Asymmetric hydrogenation reactions with Rh and Ru complexes bearing phosphine-phosphites with an oxymethylene backbone

Article abstract of DOI:10.1016/j.tetasy.2014.04.001

Phosphine-phosphites 3a and 3b, derived from diphenylhydroxymethyl phosphine have been prepared. From these ligands [Rh(COD)(3a)]BF₄ 5a and RuCl₂(3b)[(S,S)-DPEN] 6b (DPEN = 1,2-diphenylethylenediamine) were synthesized and their stru

Full text of DOI:10.1016/j.tetasy.2014.04.001

Tetrahedron: Asymmetry 25 (2014) 744–749
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Asymmetric hydrogenation reactions with Rh and Ru complexes
bearing phosphine–phosphites with an oxymethylene backbone
⇑
Patryk Kleman, Mónica Vaquero, Inmaculada Arribas, Andrés Suárez, Eleuterio Álvarez, Antonio Pizzano
Instituto de Investigaciones Químicas, Consejo Superior de Investigaciones Científicas and Universidad de Sevilla, c/Américo Vespucio 49, Isla de la Cartuja, 41092 Sevilla, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 January 2014
Accepted 3 April 2014
Phosphine–phosphites 3a and 3b, derived from diphenylhydroxymethyl phosphine have been prepared.
From these ligands [Rh(COD)(3a)]BF4 5a and RuCl2(3b)[(S,S)-DPEN] 6b (DPEN = 1,2-diphenylethylenedi-
amine) were synthesized and their structure determined by X-ray diffraction. Ligands 3 are characterized
by a small bite angle of 83°. In addition, 5a led to an active catalyst for the hydrogenation of olefins, giving
enantioselectivities of up to 96% ee. Likewise, compound 6b showed good activity and enantioselectivity
in the hydrogenation of N-1-phenyl ethylidene aniline and a completed reaction at S/C = 500 in 24 h with
83% ee.
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
hydrogenations.10g,12b In a continuation of this and as a comple-
ment to our previous work with ligands of types 1 and 2, we herein
Chiral phosphine–phosphite ligands are an important class of
ligands for asymmetric catalysis.1 From the initial application of
BINAPHOS in the asymmetric hydroformylation of olefins,2 a broad
range of ligands have been prepared and tested in diverse catalytic
reactions, exhibiting a wide scope.3–9 Regarding hydrogenation,
the application of phosphine–phosphites has led to efficient Rh,10
Ir11 or Ru12 catalysts being developed for the reduction of C@C
and C@N bonds, suitable not only for test substrates, but for more
synthetically relevant ones as well.13
Considering the potential for ligand tuning that phosphine–
phosphites allow, studies on the influence of the main ligand fea-
tures in a catalytic reaction would be important with regard to
the catalyst optimization process. In recent years we have prepared
report a study dealing with oxymethylene bridged ligands 3. These
compounds are particularly appealing from a synthetic perspec-
tive, since the corresponding hydroxyphosphine, which is the most
demanding component in the synthesis of phosphine–phosphites,
can easily be prepared in one step and high yield from diphenyl-
phosphine and formaldehyde.16 Thus, we have also reported on
the synthesis and performance of ligands 3 in several representa-
tive enantioselective hydrogenation reactions, while complemen-
tary structural information has also been obtained by X-ray
crystallography studies on their coordination complexes.
2. Results and discussion
a
library of phosphine–phosphites which possess a C–C–O
Initially, phosphine–phosphites 3a and 3b were obtained by
condensation of diphenylhydroxymethylphosphine with chloro-
phosphites 4a and 4b, respectively (Scheme 1). These compounds
were characterized by the usual analytical and spectroscopic tech-
niques and the data obtained are in accordance with the proposed
structures. Among the characterization data it should be high-
lighted that ligands 3 are characterized by two doublets in the
backbone as a common feature. Thus, ligands 1 and 2 (Fig. 1) are
characterized by oxyphenylene and oxyethylene bridge substitu-
ents, respectively. The nature of the backbone in these phos-
phine–phosphites greatly influences the conformational mobility
of the coordinated ligand and the orientation of the phosphine sub-
stituents, which may have a profound influence on the catalysis.14
In connection with this, Bakos et al. reported on the influence of
the length of the backbone in rhodium catalyzed olefin hydrogena-
tions using BINOL and H8-BINOL based ligands with oxymethylene
to oxybutylene bridges.15 We have also observed that the use of
bulkier, tert-butyl based phosphite fragments, has a profound
effect on the enantioselectivity in diverse olefin and imine
2
31P{1H} NMR with a small JPP coupling constant of ca. 4 Hz.
