme 4, product A) through the saturated ketone
(Scheme 4, product B). Several iridium complexes including
Cp*,[12,23,29] terpyridine[30] or pyrimidine[14] as ligands have been
reported to catalyse this reaction.[31]
A preliminary screening of the catalytic performance of
[IrBr(cod)(MeIm(2-methoxybenzyl))] (2) in the b-alkylation of al-
cohols was carried out in order to determine the influence of
key reaction parameters (i.e., base, solvent and temperature)
on the catalytic activity. The b-alkylation of 1-phenylethanol
with benzyl alcohol was selected as model reaction. The reac-
tions were performed at a catalyst loading of 1 mol% for 3 h
under the optimised catalytic conditions of temperature
(1108C) and solvent (0.3 mL toluene) found for the catalytic
system [Cp*IrCl2]2/NaOtBu.[12d] by using an excess of 20 mol%
of benzyl alcohol, and the results are summarised in
First, an iridium alkoxo species is generated from complex 2
and the alcohol in the presence of the base. Then, b-H elimina-
tion yields the neutral hydride intermediate and the carbonyl
compound (ketone from secondary alcohols or aldehyde from
primary alcohols). At this point, in the absence of a hydrogen
Chem. Eur. J. 2015, 21, 17877 – 17889
www.chemeurj.org
17880
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
and 6) were less effective than Cs2CO3, whereas KOtBu (Table 2,
entry 8) gave a similar conversion. However, a weaker base,
such as NaHCO3, was completely inefficient (Table 2, entry 7).
As it could be expected, only a marginal conversion was at-
tained without the iridium catalyst (Table 2, entry 9). The b-al-
kylation reactions gave the b-alkylated alcohol with moderate
selectivity because the half-reduced ketone product was pro-
duced to some extent. Thus, the highest 1,3-diphenylpropan-1-
ol/1,3-dipheynlpropan-1-one ratio (A/B) was attained when
using Cs2CO3 as base (71:29, Table 2, entry 1). The temperature
strongly influences the catalytic activity. Although the catalytic
performance was only slightly improved at 1308C, both the
conversion and the selectivity dropped when the reaction was
carried out at 908C (Table 2, entries 10 and 11). Also, reducing
the concentration by increasing the volume of toluene (1 mL)
gave a moderate conversion while maintaining the selectivity
(Table 2, entry 12) which is in accordance with the observations
made by Yamaguchi et al. for the [Cp*IrCl2]2-catalysed alkyla-
tion of 1-phenylethanol with 1-butanol, although a decrease of
the selectivity was also observed in this system.[23] Benzyl alco-
hol can also be used as solvent giving a similar conversion but
with concomitant formation of 5% of dibenzylether[32] (Table 2,
entry 13). When the catalytic reaction was carried out in benzyl
alcohol under more diluted conditions (1 mL) full conversion
to dibenzylether was achieved within 24 h (Table 2, entry 14).
Finally, the catalytic b-alkylation reaction can be carried out
without solvent although with lower conversions (Table 2,
entry 15).
Scheme 4. b-Alkylation of secondary alcohols with primary alcohols
catalysed by iridium complexes.
Table 2.[12d] It is worth noting that the selectivity is not signifi-
cantly affected by the benzyl alcohol/1-phenylethanol ratio,
however the reactions are somewhat faster when using a
moderate excess of the primary alcohol.
The b-alkylation of 1-phenylethanol catalysed by complex 2
under the standard conditions by using Cs2CO3 as base (1:100
ratio) gave a conversion of 68% of benzyl alcohol (Table 2,
entry 1). The conversion drastically dropped when the reaction
was conducted with a catalyst/base ratio of 1:50. However,
a higher ratio of 1:150 produces no significant increase of the
conversion (Table 2, entries 2 and 3). Thus, the optimum cata-
lyst/base ratio of 1:100 was used in the following experiments.
The b-alkylation reaction proceeds to a much higher conver-
sion with the base Cs2CO3 than with K2CO3 (Table 2, entries 1
and 4). Stronger bases as KOH or KHMDS (Table 2, entries 5
On the basis of the above-described results, the iridium(I)
catalysts featuring different O/N-donor-functionalised N-heter-
ocyclic carbene ligands were evaluated for the b-alkylation of
1-phenylethanol with benzyl alcohol under the optimised cata-
lytic conditions: 1 mol% catalyst loading by using Cs2CO3 as
base (catalyst/base ratio of 1:100) in toluene (3 mL) at 110 8C.
The reaction time required to reach conversions over 90% and
the attained selectivity values are summarised in Table 3.
The iridium(I) complexes 1–8 having functionalised NHC li-
gands were found to be moderately active in the b-alkylation
of 1-phenylethanol with benzyl alcohol. In general, 1-phenyl-
ethanol conversions over 90% were attained in 7–13 h with se-
lectivity values in 1,3-diphenylpropan-1-ol higher than 75%.
The cationic compound [Ir(cod)(NCCH3)(MeIm(2-methoxyben-
zyl))][BF4] (6), having a NHC ligand with a rigid O-functionalised
wingtip, is the most active in the series, with 93% conversion
within 7 h, and also the most selective, with a formation of
86% of 1,3-diphenylpropan-1-ol (Table 3, entry 6). In general,
the catalyst precursors having N-functionalised NHC ligands
are less active than those containing O-functionalised NHC li-
gands. It is worth mentioning that a similar trend had already
been observed for hydrogen-transfer reduction of unsaturated
substrates. However, the catalytic activity of the precursors
having a pyridin-2-ylmethyl wingtip, that is, complexes 3 and
7, is remarkable because it is only slightly lower than that of
precursors 1 and 5 having a 2-methoxyethyl substituent. The
neutral complex [IrBr(cod)(MeIm(2-methoxybenzyl))] (2) also
showed notable catalytic activity reaching a conversion of 92%
within 6 h, although with lower selectivity than complex 6, un-
Table 2. Influence of the base, solvent and temperature in the
b-alkylation of 1-phenylethanol with benzyl alcohol catalysed by
[IrBr(cod)(MeIm(2-methoxybenzyl))] (2).[a]
Entry
Base
Solvent
Cat./base
ratio
Conv.
[%][b]
A/B
ratio
1
2
3
4
5
6
7
8
9[c]
10
11
12
13
14[d]
15
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
1:100
1:50
68
31
69
24
45
60
3
71:29
68:32
77:23
51:49
46:54
47:53
–:–
1:150
1:100
1:100
1:100
1:100
1:100
1:100
1:100
1:100
1:100
1:100
1:100
1:100
KOH
KHMDS
NaHCO3
KOtBu
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
69
2
59:41
–:–
toluene
toluene (1308C)
toluene (908C)
toluene (1 mL)
PhCH2OH
PhCH2OH (1 mL)
-
70
34
46
64
99
55
73:27
56:44
72:28
75:25
–:–
70:30
[a] Reaction conditions: catalyst (0.03 mmol, 1 mol%), 1-phenylethanol
(3 mmol), benzyl alcohol (3.6 mmol) and base (3 mmol) in toluene
(0.3 mL) at 110 8C unless otherwise stated, 3 h. [b] Determined by GC
analysis based on the secondary alcohol by using mesitylene as internal
standard. [c] No catalyst. [d] Product=(PhCH2)2O, 24 h of reaction.
