Nickel-catalyzed reduction of ketones with water and triethylsilane

Article abstract of DOI:10.1016/j.ica.2017.06.035

The acetophenone (1a) reduction using catalytically active nickel complexes and water is an efficient and sustainable method to access a new methodology of transfer hydrogenation of ketones. When triethylsilane (Et₃SiH) was used as sacrificial agent to promote the transfer hydrogenation from water, 1-phenylethanol (2a) was obtained in excellent yield along with silanol (Et₃SiOH) as the reaction's driving force. Deuterium labeling studies were made using Et₃SiD or D₂O and these studies showed that both compounds participate as hydride sources for the ketone reduction. A scope of substrates was assessed, including a variety of mono/diketones, and α,β-unsaturated ketones, to yield the corresponding secondary alcohols and saturated ketones. Additionally, asymmetric transfer hydrogenation of mono-ketones was studied for the mixture of nickel/(bisphosphine or phospholane) as catalyst precursor, using H₂O/Et₃SiO system and ethanol as hydrogen sources.

Full text of DOI:10.1016/j.ica.2017.06.035

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Research paper
Nickel-Catalyzed Reduction of Ketones with Water and Triethylsilane
Nahury Castellanos-Blanco, Marcos Flores-Alamo, Juventino J. García
PII:
S0020-1693(17)30762-4
http://dx.doi.org/10.1016/j.ica.2017.06.035
ICA 17684
DOI:
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Inorganica Chimica Acta
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10 June 2017
Please cite this article as: N. Castellanos-Blanco, M. Flores-Alamo, J.J. García, Nickel-Catalyzed Reduction of
Ketones with Water and Triethylsilane, Inorganica Chimica Acta (2017), doi: http://dx.doi.org/10.1016/j.ica.
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017.06.035
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Nickel-Catalyzed Reduction of Ketones with Water and
Triethylsilane
Nahury Castellanos-Blanco, Marcos Flores-Alamo and Juventino J. García*
Facultad de Química, Universidad Nacional Autónoma de México, Circuito Interior, Ciudad
Universitaria, Mexico City 04510, Mexico.
juvent@unam.mx
ABSTRACT
The acetophenone (1a) reduction using catalytically active nickel complexes and water is an
efficient and sustainable method to access a new methodology of transfer hydrogenation of ketones.
When triethylsilane (Et
from water, 1-phenylethanol (2a) was obtained in excellent yield along with silanol (Et
the reaction´s driving force. Deuterium labeling studies were made using Et SiD or D O and these
3
SiH) was used as sacrificial agent to promote the transfer hydrogenation
3
SiOH) as
3
2
studies showed that both compounds participate as hydride sources for the ketone reduction. A
scope of substrates was assessed, including a variety of mono/diketones, and -unsaturated
ketones, to yield the corresponding secondary alcohols and saturated ketones. Additionally,
asymmetric transfer hydrogenation of mono-ketones was studied for the mixture of
nickel/(bisphosphine or phospholane) as catalyst precursor, using H
as hydrogen sources.
2
O/Et SiO system and ethanol
3
Keywords: ketones / water / triethylsilane / nickel / diphosphine / transfer hydrogenation
1

INTRODUCTION
Transfer hydrogenation (TH) of ketones has attracted great attention in recent years due to its
industrial application in the production of a wide range of alcohols and chiral compounds, which are
useful in pharmaceuticals and fine chemicals preparation [1-6]. Compared to the conventional
hydrogenation, which uses highly flammable molecular hydrogen, TH is a safer and atom-efficient
process, in which the reaction solvent (typically alcohols) is the source of hydrogen. TH of ketones
is typically made using isopropanol [7-13] and formate [14-17] as hydrogen donors and the
involved catalysts are regularly based on ruthenium [18-22], rhodium [23-28] and iridium [29-33].
Particularly, TH reactions involving water as hydrogen source are uncommon, due to low solubility
of substrates or instability of ancillary ligands in aqueous media [34-36]. Regarding this, only one
methodology has been reported for the hydrogenation reaction of unsaturated ketones using
magnesium/water system as hydrogen source, under catalytic palladium on activated carbon (Pd/C)
[
37]. As a result, the reaction of H
2
O and Mg forms Mg(OH) to generate hydrogen, used in the
2
hydrogenation of 4-phenyl-3-butene-2-one to obtain 4-phenyl-2-butanone in good yield (93 %).
However, to the best of our knowledge, there are no reports about the use of transition metals in
homogeneous catalysts, that use water, from which the transfer of hydrogen into ketones can be
made.
Closely related examples of metal-mediated hydrogen transfer to unsaturated substrates such as
alkenes or alkynes using water and transition metals (Ni [38], Pd [39-41] and Rh [42]) have been
documented and require a sacrificial agent (S) favoring the hydrogen release by formation of (S=O).
In our search for efficient catalysts for TH processes, we recently reported the reactivity of the
2
complex [(dippe)Ni( -C,C-alkyne)] (dippe: 1,2-bis(di-isopropyl-phosphinoethane), in the presence
of water as hydrogen source [38]. The results showed the selective production of the appropriate
2