Research from our laboratory has shown that chiral phosphine–
phosphites have broad application in the rhodium catalyzed
hydrogenation of olefins, while achiral counterparts are also of
interest in the hydrogenation of imines catalyzed by ruthenium
catalysts bearing a chiral diamine as an ancillary ligand.12b Based
upon these precedents, catalyst precursors of formula
[Rh(COD)(3a)]BF4 5a and RuCl2(4a)[(S,S)-DPEN] 6b were prepared
(Scheme 2).
⇑
Corresponding author. Tel.: +34 954489556.
E-mail address: pizzano@iiq.csic.es (A. Pizzano).
http://dx.doi.org/10.1016/j.tetasy.2014.04.001
0957-4166/Ó 2014 Elsevier Ltd. All rights reserved.

P. Kleman et al. / Tetrahedron: Asymmetry 25 (2014) 744–749
745
tBu
R1
tBu
R1
tBu
R1
O
O
O
R2
R2
O
O
R2
R2
O
O
R2
R2
O
O
Ph2P
P
Ph2P
P
Ph2P
P
tBu
R1
tBu
R1
tBu
R1
3
1
2
a: R1 = R2 = Me
b: R1 = tBu, R2 = H
Figure 1. Structure of the phosphine–phosphite ligands.
O
O
PPh2
O
O
NEt3
Cl
P
Ph2P
P
+
O
OH
3
4
tBu
tBu
tBu
tBu
O
O
O
O
O
O
O
P
b
:
=
P
a:
=
P
P
O
tBu
tBu
Scheme 1. Synthesis of oxymethylene bridged ligands 3.
3a
3a
[Rh(COD)2]BF4
[Rh(COD) ]BF4
5a
(i) 3b
Ru(η3-2-Me-C3H4)2(COD)
Ru(Cl)2(3b)[(S,S)-DPEN]
(ii) HCl (2 equiv),
6b
Figure 2. ORTEP view of complex 5a.
(S,S)-DPEN
Scheme 2. Preparation of complexes 5a and 6b.
(b)
(a)
With the intention of obtaining information about the structure
of coordinated ligands 3, complexes 5a and 6b were characterized
by X-ray diffraction. The Rh compound 5a has a square-planar
structure (Fig. 2). The calculation of the distance from the rhodium
atom to the olefin bond centroids gave values of 2.209 and 2.171 Å,
thus reflecting the expected higher trans-influence of the phos-
phite fragment.17 These distances are relatively high considering
the range for diphosphine derivatives, which typically oscillate
between 2.10 and 2.17 Å.18 In contrast to the typical clockwise/
counterclockwise turn observed for the COD derivatives of chiral
diphosphines that minimize the steric interactions,18 the coordina-
tion of COD in 5a showed a displacement of both olefin centroids
above the coordination plane. Thus the C(39) and C(42) olefinic
carbons nearly lie in the equatorial plane. This structural feature,
enabled by the C1 symmetry of the chiral ligand, as well as the rel-
atively long Rh–olefin bonds, can be attributed to the high steric
hindrance caused by both of the phosphorus functionalities of
the phosphine–phosphite ligand, particularly below the coordina-
tion plane by the aryl ring of the biphenyl defined by C(11) and
the edge oriented phenyl substituent defined by C(26). Moreover,
as observed before in the structures of ligands 1a and 2a, the
PPh2 fragment displays a typical propeller-like arrangement of
the phenyl substituents with that above the coordination plane
in a pseudoaxial position and the phenyl below the plane in a
pseudoequatorial position. The structure is characterized by a bite
angle of 82.6 degrees, which is in the range observed for ethane
O
O
109.5
109.5
116.5
105.7
116.5
106.6
P
P
P
P
82.9
82.6
114.7
114.3
Ru
Rh
Figure 3. Angles (degrees) found in the metallacycles formed by 5a (a) and 6b (b).
