Transfer hydrogenation of ketones, nitriles, and esters catalyzed by a half-sandwich complex of ruthenium

Article abstract of DOI:10.1002/cctc.201402780

Half-sandwich complexes [Cp(PiPr₃)Ru(CH₃CN)₂]PF₆ (1; Cp = cyclopentadienyl) and [Cp(phen)Ru(CH₃CN)]PF₆ (2; Cp = pentamethylcyclopentadienyl, phen = phenanthroline) catalyse the transfer hydrogenation of ketones to alcohols, aldimines to amines, and nitriles to imines under mild conditions. In the latter process, the imine products come from the coupling of the amines formed initially with acetone derived from the reducing solvent (isopropanol). Among functionally substituted nitriles, the aldo and keto groups are reduced concomitantly with the cyano group, whereas ester and amido groups are tolerated. Amides and alkyl esters are not reduced under these conditions even upon heating to 70°C. However, phenylbenzoates and trifluoroacetates are reduced to alcohols. Kinetic studies on the reduction of acetophenone in isopropanol established that the reaction is first order in both the substrate and the alcohol. Stoichiometric mechanistic studies showed the formation of a hydride species. A hydride mechanism was proposed to account for these observations.

Full text of DOI:10.1002/cctc.201402780

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DOI: 10.1002/cctc.201402780
Transfer Hydrogenation of Ketones, Nitriles, and Esters
Catalyzed by a Half-Sandwich Complex of Ruthenium
[a]
Sun-Hwa Lee and Georgii I. Nikonov*
Half-sandwich complexes [Cp(PiPr )Ru(CH CN) ]PF (1; Cp=cy-
with the cyano group, whereas ester and amido groups are
tolerated. Amides and alkyl esters are not reduced under these
conditions even upon heating to 708C. However, phenylben-
zoates and trifluoroacetates are reduced to alcohols. Kinetic
studies on the reduction of acetophenone in isopropanol es-
tablished that the reaction is first order in both the substrate
and the alcohol. Stoichiometric mechanistic studies showed
the formation of a hydride species. A hydride mechanism was
proposed to account for these observations.
3
3
2
6
clopentadienyl) and [Cp*(phen)Ru(CH CN)]PF6 (2; Cp*=pen-
3
tamethylcyclopentadienyl, phen=phenanthroline) catalyse the
transfer hydrogenation of ketones to alcohols, aldimines to
amines, and nitriles to imines under mild conditions. In the
latter process, the imine products come from the coupling of
the amines formed initially with acetone derived from the re-
ducing solvent (isopropanol). Among functionally substituted
nitriles, the aldo and keto groups are reduced concomitantly
Introduction
Catalytic transfer hydrogenation (TH) is employed widely for
sis of secondary amines is allowed because of a concomitant
reductive amination of acetone, derived from isopropanol,
[
1]
the reduction of unsaturated organic molecules. In this
[
1,2]
[2,3]
[4]
[14]
method, alcohols,
reduced heterocycles
formates,
aminoboranes and some
with the primary amine formed at the TH stage. To the best
[
2,5,6]
are used as the source of one or
of our knowledge, no example of the TH of esters to either al-
cohols or aldehydes has been reported to date.
more equivalents of hydrogen that is transferred to the sub-
strate usually with the assistance of a catalyst. TH avoids the
high pressures usually required for catalytic hydrogenation but
often requires elevated temperatures. The usual substrates for
Recently, we have shown the application of half-sandwich
complexes of Ru for the chemoselective hydrosilylation of ni-
[
15]
[16]
[17]
[18]
triles, pyridines, acid chlorides and secondary amides
and we have provided some insights into the mechanism of
[
2,3a,7]
TH are ketones and, to a lesser extent, imines.
Other sub-
[
16,19]
strates have been studied much less, and the highly efficient
bifunctional Noyori/Ikariya systems are inactive towards such
potentially sensitive functional groups as ester, sulfone, nitro,
these reactions.
Analysis of the current mechanistic pro-
posals for TH suggested that our Ru systems can also be effi-
[1]
cient catalysts for TH. Therefore, we attempted to verify this
hypothesis, and the results of our studies are reported here,
which includes the coupling of nitriles with isopropanol to
give imines and the first observation of the TH of esters to al-
cohols.