Chem. Eur. J. 2015, 21, 17877 – 17889
www.chemeurj.org
17881
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
alkyl/aryl substituents, but lacking a functionalised NHC ligand,
is inferior both in terms of activity and selectivity under the
same catalytic conditions (Table 3, entries 9 and 10).
Table 3. b-Alkylation of 1-phenylethanol with benzyl alcohol catalysed by
NHC-carbene iridium(I) catalysts having different N- and O-functionalised
NHC ligands.[a,b]
A range of secondary and primary alcohols was selected to
determine the substrate scope under the optimised conditions
by using the more efficient catalyst precursors [IrBr(cod)-
(MeIm(2-methoxybenzyl))] (2) and [Ir(NCCH3)(cod)(MeIm(2-me-
thoxybenzyl))][BF4] (6) both with a rigid O-functionalised
wingtip in the NHC ligand (Table 4).
Entry
Catalyst
Time
[h]
Conv.
[%][b]
A/B
ratio
The b-alkylation of 1-phenylethanol proceeds efficiently with
different para-substituted benzyl alcohols regardless of the
electronic character of the substituent. The cationic catalyst
precursor 6 was somewhat more active than the neutral
precursor 2 also providing a higher selectivity to 1,3-diphenyl-
propan-1-ol. Conversions over 90% were typically reached
after 7–9 h (Table 4, entries 1–7). Interestingly, almost complete
selectivity in the b-alkylated alcohol product was attained
when using catalyst precursor 2 by changing the catalyst/base
ratio to 1:150 (Table 4, entry 2).
1
10
93
74:26
2
3
4
9
13
27
92
91
93
76:24
77:23
75:25
Straight chain alcohols, such as butan-1-ol and 3-phenyl-
propan-1-ol, were also efficient as alkylating agents although
at slightly slower rates with lower selectivity values (Table 4,
entries 8–12). Interestingly no self-condensation products were
observed in any case. As it was observed before, catalyst pre-
cursor 2 allows increasing the selectivity in 1-phenylhexan-1-ol
from 58 to 98% when using a catalyst/base ratio of 1:150
(Table 4, entries 10 and 11).
5
11
96
77:23
The b-alkylation of 1-phenyl-1-propanol with benzyl alcohol
proceeds at lower rate compared to1-phenylethanol exhibiting
also lower selectivity (Table 4, entries 1 and 13). The electronic
effects on the secondary alcohol have also been studied. Thus,
the presence of an electron-withdrawing group negatively af-
fects both the activity and the selectivity as can be seen in the
b-alkylation of 1-(4-bromophenyl)ethanol with benzyl alcohol
(Table 4, entries 1 and 14). However, electron-donating groups
have a positive influence and 1-(4-methylphenyl)ethanol was
efficiently alkylated within 12 h with complete selectivity
without adding an additional base (Table 4, entries 1 and 15).
Propan-2-ol was also successfully alkylated by using benzyl
alcohol and butan-1-ol derivatives although with moderate se-
lectivity values (Table 4, entries 16–21). Again, a notable selec-
tivity improvement was observed when the amount of Cs2CO3
was raised until 150 mol%. Under these conditions, the b-alky-
lation of 2-propanol with butan-1-ol catalysed by complex 6
gave a conversion of 94% within 10 h with a selectivity of
99% for heptan-2-ol (Table 4, entry 22). A similar reactivity
trend was observed in the b-alkylation of 4-phenylbutan-2-ol.
Thus, benzyl alcohol derivatives reacted faster than straight
chain alcohols with selectivity values around 65% in both
cases (Table 4, entries 23–29). Notably, the increase of the
amount of Cs2CO3 to 150 mol% allowed to reach a selectivity
of 98% in 1-phenyloctan-3-ol (Table 4, entry 29).
6
7
7
93
92
86:14
78:22
10
8
9
24
9
91
54
76:24
67:33
10
9
12
43:57
[a] Reaction conditions: catalyst (0.03 mmol, 1 mol%), 1-phenylethanol
(3 mmol), benzyl alcohol (3.6 mmol) and Cs2CO3 (3 mmol) in toluene
(0.3 mL) at 110 8C for 3 h. [b] Determined by GC analysis based on the
secondary alcohol by using mesitylene as internal standard.
The b-alkylated alcohols from the catalytic runs giving
a high selectivity (Table 4, entries 2, 11, 22 and 29, respectively)
have been isolated as colourless oils in 70–85% yield after pu-
rification by chromatography column (see the Supporting In-
formation).
derlining the positive effect of the rigid 2-methoxybenzyl
wingtip on the catalytic activity. It is noteworthy that the
catalytic performance of related iridium(I) complexes, such as
[IrCl(cod)(IMe)] (9) and [IrCl(cod)(IPr)] (10), with small and big
Chem. Eur. J. 2015, 21, 17877 – 17889
www.chemeurj.org
17882
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
(B), were formed immediately after thermal equilibra-
tion of the reaction mixture with no apparent induc-
tion period (Figure 2). Interestingly, accumulation of
the half-reduced ketone product B was observed
during the first 2 h of reaction, which suggests that
the reduction of product B is slower than the reduc-
tion of the a,b-unsaturated ketone product resultant
from the cross-condensation process, which was no
detected under these experimental conditions
(Scheme 4). On the other hand, the reaction profile
also justifies the low selectivity observed in the
tandem reaction at short reaction times and the posi-
tive influence of an excess of base on the selectivity,
because quantitative conversion and complete selec-
tivity to product A was achieved in less than 6 h by
Table 4. b-Alkylation of secondary alcohols with primary alcohols catalysed by the iri-
dium(I) complexes 2 and 6 having an NHC ligand with a 2-methoxybenzyl substituen-
t.[a,b]
Time
[h]
Conv.
[%]
Entry
Cat.
A/B ratio
1
2
3
4
5
2
9
9
7
9
7
92
97
93
92
93
76:24
2[c]
6
99:1 (81%)[d]
86:14
2
6
74:26
85:15
6
7
8
9
2
6
2
6
9
7
91
94
92
91
77:23
83:17
72:28
82:18
12
10
using
a catalyst/1-phenylethanol/KHMDS ratio of
10
11
12
2
11
11
10
91
92
92
58:42
1:10:15.
2[c]
6
98:2 (78%)[d]
64:36
Mechanistic studies
13
14
15
2
2
2
12
12
12
89
93
99
65:35
The mechanism of the transition-metal-catalysed b-al-
kylation of secondary alcohols with primary alcohols
combines the hydrogen-transfer oxidation of both al-
cohols with the reduction of the resulting unsaturat-
ed product (Scheme 4). In the catalytic cycle, the hy-
drogen atom of the substrate is transferred to
a metal catalyst generating a transient metal–hydride
species, which is delivered to the unsaturated species
after the CÀC bond formation, giving back the metal
catalyst (borrowing hydrogen or hydrogen autotrans-
fer). Thus, the metal-catalysed hydrogen transfer pro-
cess plays a fundamental role in the overall catalytic
cycle.