bridged diphosphines, while being substantially smaller than those
observed for complexes of ligands 1 and 2. The latter typically
range around 90 degrees (e.g. 90.9° in [Ir(COD)(1b)]BF4 and 88.6
in Rh(Cl)(CO)(2a)). In addition, the adoption of the five membered
metallacycle produces values for O-P-Rh and C-P-Rh angles of
114.3° and 106.6°. These values are smaller than those found for
the six membered metallacycle of the aforementioned Ir com-
pound, which show values of 115° and 121°, respectively. Compar-
ison with five membered metallacycles (Fig. 3) defined by
diphosphines indicates the similar values of the angles with the
exception of the P(1)–O(3)–C(25) angle of 116.5° (Fig. 3a), which
is wider than the typical value of 107° for P–C–C fragments in
diphosphines.
On the other hand, the Ru complex shows a distorted octahedral
structure with a cis-arrangement of the chloro ligands. Thus, the
phosphite and one of the chloro ligands occupy the axial positions
while the amine nitrogens, the remaining chloro and the phos-
phine occupy the equatorial plane (Fig. 4). As mentioned in the

746
P. Kleman et al. / Tetrahedron: Asymmetry 25 (2014) 744–749
Table 1
Olefin hydrogenation with [Rh(COD)(P-OP)]BF4 complexesa
Entry
Substrate
P–OP
Conv.
% ee (conf.)d
1
2
3
7a
7b
7c
7b
7c
7d
7e
7d
7e
(R)-3a
(R)-3a
(R)-3a
(S)-3c
(S)-3c
(R)-3a
(R)-3a
(S)-1a
(S)-1a
70
100
100
100
100
50
20
54
100
96 (S)
91 (S)
89 (R)
54 (R)
87 (S)
57 (R)
21 (R)
75 (S)
83 (S)
4c
5c
6b,c
7b,c
8b
9b
a
Reactions were carried out at room temperature with an initial hydrogen
pressure of 4 bar, in methylene chloride at a S/C = 100 unless otherwise noted.
Reaction time 24 h. Conversion was determined by chiral GC.
b
Reactions performed at 20 bar.
c
Reactions performed with the precatalyst prepared in situ.
d
Configurations were determined as previously reported.10c,16b
analogous catalyst of the longer ligand backbone 1a showed that
the proximity between the two phosphorus functionalities in ligand
3a is detrimental for these hydrogenations, since in the three cases
the catalyst bearing ligand 1a provided higher enantioselectivities
(99% ee) for the three olefins. In addition, we were interested in
investigating the influence of the size of the phosphite fragment
in oxymethylene bridged ligands. In this regard, it should be men-
tioned that literature data indicate that a catalyst bearing a BINOL
based ligand 3c, showed a 64% ee in the hydrogenation of methyl
N-acetyl-2-aminocinnamate.15 For the sake of completion we have
generated complex [Rh(COD)(3c)]BF4 in situ and performed the
hydrogenations of methyl N-acetyl-2-aminoacrylate and dimethyl
itaconate under standard conditions. Both reactions showed full
conversion and enantioselectivities of 54% and 87% ee, respectively
(entries 4 and 5). Overall, these values indicate a better perfor-
mance of the catalyst bearing the bulkier phosphite in the hydroge-
nation of the enamides, while similar results for catalysts based on
3a and 3c were obtained in the case of dimethylitaconate. However,
the bulky phosphite group, along with the short backbone, should
render a rather congested metal center that should be detrimental
for catalyst activity, as shown in the uncompleted hydrogenation of
methyl N-acetyl-2-aminocinnamate.