[
1a,e,8]
quinoline etc.
Nevertheless, the TH of some challenging
substrates has been reported. Thus, Elsevier et al. demonstrat-
ed the Pd-catalysed semi-hydrogenation of alkynes by HCO H/
2
[
3a]
NEt3. The reduction of nitro compounds to amines by for-
mates and alcohols was reported by the groups of Beller, Wil-
[
4,9,10]
liams, Sarkar and Gowda.
The TH of heteroaromatics has
Results and Discussion
gained attention in the context of the preparation of biologi-
[
11]
cally active molecules. In contrast, nitriles are not typical sub-
strates for TH and are actually often used as solvents for these
reactions. Only a few and generally low-yielding examples of
Initially,
a
series of half-sandwich complexes of Ru,
[Cp(PiPr )Ru(CH CN) ]PF (1; Cp=cyclopentadienyl), [Cp*(phen)-
3
3
2
6
Ru(CH CN)]PF (2; Cp*=pentamethylcyclopentadienyl, phen=
3
6
[
4,10,12]
nitrile TH to primary amines are known,
exception of the report of Beller and co-workers on the
Ru(p-cymene)Cl ] /1,4-bis(diphenylphosphino)butane (DPPB)
with the notable
phenanthroline), [Cp*(PiPr )Ru(CH CN)]PF (3) and Cp(PiPr )RuH
3 3 6 3 3
(4), were screened as catalysts for the TH of various ketones
[20]
[
and imines in isopropanol in the presence of a base (KOtBu).
2
2
system that catalyses the reduction of aromatic and aliphatic
To our delight, catalytic activity was observed at room tempera-
ture, and the cationic complex 1 showed the best results. In
the case of acetophenone, both good conversion and a high
isolated yield (82%) of 1-phenylethanol were achieved in only
[
13]
nitriles by 2-butanol at 1208C. Beller and co-workers also
found that if the catalyst is changed to RuCl (PPh ) the synthe-
2
3 3
[
a] Dr. S.-H. Lee, Dr. G. I. Nikonov
Chemistry Department, Brock Univeristy
7
0 min (Table 1, entry 1). We found that ketones that bear both
electron-donating and -withdrawing groups, such as methoxy,
amino and chloro groups, can be reduced into the correspond-
ing secondary alcohols with good to high yields (entries 2–4).
Even a sterically hindered substrate, such as benzophenone,
5
00 Glenridge Avenue, St. Catharines, ON L2S 3A1 (Canada)
E-mail: gnikonov@brocku.ca
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201402780.
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react
PhCH=NTs,
PhCH=NC(O)Ph
and
[
a]
Table 1. Transfer hydrogenation of ketones and imines catalysed by 1 and 2.
p-CH OC H C(CH )=NPh failed to produce the
3
6
4
3
desired amines. The latter example of an ace-
tophenone-derived ketimine that has
a strong donating group in the phenyl ring
suggests that sufficient electrophilic activa-
tion of the imine group is required for the
success of TH.
Entry Substrate
Product
1
2
t [h], conversion t [h], con-
[
%]
version [%]
Given the previous success in the applica-
tion of 1 for the chemoselective hydrosilyla-
tion of nitriles and its activity in the TH of
[
b]
[15]
1
2
3
4
70 min, 90 (82)
4.5, 92
ketones, we were interested if this catalytic
system could be applied to the reduction of
nitriles. To our delight, NMR test reactions
with benzonitrile showed that 1 catalyses the
transformation of this substrate in isopropa-
nol to N-phenyl N-isopropylidene effectively
under very mild conditions (Table 2, entry 1).
We believe that this product is obtained
from the TH of nitrile to amine followed by
in situ coupling with the alcohol-derived co-
product, acetone, to furnish the imine. In
contrast, 2 was inactive in this reaction even
at elevated temperatures (708C), whereas 3
and 4 showed comparable activity only upon
heating to 708C. Our research was in prog-
ress when Beller and co-workers reported the
first general protocols for the Ru-catalysed
[
b]
2, 75 (72)
3, 95 (67)
48, 75
29, 97
24, 97
[
b]
[
b]
3.5, 98 (86)
[
b]
5
6
100 min, 97 (60)
7, 95
[13]
TH of nitriles to primary amines and to al-
[14]
kylated secondary amines,
in which the
latter products stem from a domino se-
quence of reduction, coupling with ketone
and hydrogenation. However, both processes
require a high temperature (1208C).