51:49
99:1 (83%)[d]
16
17
2
6
10
9
94
92
62:38
66:34
18
19
20
6
6
6
9
9
92
91
91
69:31
68:32
70:30
10
Late-transition-metal-catalysed transfer hydrogena-
tion of unsaturated substrates can proceed by an
inner-sphere pathway through both monohydride or
dihydride intermediate species. However, in the case
of IrI complexes, the monohydride mechanism seems
to be operative.[33] In fact, we were able to identify
the hydrido intermediate [IrH(cod)(MeIm(2-methoxy-
benzyl))] in the transfer hydrogenation of unsaturat-
ed substrates in 2-propanol/KOH under catalytic con-
ditions. It is thus likely that this species is also a key
intermediate in the borrowing-hydrogen b-alkylation
process. Furthermore, when solutions of complexes 2
or 6 in [D8]toluene were heated in the presence of
benzyl alcohol in basic medium (KHMDS) at 110 8C
for 2 min the formation of molecular hydrogen was
detected at d=4.48 ppm.[24] Interestingly, neither cy-
clooctene nor cyclooctane, the reduction products of
the diene ligand, were detected, which strongly sup-
ports the participation “Ir(cod)” species as intermedi-
ates.
21
22
23
24
6
10
10
11
10
92
94
93
92
54:46
6c
2
99:1 (69%)[d]
65:35
6
69:31
25
26
27
6
6
6
10
9
92
94
91
65:35
65:35
52:48
13
28
29
6
6c
16
18
95
92
61:39
98:2 (85%)[d]
[a] Reaction conditions: catalyst (0.03 mmol, 1 mol%), catalyst/secondary alcohol/
Cs2CO3 ratio of 1:100:100 and primary alcohol (3.6 mmol), in toluene (0.3 mL) at 110 8C
for 3 h. [b] Determined by GC analysis based on the secondary alcohol by using mesi-
tylene as internal standard. [c] Catalyst/base ratio of 1:150. [d] Yield of the isolated b-
alkylated alcohol product A.
The b-alkylation of 1-phenylethanol with benzyl alcohol cat-
alysed by complex 2 in [D8]toluene at 808C by using KHMDS
as base was monitored by 1H NMR spectroscopy. As can be
seen in the conversion versus time plots, both products, that
is, 1,3-diphenylpropan-1-ol (A) and 1,3-diphenylpropan-1-one
In order to ascertain the possible involvement of the transi-
tion-metal catalyst also in the cross-aldol condensation step
leading to the formation of the new CÀC bond, some catalytic
test reactions were carried out. The reaction of 1-phenyletha-
Chem. Eur. J. 2015, 21, 17877 – 17889
www.chemeurj.org
17883
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
product (E)-1,3-diphenylbut-2-en-1-one, resulting from self-con-
densation of the ketone. Both facts stongly support the partici-
pation of the iridium catalyst in the cross-aldol condensation
reaction.
Enolate species are key building blocks in synthetic organic
chemistry for the formation of new carbonÀcarbon and
carbonÀheteroatom bonds.[34] Nowadays, the chemistry and re-
action mechanisms involving enolates have been established,
especially those focused on CÀC bond-formation reactions,
such as aldol condensations.[35] The cross-aldol condensation is
driven by the nucleophilic attack of the enolate, generated
under basic conditions, to the electrophile aldehyde to form
a b-hidroxyketone (Scheme 6).
Figure 2. Time dependence of the b-alkylation of 1-phenylethanol with
benzyl alcohol catalysed by complex 2 (10 mol%). The reaction was
performed in [D8]toluene (0.4 mL) at 808C by using KHMDS as base
(catalyst/1-phenylethanol/benzyl alcohol/base ratio of 1:10:11:15).
nol and benzaldehyde in the presence of complex 2 under the
standard catalytic conditions (1 mol% of complex 2, 100%
Cs2CO3, 1108C, 0.3 mL toluene) for 9 h gave a mixture of prod-
ucts, containing 13% of 1,3-diphenylpropan-1-ol (product A),
75% of 1,3-diphenylpropan-1-one (product B) and 12% of 1,3-
diphenyl-2-propen-1-one (chalcone) (GC analysis, 95% conver-
sion of 1-phenylethanol, Scheme 5a). Interestingly, the reaction
of acetophenone with benzyl alcohol under the same experi-
mental conditions gave a similar mixture. The large amount of
the saturated ketone, that is, 1,3-diphenylpropan-1-one, and
the presence the a,b-unsaturated ketone, never detected in
the catalytic reactions, is in agreement with the deficit in
reduction equivalents due to the presence of a carbonyl
compound as partner. Both catalytic tests reinforce the
participation of transfer-hydrogenation processes from the
alcohols to the unsaturated condensation products.
Scheme 6. Base-catalysed cross-aldol reaction mechanism.
In general, it is widely accepted that the simultaneous
coordination of the enolate and the electrophilic carbonyl
compound to the metal centre is required to enhance both
the reactivity and the stereoselectivity.[36] However, in the
present case, the participation of the pentacoordinated iridium
species of the type [Ir(cod)(MeImZ)(enolate)(aldehyde)] (Z=
benzyloxycarbonyl) is unlikely. In this context, it is worth of
noting the rich chemistry of the square-planar complex
[Ni(CH3)(OC(=CH2)Ph)(dippe)] (dippe=1,2-bis(diisopropylphos-
phino)ethane) having an acetophenone enolate ligand.[37]
A notable finding was that a conversion of 100% to chal-
cone, the cross-aldol condensation product, was attained in
the reaction of acetophenone with benzaldehyde in the pres-
ence of complex 2 under standard catalytic conditions in only
5 h (Scheme 5b). In sharp contrast, when the reaction was con-
ducted without catalyst 2 the aldol condensation reaction pro-
ceeds at lower rate, with only a conversion of 55% of aceto-
phenone after 24 h. GC/MS analysis of the reaction mixture
showed the expected condensation product chalcone in 82%,
but also the products of the base-induced disproportion reac-
tion of benzaldehyde (Cannizzaro reaction) and traces of the
Mechanism of the b-alkylation of alcohols catalysed by
[Ir(cod)(NHC)]+ complexes: DFT studies
The b-alkylation of phenylethanol with benzyl alcohol has
been studied computationally by means of a set of DFT
calculations by using the fragment [Ir(cod)(IMe)] as a model
of [Ir(cod)(MeIm\Z)] (\Z=O- or N-functionalised wingtip) in
the intermediates, which take part in the catalytic cycles.
The b-alkylation model process requires the previous oxida-
tion of benzyl alcohol to benzaldehyde and of phenylethanol
to acetophenone, respectively, by coordination of the respec-
tive alkoxides to the NHC catalyst. The oxidation processes are
almost thermoneutral (ꢀÀ2 kcalmolÀ1 for the formation of
acetophenone and ꢀ +2 kcalmolÀ1 for the formation of ben-
zaldehyde), and they proceed with a similar activation energy
of approximately 25 kcalmolÀ1 (Scheme 7). The resulting
square-planar hydrido complex 11 will react later in the
hydrogenation processes of the a,b-unsaturated ketone
intermediates, which will lead to the final alcohol products.