Figure 4. ORTEP view of complex 6b.
structure of 5a, 6b also displays a narrow bite angle of 82.1 degrees
(Fig. 3b). This contrasts, for instance, with the value of ethane
bridged RuCl2(1a)[(R,R)-DPEN], which displays a bite angle of
92.3 degrees. In addition, the structure shows the significant
trans-influence of the phosphite group with the Ru-Cl(1) distance
being appreciably longer than that of the Ru-Cl(2) distance
(2.461 and 2.404 Å, respectively). It is noticeable that despite com-
plexes 5a and 6b having different natures, the parameters of the
metallacycle are very similar.
Complexes 5a and 6b show in the 31P{1H} NMR spectra 2JPP cou-
pling constants, of 39 Hz and 47 Hz, respectively. These values are
significantly lower than constants found in complexes with a
longer backbone. For the sake of comparison, this coupling con-
10g
stant is 61 Hz in [Rh(COD)(1a)]BF4
and 69 Hz in RuCl2(1-
a)[(S,S)-DPEN].12b
We were also interested in comparing the performance of the
catalyst precursor 5a with those based on phosphine–phosphite
ligands 1 in the asymmetric hydrogenation of several representa-
tive olefins (Fig. 5). First, complex 5a showed full conversion and
a 91% ee in the hydrogenation of methyl N-acetyl-2-aminoacrylate
7b under mild conditions (Table 1). In the case of methyl N-acetyl-
2-aminocinnamate 7a the reaction was slower under these condi-
tions (70% conversion), but a higher enantioselectivity of 96% ee
was observed. In addition, the hydrogenation of dimethyl itaconate
also proceeded smoothly with a good enantioselectivity of 89% ee.
Comparison of these results with those obtained with the
O
O
Ph2P
P
O
3c
Compound 5a was also tested against more challenging ena-
mides derived from b-tetralone.19,20 Thus, reactions performed
with 5a were slow, giving conversions of 50% and 20% for 7d and
7e, respectively (entries 6 and 7). For comparative purposes, we
also performed hydrogenations of these substrates using
[Rh(COD)(1a)]BF4. It should be worth noting that this complex pro-
vided a moderate conversion and a respectable 75% ee for substrate
7d (entry 8), while it provided full conversion and a higher enanti-
oselectivity of 83% ee for the 8-methoxy substituted substrate 7e
(entry 9). Therefore, as observed for the previous substrates, the
shortening of the backbone is accompanied by a decrease in
enantioselectivity. Bakos et al. have observed a similar trend for
catalysts based on less sterically demanding BINOL based phos-
phine–phosphites.15
Ph
MeO2C
AcHN
CO2Me
AcHN
CO2Me
CO2Me
7c
7b
7a
OMe
MeO
NHAc
NHAc
On the other hand, the performance of Ru complex 6b in the
hydrogenation of representative imine 7f (Scheme 3) in the
presence of base has also been examined. The reaction performed
at a S/C = 100, following the usual conditions for these reactions
7e
7d
Figure 5. Olefin substrates considered in this study.

P. Kleman et al. / Tetrahedron: Asymmetry 25 (2014) 744–749
747