cis- or trans- alkene from alkynes, along with Ni(OH) and diphosphine monoxide (dippeO) that
2
correspond to the final fate of oxygen in this reaction. Consequently, the use of a silane as a
sacrificial agent (i.e. triethylsilane) allowed the selective preparation of cis-stilbene in 98 % yield at
1
80 ºC, within 48 h by formation of silanol or triethyldisiloxane.
Nevertheless, in the case of ketones, the search for improved systems that may drive the selective
reduction using simple molecules as hydrogen sources as well as the inexpensive metal-based
catalysts still represents a major challenge.
Therefore, we report herein the reactivity of [Ni(COD) ] (COD = 1,5-cyclooctadiene) and the
2
auxiliary ligand dippe using a variety of ketones in the presence of (a) water and (b)
water/triethylsilane as hydrogen donors. The results show the selective and efficient production of
secondary alcohols from the corresponding ketones and saturated ketones from dienones; overall
the process exhibits a strong dependence on the stoichiometric amount of water and silane.
RESULTS AND DISCUSSION
Catalytic hydrogenation of acetophenone using water as hydrogen donor. We first examinated
the reduction of acetophenone (1a) under similar conditions as studied before for the reduction of
ketones, but using water instead of ethanol as hydrogen source [43].
Thus, treatment of (1a) with water (300 mmol), a variety of solvents (entries 1-5, Table 1) and a
catalytic amount of [Ni(COD)
important dependence on the polarity of solvent as can be seen in Table 1. When the transfer
hydrogenation was initially carried out using H O (1 mL) as hydrogen source and solvent, in the
2
] (2 mol %) and dippe (4 mol %) at 130 ºC for 48 h, exhibited an
2
presence of 1.1 equiv of acetophenone 1a, the conversion was low (entry 1, Table 1), but this
increased with the use of THF, resulting in formation of 15 % of 1-phenylethanol (entry 3). The
reaction performed in nonpolar solvents such as toluene or hexane resulted in poor or null
3

conversions (entries 4 and 5). The inmiscibility of water in these solvents was avoided by using
THF as solvent and increasing the temperature for the process, which resulted in an improvement of
yield (15 %). However, the system gave low yields since dippe produced diphosphine monoxide,
i
i
(
Pr)
2
PCH
2
CH
2
P(O)( Pr)
2
(dippeO) as the final fate of oxygen; therefore, we decided to improve the
SiH (see Table 2) [38-41].
yield of 1-phenylethanol (2a) with the use of Et
3
a
Table 1. Nickel-Catalyzed Transfer Hydrogenation of Acetophenone with Water
b
Entry
Solvent
2a (%)
1
2
3
4
5
Water
Ethanol
THF
6
9
15
Toluene
Hexane
2
-
a
Reaction conditions: 1.1 mmol of substrate, H
2
O (300 mmol), and 1
b
mL of solvent at 130 ºC for 48 h. Yields were determined by GC-MS,
a used as internal standard.
2
Catalytic hydrogenation of acetophenone using Et
3
SiH/H
2
O. The chemoselective reduction of
1
a to produce 2a was possible on using stoichiometric amounts of Et SiH (1.2 equiv), in a good
3
yield (52 %, Table 2, entry 2) compared with the reaction in the absence of silane (15 %, entry 1).
The catalytic system performed very modest using water as solvent and hydrogen donor (entry 4),
but in absence of water (entry 3) the yield of the hydrogenation product 2a was null. Since the
transfer hydrogenation of 1a gave good yields with the use of stoichiometric amounts of Et
3
SiH and
4