As it was shown above, the experimental evidence suggests
that the cross-aldol condensation process occurs in the coordi-
nation sphere of the iridium centre. Either the alkoxo complex
[Ir(OR)(cod)(IMe)] (12) or the starting halo-complex [IrBr(co-
Scheme 5. b-Alkylation of alcohols. Catalytic test reactions for mechanistic
studies.
Chem. Eur. J. 2015, 21, 17877 – 17889
www.chemeurj.org
17884
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
ed ketone.[40] The energy profile for the formation of 3-hy-
droxy-1,3-diphenylpropan-1-one described in the Scheme 7 is
presented in Figure 4.
The possible role of the substituent on the NHC ligand in
this step has been further studied by including a 2-methoxy-
benzyl group and re-optimising the transition structure TS14–15
.
Two orientations of the substituent on this full model are pos-
sible depending on its position relative to the iridium coordi-
nation plane. The two possible transition structures have been
found and they differ in less than 0.4 kcalmolÀ1 (see the Sup-
porting Information). Both transition structures have confirmed
by checking their connection to the reaction extrema by IRC
calculations. The activation energies are 22.9 and 23.2 kcal
molÀ1, respectively, and they are almost identical to that found
for the simple model used in the study of the full cycle. This
suggests that the role of the substituent on the NHC ligand is
almost negligible in this step and it must be involved with the
alcohol oxidation process, as previously reported by us,[16a]
which is in full agreement with the experimental results shown
in Table 3 (entries 2 and 6 vs. entry 9).
Scheme 7. Proposed mechanism for the catalytic b-alkylation of secondary
alcohols with primary alcohols leading to the formation of a,b-unsaturated
ketones.
d)(IMe)] (13) can coordinate acetophenone or its enolate af-
fording compound 14. Formation of the unsaturated ketone
can occur through the attack of benzaldehyde on the b-C
atom of the O-bound enolate ligand with an activation energy
of approximately 23 kcalmolÀ1 (TS14–15, Figure 3). The transition
state (TS) TS14–15 has been located by the study of the reverse
process starting form compound 15. IRC calculations show the
connection of this TS with both compound 15 and the O-
bound enolate14. In this context, theoretical[38] and experimen-
tal[39] studies have shown the distinctive reactivity, in the aldol
reaction, of O-bound enolates compared to their possible
C-bound counterparts.
The hydrogenation of the a,b-unsaturated ketone starts by
its coordination to the hydride complex 11, which is formed in
the alcohol oxidation processes (Scheme 7). It is an endother-
mic process leading to a pentacoordinated intermediate with
square-pyramidal coordination geometry. The formulation of
five isomers is possible by coordination through the keto
group or the alkene bond. Coordination through the carbonyl
group would result in the hydrogenation of the C=O bond
leading to an alkoxo–alkene ligand. However, the h2-ketone-
bound complex is 13.5 kcalmolÀ1 above the most stable
isomer where the ligand is p-coordinated through the C=C
bond and the insertion process into the IrÀH bond requires an
activation energy of 11.8 kcalmolÀ1. This pathway represents
a total energy of 25.3 kcalmolÀ1 above the most stable isomer
and around 14 kcalmolÀ1 over the most accessible alternative
transition state. Thus, this is a high-energy process that can be
discarded as a productive pathway.
Notably, in this reaction both intervening O atoms switch
their roles as donor atom. The O atom of the benzaldehyde
molecule ends as an alkoxo group coordinated to the metal
atom, whereas the O atom of the enolate ligand is released
from the coordination sphere. The resulting alkoxo–ketone
ligand in complex 15 is de-coordinated through alcoholysis.
The subsequent hydroxo–ketone is unstable under the reac-
tion condition and eventually dehydrates to the a,b-unsaturat-
The four remaining isomers correspond to the coordination
of the olefinic bond by the two faces and in two possible ori-
entations relative to the hydrido ligand, which occupies the
apical vertex of the idealised square-pyramid coordination
polyhedron 16. All of them show the C=C bond coordinated at
the basal plane with a disposition approximately coplanar with
the IrÀH bond. The four isomers are of similar energy with just
a mere difference of 3.3 kcalmolÀ1 between the most stable
and the one of highest energy. Those coordination modes, for
which the olefin insertion results in the hydride transfer to the
b-C atom with formation of compound 17 with an a-alkyl
ketone ligand, show the lowest activation requirements either
relative to the corresponding isomer (TS16–17 at ꢀ11 kcalmolÀ1
vs. 17–18 kcalmolÀ1 for the hydride transfer to the a-C atom)
or relative to the most stable one. Accordingly, the olefin inser-
tion leading to a b-CÀH bond is kinetically favoured. The re-
sulting a-alkyl ketone complex releases the ketone by alcohol-
ysis, and the alkoxo complex formed re-enters then into the
oxidation cycle, where the starting hydrido complex 11 is re-
generated (Scheme 8 and Figure 5, cycle 1).
Figure 3. Transition state structure TS14–15with some relevant distances.
Chem. Eur. J. 2015, 21, 17877 – 17889
www.chemeurj.org
17885
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
The energy profile shown in Figure 5 is in full
agreement with the experimental observations. The
a,b-unsaturated ketone condensation product has
never been observed because of the accessible
energy barrier for the reduction of the C=C bond.
However, the half-reduced product 1,3-diphenylpro-
pan-1-one is accumulated due to the higher energy
barrier for the reduction of the C=O bond. Interest-
ingly, complete selectivity to 1,3-diphenylpropan-1-ol
can be achieved at longer reaction times or by using
an excess of base. On the other hand, the involve-
ment of the iridium catalyst in the cross-aldol con-
densation process results in the complete selectivity
to the unsaturated ketone product 1,3-diphenyl-2-
propen-1-one likely due the enhancement of the nu-
cleophilic character of the enolate by coordination to
the iridium centre. As a consequence, the attack of
the b-C atom of the activated O-bound enolate to
benzaldehyde is facilitated, which results in the selec-
tive formation of the key alkoxo–ketone species
(Scheme 7). Finally, it should be noted that the hydri-
do iridium species [IrH(cod)(NHC)] (11), which is gen-
erated in the oxidation of both alcohols, is responsi-
ble for the reduction of the a,b-unsaturated ketone
condensation product. Thus, extra addition of hydrogen donor
and acceptor molecules is not required, what makes this base-
dependent catalytic system a highly atom-economic process
with H2O as the only reaction byproduct.
Figure 4. Energy profile for the formation of 3-hydroxy-1,3-diphenylpropan-1-one
through the catalytic cycle proposed in Scheme 7.
The resulting ketone is eventually hydrogenated to its alco-
hol by the hydrido complex 11. Coordination of the 1,3-di-
phenyl-propan-1-one to compound 11 is an endothermic pro-
cess as the pentacoordinated intermediate 18 is 30.1 kcalmolÀ1
above the reactants. The subsequent insertion process requires
an activation energy of 6.7 kcalmolÀ1 through the transition
state TS18–19 to eventually release 1,3-di-phenyl-propan-1-ol by
alcoholysis, which forms an alkoxo complex that turns back
into the alcohol oxidation cycle (Scheme 8 and Figure 5,
cycle 2).