1, 99
4.5, 99
[c]
7
8
–
NR
–
We then examined the substrate scope of
this new catalytic reaction. In all cases imine
products derived from the coupling with ace-
tone were observed in NMR tube reactions.
Given the instability of imines, in preparative-
scale reactions the products were hydrolysed
and precipitated with dry HCl in the form of
ammonium salts. Benzonitrile, which bears
a para-acetyl substituent, initially showed
a fast reduction of the keto group (30 min)
and was reduced fully after 18 h (Table 2,
entry 2). The reaction of electron-rich 4-me-
thoxybenzonitrile also produced the desired
imine in high yield after 18 h (entry 3),
whereas the related TH of para-amino benzo-
nitrile was achieved in only 3 h (entry 4). Sim-
ilar to the previous observation by Beller
[
b]
22, 88 (34)
35 min, 99
9
24, 32
–
[a] 5 mol% Ru catalyst, 10 mol% tBuOK, 0.1 mmol substrate, isopropanol (0.5 mL), room tem-
perature. [b] Isolated yield [%], 1 mmol substrate. [c] Fast decomposition of the catalyst. NR=
No reaction.
[14]
can be hydrogenated in a relatively short time (entry 5) as well
as alkyl ketones (entry 6). However, the attempted reduction of
an aryl ketone that bears the sensitive nitro group resulted in
the rapid decomposition of the catalyst (entry 7). We also ob-
served catalytic TH of an aldimine and a ketimine to secondary
et al., the ester group of ethyl 4-cyanobenzoate was not re-
duced but underwent transesterification with isopropanol,
whereas the cyano moiety was transformed into the imino
group (entry 5). If 4-cyanobenzaldehyde was used as the sub-
strate, full conversion was achieved in 24 h. However, the reac-
tion produced a mixture of several compounds, and the fully
amines
(entries 7
and
8),
whereas
attempts
to
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though a much longer reaction time (three
days) and higher temperature (708C) were re-
quired (entry 8). However, alkyl nitriles that
[
a]
Table 2. TH of nitriles to imines.
bear
a
double bond, both conjugated
(
entry 9) and non-conjugated (entry 10), did
Entry Substrate
Product
t [h] Conversion
%]
not give the reduction products, presumably
because the chelating 1,3-azobutadiene unit
poisons the catalyst and because (E)-pent-3-
enenitrile (entry 10) can isomerise into a conju-
gated system in the presence of a base. A
similar problem has been noted previously in
the hydrosilylation of conjugated unsaturated
[
[
b]
1
5.5 99 (71)
[15]
0.5 99
nitriles by 1. However, valeronitrile was re-
duced to amine, which then coupled with the
acetone formed in situ to give the imine
2
(
entry 11). Further reduction to imine (cf. en-
[
b]
tries 8 and 9 in Table 1) does not occur be-
cause of catalyst decomposition.
18
99 (63)
The catalytic hydrogenation of esters is an
[21]
area of active research. Although hydrogen
is the most attractive reducing agent from an
economic point of view, most of the known
catalysts for ester hydrogenation operate at
high hydrogen pressure (up to 50 atm) and
elevated temperatures (up to 1008C), and
therefore, require the use of special equip-
ment. In this regard, TH offers certain advan-
tages in terms of safety and operational sim-
plicity. To the best of our knowledge, there
have been no reports on the TH of esters by
alcohols, and therefore, we became interested
in the application of 1 in this reaction. Similar
to the reduction of ethyl 4-cyanobenzoate
[
[
b]
b]
3
4
18 99 (65)
3
99 (91)
[
b]
5
18 99 (62)
6
7
24 52
(
Table 2, entry 5), we subjected alkyl esters to
catalytic TH conditions, which resulted only in
transesterification even upon heating to
[
b]
24 99 (91)
[20]
7
08C. However, to our delight, the attempt-
ed TH of phenyl benzoates led to the reduc-
tion to benzyl alcohols (Table 3). The reduc-
tion of 4-methylphenyl benzoate was ach-
ieved at room temperature to give a mixture
of benzyl alcohol and p-cresol as major prod-
ucts (Table 3, entry 1). The formation of
p-cresol was monitored to show full conver-
sion after three days. Interestingly, at this
point the ratio of benzyl alcohol and p-cresol
was 0.7:1 instead of the theoretical ratio of
[
c,d]
[b]
8
9
72 93 (79)
–
–
–
–
NR
NR
[
e]
1
0
11
48 99
[
[
[
a] 5 mol% 1, 10 mol% tBuOK, 0.1 mmol substrate, isopropanol (0.5 mL), room temperature.
b] Isolated yields of ammonium salt after hydrolysis of imine. [c] 708C. [d] 85% in 2 d.
e] 868C.