water; therefore, we optimized the amount of Et
3
SiH (equiv) and H
2
O (mmol) necessary to produce
2
a (Figure 1).
a
Table 2. Reduction of acetophenone using the Et
3
SiH-H O system
2
Silane
2
H O
b
Entry
Solvent
2a (%)
(equiv)
(mmol)
300
300
-
1
2
3
4
THF
THF
THF
-
15
52
-
1.2
1.2
1.2
H
2
O
300
39
a
2
Unless otherwise noted, the reactions were made using ketone 1a (1.1 mmol), water (300 mmol), [Ni(COD) ] (0.002
b
mmol), dippe (0.004 mmol) and THF (3 mL). Yields were determined by GC-MS, 2a used as internal standard.
According to the results in Figure 1 (a), the TH reaction appears to proceed most efficiently if an
excess of Et SiH is used to achieve full conversion of acetophenone to produce 2a (99 %) and the
use of less than 2.2 equiv gave poor to good yields of 2a (52 -89 %). In addition, the use of 2.2
equiv. of Et SiH and increasing the amount of water (50 to 600 mmol), reached a maximum on
3
3
using 300 mmol (Figure 1 (b)). Both time and temperature for this process were optimized (130 º
C, 2 d) see SI (Figures S1-S2). The improved yields of 2a using water and silane demonstrated that
Et
3
SiH participates as sacrificial agent and hydride source [38, 44-49]. Isotopic labeling
experiments regarding hydride insertion will be presented ahead (vide infra).
5

Figure 1. (a) Effect of silane (equiv) on the TH reaction using 1a (1.1 mmol), H
mL), 130 ºC, and 2 d. (b) Effect of water (mmol) on the TH using 1a (1.1 mmol), Et
3 mL), 130 ºC and 2 d.
2
O (300 mmol), THF (3
3
SiH (2.2 mmol), THF
(
The use of an alternative silane such as Ph
probably due to the increased reactivity and instability of phenylsilane in water [50-53]. Thus, the
combination of Et SiH (2.2 equiv) and water (300 mmol), with [Ni(COD) ] (2 mol %) and dippe (4
3
SiH decreased the yield (Table 3, entries 3 and 4),
3
2
mol %), gave the best catalytic system at 130 ºC for 48 h (Table 3, entry 2) see SI, Figures S4-S5.
a
Table 3. Use of silanes
b
Entry
Silane
(equiv)
1.2
2a (%)
52
1
2
3
4
Et
Et
3
3
SiH
SiH
2.2
99
PhSiH
3
1.2
13
PhSiH
3
2.2
22
a
Unless otherwise noted, the reactions were conducted using ketone 1a (1.1
mmol), water (300 mmol), [Ni(COD) ] (0.002 mmol), dippe (0.004 mmol) and
THF (3 mL). Yields were determined by GC-MS, 2a used as internal standard.
2
b
6

We investigated further on the mechanism of hydride insertion using deuterium oxide (D
Et SiH, considering the mechanistic proposal depicted in Scheme 1. The reaction of [Ni(COD)
with dippe (b) and substrate 1a at room temperature, THF-d , for 24 h gives a mixture of
2
O) and
3
2
] (a)
8
3
1
1
compounds [Ni(dippe)
2
] as a singlet at 53.8 ppm [43, 54-56] (60 %) in P{ H} NMR and two small
2
doublets between 71 and 65 ppm (40 %) with JP-P = 70.36 Hz, characteristic of similar nickel(0)
2
complexes with diphosphine ligands in agreement with  -C=O coordination of ketones proposed
2
for complex [(dippe)Ni( -C,O-acetophenone)] (d) (see SI, Figure S10) [54-56].
The reaction of complexes (c) and (d) with D
2
O and Et
3
SiH at room temperature resulted in the
formation of a small singlet at 3.7 ppm in the H NMR spectra, assigned to OH in 1-phenylethanol
Figure 2); this signal increased at high temperatures (70 ºC, Figure 2). By using this reaction
mixture monodeuterated 1-phenylethanol 2b (C DOH) was obtained at 100 ºC for 15 h in THF-
. On quenching the reaction to the open atmosphere the mass of monodeuterated product was
confirmed (Figure S7). The expected by-products were also confirmed as the deutero-silanol
Figure S6), diphosphine monoxide (dippeO) and diphosphine dioxide (dippeO ) (SI, Figure S10).
We studied next the use of both systems Et SiH/D O or Et SiD/H O with catalytic loads of
Ni(COD) ] and dippe (Table 4), the results confirm that only one deuterium atom was incorporated
in each case (m/z= 123, entries 2-3), to produce 1-phenylethanol in good yields (82 % and 89 %
respectively) compared to the complete protio- system Et SiH/H O (yield 100%), with a m/z= 122
Table 4, entry 1). The fragmentation pattern of each product allowed to establish the position
where deuterium (D) was incorporated (see SI, Figures S7-S8); thus, D from D O was incorporated
SiD was incorporated at the
1
(
8
H
8
d
8
(
2
3
2
3
2
[
2
3
2
(
2
into the quaternary carbon in the carbonyl group of 1a, and D from Et
oxygen of the same group as depicted in Scheme 1.
3
7

Scheme 1. Preparation of monodeuterated 1-phenylethanol
(
2b, OH)
(
2b, Ph)
3
(2b, CH )
1
5 h, 100 ºC
8
h, 70 ºC
(
3
1a, CH )
1
5 h, 50 ºC
(
1a, Ph)
THF-d
8
THF-d
8
0
h, 25 ºC
1
Figure 2. H-NMR spectra of reaction between 1b and D
2
O-Et
3
SiH (THF-d , 300 MHz)
8
8

a
Table 4. Catalytic Hydrogenation of 1a using Deuterated Systems
b
Entry
Deuterated System
1-phenylethanol (%)
m/z
1
2
3
Et
3
SiH-H
SiH-D
SiD-H
2
O
100
89
122
123
123
Et
3
2
O
Et
3
2
O
82
a
Unless otherwise noted, the reactions were conducted using ketone 1a (1.1 mmol), water
300 mmol), silane (2.2 equiv), [Ni(COD) ] (0.002 mmol), dippe (0.004 mmol) and THF (3
mL). Yields were determined by GC-MS, 2a used as internal standard.
(
2
b
To extend the scope of this methodology, TH was found to be applicable to a variety of aromatic
and aliphatic ketones (Table 5). As found, substitution on the benzene rings of the acetophenone
with only one fluorine did not inhibit the reaction (80 %, entry 2), but the poly-fluorobenzenic ring
(
1-(perfluorophenyl)ethanone) severely decreased the yield (entry 3), perhaps due to an increased
– acceptor capacity at the C=O moiety due to the presence of fluorine substituents in the aromatic

ring, making more difficult the oxidative addition of water, vide infra (step D to E Scheme 2). A
good yield was achieved for benzophenone (85 %, entry 5) and in the case of a bulky aliphatic
ketone such as adamantan-2-one, an excellent yield (94 %) was obtained.
9

a
Table 5. Scope of TH reaction
b
b
Entry
Reagent
Product
Conv. 1 (%)
Yield (%)
1
99
99
2
3
80
40
80
40
c
4
100
85
94
85
5
a
Unless otherwise noted, the reactions were conducted using ketone 1a (1.1 mmol), water (300 mmol), silane (2.2
b
equiv), [Ni(COD) ] (0.002 mmol), dippe (0.004 mmol) and THF (3 mL). Yields were determined by GC-MS, 2a
used as internal standard. Hydrosilylation product was obtained in 6 % of yield.
2
c
A mechanistic proposal considering the experimental observations above discussed is presented in
Scheme 2 (vide supra); thus, seems to be likely that transfer hydrogenation proceeds via addition of
H
2
O to form E. Then a hydride addition into the carbonyl moiety produces F, followed by the
addition of Et SiH to release Et SiOH along with the addition of a hydride to yield G (see SI,
Figure S8). The formation of a strong Si-O bond provides the driving force behind the reaction.
3
3
1
0

The resulting nickel-hydride complex undergoes a reductive elimination of the secondary alcohol 2
and further coordination with ketone 1 closes the cycle.
Scheme 2. Proposed Mechanism for TH of ketones with Et
3
SiH-H O system
2
Next, we assessed the chemo-selectivity using closely related substrates (benzyl and -
unsaturated ketones, Tables 6 and 7). The results for benzyl (3a) (Table 6) gave low yield (20%)
1
1

for the reduction product 2-hydroxy-1,2-diphenylethanone (3b) using the previously established
catalytic conditions (entry 1), consequently we investigated the effect of auxiliary ligand, time and
temperature. A good yield and selectivity for 3b was obtained on increasing the temperature to 180
ºC, 48 h (77 %, entry 4), a similar yield was achieved with dcype at 150 ºC (66 %, entry 3).
a
Table 6. Reduction of Benzyl using Et
3
SiH-H O
2
b
b
Entry
Phosphine
dippe
T (ºC)
130
Conv. 3a (%)
3b (%)
3c (%)
1
2
20
52
89
87
20
-
-
52
-
dippe
150
c
3
dcype
150
66
77
c
4
dippe
180
-
a
Unless otherwise noted, the reactions were conducted using ketone 1a (1.1 mmol), water (300
b
mmol), silane (2.2 equiv), [Ni(COD) ] (0.002 mmol), dippe (0.004 mmol) and THF (3 mL). Yields
2
c
were determined by GC-MS, 2a used as internal standard. 1,2-diphenylethanone was obtained in 10
of yield.
%
Then, we explored the reactivity of a variety of -unsaturated ketones (4a-4f, Table 7).
Therefore, [Ni(COD)] , diphosphine dippe and the mixture Et SiH/H O was tested in the reduction
of chalcone 4a. When the reaction was performed at 130 ºC, 72 h, the reduced product 5a (91 %)
was obtained as a main product (Table 7). As expected, the use of a CH substituent instead of a Ph
group in the R position of the enone (4b, Table 7) gave a lower yield (5b, 64 %) due the increased
electron density at the conjugated carbonyl group. When the reaction was performed with other
2
3
2
3
2
1
2

symmetric dienones, such as 1,5-diphenyl-1,4-pentadien-3-ones (4c-4e), the corresponding
saturated ketone was obtained preferably with both, dba (dibenzylideneacetone, 4c) and the
analogous structure using CF
found that dienone 4d with electron-donating substituent OCH
product 6d in high yield (95 %, Table 7). An asymmetric 1-(4-(dimethylamino)phenyl)-5-
3
in para position on the aromatic ring (67 %-5c and 44 %-5e). It was
3
, was selective to yield the conjugate
(
thiophen-2-yl)penta-1,4-dien-3-one, 4f, gives the enone 6f in good yield (87 %) and a saturated
2
ketone in lower yield (13 %, 5f). The use of 4f allowed the isolation of complex [(dippe)Ni( -
C,C -C17H17NOS)] (h) prior to be reduced since the distance C(8)-C(7) 1.325(5) Å is characteristic

for a C=C bond (Figure 4).
The Ni(0) center has a slightly distorted trigonal-planar geometry coordinated to the enone moiety
2
in an  -C,Cway, where the C-C bond length of the olefin in the unsaturated ketone is enlarged
by 0.99 Å upon coordination in compound (h) (1.429 Å) relative to the free ligand (1.328 Å),
similar to closely related complexes previously reported [56]. This complex was also prepared
independently in high yield reacting enone 4f with [(dippe)Ni(-H)] complex (see Experimental
2
Section).
1
3

Table 7. Catalytic hydrogenation of -unsaturated ketones with Et
3
SiH-H O
2
b
Yield (%)

-Unsaturated Ketone
4(a-f)
5(a-f)
6(c-f)
4
a R
1
: Ph R
2
: Ph
: CH
5
a
91 %
4
b R
1
: Ph R
2
3
5b 64 %
4
4
4
c R
d R
e R
1
: H
: p-OCH
: p-CF -Ph
5c 67 %
6c 32 %
5
d
5 %
6d 95 %
6e 34 %
1
3
-Ph
5
e
44 %
1
3
5
f
13 %
6f 87 %
4f
a
Unless otherwise noted, the reactions were conducted using -unsaturated ketones (1.1 mmol), water (300
b
mmol), silane (2.2 equiv), [Ni(COD)
2
] (0.002 mmol), dippe (0.004 mmol) and THF (3 mL). Yields were
determined by GC-MS, 4a used as internal standard.
1
4

2
Figure 4. ORTEP drawing of [(dippe)Ni( -C,C-C17
H
17NOS)] (h), showing 50% probability
ellipsoids. Selected bond distances [Å]: C(10)-C(11) 1.429(5), P(2)-Ni(1) 2.1599(9), P(1)-Ni(1)
2
.1621(9), Ni(1)-C(11) 2.002(3), Ni(1)-C(10) 1.975(3), C(8)-C(7) 1.325(5). Selected bond angles
[
°]: C(10)-Ni(1)-C(11) 42.10(2), C11-Ni(1)-P(1) 110.74(10), P(2)-Ni(1)-P(1) 91.15(3), P(2)-Ni(1)-
C(10) 116.29(10).
Enantioselective Ketone Hydrogenation. Considering the results of a Ni catalyst based on (P-P)
biphosphine ligand we were curious to use asymmetric (P-P) ancillary ligands for this
transformation. Thus, we used commercially available BPE (Bis-Phospholane Ethane) as ligand in
the transfer hydrogenation reaction. The use of [Ni(COD)
O/Et SiH as hydrogen source was investigated in the hydrogenation of a 1-(4-fluorophenyl)-
ethanone 1b to give the corresponding alcohol (S)-2b in good conversion (81 %) with 40 % ee at
50 ºC (Table 8, entry 1). The phospholane ligand (R,R)-BPE was completely inactive in the
2
] complex, (S,S)-BPE ligand and
H
2
3
1
asymmetric hydrogenation of 1b (Table 8, entry 2).
Our group recently reported on the use of nickel/phosphine catalyst for transfer hydrogenation of
ketones using ethanol as a safe and cheap hydrogen source [43]. In the current case, using ethanol as
reactant and solvent, yield a good stereo-induction ((S)-2b, 71 %) (Table 8, entry 3). In a closely
1
5

related report, Liu et al. informed that the complex [IrCp*Cl
2
]
2
catalyzed the transfer hydrogenation
t
of acetophenones with ethanol as the hydrogen donor, but using stoichiometric quantities of BuOK
[
57]. Herein, the reaction proceed in the absence of base. However, the performance of other chiral
bisphosphines was rather modest.
Table 8. Enantioselective reduction of ketones
c
d
Entry
Ligand
Hydrogen Donor
Conv. 1 (%)
ee (%)
a
1
(S,S)-iPr-BPE
Et
Et
3
3
SiH / H
2
O
O
22
2
a
2
(R,R)-iPr-BPE
(S,S)-iPr-BPE
SiH / H
2
0
71
100
72
0
0
b
3
EtOH
EtOH
EtOH
EtOH
71
59
39
0
b
4
(S,S)-iPr-Duphos
(S,S)-Et-Ferrocelane
(S)-BINAP
b
5
b
6
a
Unless otherwise noted, the reactions were conducted using ketone 1b (1.1 mmol), Hydrogen Donor (water (300
b
2
mmol), silane (2.2 equiv)), [Ni(COD) ] (0.002 mmol), (S,S)-BPE (0.003 mmol) and THF (3 mL). The reactions were
conducted using ketone 1b (1.1 mmol), hydrogen donor (ethanol (3 mL)), [Ni(COD)
2
] (0.002 mmol) and (S,S)-Ligand
c
d
(0.003 mmol). Conversions were determined by GC-MS analysis, 2a used as internal standard. Determined by HPLC
using a chiral column, and the configuration was determined as (S).
1
6

CONCLUSIONS
In summary, we have developed a chemoselective transfer hydrogenation of ketones and -
unsaturated ketones catalyzed by [Ni(0)] complexes, using water and triethylsilane as hydrogen
source. This represents an attractive methodology to prepare secondary alcohols from monoketones,
diols from diketones and saturated ketones from -unsaturated enones. Moreover, with
nickel/(S,S)-phospholane catalyst and ethanol as the hydrogen source a monoketone 1b was
hydrogenated to chiral alcohol (S)-2b in good yield and enantio-selectivity.
EXPERIMENTAL SECTION
Unless otherwise noted, all manipulations were performed using standard Schlenk techniques in an
inert-gas/vacuum double manifold or under an argon atmosphere (Praxair 99.998) in an MBraun
UniLab glovebox (1 ppm H
2
O and O
2
). All liquid reagents were purchased as reagent grade and
] were acquired from Aldrich and stored in a
were degassed before use. All ketones and [Ni(COD)
2
glovebox for their use. The enones were prepared by an aldol condensation, following the method
of Masuda et al [58]. The solvents were dried using standard techniques and stored in the glovebox
before use. Deuterated solvents (D
2
O, Et
3
SiD, THF-d
8
, CDCl ) were purchased from Cambridge
3
Isotope Laboratories and were stored under 4 Å molecular sieves for 24 h before use. NMR spectra
were recorded at room temperature on a 300 MHz Varian Unity spectrometer unless otherwise
1
noted. H NMR spectra ( parts per million) are reported relative to the residual protio-solvent.
1
3
1
31
1
C{ H} spectra give the characteristic carbon signal of each solvent. P{ H} NMR chemical shifts
(
 parts per million) are reported relative to external 85% H PO . Coupling constants (J values) are
3
4
given in Hz. The following abbreviations were used for the NMR data: s = singlet; d = doublet; t =
triplet, m = multiplet and br=broad. GC-MS determinations were performed using an Agilent
Technologies G3171A equipped with a column: 5 % phenylmethylsilicone, 30 m * .25 mm * .25
1
7


m. Chiral HPLC analysis was performed on a Waters 1525, UV-visible dual (Waters 2487)
instrument using Chiracel OJ 4.6 * 250 mm 10 m column at 25 ºC and a mixture of HPLC-grade
1
13
1
hexanes and ethanol (90/10) as eluent, flow rate = 0.6 mL/min. H and C{ H} NMR spectra of the
reduction products were obtained in CDCl . Catalytic experiments were carried out in a 100 mL
3
stainless steel Parr, T315SS reactor. Elemental analyses (EAs) were performed by USAI-UNAM
using a PerkinElmer microanalizer 2400.
Reduction of acetophenone (1a) with [Ni(COD)
2
] and dippe, using H
2
O/ Et SiH. In a 150 mL
3
Schlenk flask fitted with a Rotaflo valve, compound 1a (0.065 g, 0.545 mmol, 50 equiv.) was
reacted with [Ni(COD)
equiv.), H
2
] (0.003 g, 0.0109 mmol, 1 equiv.), dippe (0.0057 g, 0.0218 mmol, 2
4
2
O (327 mmol, 3*10 equiv, 5.8 mL) and Et
3
SiH (0.151 g, 1.30 mmol, 1.2 equiv.), using
THF (3 mL) as solvent. Heating was resumed until complete consumption of 1a was reached,
according to GC-MS chromatography, which occurred after 2 days at 130 ºC. Exposing the system
to the open atmosphere quenched the reaction and yellow colored or colorless solutions were
formed. The mix was extracted 3 times with CH
2
Cl
2
(15 mL), dried over Na
2
SO , and concd.
4
Identification of synthetic product (2b) was based on spectroscopic methods.
Deuterium labeling using D
solution of 1a (4.36 mg, 0.036 mmol), [Ni(dippe)
THF-d , and to these was added 100 equiv. of D O (72.76 mg, 3.63 mmol) and 1 equiv. of Et
4.22 mg, 0.036 mmol). The mixture was then heated in a thermostatted silicon oil bath. For the
2
O. A NMR tube with J. Young´s valve was charged in a run with
] (c) (21.14 mg, 0.036 mmol) using 0.7 mL of
SiH
2
8
2
3
(
reaction in THF-d
8
at 100 ºC, the NMR tube was heated and monitored over 15 hours (Figure 2,
2
vide supra) The formation of [(dippe)Ni( -C,O-C
8
8
H O)] (d) and monodeuterated product 2b was
1
31
1
determined by H and P{ H} NMR (Figure 2 and Figure S10, respectively). After this time, the
1
8

tube was opened to uncontrolled atmosphere; the remaining volatiles were removed in vacuum
using an Schlenk line. Formation of a small amount of a green solid was detected during the course
of the reaction, identified as Ni(OH)
2
. The mix was extracted 3 times with CH
2
Cl
2
(15 mL), dried
over Na SO , and concentrated. Identification of (2b), and phosphine oxides were made by GC-MS
2
4
chromatography.
Metal-catalyzed reduction of (1a) with [Ni(COD) ] and dippe using D-labeled systems. (a)
2
2
D O. In a 150 mL Schlenk flask fitted with a Rotaflo valve, charged with 1a (0.065 g, 0.545 mmol,
5
0 equiv.), [Ni(COD)
2
] (0.003 g, 0.0109 mmol, 1 equiv.), dippe (0.0057 g, 0.0218 mmol, 2 equiv.),
4
Et
3
SiH (0.277 g, 2.39 mmol, 2.2 equiv.), D
2
O (327 mmol, 3*10 equiv, 5.95 mL) and THF (3 mL).
The solution was heated with vigorous stirring at 130 ºC during 48 hours. After this, the Schlenk
flask was opened in a well-vented hood prior to workup. A colorless solution was formed. The mix
was extracted 3 times with CH
2
Cl
2
(15 mL), dried over Na
2
SO , and concd. Identification of
4
synthetic product monodeuterated 1-phenylethanol was based on spectroscopic methods. During the
reaction monitoring, yields and conversions were determined by GC-MS chromatography (Table 4,
entry 2). (b) Et
g, 0.545 mmol, 50 equiv.), [Ni(COD)
mmol, 2 equiv.), H
3
SiD. In a 150 mL Schlenk flask fitted with a Rotaflo valve, charged with 1a (0.065
2
] (0.003 g, 0.0109 mmol, 1 equiv.), dippe (0.0057 g, 0.0218
4
2
O (327 mmol, 3*10 equiv, 5.8 mL), Et
3
SiD (0.29 g, 2.4 mmol, 2.2 equiv.) and
THF (3 mL). The solution was heated with vigorous stirring at 130 ºC during 48 hours. After this,
the Schlenk flask was opened in a well-vented hood prior to workup. A colorless solution was
formed. The mix was extracted 3 times with CH
2
Cl
2
(15 mL), dried over Na
2
SO , and concd.
4
Identification of synthetic product monodeuterated 1-phenylethanol was based on spectroscopic
methods. During the reaction monitoring, yields and conversions were determined by GC-MS
chromatography (Table 4, entry 3).
1
9

Catalytic Reduction of Ketones Using [Ni(0)] in the presence of THF. All reactions were made
in a 150 mL Schlenk flask fitted with a Rotaflo valve, typically charged with [Ni(COD) ] (0.022
mmol), dippe (0.044 mmol) and the corresponding ketone (1.1 mmol), silane (2.2 equiv), water
300 mmol) and THF (3 mL). The solution was heated with vigorous stirring at 130 ºC for the
2
(
corresponding reaction time. After this, the reactor was opened in a well-vented hood prior to
workup. Yellow colored or colorless solutions were formed. The mix was extracted 3 times with
CH
2
Cl
2
(15 mL), dried over Na
2
SO , and concd. Identification of synthetic product (2a) was based
4
on spectroscopic methods. During the reaction monitoring, yields and conversions were determined
1
by GC-MS chromatography. Products and intermediates were characterized by H NMR and
1
3
1
C{ H} NMR after column chromatography purification using n-hexanes/THF mixtures using
silica gel.
2
Preparation of [(dippe)Ni( -C,C-C17
H17NOS)] (h). The reaction between C17H17NOS (0.030
5
-5
g, 9.65*10 mol) and [(dippe)Ni(-H)]
2
(0.034 g, 4.81*10 mol) in Methanol-d
4
. (1 mL) yield de
2
mononuclear complex [(dippe)Ni( -C,C-C17
H17NOS)] (h). Immediate effervescence due to the
reductive elimination of H
2
was observed during mixing. The resulting solution was analyzed by
NMR spectroscopy: P{ H} NMR (121.32 MHz, Methanol-d , r.t.) δ =75,12 (d, JP-P =57.02 Hz); δ
at -26 ºC in a drybox allowed the
3
1
1
4
=73,6 (d, JP-P =57.02 Hz). Slow evaporation of Methanol-d
4
+
crystallization of the pure product. [MS-EI , m/z (%) 603 (3 %)].
X-ray structure determination. The crystal for compound (h) was cryoprotected using Paratone-N
and mounted on glass fibers; then, the crystals were immediately cooled at 130 K using Cryojet
cryostream (Oxford Cryosystems device). Diffraction data were collected on an Oxford Diffraction
2
0

Gemini diffractometer with a CCD-Atlas area detector using a radiation source graphite
monochromator, Mo K = 0.71073 Å. CrysAlisPro and CrysAlis RED software packages were used
for data collection and integration [59]. The double pass method of scanning was used to exclude
any noise. The collected frames were integrated by using an orientation matrix determined from the
narrow frame scans. Final cell constants were determined by a global refinement; collected data
were corrected for absorbance by using analytical numeric absorption correction [60] using a
multifaceted crystal model based on expressions upon the Laue symmetry using equivalent
reflections. Structure solution and refinement were carried out with the SHELXS-2014 and
SHELXL-2014 packages [61], WinGX v2014.1 software was used to prepare material for
2
publication [62, 63]. Full-matrix least-squares refinement was carried out by minimizing (Fo –
2
2
Fc ) . All non-hydrogen atoms were refined anisotropically. H atoms attached to C atoms were
placed in geometrically idealized positions and refined as riding on their parent atoms, with C–H =
0
.95– 1.00 Å and with Uiso(H) = 1.2Ueq(C) for aromatic methyne and methylene groups, and
Uiso(H) = 1.5Ueq(C) for methyl groups. Crystal data and experimental details of the structure
determination of h are listed in the Supporting Information (see Table S1 to Table S4 at SI section)
[
62, 63]. Crystallographic data have been deposited at the Cambridge Crystallographic Data Center
number CCDC 1548929. Copies of the data can be obtained free of charge on application to CCDC,
2 Union Road, Cambridge CB2 1EZ, UK. E-mail: deposit@ccdc.cam.ac.uk.
1
ASSOCIATED CONTENT
2
1


Supporting Information available. Includes complete experimental procedures, selected
NMR spectra, and GC-MS determinations of all products. This material is available free of
charge via the Internet.
AUTHOR INFORMATION
Corresponding Author
E-mail: juvent@unam.mx
ACKNOWLEDGMENTS
We thank CONACYT (0178265) and PAPIIT-DGAPA-UNAM (IN-202516) for their financial
support to this work. N.C.-B. thanks CONACYT for a graduate studies grant. Also, we thank Dr.
Alma Arévalo for her technical support.
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2
6

Highlights

ketone reduction

transfer hydrogenation

water and silanes
catalytic process
enantio selectivity


2
7

2
8