Finally, it is worth mentioning that the results described
herein are in sharp contrast with those previously reported by
GrØe and co-workers on the tandem isomerisation–aldolisation
reaction between allylic alcohols and aldehydes[41] mediated by
an iron catalyst. It has been shown that the role of the iron
catalysts is to promote the allylic alcohol to enol isomerisation
affording the free enol, which adds to the aldehyde
in a carbonyl-ene type reaction.[42] Thus, the aldol
product is formed by reaction between the aldehyde
and the free enol outside the coordination sphere of
the metal centre.
Conclusion
Iridium(I)-cyclooctadiene complexes having a NHC
ligand with a O- or N-functionalised wingtip have
shown to be efficient precatalysts for the Oppenauer-
type oxidation of alcohols and the b-alkylation of sec-
ondary alcohols with primary alcohols. The catalyst
precursors having a NHC ligand with a 2-methoxy-
benzyl wingtip efficiently catalysed the coupling of
a range of secondary alcohols with several para-sub-
stituted benzyl and straight-chain primary alcohols,
in the presence of a base, to produce the corre-
sponding b-alkylated alcohols with moderate selec-
tivity. Interestingly, complete selectivity can be ach-
ieved if a larger excess of the base is used. Experi-
mental mechanistic studies on this hydrogen auto-
transfer process suggest the participation of the iridi-
Scheme 8. Proposed mechanisms for the catalytic reduction of the condensed a,b-un-
saturated ketones.
Chem. Eur. J. 2015, 21, 17877 – 17889
www.chemeurj.org
17886
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Figure 5. Formation of 1,3-diphenylpropan-1-one and 1,3-diphenylpropan-1-ol. Energy profiles for cycles 1 and 2 presented in Scheme 8.
Catalyst synthesis
um catalyst in the cross-aldol condensation reaction, leading
to the a,b-unsaturated ketone product. A theoretical study of
the full reaction mechanism, including both the dehydrogena-
tion, condensation and hydrogenation steps, has been carried
out. DFT calculations have revealed that the key step leading
to the formation of the new CÀC bond proceeds through
a square-planar intermediate having an O-bound enolate, gen-
erated in basic medium, which reacts with the electrophilic al-
dehyde to form a b-alkoxoketone, which is shifted out of the
metal coordination sphere by alcoholysis and dehydrated
under the reaction conditions to the a,b-unsaturated ketone.
On the other hand, it has been found that the substituent on
the NHC ligand has an almost negligible influence in this step
although a significant influence in the alcohol oxidation pro-
cess has been identified.
The iridium(I) complexes containing O- and N-donor-functionalised
NHC ligands [IrX(cod)(MeIm\Z)] (1–4, X=Cl or Br; \Z=2-methox-
yethyl, 2-methoxybenzyl, pyridin-2-ylmethyl and 3-dimethylamino-
propyl) were synthesised by reaction of the corresponding imida-
zolium salt with the dinuclear complex [{Ir(m-OMe)(cod)}2] following
the procedure previously described.[16] The cationic complexes
[Ir(NCCH3)(cod)(MeIm\Z)]BF4 (5 and 6, \Z=2-methoxyethyl and 2-
methoxybenzyl) were prepared by abstraction of the bromido
ligand in the corresponding neutral complexes by AgBF4 in the
presence of acetonitrile. The cationic complexes having the coordi-
nated N-donor set [Ir(cod)(MeIm\Z)]BF4 (7 and 8, \Z=pyridin-2-yl-
methyl and 3-dimethylaminopropyl) were prepared following
a
two-step procedure involving the intermediate NHC–silver
complex and the solvate complex [Ir(cod)(OCMe2)2]BF4.[16]
Oppenauer-type oxidation of alcohols
Experimental Section
The catalytic oxidation reactions were carried out under an argon
atmosphere in thick glass reaction tubes fitted with a greaseless
high-vacuum stopcock. In a typical experiment, the reactor was
charged with a solution of the substrate (3 mmol) in toluene
(0.3 mL), the internal standard (mesitylene, 70 mL, 0.50 mmol), the
hydrogen acceptor (3 mmol), the base (3 mmol) and the catalyst
(0.03 mmol, 1 mol%). The resulting mixture was stirred at room
temperature until complete dissolution of the catalyst and then
placed in a thermostated oil bath at the required temperature, typ-
ically 110 8C. Conversions were determined by using gas chroma-
tography analysis under the following conditions: column temper-
ature=80 (2 min) to 2208C with a heating rate of 108CminÀ1 at
a flow rate of 1 mLminÀ1 by using ultra pure He as carrier gas.
Scientific equipment
1H NMR spectra were recorded on a Bruker Avance 300 (300.1276
and 75.4792 MHz for 1H and 13C, respectively) or on a Bruker
Avance 400 (400.1625 and 100.6127 MHz for H and 13C, respective-
ly) spectrometer. The catalytic reactions were analysed on an Angi-
lent 4890 D system equipped with an HP-INNOWax capillary
column (0.4 mm film thickness, 25 m”0.2 mm i.d.) by using mesity-
lene as internal standard. Organic compounds were identified by
gas chromatography/mass spectrometry (GC/MS) by using an Agi-
lent 6890 GC system with an Agilent 5973 MS detector, equipped
with a polar capillary column HP-5MS (0.25 mm film thickness,
30 m”0.25 mm i.d.).
1
Chem. Eur. J. 2015, 21, 17877 – 17889
www.chemeurj.org
17887
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
b-alkylation of secondary alcohols with primary alcohols
fully acknowledged. J.F.-T. thanks the Spanish MICINN for a pre-
doctoral fellowship. The authors gratefully acknowledge the
resources from the supercomputer “Caesar-Augusta” (node of
the Spanish Supercomputer Network) and the technical
expertise and assistance provided by the BIFI-Universidad de
Zaragoza.
The catalytic b-alkylation reactions of alcohols were carried out
under an argon atmosphere in thick glass reaction tubes fitted
with a greaseless high-vacuum stopcock. In a typical experiment,
the reactor was charged with a solution of the primary alcohol
(3.6 mmol) and the secondary alcohol (3 mmol) in toluene (0.3 mL),
the internal standard (mesitylene, 70 mL, 0.5 mmol), the base
(Cs2CO3, 3 mmol) and the catalyst (0.03 mmol, 1 mol%). The result-
ing mixture was stirred at room temperature until complete disso-
lution of the catalyst and then placed in a thermostated oil bath at
the required temperature, typically 110 8C. Conversions were deter-
mined by using gas chromatography analysis under the following
conditions: column temperature=80 (2 min) to 2208C at a heating
rate of 108CminÀ1 at a flow rate of 1 mLminÀ1 by using ultra pure
He as carrier gas.
Keywords: alcohols · alkylation · heteroditopic NHC ligands ·
iridium · N-heterocyclic carbenes · oxidation
[1] a) Topics of Organometalic Chemistry, Vol. 34: Iridium Catalysis (Ed.: P. G.
Andersson), Springer, Berlin, 2011; b) Iridium Complexes in Organic Syn-
thesis (Eds.: L. A. Oro, C. Claver), Wiley-VCH, Weinheim, 2009; c) S. Gladi-
ali, E. Alberico, Chem. Soc. Rev. 2006, 35, 226–236.