1
:1, which indicates that there must be
(
an)other, yet unaccounted for byproduct(s)
of this reaction. Phenyl benzoate was convert-
ed into benzyl alcohol in a moderate yield
(
entry 2). In this case, the reaction takes place
reduced product was obtained in only 52% NMR yield
entry 6). Benzonitrile, which has an amide group, was reduced
at 708C but stops after one day. Partial reduction of phenyl 4-
chlorobenzoate was also achieved after one day, but no further
conversion was observed after monitoring for three days
(entry 3). However, a phenyl benzoate derivative that has an
(
selectively under these conditions to the corresponding imine
in high yield, which did not affect the amido functionality
(entry 7). The reduction of nicotinonitrile was also achieved, al-
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underwent rapid transesterification fol-
lowed by the production of the reduc-
tion product, 2,2,2-trifluoroethanol (en-
tries 2 and 3).
[
a]
Table 3. Reactions of esters with isopropanol mediated by 1.
[
b]
Entry Substrate
Product
t [h]
Yield [%]
48
Cumulatively, these results indicate
that: 1) TH is slower than transesterifica-
tion and 2) the reduction is facilitated
by the presence of accepting groups
that enhance the electrophilicity of the
substrate. Furthermore, our studies es-
tablished that the reduction of inactive
phenyl esters can take place only before
the transesterification is complete. A
strong electron-withdrawing group at
1
24
[
d]
2
3
24
24
45
the carbonyl centre, such as F C, can
[
d]
3
15
overcome the donating ability of an
alkyl substituent at the ester oxygen
atom (Table 4, entry 2). However, the re-
action of dimethyl terephthalate
(Table 3, entry 5) produced only the
transesterification product, which sug-
gests that the accepting effect of an
ester group in the para position of
a benzoate is not strong enough to
compensate for the donating effect of
an alkyl group at the oxygen atom.
Overall, the success of ester reduction is
the function of the electrophilicity at
the carbonyl centre.
[
e]
4
5
–
72
NR
20 min 100
[
a] 5 mol% 1, 10 mol% tBuOK, 0.1 mmol substrate, isopropanol (0.5 mL), room temperature. [b] NMR
yield was calculated based on the formation of phenol derivatives. [c] The ratio of benzyl alcohol and
phenol derivatives in isopropanol solution observed by H NMR spectroscopy. [d] 708C. [e] 848C.
The observed reactivity of nitriles and
ketones under mild conditions is very
unusual, which suggests that a new
mechanism may be involved. Previous
1
electron-donating methoxy group was not reduced even after
an extended period of time and heating to 848C (entry 4).
The realisation of the TH of phenyl benzoates but the lack
of reduction for alkyl esters suggests that this catalytic process
requires substrates that are activated electrophilically. We be-
lieve that the difference between the phenyl and alkyl esters
can be then attributed to the difference in electro-
studies on the catalytic reduction of nitriles and pyridines by
silanes suggested the occurrence of an ionic hydrosilylation
[16,19]
mechanism,
so we wondered if any analogy can be drawn
with these previous studies. As our system does not have a co-
[1f,22]
operative or bifunctional ligand,
we considered two possi-
ble reaction pathways. First, in the classical Meerwein–Ponn-
2
3
negativity between the sp - and sp -hybridised
carbon atoms in the phenyl and alkyl esters, re-
spectively, and/or to the mesomeric conjugation of
the phenyl p system with the p orbital of the ester
oxygen atom, which reduces the p donation from
the ester oxygen atom to the carbonyl group and
thus increases its electrophilicity.
[
a]
Table 4. TH of activated acetates.