amine (0.058 g, 0.57 mmol) in toluene (10 mL). Reaction mixture
was stirred for 15 h, the resulting suspension filtered and the solu-
tion obtained evaporated under reduced pressure. The oil obtained
was dissolved in diethyl ether and filtered through a short pad of
neutral alumina. The solution was evaporated to yield 3a as a
N
HN
H2
t
white solid (0.228 g, 80% yield). [a]
20 = À392 (c 1.0, THF); 1H
6b
, K BuO
D
8f
NMR (CDCl3, 400 MHz): d 1.32 (s, 9H, CMe3), 1.42 (s, 9H, CMe3),
2.96 (s, 3H, Me), 1.84 (s, 3H, Me), 2.22 (s, 3H, Me), 2.24 (s, 3H,
Me), 3.70 (ddd, JHP = 4.1, 7.0 Hz, JHH = 12.8 Hz, 1H, PCHH), 4.69
(ddd, JHP = 5.0, 7.4 Hz, JHH = 12.8 Hz, 1H, PCHH), 7.08 (s, 1H, Ar-H),
7.14 (s, 1H, Ar-H), 7.27–7.43 (m, 10H, PPh2); 31P{1H} NMR (CDCl3,
162 MHz): d À14.0 (d, JPP = 4 Hz; PC), 125.4 (d, JPP = 4 Hz; PO);
13C{1H} NMR (CDCl3, 125 MHz): d 16.6 (Me), 16.8 (Me), 20.5
(Me), 20.6 (Me), 31.1 (CMe3), 31.5 (d, JCP = 5 Hz, CMe3), 34.7 (2
CMe3), 63.3 (dd, JCP =15, 3 Hz, PCH2O), 127.9 (CH arom), 128.3
(CH arom), 128.4 (CH arom), 128.5 (CH arom), 128.5 (CH arom),
128.5 (CH arom), 128.7 (CH arom), 129.1 (CH arom), 130.9 (d,
JCP = 2 Hz, Cq arom), 131.7 (d, JCP = 5 Hz, Cq arom), 131.8 (Cq arom),
132.5 (Cq arom), 132.8 (CH arom), 133.0 (CH arom), 133.7 (CH
arom), 133.8 (CH arom), 134.6 (Cq arom), 135.1 (Cq arom), 135.6
(d, JCP = 11 Hz, Cq arom), 136.1 (d, JCP = 11 Hz, Cq arom), 136.9 (Cq
arom), 138.3 (Cq arom), 145.7 (d, JCP = 3 Hz, Cq arom), 145.9 (d,
JCP = 3 Hz, Cq arom); HRMS (EI): m/z 598.2755, [M]+ (exact mass
calcd for C37H44O3P2: 598.2766).
7f
83 % ee
Scheme 3. Hydrogenation of imine 7f.
(i.e. 20 bar of hydrogen, 60 °C and [KOBut]/[Ru] = 100), showed full
conversion and a good enantioselectivity of 83% ee. The catalyst
showed a remarkable activity and was able to complete a reaction
performed at a S/C = 500 in 24 h, without a decrease in the enanti-
oselectivity. Most interestingly, this catalyst outperformed ethyl-
ene bridged complex RuCl2(1a)[(S,S)-DPEN], which showed 72%
conversion and 73% ee at S/C = 100.12b
3. Conclusion
Phosphine–phosphite ligands 3a and 3b have been prepared
and applied in representative olefin and imine asymmetric hydro-
genation reactions. These ligands are characterized by a narrow
bite angle which brings the substituents of both phosphorus func-
tionalities closer thus producing a rather congested metal environ-
ment. The Rh catalyst generated from 5a gave moderate to high
enantioselectivities in the hydrogenation of methyl N-acetyl-2-
aminocinnamate, methyl N-acetyl-2-aminoacrylate, and dimethyl
itaconate, but it did not improve the results provided by the oxy-
ethylene counterpart catalyst. In contrast, the Ru complex bearing
the achiral 3b outperformed the catalyst bearing an oxyethylene
fragment. These results along with the very simple preparation of
diphenylhydroxymethylphosphine, contribute to the interest of
phosphine–phosphites 3 in asymmetric hydrogenation reactions.
4.3. Compound 3b
An ampoule was charged with diphenylhydroxymethylphos-
phine (0.096 g, 0.44 mmol) and chlorophosphite 4b (0.209 g,
0.44 mmol). The solids were dissolved in toluene (15 mL) and tri-
ethylamine was added (0.089 g, 0.88 mmol). The mixture was stir-
red for 24 h, filtered, and brought to dryness. The residue was
dissolved in diethyl ether, passed through a short pad of neutral
alumina and brought to dryness. Ligand 3b was obtained as a white
foamy solid (0.203 g, 70% yield). 1H NMR (CD2Cl2, 500 MHz): d 1.33
(s, 18H, CMe3), 1.42 (s, 18H, CMe3), 4.43 (t, JHP = 5.7 Hz, 2H, PCH2),
7.15 (d, JHH = 2.5 Hz, 2H, Ar-H), 7.27–7.38 (m, 10H, Ar-H), 7.43 (d,
JHH = 2.5 Hz, 2H, Ar-H); 31P{1H} NMR (CD2Cl2, 162 MHz): d À15.5
(d, JPP = 6 Hz, PC), 135.6 (d, JPP = 6 Hz, PO); 13C{1H} NMR (CD2Cl2,
125 MHz): d 31.3 (2 CMe3), 31.8 (2 CMe3), 35.1 (2 CMe3), 35.8 (2
CMe3), 64.4 (d, JCP = 13 Hz, PCH2O), 124.8 (2CH arom), 126.8 (2CH
arom), 128.8 (d, JCP = 7 Hz, 4CH arom), 129.3 (2Cq arom), 132.9
(2Cq arom), 133.4 (d, JCP = 18 Hz, 4CH arom), 136.0 (d, JCP = 12 Hz,
2Cq arom), 140.3 (2Cq arom), 146.5 (d, JCP = 5 Hz, 2Cq arom),
147.3 (2Cq arom); HRMS (EI): m/z 655.3451, [M]+ (exact mass calcd
for C41H53O3P2: 654.3392); Elem. Anal. Calcd for C41H53O3P2 (%): C,
75.20; H, 8.00. Found: C, 75.21; H, 8.09.
4. Experimental
4.1. General
All reactions and manipulations were performed under an
atmosphere of nitrogen or argon, either in a Braun Labmaster
100 glovebox or using standard Schlenk-type techniques. All sol-
vents were distilled under nitrogen with the following desiccants:
sodium-benzophenone-ketyl for diethyl ether (Et2O) and tetrahy-
drofuran (THF); sodium for hexanes and toluene; CaH2 for dichlo-
romethane (CH2Cl2); and NaOiPr for isopropanol (iPrOH).
Ru(COD)(2-methylallyl)2 was prepared as described previously.21
All other reagents were purchased from commercial suppliers
and used as received. IR spectra were recorded on a Bruker Vector
22 spectrometer. NMR spectra were obtained on Bruker DPX-300,
DRX-400, or DRX-500 spectrometers. 31P{1H} NMR shifts were ref-
erenced to external 85% H3PO4, while 13C{1H} and 1H shifts were
referenced to the residual signals of deuterated solvents. All data
are reported in ppm downfield from Me4Si. All NMR measurements
were carried out at 25 °C. HPLC analyses were performed by using
a Waters 2691. HRMS data were obtained on a JEOL JMS-SX 102A
mass spectrometer in the General Services of Universidad de Sevil-
la (CITIUS). Optical rotations were measured on a Perkin–Elmer
Model 341 polarimeter.
4.4. Compound [Rh(COD)(3a)]BF4 5a
A solution of phosphine–phosphite 3a (0.125 g, 0.21 mmol) in
CH2Cl2 (5 mL) was slowly added over a solution of [Rh(COD)2]BF4
(0.081 g, 0.20 mmol) in CH2Cl2 (5 mL) cooled at 0 °C. The reaction
mixture was stirred for 3 h at room temperature, concentrated to
approximately half of the initial volume, and filtered. The resulting
solution was evaporated under reduced pressure and the resulting
solid was purified by recrystallization from a CH2Cl2/Et2O 1:1 mix-
ture, yielding 5a as orange crystals (0.088 g, 47% yield). 1H NMR
(CD2Cl2, 500 MHz): d 1.39 (s, 9H, CMe3), 1.44 (s, 9H, CMe3), 1.76
(s, 3H, Me), 1.86 (s, 3H, Me), 2.01 (m, 1H, CHH, COD), 2.15 (m, 1H,
CHH, COD), 2.28 (s, 3H, Me), 2.31 (s, 3H, Me), 2.39 (m, 5H, CHH,
COD), 2.58 (m, 1H, CHH, COD), 4.32 (m, 1H, @CH COD), 4.60 (m,
2H, @CH COD), 5.27 (m, 1H, @CH COD), 7.27 (s, 1H, Ar-H), 7.28 (s,
1H, Ar-H), 7.63 (m, 10H, PPh2); 31P{1H} NMR (CDCl3, 162 MHz): d
63.7 (dd, JRhP = 153 Hz, JPP = 39 Hz, PC), 156.9 (dd, JRhP = 255 Hz,
JPP = 40 Hz, PO); 13C{1H} NMR (CD2Cl2, 125 MHz): d 16.6 (Me), 16.8
4.2. Compound 3a
A
solution of diphenylhydroxymethyl phosphine (0.103 g,
0.48 mmol) dissolved in toluene (10 mL) was added dropwise over
a solution of chlorophosphite 4a (0.201 g, 0.48 mmol) and triethyl-

748
P. Kleman et al. / Tetrahedron: Asymmetry 25 (2014) 744–749
(Me), 20.4 (Me), 20.5 (Me), 28.7 (CH2), 29.8 (CH2), 30.5 (CH2), 31.7
(CMe3), 31.9 (CH2), 32.2 (CMe3), 35.2 (CMe3), 35.3 (CMe3), 68.4
(dd, JCP = 18, 30 Hz; PCH2O), 97.9 (dd, JCP = 10, 6 Hz, @CH COD),
109.3 (m, 2 @CH COD), 112.2 (dd, JCP = 10, 6 Hz, @CH COD), 126.6
(d, JCP = 43 Hz; Cq arom), 128.8 (d, JCP = 46 Hz; Cq arom), 129.1 (CH
arom), 129.2 (Cq arom), 129.5 (CH arom), 129.7 (Cq arom), 130.3
(CH arom), 130.4 (CH arom), 130.5 (CH arom), 130.6 (CH arom),
132.8 (CH arom), 132.9 (2CH arom), 133.0 (CH arom), 133.1 (CH
arom), 133.2 (CH arom), 134.8 (Cq arom), 135.0 (Cq arom), 136.1
(Cq arom), 136.7 (Cq arom), 137.2 (2Cq arom), 144.2 (d, JCP = 6 Hz;
Cq arom), 144.7 (d, JCP = 14 Hz; Cq arom); Elem. Anal. Calcd for
4.7. Procedure for the hydrogenation of enamides 7d and 7e
In a glovebox, the appropriate olefin (0.042 mmol), phosphine–
phosphite ligand (0.46 lmol), and [Rh(COD)2]BF4 (0.42 lmol) from
freshly prepared stock solutions in CH2Cl2 (total volume = 0.5 mL),
were added to a 2 mL glass vial. Vials were placed in a steel reac-
tion vessel model HEL CAT18 that held up to eighteen reactions.
The reactor was purged three times with H2 and finally pressurized
to the required pressure. In the case of deuteration reactions, the
reactor was purged with Ar, partially evacuated under vacuum,
and filled with D2 at 20 atm. After the desired reaction time, the
reactor was slowly depressurized, the solutions were evaporated
and the conversions were determined by 1H NMR spectroscopy.
The resulting mixtures were dissolved in EtOAc, and filtered
through a short pad of silica to remove catalyst impurities. Enan-
tiomeric excess was analyzed by chiral HPLC, as follows: N-(7-
methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-acetamide 8d: HPLC,
Daicel Chiralcel OJ-H, n-hexane/i-PrOH, 90:10, t1 = 20.6 min,
t2 = 32.9 min; N-(8-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-
acetamide 8e: HPLC, Daicel Chiralcel OJ-H, n-hexane/i-PrOH
90:10, t1 = 12.1 min., t2 = 13.5 min.
C45H56BF4O3P2Rh (%): C, 60.28; H, 6.30. Found: C, 60.05; H, 6.47
4.5. Compound [RuCl2(3b)[(S,S)-DPEN)] 6b
3-2-MeC3H4)2 (0.072 g, 0.20 mmol) and
A solution of Ru(COD)(
g
3b (0.078 g, 0.12 mmol) in n-hexane (5 mL) was heated at reflux
for 5 h. The mixture was evaporated under reduced pressure and
the residue was dissolved in CH2Cl2 (3 mL). The solution was added
dropwise over a solution of (S,S)-DPEN (0.043 g, 0.20 mmol) and
HCl (8 mL, 0.05 M in Et2O) cooled at À20 °C. The resulting mixture
was stirred for 30 min at room temperature, evaporated under vac-
uum, and the residue was purified by column chromatography
using a cyclohexane/Et2O 1:1 mixture to give a yellow solid
(0.057 g, 25%). 1H NMR (CD2Cl2, 500 MHz): d 1.06 (s, 9H, CMe3),
1.12 (s, 9H, CMe3), 1.30 (s, 9H, CMe3), 1.37 (s, 9H, CMe3), 2.99
(m, 1H, NHH), 3.16 (m, 1H, NHH), 3.96 (m, 1H, NHH), 4.11 (m,
1H, NHH), 4.26 (ddd, JHH = 11.8 Hz, JHH = 4.5 Hz, JHH = 4.5 Hz, 1H,
CHNH2), 4.40 (ddd, JHH = 11.8 Hz, JHH = 4.3 Hz, JHH = 4.3 Hz, 1H,
CHNH2), 4.94 (m, 2H, PCH2), 6.95 (m, 3H, 3H arom), 7.07 (m, 4H,
4H arom), 7.13 (m, 6H, 6H arom), 7.31 (m, 3H, 3H arom), 7.36
(m, 4H, 4H arom), 7.72 (m, 4H, 4H arom); 31P NMR (CD2Cl2,
202.5 MHz,): d 69.7 (d, PC, JPP = 47 Hz), 171.9 (d, PO); 13C NMR
(CD2Cl2, 125 MHz): d 30.2 (CMe3), 31.4 (CMe3), 31.5 (CMe3), 31.8
(CMe3), 32.2 (CMe3), 34.7 (d, JCP = 4 Hz, CMe3), 36.6 (CMe3), 36.8
(CMe3), 63.3 (s, 2CH, CHNH2), 67.8 (dd, JCP = 34 Hz, J = 14 Hz,
PCH2), 125.9 (CH arom), 126.2 (CH arom), 127.4 (CH arom), 127.7
(CH arom), 127.8 (2CH arom), 127.9 (2CH arom), 128.5 (2CH arom),
128.6 (CH arom), 128.6 (CH arom), 128.7 (2CH arom), 129.3 (2CH
arom), 129.5 (2CH arom), 130.3 (2CH arom), 131.1 (Cq arom),
131.8 (d, JCP = 3 Hz, Cq arom), 133.6 (CH arom), 133.7 (2CH arom),
133.8 (CH arom), 134.7 (Cq arom), 134.8 (Cq arom), 135.0 (Cq
arom), 135.1 (Cq arom), 140.1 (Cq arom), 140.2 (2Cq arom), 140.5
(Cq arom), 146.6 (d, JCP = 38 Hz, Cq arom), 146.7 (d, JCP = 33 Hz, Cq
arom). Elem. Anal. Calcd for C55H68Cl2N2O3P2Ru (%): C, 63.58; H,
6.60; N, 2.70. Found: C, 63.51; H, 6.81; N, 2.76.
4.8. Hydrogenation of imine 7f
In a glovebox, an HEL pressure reactor (20 mL) was charged
with imine 7f (0.18 mmol), Ru complex 6b (1.8 l
mol), tBuOK
(22.0 mg, 0.18 mmol), and isopropanol (2.0 mL). The reactor was
purged three times with H2, pressurized at 20 atm, and heated at
60 °C. After 24 h, the reactor was slowly depressurized, the solu-
tion was evaporated, and the conversion was determined by 1H
NMR. The resulting mixture was dissolved in CH2Cl2, treated with
2 mL of HCl (2 M), and stirred for 20 min. A saturated aqueous
solution of NaHCO3 (3 mL) was added to the mixture, the organic
layer was separated, dried over magnesium sulfate, and concen-
trated. Enantiomeric excesses were analyzed by chiral HPLC, as
follows: N-phenyl-1-phenylethylamine 8f: Chiralcel OJ-H,
hexane–iPrOH (93:7), flow 1.0 mL/min, t1 = 23.0 min (R),
t2 = 26.6 min (S).
Acknowledgements
MICINN (CTQ2009-11867, FEDER support) and Junta de And-
alucía (2008/FQM-3830 and 2009/FQM-4832) are acknowledged
for financial support.
References
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