[2] a) O. Prakash, K. N. Sharma, H. Joshi, P. L. Gupta, A. K. Singh, Organome-
tallics 2014, 33, 983–993; b) R. Levy, C. Azerraf, D. Gelman, K. Rueck-
Braun, P. N. Kapoor, Catal. Commun. 2009, 11, 298–301; c) F. Hanasaka,
K.-I. Fujita, R. Yamaguchi, Organometallics 2006, 25, 4643–4647; d) A.
Nait Ajjou, Tetrahedron Lett. 2001, 42, 13–15.
[3] a) Q. Yang, Q. Wang, Z. Yu, Chem. Soc. Rev. 2015, 44, 2305–2329; b) C.
Gunanathan, D. Milstein, Science 2013, 341, 1229712; c) S. Pan, T. Shiba-
ta, ACS Catal. 2013, 3, 704–712; d) G. Guillena, D. J. Ramón, M. Yus,
Chem. Rev. 2010, 110, 1611–1641; e) X. Cui, F. Shi, M. Tse, D. Goerdes, K.
Thurow, M. Beller, Y. Deng, Adv. Synth. Catal. 2009, 351, 2949–2958;
f) M. H. S. A. Hamid, P. A. Slatford, J. M. J. Williams, Adv. Synth. Catal.
2007, 349, 1555–1575.
The reaction mixture was cooled to room temperature and the
solution was passed through a short alumina column in order to
remove the catalyst. The toluene solution was concentrated to
a final volume of 3 mL and then eluted through a silica gel column
by using ethyl acetate/hexane (1:15) as eluent. NMR spectroscopic
data for the b-alkylated alcohol products are given in the Support-
ing Information.
Monitoring of the oxidation of 1-phenylethanol catalysed by
using complex 6
[4] a) W. Bai, G. Jia, Inorg. Chim. Acta 2015, 431, 234–241; b) D. Wang, K.
Zhao, X. Yu, H. Miao, Y. Ding, RSC Adv. 2014, 4, 42924–42929; c) X.
Chang, L. W. Chuan, L. Yongxin, S. A. Pullarkat, Tetrahedron Lett. 2012,
53, 1450–1455; d) C. Xu, L. Y. Goh, S. A. Pullarkat, Organometallics 2011,
30, 6499–6502; e) H. W. Cheung, T. Y. Lee, H. Y. Lui, C. H. Yeung, C. P.
Lau, Adv. Synth. Catal. 2008, 350, 2975–2983; f) R. Martínez, D. J.
Ramón, M. Yus, Tetrahedron 2006, 62, 8982–8987; g) C. S. Cho, B. T. Kim,
H.-S. Kim, T.-J. Kim, S. C. Shim, Organometallics 2003, 22, 3608–3610.
[5] a) Y. Obora, ACS Catal. 2014, 4, 3972–3398; b) S. Bhat, V. Sridharan,
Chem. Commun. 2012, 48, 4701–4703; c) B. Anxionnat, D. G. Pardo, G.
Ricci, J. Cossy, Org Lett. 2011, 13, 4084–4087; d) Y. Iuchi, Y. Obora, Y.
Ishii, J. Am. Chem. Soc. 2010, 132, 2536–2537; e) T. Jensen, R. Madsen, J.
Org. Chem. 2009, 74, 3990–3992; f) Y. M. A. Yamada, Y. Uozumi, Org.
Lett. 2006, 8, 1375–1378; g) C. Lçfberg, R. Grigg, M. A. Whittaker, A.
Keep, A. Derrick, J. Org. Chem. 2006, 71, 8023–8027; h) M. S. Kwon, N.
Kim, S. H. Seo, I. S. Park, R. K. Cheedrala, J. Park, Angew. Chem. Int. Ed.
2005, 44, 6913–6915; Angew. Chem. 2005, 117, 7073–7075; i) K. I.
Fujita, C. Asai, T. Yamaguchi, F. Hanasaka, R. Yamaguchi, Org. Lett. 2005,
7, 4017–4019; j) K. Taguchi, H. Nakagawa, T. Hirabayashi, S. Saka guchi,
Y. Ishii, J. Am. Chem. Soc. 2004, 126, 72–73.
To a solution of [Ir(NCCH3)(cod)(MeIm\Z)]BF4 (6, \Z=2-methoxy-
benzyl) (18 mg, 0.030 mmol) and Cs2CO3 (98 mg, 0.30 mmol) in
[D6]acetone (0.5 mL, NMR tube) was added 1-phenylethanol (36 mL,
0.30 mmol). The reaction progress was monitored by NMR spec-
troscopy at 408C. The conversion of 1-phenylethanol to aceto-
phenone was quantified by integration of the 1H NMR spectrum.
Monitoring of the b-alkylation of 1-phenylethanol with
benzyl alcohol catalysed by complex 2
To
a solution of [[IrBr(cod)(MeImR] (2, R=2-methoxybenzyl)
(17 mg, 0.030 mmol) and potassium hexamethyldisilazide (KHMDS)
(89 mg, 0.45 mmol) in [D8]toluene (0.5 mL, NMR tube) were added
sequentially 1-phenylethanol (36 mL, 0.30 mmol) and benzyl alcohol
(37 mL, 0.36 mmol). The reaction progress was monitored by NMR
spectroscopy at 808C. The conversion of 1-phenylethanol to 1,3-di-
phenyl-1-propanol and 1,3-diphenyl-1-propanone was quantified
1
by integration of the H NMR spectrum.
[6] a) Y. Iuchi, M. Hyotanishi, B. E. Miller, K. Maeda, Y. Obora, Y. Ishi, J. Org.
Chem. 2010, 75, 1803–1806; b) A. E. W. Ledger, P. A. Slatford, J. P. Lowe,
M. F. Mahon, M. K. Whittlesey, J. M. J. Williams, Dalton Trans. 2009, 716–
722; c) R. Grigg, C. Lofberg, S. Whitney, V. Sridharan, A. Keep, A. Derrick,
Tetrahedron 2009, 65, 849–854; d) S. J. Pridmore, J. M. J. Williams, Tetra-
hedron Lett. 2008, 49, 7413–7415; e) M. I. Hall, S. J. Pridmore, J. M. J.
Williams, Adv. Synth. Catal. 2008, 350, 1975–1978; f) M. Morita, Y.
Obora, Y. Ishii, Chem. Commun. 2007, 2850–2852; g) P. A. Slatford, M. K.
Whittlesey, J. M. J. Williams, Tetrahedron Lett. 2006, 47, 6787–6789.
[7] a) T. Matsu-ura, S. Sakaguchi, Y. Obora, Y. Ishii, J. Org. Chem. 2006, 71,
8306–8308; b) C. Carlini, A. Macinai, A. M. Raspolli Galletti, G. Sbrana, J.
Mol. Catal. A 2004, 212, 65–70; c) C. Carlini, M. Di Girolamo, A. Macinai,
M. Marchionna, M. Noviello, A. M. Raspolli Galletti, G. Sbrana, J. Mol.
Catal. A 2003, 204, 721–728.