Entry Substrate
Transesterification t [h], con- Reduction
product
t [h], con-
version [%]
version [%] product
1
2
3
24, 67
24, 13
24, 60
24, 30
To test this hypothesis, activated acetates were
studied. In the case of phenyl acetate, a mixture of
the transesterification and reduction products, iso-
propylacetate (67%) and ethanol (13%), respective-
ly, was obtained after one day at room temperature
2
1
0 min,
00
2
1
0 min,
00
(Table 4, entry 1). We then tried to enhance this me-
diocre activity by introducing electron-withdrawing
groups in the alkyl chain. Indeed, both ethyl and
phenyl trifluoroacetates showed significant reactivi-
ty. Under our catalytic conditions both substrates
[
a] 5 mol% 1, 10 mol% tBuOK, 0.1 mmol substrate, isopropanol (0.5 mL), room tempera-
ture.
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dorf–Verley reduction the hydride is transferred directly from
a hydrogen donor to a hydrogen acceptor if both are attached
[
23]
to the same metal centre. Second, the usual hydride mecha-
nism implies the formation of a metal hydride species from al-
cohol, which then undergoes substrate insertion into the MÀH
[
24,25]
bond.
To distinguish between these two possibilities, a stoi-
chiometric reaction between 1, base and isopropanol in a 1:1:1
ratio in [D ]PhCl was studied at low temperature. A ruthenium
5
hydride complex 5, characterised by the hydride resonance at
d=À10.80 (d, J(HÀP)=40.2 Hz) and presumably formed by
a b-hydride elimination from an alkoxide intermediate, was ob-
served by NMR spectroscopy at À158C, which thus lends some
support to the hydride mechanism. The catalytic reduction of
acetophenone was then studied by using the initial rate analy-
sis. To this end, we performed the reactions under pseudo-
first-order conditions (10- to 30-fold excess of alcohol relative
to acetophenone) and monitored the disappearance of the Me
resonance. Linearisation of the data in the plot of
Àln([ketone]/[ketone] ) versus time established the first-order
0
dependence of the reaction rate on the substrate (Figure 1).
Scheme 1. Proposed hydride mechanism of TH by the pre-catalyst 1.
tent with the observed kinetics and, therefore, is a realistic
working hypothesis.
According to this mechanistic proposal, the hydride spe-
cies 5 undergoes displacement of the second nitrile molecule
by the isopropanol solvent to generate a reactive hydride 6.
II
The latter Ru complex features a combination of a hydridic
RuÀH bond and an OÀH bond acidified by alcohol coordina-
Figure 1. Kinetics of transfer hydrogenation of acetophenone in [D
28C in the presence of 25 equivalents of isopropanol.
5
]PhCl at
tion to the Lewis acidic metal. In analogy with Noyori-type bi-
[1f,22d]
2
functional catalysis,
an unsaturated X=C bond can be re-
duced by a synchronised proton transfer from the OH to the
hard X end (O or N), which thus activates the substrate electro-
philically, followed by hydride transfer to the carbon atom. The
ruthenium alkoxide intermediate thus produced then under-
goes a b-hydride shift, which completes the cycle after the dis-
sociation of acetone.
A plot of the change of the effective rate constant keff
against the amount of isopropanol used afforded a linear de-
pendence, which indicates that the reaction is also first order
[
20]
in the alcohol. Similarly, the amount of the Ru complex was
varied from 4 to 7% with fixed amounts of the substrate and
alcohol (in a 1:35 ratio), which resulted in a linear increase of
the reaction rate, consistent with a catalytic reaction. Finally,
the effect of acetonitrile was tested. The addition of
The difference in reactivity between nitriles and esters then
comes from the different basicity of the X atom. For the more
basic nitrile, activation by forming a H bond with the OH
group is significant, whereas sufficient electrophilic activation
within the substrate is required for the less basic ester.
0
.25–1 equivalents of NCCH3 relative to 1 resulted in a de-
creased rate of reaction. The dependence of the effective rate
constant on the nitrile concentration was then linearised in the
plot of 1/keff versus [NCCH ], which suggests that nitrile dissoci-
3
Conclusion
ation is a step in the overall catalytic cycle. Altogether, these
experiments result in the kinetic law rate=k[Ru][ketone][alco-
hol]/(constant+[nitrile]). However, this kinetic law does not
allow us to underpin the exact sequence of mechanistic
events, and in particular the order in which the alcohol and
substrate add to the catalyst. Nevertheless, taken together
with the outcome of the stoichiometric reactions and by analo-
Ru complexes 1 and 2 catalyse the transfer hydrogenation of
ketones, aldimines and nitriles under mild conditions. Alde-
hydes and ketones are more reactive than nitriles and are re-
duced first, whereas amides and alkyl esters are not hydrogen-
ated even upon heating to 708C. However, more electrophilic
phenyl benzoates and trifluoroacetates can be partially re-
duced to alcohols. Although the efficiency of this reaction is
low, it is the first example of such a reductive transformation
and serves as a proof of principle for further research in this
[
15,16]
gy with the ionic mechanisms studied previously,
the reac-
tion sequence shown in Scheme 1 can be suggested as a possi-
ble mechanistic scenario. This mechanistic proposal is consis-
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area. Mechanistic studies with acetophenone in isopropanol
showed that the reaction is first order in both the substrate
and the alcohol, whereas low-temperature NMR spectroscopy
showed the formation of ruthenium hydride species, which
suggests that a usual hydride mechanism can operate in these
reactions.
matography over silica using 15:1 hexane/ethyl acetate (1% Et N)
3
as the eluent. Benzaldehyde was removed under vacuum to afford
the product PhCH NHPh as a yellow oil (0.062 g, 34% yield).
2
1
H NMR (CH CH(OH)CH , CDCl ): d=7.62 (d, J(HÀH)=7.46 Hz, 2,
3
3
3
Ph), 7.52 (t, J(HÀH)=7.90 Hz, 2, Ph), 7.43 (t, J(HÀH)=7.46 Hz, 1, Ph),
7
6
.29 (t, J(HÀH)=7.46 Hz, 2, Ph), 6.91 (d, J(HÀH)=7.46 Hz, 2, Ph),
.84 (d, J(H-H)=7.46 Hz, 2, Ph), 4.58 ppm (d, J(HÀH)=5.82 Hz, 2,
1
13
CH ); HÀ C HSQC (CDCl ): d=129.5 (s, Ph), 128.4 (s, Ph), 128.2 (s,
2
3
Ph), 127.7 (s, Ph), 117.4 (s, Ph), 113.0 (s, Ph), 48.2 ppm (PhCH ).
2
Experimental Section
All manipulations were performed using conventional high-
vacuum or nitrogen-line Schlenk techniques. Solvents were pre-
dried by using Grubbs-type purification columns and stored in am-
poules equipped with a Teflon valve. Deuterated solvents were
dried over sodium, potassium or CaH2 as appropriate, distilled
under reduced pressure and stored in ampoules with a Teflon
valve. NMR samples were prepared in New Era tubes equipped
with J. Young-type Teflon valves. NMR spectra were recorded by
General procedure for the reduction of nitriles to imines
In a representative procedure, 1 (2.5 mol%) was added to a solu-
tion of PhCN (82.5 mL, 0.8 mmol) and tBuOK (4.48 mg, 0.04 mmol)
in isopropanol (4 mL). The progress of the reaction was monitored
by NMR spectroscopy at RT. The imine PhCH N=C(CH ) was ob-
2
3 2
1
tained as the major product. H NMR (CH CH(OH)CH ): d=7.51 (m,
, Ph), 4.80 (s, 2, CH ), 2.42 (s, 3, CH ), 2.27 ppm (s, 3, CH ); H NMR
2 3 3
3
3
1
5
1
13
using Bruker DPX-300 ( H, 300 MHz; C, 75.4 MHz) and/or Bruker
(
2
C D ): d=7.57 (d, J(HÀH)=6.89 Hz, 2, Ph), 7.35 (t, J(HÀH)=7.16 Hz,
1
13
1
6
6
DPX-600 ( H, 600 MHz; C, 150.8 MHz) spectrometers at 298 K. H
, Ph), 7.24 (t, J(HÀH)=7.42 Hz, 1, Ph), 4.41 (s, 2, PhCH N), 1.97 (s, 3,
13
2
and C NMR spectra were referenced internally to residual protio-
solvent ( H) or solvent ( C) resonances and are reported relative to
1
13
NC(CH ) ), 1.44 ppm (s, 3, NC(CH ) ); HÀ C HSQC (C D ): d=166.0
1
13
3 2
3 2
6
6
(
s, NC(CH ) ), 141.1 (s, Ph), 128.3 (s, Ph), 127.9 (s, Ph), 126.2 (s, Ph),
3 2
tetramethylsilane (d=0 ppm). Chemical shifts are quoted in d
5
5.1 (s, PhCH ), 28.7 (s, NC(CH ) ), 17.6 ppm (s, NC(CH ) ); IR (neat):
2 3 2 3 2
[
ppm], and coupling constants in Hertz. IR spectra were recorded
À1
u (C=N)=1666 cm .
by using a PerkinElmer 1600 FTIR spectrometer as Nujol mulls be-
tween NaCl windows. All chemicals were purchased from Sigma–
Aldrich and Alfa Aesar and were used without further purification.
CDCl3, C D and C D Cl were purchased from Cambridge Isotope
HCl (1m, 1.8 mL) was added to a solution of PhCH
N=C(CH ) and
3 2
2
1 in isopropanol. The mixture was stirred for 1 h after which the
imine was hydrolysed. After the removal of volatiles under
vacuum, a light pink solid was obtained. The solid was washed
6
6
6
5
Laboratories. These NMR solvents were dried over CaH before use.
2
2
-Propanol was dried over molecular sieves (4 ꢁ) overnight and
with hexane and dried. The ammonium salt [PhCH
2
NH
3
]Cl was ob-
tained as a pale yellow solid (0.081 g, 71% yield). H NMR (D O):
O): d=
).
1
used without further purification. CH CN, Et O and hexane were
dried by using a Grubbs-type solvent purification system supplied
by Innovative Technology. Complexes 1, 2, 3 and 4 were prepared
according to literature procedures.
2
3
2
1
13
d=7.39 (m, 5, Ph), 4.10 ppm (s, 2, PhCH
); HÀ C HSQC (D
2
2
À1
129.4 (s, Ph), 43.3 ppm (s, PhCH ); IR (neat): n˜ =3391 cm (NH
2
3
[16b,26–28]
Acknowledgements
General procedure for the reduction of ketones to alcohols
This work was supported by a DG NSERC grant to G.I.N.
In a representative procedure, 1 (2.5 mol%) was added to a solu-
tion of PhCOCH3 (120.2 mL, 1.0 mmol) and tBuOK (11.2 mg,
0
.1 mmol) in isopropanol (4 mL). The progress of the reaction was
Keywords: cyclopentadienyl ligands
ketones · reaction mechanisms · ruthenium
·
hydrogenation
·
monitored by NMR spectroscopy at RT. The alcohol PhCH(OH)CH3
was obtained as the product. After the reaction was completed,
H O was added to the reaction flask to deactivate the catalyst.
Then the precipitate was removed by filtration, and the filtrate was
2
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.37 Hz, 2, Ph), 7.52 (t, J(HÀH)=7.37 Hz, 2, Ph), 7.43 (t, J(HÀH)=
.37 Hz, 1, Ph), 5.09 (q, 1, CH), 1.72 ppm (d, J(HÀH)=6.37 Hz, 3,
1
13
CH ); HÀ C HSQC (CH CH(OH)CH , CDCl ): d=128.1 (s, Ph), 126.7
3
3
3
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s, Ph), 125.4 (s, Ph), 69.1 (s, PhCH(OH)CH ), 25.1 ppm (s,
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In a representative procedure, 1 (2.5 mol%) was added to a solu-
tion of PhCH=NPh (183.3 mg, 1.0 mmol) and tBuOK (11.2 mg,
[
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2
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ÞÞ
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FULL PAPERS
www.chemcatchem.org
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Received: September 28, 2014
Published online on && &&, 0000
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&& – &&
Transfer Hydrogenation of Ketones,
Nitriles, and Esters Catalyzed by
a Half-Sandwich Complex of
Ruthenium
Scope out the scope: Half-sandwich
complexes of Ru catalyze the transfer
hydrogenation of ketones to alcohols,
aldimines to amines, and nitriles to
imines under mild conditions. In the
latter process, the imine products come
from coupling of the amines formed ini-
tially with acetone derived from the re-
ducing solvent (isopropanol).
ꢀ
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