Calculation details
DFT calculations have been carried out with Gaussian 09[43] by
using the B3PW91 functional with a 6-31G** basis set for all atoms
but Ir where the LANL2DZ basis set and pseudopotential has been
used supplemented with an additional f function.[44] All the minima
have been characterised by frequency calculation. Additionally, the
transition structures have been checked by examining visually the
imaginary frequency and by IRC calculations. The structure in
Figure 3 has been depicted by using CYLview. 1.0b.[45]
[8] a) S. Musa, L. Ackermann, D. Gelman, Adv. Synth. Catal. 2013, 355,
3077–3080; b) I. S. Makarov, R. Madsen, J. Org. Chem. 2013, 78, 6593–
6598; c) D. Srimani, E. Balaraman, B. Gnanaprakasam, Y. Ben-David, D.
Milstein, Adv. Synth. Catal. 2012, 354, 2403–2406; d) D. Spasyuk, S.
Smith, D. G. Gusev, Angew. Chem. Int. Ed. 2012, 51, 2772–2775; Angew.
Chem. 2012, 124, 2826–2829; e) D. Spasyuk, D. G. Gusev, Organometal-
lics 2012, 31, 5239–5242; f) M. Nielsen, H. Junge, A. Kammer, M. Beller,
Angew. Chem. Int. Ed. 2012, 51, 5711–5713; Angew. Chem. 2012, 124,
Acknowledgements
Financial support from the Spanish Ministry of Economy and
Competitiveness (MINECO/FEDER, Project CTQ2013-42532-P),
the MICINN (Project ConsoliderIngenio 2010 CSD2009-00050)
and the Diputación General de Aragón (DGA/FSE-E07) is grate-
Chem. Eur. J. 2015, 21, 17877 – 17889
www.chemeurj.org
17888
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
5809–5811; g) C. Gunanathan, D. Milstein, Acc. Chem. Res. 2011, 44,
588–602; h) S. Musa, I. Shaposhnikov, S. Cohen, D. Gelman, Angew.
Chem. Int. Ed. 2011, 50, 3533–3537; Angew. Chem. 2011, 123, 3595–
3599.
1490–1492; c) K. Fujita, S. Furukawa, R. Yamaguchi, J. Organomet.
Chem. 2002, 649, 289–292.
[24] X.-Y. Yu, B. O. Patrick, B. R. James, Organometallics 2006, 25, 4870–4877.
[25] T. Suzuki, Chem. Rev. 2011, 111, 1825–1845.
[9] a) F. E. Hahn, M. C. Jahnke, Angew. Chem. 2008, 120, 3166–3216; Angew.
Chem. Int. Ed. 2008, 47, 3122–3172; b) C. M. Crudden, D. P. Allen, Coord.
Chem. Rev. 2004, 248, 2247–2273; c) W. A. Herrmann, Angew. Chem. Int.
Ed. 2002, 41, 1290–1309; Angew. Chem. 2002, 114, 1342–1363.
[10] a) L. Benhamou, E. Chardon, G. S. Lavigne Bellemin-Laponnaz, V. CØsar,
Chem. Rev. 2011, 111, 2705–2733; b) E. Peris, Top. Organomet. Chem.
2007, 21, 83–116.
[11] a) G. Lµzaro, V. Polo, F. J. Fernµndez-lvarez, P. García-OrduÇa, F. J.
Lahoz, M. Iglesias, J. J. PØrez-Torrente, L. A. Oro, ChemSusChem 2015, 8,
495–503; b) Q. Zhou, Y.-N. Wang, X.-Q. Guo, X.-H. Zhu, Z.-M. Li, X.-F.
Hou, Organometallics 2015, 34, 1021–1028; c) E. L. Kolychev, S. Kronig,
K. Brandhorst, M. Freytag, P. G. Jones, M. Tamm, J. Am. Chem. Soc. 2013,
135, 12448–12459; d) G. Guisado-Barrios, J. Hiller, E. Peris, Chem. Eur. J.
2013, 19, 10405–10411; e) L. Wu, L. Falivene, E. Drinkel, S. Grant, A.
Linden, L. Cavallo, R. Dorta, Angew. Chem. Int. Ed. 2012, 51, 2870–2873;
Angew. Chem. 2012, 124, 2924–2927; f) E. Peris, R. H. Crabtree in Iridium
Complexes in Organic Synthesis (Eds.: L. A. Oro, C. Claver), Wiley-VCH,
Weinheim, 2009, pp. 39–54; g) I. E. Markò, S. St›rin, O. Buisine, G.
Mignani, P. Branlard, B. Tinant, J. P. Declercq, Science 2002, 298, 204–
206; h) M. S. Sanford, J. A. Love, R. H. Grubbs, Organometallics 2001, 20,
5314–5318.
[12] a) R. Kawahara, K. Fujita, R. Yamaguchi, J. Am. Chem. Soc. 2012, 134,
3643–3646; b) T. Matsu-ura, S. Sakaguchi, Y. Obora, Y. Ishii, J. Org. Chem.
2006, 71, 8306–8308; c) G. Onodera, Y. Nishibayashi, S. Uemura, Angew.
Chem. Int. Ed. 2006, 45, 3819–3822; Angew. Chem. 2006, 118, 3903–
3906.
[13] A. Pontes da Costa, M. Viciano, M. Sanaffl, S. Merino, J. Tejada, E. Peris, B.
Royo, Organometallics 2008, 27, 1305–1309.
[14] D. Gnanamgari, E. L. O. Sauer, N. D. Schley, C. Butler, C. D. Incarvito, R. H.
Crabtree, Organometallics 2009, 28, 1–325.
[26] M. L. S. Almeida, M. Beller, G.-Z. Wang, J.-E. Backvall, Chem. Eur. J. 1996,
2, 1533–1536.
[27] a) M. C. Warner, J.-E. Bäckvall, Acc. Chem. Res. 2013, 46, 2545–2555;
b) B. Martín-Matute, J. B. Šberg, M. Edin, J.-E. Bäckvall, Chem. Eur. J.
2007, 13, 6063–6072; c) B. Martín-Matute, K. Bogµr, M. Edin, F. B.
Kaynak, J.-E. Bäckvall, Chem. Eur. J. 2005, 11, 5832–5842.
[28] G. Guillena, D. J. Ramón, M. Yus, Angew. Chem. Int. Ed. 2007, 46, 2358–
2364; Angew. Chem. 2007, 119, 2410–2416.
[29] R. Yamaguchi, K. Fujita in Ligand Platforms in Homogenous Catalytic Re-
actions with Metals, Wiley, New York, 2015, Chapter 2.
[30] D. Gnanamgari, C. H. Leung, N. D. Schley, S. T. Hilton, R. H. Crabtree, Org.
Biomol. Chem. 2008, 6, 4442–4445.
[31] K. Shimizu, Catal. Sci. Technol. 2015, 5, 1412–1427.
[32] A. Prades, R. Corberµn, M. Poyatos, E. Peris, Chem. Eur. J. 2008, 14,
11474–11479.
[33] a) M. Albrecht, J. R. Miecznikowski, A. Samuel, J. W. Faller, R. H. Crabtree,
Organometallics 2002, 21, 3596–3604; b) O. Pàmies, J.-E. Bäckvall,
Chem. Eur. J. 2001, 7, 5052–5058.
[34] a) N. Ahlsten, A. Bartoszewicza, B. Martín-Matute, Dalton Trans. 2012, 41,
1660–1670; b) T. D. Sheppard, Synlett 2011, 1340–1344.
[35] A. Marrone, A. Renzetti, P. De Maria, S. GØrard, J. Sapi, A. Fontana, N. Re,
Chem. Eur. J. 2009, 15, 11537–11550.
[36] a) M. Sodeoka, Y. Hamashima, Bull. Chem. Soc. Jpn. 2005, 78, 941–956;
b) J. Nokami, T. Mandai, H. Watanabe, H. Ohyama, J. Tsuji, J. Am. Chem.
Soc. 1989, 111, 4126–4127.
[37] J. Cµmpora, I. Matas, P. Palma, E. lvarez, C. Graiff, A. Tiripicchio, Orga-
nometallics 2007, 26, 5712–5721.
[38] Y.-F. Yang, T. Shi, X.-H. Zhang, Z.-X. Tang, Z.-Y. Wen, J.-M. Quan, Y.-D. Wu,
Org. Biomol. Chem. 2011, 9, 5845–5855.
[39] a) J. Cµmpora, C. M. Maya, P. Palma, E. Carmona, E. GutiØrrez-Puebla, C.
Ruiz, J. Am. Chem. Soc. 2003, 125, 1482–1483; b) R.-H. Hsu, J.-T. Chen,
G.-H. Lee, Y. Wang, Organometallics 1997, 16, 1159–1166; c) G. A.
Slough, R. G. Bergman, C. H. Heathcock, J. Am. Chem. Soc. 1989, 111,
938–949.
[40] L. A. Paquette, J. E. Hofferberth, Org. React. 2003, 62, 477–567.
[41] a) A. Bartoszewicz, M. Livendahl, B. Martín-Matute, Chem. Eur. J. 2008,
14, 10547–10550; b) D. Cuperly, J. Petrignet, C. CrØvisy, R. GrØe, Chem.
Eur. J. 2006, 12, 3261–3274; c) D. Cuperly, C. CrØvisy, R. GrØe, Synlett
2004, 93–96; d) M. Uma, M. Davies, C. CrØvisy, R. GrØe, Tetrahedron Lett.
2001, 42, 3069–3172; e) C. CrØvisy, M. Wietrich, V. Le Boulaire, M. Uma,
R. GrØe, Tetrahedron Lett. 2001, 42, 395–398.
[15] A. Bartoszewicz, R. Marcos, S. Sahoo, A. K. Inge, X. Zou, B. Martín-
Matute, Chem. Eur. J. 2012, 18, 14510–14519.
[16] a) M. V. JimØnez, J. Fernµndez-Tornos, J. J. PØrez-Torrente, F. J. Modrego,
S. Winterle, C. Cunchillos, F. J. Lahoz, L. A. Oro, Organometallics 2011,
30, 5493–5508; b) M. V. JimØnez, J. Fernµndez-Tornos, J. J. PØrez-Tor-
rente, F. J. Modrego, P. García-OrduÇa, L. A. Oro, Organometallics 2015,
34, 926–940.
[17] H. Türkmen, T. Pape, F. E. Hahn, B. C¸etinkaya, Eur. J. Inorg. Chem. 2008,
5418–5423.
[18] A. Binobaid, M. Iglesias, D. Beetstra, A. Dervisi, I. Fallis, K. J. Cavell, Eur. J.
Inorg. Chem. 2010, 5426–5431.
[19] For related mechanistic studies on the alkylation of amines with alco-
hols, see: a) A. Bartoszewicz, G. Gonzµlez Miera, R. Marcos, P.-O. Norrby,
B. Martín-Matute, ACS Catal. 2015, 5, 3704–3716; b) D. Weickmann, W.
Frey, B. Plietker, Chem. Eur. J. 2013, 19, 2741–2748; c) P. Fristrup, M.
Tursky, R. Madsen, Org. Biomol. Chem. 2012, 10, 2569–2577; d) D. Bal-
cells, A. Nova, E. Clot, D. Gnanamgari, R. H. Crabtree, O. Eisenstein, Or-
ganometallics 2008, 27, 2529–2535.
[20] a) M. C. Jahnke, T. Pape, E. F. Hahn, Eur. J. Inorg. Chem. 2009, 1960–
1969; b) M. V. JimØnez, J. J. PØrez-Torrente, M. I. BartolomØ, V. Gierz, F. J.
Lahoz, L. A. Oro, Organometallics 2008, 27, 224–234; c) Z. Fei, W. H.
Ang, D. Zhao, R. Scopelliti, E. E. Zvereva, S. A. Katsyuba, P. J. Dyson, J.
Phys. Chem. B 2007, 111, 10095–10108; d) P. Wasserscheid, T. Welton in
Ionic Liquids in Synthesis, Wiley-VCH, Weinheim, 2003; e) D. S. McGuin-
ness, K. J. Cavell, Organometallics 2000, 19, 741–748.
[21] a) D. Xu, S. Wang, Z. Shen, C. Xia, W. Sun, Org. Biomol. Chem. 2012, 10,
2730–2732; b) M. K. Brown, M. M. Blewett, J. R. Colombe, E. J. Corey, J.
Am. Chem. Soc. 2010, 132, 11165–11170; c) G. Maayan, R. Neumann,
Catal. Lett. 2008, 123, 41–45; d) A. N. Ajjou, J.-L. Pinet, Can. J. Chem.
2005, 83, 702–710.
[22] a) K. Fujita, T. Uejima, R. Yamaguchi, Chem. Lett. 2013, 42, 1496–1498;
b) A. Miyata, M. Murakami, R. Irie, T. Katsuki, Tetrahedron Lett. 2001, 42,
7067–7070.
[42] D. Cuperly, C. CrØvisy, R. GrØe, Synlett 2004, 93–96.
[43] Gaussian 09, Revision D.01, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E.
Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Men-
nucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian,
A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara,
K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O.
Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro,
M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Ko-
bayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyen-
gar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B.
Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann,
O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin,
K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg,
S. Dapprich, A. D. Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cio-
slowski, D. J. Fox, Gaussian Inc., Wallingford CT, 2009.
[44] A. Ehlers, M. Bçhme, S. Dapprich, A. Gobbi, A. Hçllwarth, V. Jonas, K.
Kçhler, R. Stegmann, A. Veldkamp, G. Frenking, Chem. Phys. Lett. 1993,
208, 111 –114.
[45] C. Y. Legault, CYLview, 1.0b, (http://www.cylview.org), UniversitØ de
Sherbrooke, 2009.
Received: July 24, 2015
Published online on October 23, 2015
[23] a) F. Hanasaka, K. Fujita, R. Yamaguchi, Organometallics 2005, 24, 3422–
3433; b) F. Hanasaka, K. Fujita, R. Yamaguchi, Organometallics 2004, 23,
Chem. Eur. J. 2015, 21, 17877 – 17889
www.chemeurj.org
17889
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim