Synthesis of Enantiomerically Pure and Racemic Benzyl-Tethered Ru(II)/TsDPEN Complexes by Direct Arene Substitution: Further Complexes and Applications

Article abstract of DOI:10.1021/acs.organomet.7b00731

The use of a direct arene-exchange method for the synthesis of benzyl-tethered arene/Ru/TsDPEN complexes for use in asymmetric transfer hydrogenation is reported. A series of complexes tethered through a three-carbon linear chain was also prepared. The arene-exchange approach significantly simplifies the synthetic approach to this class of catalyst and permits the ready formation of modified analogues. The approach also provides a route to racemic catalysts for use in general reductions with either hydrogen or transfer hydrogenation.

Full text of DOI:10.1021/acs.organomet.7b00731

Article
Cite This: Organometallics XXXX, XXX, XXX−XXX
Synthesis of Enantiomerically Pure and Racemic Benzyl-Tethered
Ru(II)/TsDPEN Complexes by Direct Arene Substitution: Further
Complexes and Applications
Rina Soni, Katherine E. Jolley, Silvia Gosiewska, Guy J. Clarkson, Zhijia Fang,† Thomas H. Hall,
Ben N. Treloar, Richard C. Knighton, and Martin Wills*
The Department of Chemistry, The University of Warwick, Coventry CV4 7AL, U.K.
S
* Supporting Information
ABSTRACT: The use of a direct arene-exchange method for the synthesis of benzyl-tethered arene/Ru/TsDPEN complexes for
use in asymmetric transfer hydrogenation is reported. A series of complexes tethered through a three-carbon linear chain was also
prepared. The arene-exchange approach significantly simplifies the synthetic approach to this class of catalyst and permits the
ready formation of modified analogues. The approach also provides a route to racemic catalysts for use in general reductions with
either hydrogen or transfer hydrogenation.
INTRODUCTION
■
Tethered Ru/TsDPEN catalysts, typified by complex 1, which
we first reported in 2005,1 are derivatives of the widely used
Noyori−Ikariya catalysts 2 commonly used in asymmetric
hydrogenation (AH) and asymmetric transfer hydrogenation
(ATH) of ketones and imines.2 The high levels of catalytic
activity and versatility exhibited by the tethered catalysts 1 is
likely to be, at least in part, the result of the high stability of
these complexes due to the three-point attachment of the
ligand to the ruthenium.3 Several synthetic applications of the
tethered catalysts have now been reported,1,4 including industrial
applications to, for example, pharmaceutical targets. Closely
related complexes, such as DENEB 35 and sulfamoyl derivatives
4,6 which were reported after our initial publications on tethered
catalysts for reductions, have also been used in a number of
synthetic transformations (Figure 1).
Figure 1. Tethered and nontethered complexes for asymmetric
transfer hydrogenation (ATH) of ketones and imine R,R enantiomers
illustrated throughout. Complexes 5 and 6 were prepared through an
arene-exchange strategy.
In 2013, we reported the first examples of the direct synthesis
of tethered TsDPEN complexes through the use of an “arene-
substitution” process in which a more electron rich aromatic
ring on the new ligand replaced a less electron rich ring on a
dimeric Ru(II) precursor (Scheme 1).7 Prior to our report,
we were aware of only two examples of related substitu-
tions within Ru(II) arene complexes, both of which con-
tained aliphatic three-carbon tethers to a single amine group.8
This is in sharp contrast to arene-exchange reactions in com-
plexes based on phosphines, of which numerous examples
exist.9
The arene-substitution route offers potential advantages over
the longer-established approach in which a cyclohexadiene pre-
cursor ligand is reacted with ruthenium trichloride (Scheme 2).
Specifically (1) there is no requirement to carry out a Birch
reduction, as the precursor complex ligand to the dimer can be
prepared on a multigram scale through a Diels−Alder reaction,10
Received: September 28, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.7b00731
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Scheme 1. Approach to Tethered Ru(II) Complexes via Arene Substitution
benzaldehyde (13); the latter was prepared by a Pd-catalyzed
Suzuki coupling of o-bromobenzaldehyde with p-methoxy-
phenylboronic acid.13 Using the arene-substitution method
with the ruthenium dimer [(C6H5CO2Et)RuCl2]2,7,10 we were
able to form the known complex (R,R)-7 in just two linear steps
from TsDPEN (Scheme 4). The novel p-methoxyphenyl-
tethered complex (R,R)-11 was prepared on a >700 mg scale,
and its structure was confirmed by X-ray crystallographic
analysis (Figure 2). In common with the majority of complexes
of this type, the configuration at the Ru atom (S) is controlled
by the stereochemistry of the diamine ligand, with the Ru−Cl
and N−H bonds being on the same side and approximately
parallel to each other. Complex (R,R)-11 appears to be formed
as a single diastereoisomer. In reductions with Ru(II)/TsDPEN
complexes of this type, under catalytic conditions the hydride is
generated.14 Through this process, the chirality is efficiently
transferred to the product in the subsequent hydrogen-transfer
process (vide infra).
We also prepared complexes (R,R)-14, (S,S)-15, and (S,S)-16,
containing the benzyl tether but with a p-iodophenylsulfonyl
group (IPS) in place of p-toluenesulfonyl (Ts) (Scheme 5).
These complexes have the potential to be attached to supports
such as soluble polymers through Pd-catalyzed coupling reac-
tions13 and proved to be equally stable and facile to isolate
while exhibiting excellent reactivity and enantioselectivity.
Their synthesis followed essentially the same route as before,
from the IPS ligands 17−19, respectively, which were in turn
prepared using aldehydes 13, 20, and 21.15−17 Again, the new
aldehydes were prepared through a Pd-catalyzed Suzuki coupling
reaction of 2-bromobenzaldehyde with the corresponding
methoxy-substituted boronic acids.13
Scheme 2. Synthetic Approach to Tethered Complexes via a
Hexadiene
(2) the method allows a range of complexes, including 5 and 6
(Figure 1) to be prepared efficiently,11 and (3) the wider range
of complexes offers some advantages in the reductions of certain
ketones, for example acetophenone derivatives containing an
o-methoxy group.7
Recently, we reported the synthesis and catalytic applications
of tethered complex 7 containing a benzyl-tethered structure;
however, the synthesis required the lengthy formation of a
1,3-cyclohexadiene derivative (8) that was then complexed with
RuCl3 (Scheme 3).12 The synthesis of 8 itself required three
steps from 2-bromobenzaldehyde and cyclohexenone.
In this paper, we report extensions of the arene-exchange
methodology to a range of new complexes, notably those linked
through a benzyl tether as in complex 7, which now allows
these complexes to be accessed through a short route of just
three linear steps from commercially available starting materials.
Further examples of the arene-exchange approach to new
catalysts and examples of their extended applications in ATH
reactions are also described.
In addition, we have examined the extension of the scope of
the arene-substitution process to catalysts (R,R)-22−24
containing the more established three-carbon saturated hydro-
carbon tether via the reaction of the respective ligands (R,R)-
25−27 with [(C6H5CO2Et)RuCl2]210 (Figure 3). The use of an
iodo-substituted sulfonamide was also tolerated in this reaction,
and in addition a derivative containing a TMS-protected
acetylene group ((R,R)-23) was prepared. To assist in the
aqueous solubility of the catalyst, which may be valuable in
RESULTS AND DISCUSSION
■
The ligand precursors (R,R)-9 and (R,R)-10 to the known
complex (R,R)-7 and the novel p-methoxy derivative (R,R)-11,
respectively, were made by reductive amination of TsDPEN
with o-phenylbenzaldehyde (12) and o-(p-methoxyphenyl)-
Scheme 3. Published Synthetic Approach to Benzyl-Tethered Complexes, via a Hexadiene
B
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Scheme 4. Synthesis of Benzyl-Tethered Catalysts (R,R)-7 and (R,R)-11 via an Arene-Exchange Route
Figure 3. Iodo-, alkyne-, and PEG-containing tethered Ru(II)
complexes containing the aliphatic three-carbon tether and their
respective ligand precursors.
Figure 4. Racemic catalysts formed via the arene-exchange approach.
Figure 2. X-ray crystallographic structure of benzyl-tethered catalyst
(R,R)-11.
three new complexes 28−30, two of which contain the larger
triisopropylphenylsulfonyl (Tris) group (Figure 4). The X-ray
crystallographic structure of the benzyl-tethered complex 29
was also obtained (Figure 5).
certain applications, complex (R,R)-24 containing a PEG chain
was also prepared (Figure 3) using the arene-exchange
methodology.
All of the catalysts were tested against acetophenone to
establish that they were efficient in this capacity, using the
5/2 formic acid/triethylamine azeotrope (FA/TEA) as both
solvent and reducing agent (Table 1). The applications of the
unsubstituted benzyl-tethered complex 7 have already been
reported.12 The new p-OMe complex (R,R)-11 gave equally
good results, reducing acetophenone in up to 98% ee. Using the
IPS derivative (R,R)-14, acetophenone was reduced with an
enantioselectivity of 96.8% and 99.7% conversion after 24 h.
These results compare favorably in terms of enantioselectivity
and conversion to those achieved by both the original “3C”-
tethered catalyst 11 and the p-methoxy-3C-tethered catalyst 5.7
Slightly lower conversions and enantioselectivities were
observed using the m-methoxy-substituted catalysts (S,S)-15
Given the promising results obtained using TsDPEN and its
close derivatives, we examined the application of the arene-
exchange method to the synthesis of racemic complexes.
In attempts to prepare precursor ligands, the reaction of
TsNHCH2CH2NH2 (TsEN) with 3-(4-methoxyphenyl)-
propanol proved frustrating due to multiple alkylation
reactions, whether either the triflate intermediate strategy or
the reductive amination approach were employed. It was
however possible to complete the formation of the benzyl-
tethered ligands in high yield and subsequently complexes
28−30 (Figure 4). Racemic complexes containing linear three-
carbon tethers have been reported previously;1d,e however, the
arene-exchange application was extended to the synthesis of the
a
Scheme 5. Synthesis of IPS Catalysts (R,R)-14, (S,S)-15, and (S,S)-16 via an Arene-Exchange Route
a
Although the synthesis illustrates the R,R enantiomer, (S,S)-15 and 16 were prepared in this study.
C
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Figure 6. Ketones reduced using complexes (R,R)-11, (R,R)-14, (S,S)-
15 and (S,S)-16.
level, 250−300 mg of substrate requires just ca. 3 mg of catalyst.
Although not all substrates were tested with all catalysts at
lower loadings, we are confident that they exhibit similar activity.
The dimethoxy and trimethoxy catalysts (S,S)-15 and (S,S)-16
were also used in the reductions of representative ketones
(Table 2).
Figure 5. X-ray crystallographic structure of racemic, benzyl-tethered
triisopropylphenylsulfonyl complex 29.
and (S,S)-16. This was not unexpected1,7 and is discussed later
in this paper. All three catalysts (R,R)-22−24 gave reduction
products in essentially complete conversion and ees in excess of
96%.
The PEG-containing catalyst (R,R)-24 was also tested in
aqueous solution (Table 1) and gave excellent results in this
medium. Under these conditions, sodium formate was used in
place of formic acid as the hydrogen source. In these reactions
either water or a water/methanol mixture could be used as the
solvent and 99% conversion to a product of 97% ee could be
achieved within 2 h. At a lower loading of 0.2 mol %, 88%
conversion/96% ee was achieved after 25.5 h.
The new complexes (R,R)-11 and (R,R)-14 were tested in
a wider range of ATH reactions focusing predominantly on
acetophenone derivatives (Figure 6). In these reductions
(Table 2) typically 1 mol % of catalyst was used at 45 °C
in the 5/2 formic acid/triethylamine azeotrope (FA/TEA);
however, in the case of (R,R)-11, a lower catalyst loading was
also used in order to test the practicality of the method. At this
With the exception of acetyl cyclohexane (cyclohexyl methyl
ketone; Table 1), the absolute sense of all of the reductions
using (R,R)-11 and (R,R)-14 are likely to result from a similar
range of interactions in the reduction transition state (TS).
Recent detailed computational work has revealed a combina-
tion of stabilization of the favored TS by electrostatic catalyst/
substrate CH/π interactions and a more significant destabiliza-
tion of the disfavored TS by SO2 lone pair/π repulsion (both
illustrated in Figure 7).14 Because this stabilization is not
available to cyclohexyl methyl ketone, this substrate represents
a challenging substrate for ATH catalysts.1 The reduction of
acetyl cyclohexane proceeds with significantly reduced ee
because the enantioselectivity between the two faces of the
ketone is not determined by electrostatic effects involving an
arene ring in the substrate. Although the control is weaker, the
favored reduction TS is likely to be stabilized by an SO2 lone
pair/C−H attraction (Figure 8), resulting in formation of the
a
Table 1. ATH of Acetophenone Using Catalysts (R,R)-11, (R,R)-14, (S,S)-16, and (R,R)-22−24
entry
catalyst
S/C
solvent
FA/TEA
temp/°C
time/h
conversn/%
ee/%
1
2
3
4
5
6
7
8
9
(R,R)-11
(R,R)-14
(S,S)-15
(S,S)-16
(R,R)-22
(R,R)-23
(R,R)-24
(R,R)-24
(R,R)-24
200
100
100
100
100
100
100
100
100
40
40
40
40
40
40
40
60
60
60
60
60
24
24
51
51
7
100
>99
96
98 (R)
97 (R)
93 (S)
89 (S)
97 (R)
96 (R)
97 (R)
97 (R)
97 (R)
97 (R)
97 (R)
96 (R)
FA/TEA
FA/TEA
FA/TEA
FA/TEA
FA/TEA
FA/TEA
H2O
90
>99
>99
>99
99
22
4
1
H2O/MeOH (1/1)
1
95
2
99
10
(R,R)-24
500
H2O/MeOH (1/1)
3
33
25.5
88
a
Conversion and ee were determined by GC. For entries 8−10, sodium formate (5 equiv) was used as the hydrogen source.
D
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Table 2. Ketone Reductions using (R,R)-11, (R,R)-14, (S,S)-15, and (S,S)-16
a
a
entry
ketone
catalyst
S/C
time/h
conversn/%
yield/%
ee/%
1
acetophenone
o-OMe (31)
p-OMe (32)
o-Cl (33)
(R,R)-11
(R,R)-11
(R,R)-11
(R,R)-11
(R,R)-11
(R,R)-11
(R,R)-11
(R,R)-11
(R,R)-11
(R,R)-11
(R,R)-11
(R,R)-11
(R,R)-11
(R,R)-14
(R,R)-14
(R,R)-14
(R,R)-14
(R,R)-14
(R,R)-14
(R,R)-14
(R,R)-14
(R,R)-14
(S,S)-15
(S,S)-16
(S,S)-15
(S,S)-16
(S,S)-15
400
400
400
400
400
400
400
400
400
400
400
400
400
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
72
72
72
72
72
72
72
72
72
72
72
72
72
23
23
23
25
21.5
26
26
21.5
41
65
65
65
65
41
41
100
100
100
100
100
100
100
100
100
100
100
100
100
>99
97
84
73
82
87
67
79
86
59
88
75
79
86
78
68
65
72
61
63
59
51
65
60
98 (R)
87 (R)
99 (R)
90 (R)
87 (R)
97 (S)
94 (R)
99 (R)
2
3
4
5
p-Cl (34)
6
α-Cl (35)
7
PhCOEt (36)
furyl (37)
8
b
9
cyclohexyl (38)
OPh (39)
48 (S)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
93 (S)
95 (R)
99 (R)
99 (R)
97 (R)
87 (R)
96 (R)
88 (R)
94 (R)
97 (S)
94 (R)
94 (R)
p-CF3 (40)
tetralone (41)
chromanone (42)
acetophenone
o-OMe (31)
p-OMe (32)
o-Cl (33)
94
>99
99
p-Cl (34)
α-Cl (35)
>99
99
PhCOEt (36)
furyl (37)
99
b
cyclohexyl (38)
o-OMe (31)
o-OMe (31)
p-OMe (32)
p-OMe (32)
cyclohexyl (38)
cyclohexyl (38)
>99
86
46 (S)
c
n/a
68 (S)
87 (S)
82 (S)
85 (S)
c
76
n/a
c
82
n/a
c
93
n/a
b
97
60
71 (R)
c
b
(S,S)-16
44
n/a
51 (R)
a
b
c
Conversion and ee were determined by GC. ee was determined by acetylation of alcohol followed by GC. The reduction product was not
isolated.
S enantiomer of the product using R,R-configuration catalysts.
The reduction of α-chloro- and α-phenoxyacetophenone,
however, produces the S enantiomer despite being stabilized
by CH−π interactions (Figure 7), due to reversal of the Cahn−
Ingold--Prelog priorities of the groups.
It was anticipated, given the precedents in this area, that the
di- and trimethoxy catalysts (S,S)-15 and (S,S)-16 would
exhibit reduced selectivity for the ATH of acetophenone deriv-
atives, owing to a reduction in the stabilization of the favored
TS by an increase in the steric hindrance around the η6-arene
ring (Figure 7). In this event a small decrease in ee was observed.
The configurations are of course reversed relative to the
other catalysts because of the change in the absolute con-
figuration of the catalyst. However, this modification would be
predicted to increase the selectivity of cyclohexyl methyl ketone
reduction due to the increase in steric hindrance in the
same region (Figure 8), and indeed this proved to be the case
(Table 2).1f,7
Ortho-substituted acetophenone derivatives were reduced
with the lowest enantioselectivities, with o-methoxyacetophe-
none (31) and o-chloroacetophenone (33) being reduced in
87% and 90% yields, respectively, by (R,R)-11 and 87% and
88% ee by (R,R)-14. This reduction of enantioselectivity is
most likely due to the increased steric hindrance around the
ketone. It is noteworthy, however, that the reduction of
Figure 7. Interactions between asymmetric catalysts and acetophenone
derivatives, with the favored mode of reduction illustrated.14
o-methoxyacetophenone using the trimethoxy catalyst (S,S)-16
exhibits enantioselectivity very similar to that of the methoxy
E
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have recently developed. These complexes, and related racemic
derivatives, are competent catalysts for the asymmetric transfer
hydrogenation of ketones and for the racemic reduction of
ketones via transfer hydrogenation or hydrogenation with
hydrogen gas at low loadings.
EXPERIMENTAL SECTION
■
General Experimental Considerations. All reagents and
solvents were used as purchased and without further purification.
All reactions were carried out under a nitrogen atmosphere unless
otherwise specified. Reactions at elevated temperature were main-
tained by thermostatically controlled aluminum heating blocks. A tem-
perature of 0 °C refers to an ice slush bath. NMR spectra were
recorded on a Bruker AV (250 MHz), Bruker DPX (300 or 400 MHz),
Bruker DRX (500 MHz), or Bruker AV-II instrument (700 MHz).
All chemical shifts are reported in ppm and are referenced to the
solvent chemical shift, and coupling constants are given in Hz. Mass
spectra were recorded on an Esquire 2000 instrument, and high-
resolution mass spectra were recorded on a Bruker Micro ToF
or MaXis apparatus. IR spectra were recorded on a PerkinElmer
spectrum100 instrument, and peaks are reported in wavenumbers.
The optical rotations were measured on an Optical Activity Ltd.
AA-1000 instrument. The chiral GC measurements were done on a
PerkinElmer 8500 or Hewlett-Packard 1050 instrument linked to a
PC running DataApex Clarity software. Melting points were deter-
mined on a Stuart Scientific melting point apparatus and are uncorrected.
Flash column chromatography was performed using silica gel of
mesh size 230−400. Thin-layer chromatography was carried out on
aluminum-backed silica gel 60 (F254) plates, visualized using 254 nm
UV light or iodine stains as appropriate.
Figure 8. Interactions between asymmetric catalysts and acetyl
cyclohexane, with the favored mode of reduction illustrated.14
catalysts (R,R)-11 and (R,R)-14 (87% ee), whereas the
dimethoxy catalyst (S,S)-15 gave a product with the lowest ee
(66% ee). This indicates that a secondary effect from the
p-methoxy group on the catalyst, with this particular substrate,
might be operating.
Dichloro(ethyl benzoate)ruthenium(II) Dimer.10 Ethyl 1,4-
cyclohexadene-1-carboxylate (1.04 g, 6.19 mmol, 4.1 equiv) and
ruthenium trichloride hydrate (0.398 g, 1.52 mmol assuming x = 3,
1 equiv) were combined together in a dried and nitrogen-purged flask
connected to a condenser. Dry EtOH (20 mL) was then added, and
the reaction mixture was stirred at reflux for 22 h. The reaction mixture
was cooled and filtered, and the solid residue was washed with hexane
and Et2O to leave the product as an orange solid (0.433 g, 0.67 mmol,
88.3%): mp 233.1−237.4 °C; νmax 3078, 2999, 2988, 2945, 2900, 1720,
1512, 1469, 1396, 1287, 1267, 1104, 1021, 977 cm−1; δH (400 MHz,
DMSO-d6) 6.69 (2 H, d, J = 6.1, o-ArH), 6.29 (1 H, t, J = 5.7, p-ArH),
6.04 (2 H, t, J = 6.1, m-ArH), 4.34 (2 H, q, J = 7.1, CH2), 1.32 (4 H, t,
J = 7.1, CH3); δC (126 MHz, CDCl3) 164.35, 92.95, 92.30, 85.69,
82.96, 62.59, 40.49, 40.32, 40.15, 39.99, 39.82, 39.65, 39.48, 14.73.
The novel racemic catalysts 28−30 were tested in the reduc-
tion of ketones using both transfer hydrogenation and hydro-
genation with hydrogen gas and proved to be competent
catalysts. Even at loadings as low as S/C = 500, near-complete
reduction was achieved using FA/TEA, although higher
loadings were used to ensure full reduction. In the hydroge-
nation tests, again at S/C = 500 loadings, reductions were
complete within 16 h, although the conversions dropped off
significantly at the lower loading of S/C = 1000 (Table 3).
In conclusion, we have demonstrated that a series of benzyl-
tethered arene/Ru(II)/TsDPEN complexes, which are difficult
to prepare through the hexadiene approach, may be readily
prepared using the alternative arene-swapping method that we
Table 3. Acetophenone Reduction Using Racemic Catalysts 28−30
entry
catalyst
reagent
solvent
S/C
temp/°C
time/h
conversn/%
1
28
29
29
29
29
30
29
29
30
29
29
29
30
30
30
FA/TEA
FA/TEA
FA/TEA
FA/TEA
FA/TEA
FA/TEA
HCOONa
HCOONa
HCOONa
H2 gas
100
100
100
500
500
500
100
100
100
250
500
1000
250
500
1000
28
28
28
60
60
60
40
60
60
60
60
60
60
60
60
24.5
6
100
35
2
3
23
4.5
5.0
4.0
6
100
99
4
5
99
6
100
100
>99
100
>99
99
7
H2O
8
H2O
1.5
2.5
16
16
16
16
16
16
9
H2O
10
11
12
13
14
15
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
H2 gas
H2 gas
21
H2 gas
>99
100
77.3
H2 gas
H2 gas
F
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((R,R)-2-N-(([1,1′-Biphenyl]-2-ylmethyl)amino)-1,2-dipheny-
−CH of Ru−Ar), 4.95 (1H, d, J = 12.0, −CHNH−CH2−), 4.70 (1H,
J = 13.5, -NH−CHH−), 4.10 (1H, d, J = 11.3, −CHNTs), 3.85 (1H,
d, J = 13.5, −NH−CHH−), 3.25 (1H, dd, J = 12.0, 11.3, −CHNH−
CH2−), 2.21 (3H, s, −CH3) ppm; δC (75 MHz, CDCl3): 141.18,
138.73, 137.94, 134.73, 133.12, 132.30, 131.08, 129.38, 129.15, 128.77,
128.14, 128.03, 127.30, 126.81, 126.22, 125.73, 96.06 (RuAr), 94.77
(RuAr), 94.63 (RuAr), 78.27 (RuAr), 77.15 (RuAr), 75.71 (CH),
68.45 (CH), 52.89 (CH2), 20.61 (CH3); m/z ESI-MS [M − Cl]+
633.1.
lethyl)-4-methylbenzenesulfonamide (9).
4′-Methoxybiphenyl-2-carbaldehyde (13).15
To a mixture of (R,R)-TsDPEN (0.200 g, 0.546 mmol, 1.0 equiv) and
MS 4A (0.4 g) in dry methanol (10 mL) was added biphenyl-2-
carboxaldehyde (0.101 mL, 0.628 mmol, 1.15 equiv) followed by
acetic acid (two to three drops). The mixture was stirred at room
temperature under an inert atmosphere for 4.5 h to form the imine.
To this was added NaBH3CN (0.142 g, 2.266 mmol, 4.15 equiv),
and the resulting mixture was stirred at room temperature for 18 h.
The reaction mixture was filtered and concentrated to give a residue.
This was dissolved in DCM (20 mL) and washed with 1 M NaOH
(2 × 15 mL), dried over anhydrous Na2SO4, and filtered, and the
solvent was removed to give the crude product. The crude compound
was purified by flash column chromatography over silica gel using
EtOAc/petroleum ether (7/3) to give (R,R)-9 as a white solid
(0.195 g, 0.367 mmol, 67%): HRMS found 533.2262 (C34H32N2O2S −
H+ requires 533.2257, error −0.3 ppm); νmax 3265, 3059, 3028, 2855,
1598, 1453, 1324, 1153, 1090, 916, 748, 666 cm−1; δH (400 MHz,
CDCl3) 7.33−7.27 (7H, m, −CH of phenyl), 7.21−7.17 (2H, m, −CH
of phenyl), 7.12−7.09 (4H, m, −CH of phenyl), 7.05−7.01 (4H, m,
−CH of phenyl), 6.96 (2H, d, J = 8.4, −CH of phenyl), 6.88−6.86
(2H, m, −CH of phenyl), 6.75−6.73 (2H, m, −CH of phenyl), 5.88
(1H, br d, J = 3.4, -NHTs), 4.17 (1H, dd, J = 6.6, 3.4, −CHNHTs),
3.52 (1H, d, J = 12.6, −CHNHCHH−), 3.51 (1H, d, J = 6.6,
−CHNHCH2−), 3.29 (1H, d, J = 12.6, −CHNHCHH−), 2.31 (3H, s,
−CH3), 1.39 (1H, br s, -NH−CH2−) ppm; δC (100 MHz, CDCl3)
142.59, 142.22, 141.07, 138.79, 138.50, 137.06, 136.72 (all C to here),
130.11, 130.11, 129.67, 129.15, 129.07, 128.84, 128.44, 128.30, 128.28,
127.98, 127.75, 127.70, 127.49, 127.39, 126.98 (all ArCH), 67.21
(CH). 63.03 (CH), 48.98 (CH2), 21.44 (CH3) ppm; m/z ESI-MS
[M + H]+ 533.2.
Methoxyboronic acid (0.246 g, 1.62 mmol, 1.18 equiv), palladium
tetrakis (0.022 g, 0.019 mmol, 0.014 equiv), and sodium carbonate
(0.214 g, 2.02 mmol, 1.46 equiv) were dissolved in DMF (10 mL).
2-Bromobenzaldehyde (0.255 g, 1.38 mmol, 1 equiv) was added drop-
wise over 5 min to the mixture, which was then stirred at 156 °C for
20 h. The mixture was cooled to room temperature before ethyl acetate
(50 mL) and then a saturated solution of sodium bicarbonate (30 mL)
were added. Following extraction with ethyl acetate (2 × 30 mL), the
organic extracts were washed with brine (4 × 25 mL), dried
(anhydrous sodium sulfate), and concentrated under reduced pressure
to give an oil. The crude product was purified by column chromatog-
raphy on silica (8.03 g of silica, eluation using 200 mL of 10% EtOAc/
petroleum ether) to give as a white powder 4′-methoxydiphenyl-2-
carbaldehyde (13; 0.25 g, 1.18 mmol, 86%): TLC 20% EtOAc/
petroleum ether, silica, Rf = 0.36, UV light; mp 52.8−53.7 °C; νmax 2999,
2974, 2938, 2752, 1683, 1595, 1509, 1441, 1393, 1296, 1242, 1183,
1030 cm−1; δH (300 MHz, CDCl3) δ 10.01 (1 H, s, HCOAr), 8.02
(1 H, d, J = 7.7, ArH), 7.59−7.68 (1 H, t, J = 7.4, ArH), 7.42−7.52
(2 H, m, ArH), 7.32 (2 H, d, J = 7.5, o-H−Ar−OMe), 7.02 (2 H, d, J =
7.5, m-H−Ar−OMe), 3.89 (3 H, s, CH3) ppm; δC (126 MHz, CDCl3)
δ 192.68, 159.71, 145.67, 133.77, 133.54, 131.31, 130.80, 130.03,
127.63, 127.39, 113.95, 77.47, 77.04,76.62, 55.41 ppm; m/z (ESI+)
235.0 ((M + Na)+, 100%).
((R,R)-2-N-((4′-Methoxy-[1,1′-biphenyl]-2-ylmethyl)amino)-
1,2-diphenylethyl)-4-methylbenzenesulfonamide (10).
N-((R,R)-2-(([1,1′-Biphenyl]-2-ylmethyl)amino)-1,2-dipheny-
lethyl)-4-methylbenzenesulfonamide Ruthenium(II) Chloride
Complex (7).12
To a solution of 4′-methoxybiphenyl-2-carbaldehyde (13; 2.02 g,
9.50 mmol) and (R,R)-TsDPEN (3.48 g, 9.52 mmol) in MeOH
(25 mL) at room temperature were added a few drops of CH3CO2H.
The mixture was stirred overnight, and then NaBH4 (800 mg,
20.00 mmol) was added, along with MeOH (20 mL). The reaction
mixture was stirred at room temperature for 18 h, after which the
MeOH was removed by evaporation. The reaction was quenched
with saturated aqueous NaHCO3 (150 mL) and extracted with EtOAc
(3 × 150 mL). The combined organic layers were washed with
saturated NaCl (100 mL), dried over Na2SO4, and concentrated.
The crude product was purified by silica gel column chromatography
(eluent hexane/EtOAc 4/1−3/1) to afford (R,R)-10 as a white solid
((R,R)-2-N-(([1,1′-Biphenyl]-2-ylmethyl)amino)-1,2-diphenylethyl)-
4-methylbenzenesulfonamide (9; 0.050 g, 0.094 mmol, 1.0 equiv) and
[Ru (C6H5CO2Et)Cl2]2 (0.030 g, 0.047 mmol, 0.5 equiv) in dry DCM
(1.5 mL) was placed in a glass tube under N2. The tube was sealed,
and the mixture was stirred at room temperature for 30 min to give a
brick red solution and heated at 90 °C for 49 h. The reaction was
followed by TLC and mass spectrometric analysis. The reaction
mixture was cooled to room temperature and concentrated to give a
dark brown residue. The residue was dissolved in diethyl ether, and
then the solvent volume was reduced in order to precipitate the crude
product, which was isolated by filtration and dried to give a dark
brown solid. The solid was purified by column chromatography over
Florisil using DCM/MeOH (97/3 to 85/15) to give (R,R)-7 as a
brown solid (0.030 g, 0.045 mmol, 47.8%): HRMS found 633.1159
(C34H31N2O2RuS − Cl+ requires 633.1153, error −1.4 ppm); δH
(300 MHz, CDCl3) 7.61−7.53 (2H, m, ArH), 7.42−7.37 (1H, m, ArH),
7.21 (2H, d, J = 8.1, m−CH−SO2−ArH), 7.16−7.10 (3H, m, ArH),
6.91 (1H, d, J = 7.5, ArH), 6.79 (2H, d, J = 8.1, o-CH−SO2ArH),
6.75−6.70 (3H, m, 2−CH−ArH, −CH of Ru−Ar), 6.62−6.57 (3H, m,
-ArH), 6.44 (2H, d, J = 7.2, ArH), 6.11−6.02 (2H, m, −CH of
Ru−Ar), 5.18 (1H, d, J = 5.7, −CH of Ru−Ar), 5.10 (1H, d, J = 5.0,
24
(5.10 g, 9.07 mmol, 96%): [α]D −27.6 (c 0.4 in CHCl3) (R); mp
57 °C; ESI found M+ + H 563.2363, calcd for C35H34N2O3S (M)
563.2363; νmax 3258, 3027, 1242, 1153, 762, 698, 666, 559, 546 cm−1;
δH (400 MHz, CDCl3) 7.31−6.99 (14H, m, ArH), 6.95 (2H, d, J = 8.0,
ArH), 6.89−6.82 (4H, m, ArH), 6.78−6.75 (2H, m, ArH), 5.97 (1H,
br, NHTs), 4.18 (1H, d, J = 7.5, CHNHTs), 3.83 (3H, s, OCH3), 3.54
(1H, d, J = 12.2, HCH), 3.53 (1H, d, J = 7.2, CHNH), 3.29 (1H, d, J =
12.2, HCH), 2.93 (3H, s, CH3), 1.44 (1H, br, NH); δC (100 MHz,
CDCl3) 158.7, 142.6, 141.9, 138.8, 138.5, 137.0, 136.9, 130.4, 129.9
(2C), 129.8, 129.1 (2C), 128.3 (2C), 128.0 (2C), 127.5 (2C), 127.4
G
DOI: 10.1021/acs.organomet.7b00731
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
(4C), 127.3 (2C), 127.0 (2C), 113.7 (2C), 67.3, 63.1, 55.3, 49.1, 21.5;
m/z (ESI-MS) 563.1 (M + H)+.
3′,5′-Dimethoxybiphenyl-2-carbaldehyde (20).16
N-((R,R)-2-((4′-Methoxy-[1,1′-biphenyl]-2-ylmethyl)amino)-
1,2-diphenylethyl)-4-methylbenzenesulfonamide Ruthenium-
(II) Chloride Complex (11).
3,5-Dimethoxyboronic acid (0.232 g, 1.27 mmol, 1.11 equiv),
palladium tetrakis (0.011 g, 0.010 mmol, 0.095 equiv), and sodium
carbonate (0.174 g, 1.64 mmol, 1.42 equiv) were combined in DMF
(8 mL). 2-Bromobenzaldehyde (0.213 g, 1.15 mmol, 1 equiv) was
added dropwise into the mixture over 5 min, which was then stirred at
155 °C for 21 h. The mixture was cooled to room temperature before
ethyl acetate (30 mL) and then a saturated solution of sodium
bicarbonate (20 mL) were added. Following extraction with ethyl
acetate (4 × 30 mL), the organic extracts were washed with brine
(4 × 25 mL), dried (anhydrous sodium sulfate), and concentrated
under reduced pressure to give an oil. The crude product was purified
by column chromatography on silica (16.5 g of silica, elution using
300 mL of 10% EtOAc/petroleum ether) to give 3′,5′-dimethoxy-
biphenyl-2-carbaldehyde (20; 0.234 g, 0.96 mmol, 84%) as a white
powder: TLC 12% EtOAc/petroleum ether, silica, Rf = 0.39, UV light;
mp 74.5−75.9 °C; νmax 3057, 3006, 2952, 2932, 2872, 2831, 2754,
1689, 1589, 1454, 1417, 1387, 1347, 1203, 1152, 1061, 1027 cm−1; δH
(500 MHz, CDCl3) δ (ppm) 10.02 (1 H, s, HCOAr), 8.02 (1 H, dd,
J = 7.8, 0.9, ArH), 7.63 (1 H, dt, J = 15.1, 7.6, ArH), 7.44−7.53 (2 H,
m, ArH), 6.55 (1 H, t, J = 2.3, o,o-H−Ar(OMe)2), 6.52 (2 H, d, J = 2.1,
o,p-H−Ar(OMe)2), 3.84 (6 H, s, (CH3)2); δC (126 MHz, CDCl3)
δ (ppm) 192.40, 160.62, 145.91, 139.77, 133.76, 133.47, 130.39,
127.87, 127.33, 108.43, 105.50, 100.02, 99.45, 77.26, 76.74, 55.46; m/z
(ESI+) 265.1 ((M + Na)+, 100%).
[Ru(C6H5CO2Et)Cl2]2 (674 mg, 1.06 mmol) and (R,R)-2-((4′-
methoxy-[1,1′-biphenyl]-2-ylmethyl)amino)-1,2-diphenylethyl)-4-
methylbenzenesulfonamide (10; 1.79 g, 3.07 mmol) were dissolved in
CH2Cl2 (80 mL); after 0.5 h, CH2Cl2 was removed and chlorobenzene
(180 mL) was added. The degassed mixture was heated to 95 °C for
4 h, and then the solvent was removed by evaporation. The resulting
solid was purified by silica gel column chromatography (eluent first
CH2Cl2/EtOAc 6/1 to remove excess ligand and then CH2Cl2/MeOH
30/1) to afford (R,R)-11 as a brown powder (734 mg, 1.02 mmol,
49%): HRMS found (ESI) (M − Cl−)+ 663.1259, calcd for
C35H33N2O3RuS (M) 663.1255; νmax 3196, 1543, 1276, 1249, 1130,
1028, 698, 665, 577 cm−1; δH (400 MHz, CDCl3) 7.65 (1H, d, J = 7.5,
ArH), 7.57 (1H, t, J = 7.5, ArH), 7.42 (1H, t, J = 7.5, ArH), 7.22 (2H,
d, J = 8.1, ArH), 7.15−7.05 (3H, m, ArH), 7.00 (1H, d, J = 7.5, ArH),
6.85 (2H, d, J = 8.0, ArH), (1H, d, J, ArH), 6.72 (1H, t, J = 7.2, ArH),
6.65 (1H, m, ArH), 6.58 (2H, t, J = 7.9, ArH), 6.42 (1H, d, J = 5.8,
ArH), 6.39 (2H, d, J = 7.7, Ru−ArH), 5.88 (1H, d, J = 6.5, Ru−ArH),
5.42 (1H, d, J = 5.8, Ru−ArH), 5.15 (1H, d, J = 6.5, Ru−ArH), 4.90
(1H, d, J = 12.2, NH), 4.62 (1H, dd, J = 14.4, 2.2, CHNTsRu), 4.20
(3H, s, OCH3), 4.10 (1H, d, J = 11.4, HCH), 3.82 (1H, d, J = 14.1,
CHNH), 3.09 (1H, t, J = 11.4, HCH), 2.93 (3H, s, CH3); δC
(100 MHz, CDCl3) 142.2, 139.3, 138.5, 134.3, 132.6, 132.0 (2C),
130.3, 129.7, 129.5, 129.1 (2C), 128.7 (2C), 128.5, 128.0 (2C), 127.4
(2C), 126.6 (2C), 126.3 (2C), 81.3 (2C), 80.7 (2C), 76.6, 75.4, 69.1,
57.4, 53.9, 21.2; m/z (ESI-MS) (M − Cl−)+ 663.1.
3′,4′,5′-Trimethoxybiphenyl-2-carbaldehyde (21).17
3,4,5-Trimethoxyboronic acid (0.754 g, 3.56 mmol, 1.20 equiv),
palladium tetrakis (0.036 g, 0.031 mmol, 0.011 equiv), and sodium
carbonate (0.477 g, 4.50 mmol, 1.52 equiv) were combined in DMF
(20 mL). 2-Bromobenzaldehyde (0.549 g, 2.96 mmol, 1 equiv) was
added dropwise into the mixture over 5 min, which was then stirred at
170 °C for 18.5 h. The mixture was cooled to room temperature
before ethyl acetate (50 mL) and then a saturated solution of sodium
bicarbonate (30 mL) were added. Following extraction with ethyl
acetate (6 × 30 mL), the organic extracts were washed with brine
(4 × 50 mL), dried (anhydrous sodium sulfate), and concentrated
under reduced pressure to give an oil. The crude product was purified
by column chromatography on silica (21.2 g of silica, elution using
300 mL of 12% EtOAc/petroleum ether) to give 3′,4′,5′-trimethoxy-
biphenyl-2-carbaldehyde (21) as a white powder (0.655 g, 2.40 mmol,
81%): TLC 12% EtOAc/petroleum ether, silica, Rf = 0.12, UV light;
mp 89.8−92.1 °C; νmax 3059, 3003, 2969, 2940, 2839, 1681, 1582,
1507, 1454, 1410, 1346, 1292, 1237, 1122, 996 cm−1; δH (500 MHz,
CDCl3) δ 10.02 (1 H, s, HCOAr), 8.01 (1 H, dd, J = 7.8, 0.9, ArH),
7.64 (1 H, td, J = 7.6, 1.4, ArH), 7.45−7.52 (2 H, m, ArH), 6.57 (2 H,
s, o,p,o-H−Ar−(OMe)3), 3.92 (3H, s, o,o-(OMe)2−Ar−OCH3), 3.89
(6 H, s, (o,m-(OMe)2−Ar−OCH3)2) ppm; δC (126 MHz, CDCl3)
δ 192.49, 153.12, 145.96, 138.01, 133.89, 133.51, 133.41, 130.51,
127.83, 127.47, 107.42, 77.29, 77.03, 76.78, 61.00, 56.26 ppm; m/z
(ESI+) 295.0 ((M + Na)+, 100%).
((S,S)-N-2-Amino-1,2-diphenylethyl)-4-iodobenzenesulfona-
mide.
(S,S)-Diphenylethyldiamine (DPEN) (2.12 g, 10 mmol, 1 equiv) was
added to potassium carbonate (1.38 g, 10 mmol, 1 equiv) in DCM
(30 mL) and water (25 mL), and this mixture was then degassed.
4-Iodobenzenesulfonyl chloride (3.05 g, 10 mmol) in DCM (20 mL)
was added dropwise, with stirring at 0 °C, over 25 min. The mixture
was warmed to room temperature, stirred for 4 days, and monitored by
TLC. Neutralization was carried out by saturated aqueous ammonium
chloride (25 mL), and the mixture was stirred for 3 days. Subsequent
extraction with DCM (4 × 100 mL), drying (Na2SO4), filtering, and
then concentration under reduced pressure gave the product as white
crystals (4.73 g, 9.88 mol, 99.01%): TLC 50% EtOAc/petroleum
ether, silica, Rf = 0.1, UV light; mp 180.8−182.4 °C; [α]D 6.18 (c 0.06
in CHCl3) R,R enantiomer; HRMS found (ESI) [M + H]+, 479.0291,
calcd for C20H20IN2O2S 479.0285; νmax 3335, 3021, 2873, 2853, 1570,
1451, 1318, 1148, 1091, 1053, 1022 cm−1; δH (500 MHz, CDCl3)
δ 7.50 (2 H, d, J = 8.6, I−ArH), 7.12−7.31 (11 H, m, ArH), 7.10 (2 H,
d, J = 8.7, SO2−ArH), 6.15 (1 H, br s, NH), 4.42 (1 H, d, J = 4.5, CH),
4.19 (1 H, d, J = 4.6, CH), 1.41 (2 H, br s, NH2) ppm; δC (126 MHz,
CDCl3) δ 141.18, 139.78, 139.19, 137.68, 128.57, 128.47, 128.11,
127.60, 126.84, 126.30, 99.25, 77.27, 77.01, 76.76, 63.05, 60.22 ppm;
m/z (ESI+) 479 ((M + H)+, 100%).
((R,R)-2-N-((4′-Methoxy-[1,1′-biphenyl]-2-ylmethyl)amino)-
1,2-diphenylethyl)-4-iodobenzenesulfonamide (17).
H
DOI: 10.1021/acs.organomet.7b00731
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
4′-Methoxybiphenyl-2-carbaldehyde (13; 0.877 g, 1.83 mmol, 1 equiv),
(R,R)-N-(2-amino-1,2-diphenylethyl)-4-iodobenzenesulfonamide
(0.406 g, 1.91 mmol, 1.04 equiv), and 4A-MS (1.127 g) were
combined in dry methanol (45 mL). Acetic acid (0.121 g, 2.01 mmol,
1.10 equiv) was injected, and the reaction mixture was stirred at room
temperature for 6 h and monitored by TLC. Then sodium cyano-
borohydride (0.478 g, 7.61 mmol, 4.15 equiv) was added in one
portion and the reaction mixture was stirred for 4 days. The mixture
was filtered through Celite, concentrated, suspended in NaOH (1 M,
88 mL), and extracted with DCM (6 × 90 mL). The combined
organic extracts were washed with brine, dried (anhydrous sodium
sulfate), and concentrated under reduced pressure to give the product
(R,R)-17 as a white solid (1.07 g, 1.59 mmol, 86.8%): TLC 20% ethyl
acetate/79% petroleum ether/1% trimethylamine, silica, Rf = 0.24,
UV light; mp 62.5−71.8 °C; [α]D (R) −6.81 (c 0.43 in CHCl3);
HRMS found (ESI) [M + H]+ 675.1178, calcd for C34H32IN2O3S
675.1173; νmax 3273, 3060, 3027, 2934, 2834, 1610, 1569, 1514, 1453,
1242, 1157, 1088, 1034, 1004, 833, 762, 729, 697 cm−1; δH (500 MHz,
CDCl3) δ (ppm) 7.51 (2 H, d, J = 8.5, o-I−ArH), 7.23−7.41 (3 H, m,
ArH), 7.06−7.23 (10 H, m, ArH and o-SO2−ArH), 7.04 (2 H, d, J =
8.7, o-H−Ar−OMe), 6.92 (2 H, d, J = 7.2, ArH), 6.87 (2 H, d, J = 8.5,
m-H−Ar−OMe), 6.80 (2 H, d, J = 7.2, ArH), 6.01 (1 H, br s,
SO2NH), 4.23 (1 H, d, J = 6.7, CH), 3.88 (3 H, s, OCH3), 3.53−3.59
(2 H, m, N−CHH−Ar and CH), 3.32 (1 H, d, J = 12.2, N−CHH−
Ar), 1.40 (1 H, br s, NH); δC (126 MHz, CDCl3): 158.93, 158.65,
141.87, 141.04, 139.83, 138.63, 138.16, 137.60, 137.37, 136.76, 133.55,
133.38, 133.00, 131.32, 130.80, 130.47, 130.24, 130.04, 129.84, 129.71,
128.57, 128.50, 128.40, 128.32, 128.15, 127.72, 127.64, 127.53, 127.47,
127.39, 127.33, 127.28, 126.98, 114.18, 113.95, 113.72, 99.29, 77.30,
77.04, 76.79, 67.13, 66.99, 63.34, 63.18, 63.10, 55.42, 55.32, 49.13,
48.82; m/z (ESI−) 673.0 ([M − H+]−, 100%), 709.0 ((M + Cl−)−,
30%).
139.89, 138.60, 137.97, 137.52, 136.61, 130.02, 129.53, 128.33, 128.30,
128.02, 127.63, 127.47, 127.39, 127.35, 127.27, 127.19, 106.94, 99.30,
99.25, 77.25, 76.74, 67.16, 63.07, 55.36, 49.15; m/z (ESI+) 705.1
([M + H]+, 100%), 727.1 ([M + Na]+, 10%).
N-((S,S)-2-((3′,4′,5′-Trimethoxy-[1,1′-biphenyl]-2-ylmethyl)-
amino)-1,2-diphenylethyl)-4-iodobenzenesulfonamide (19).
3′,4′,5′-Trimethoxybiphenyl-2-carbaldehyde (21; 0.763 g, 1.59 mmol,
1 equiv), ((S,S)-N-2-amino-1,2-diphenylethyl)-4-iodobenzenesulfona-
mide (0.507 g, 1.86 mmol, 1.17 equiv), and 4A-MS (0.943 g) were
added together in dry methanol (40 mL). Acetic acid (0.108 g, 1.8 mmol,
1.13 equiv) was injected, and the reaction mixture was stirred at room
temperature for 6.5 h, and monitored by TLC. Then sodium cyano-
borohydride (0.432g, 6.873 mmol, 4.31 equiv) was added in one
portion and the reaction mixture was stirred for 3 days. The mixture
was filtered through Celite, concentrated, suspended in NaOH (1 M,
40 mL), and extracted with DCM (5 × 80 mL). The combined
organic extracts were washed with brine, dried (anhydrous sodium
sulfate), and concentrated under reduced pressure to give the product
(S,S)-19 as white crystals (0.890 g, 1.21 mmol, 76%): TLC 20% ethyl
acetate/79% petroleum ether/1% trimethylamine; mp 80.9−84.7 °C;
[α]D (S) −8.02 (c 0.29 in CHCl3); HRMS found (ESI) [M + H]+
735.1390 calcd for C36H36IN2O5S 735.1384; νmax 3269, 3238, 3059,
3027, 3000, 2932, 2834, 2332, 1570, 1453, 1407, 1342, 1236, 1156,
1123, 1005, 816, 765, 729, 698 cm−1; δH (500 MHz, CDCl3) 7.48
(2 H, d, J = 8.5, o-I-ArH), 7.31−7.35 (2 H, m, ArH), 7.24 (2 H, td, J =
4.4, 1.3, ArH), 7.04−7.16 (6 H, m, ArH and o-SO2−ArH), 7.06 (2 H,
d, J = 8.5, ArH), 7.02 (2 H, t, J = 7.6, ArH), 6.85 (2 H, d, J = 7.2, ArH),
6.73 (2 H, d, J = 7.2, ArH), 6.40 (2 H, s, H−Ar−(OMe)3), 6.10 (1 H,
br s, HN−SO2), 4.24 (1 H, d, J = 7.5, CH), 3.93 (3 H, s, p-(OCH3)),
3.86−3.90 (1 H, m), 3.78 (6 H, s, m-(OCH3)2), 3.57−3.65 (2 H, m,
N−CHH−Ar and CH), 3.39 (1 H, d, J = 12.8, N−CHH−Ar), 1.51
(1 H, br s, CH−NH−CH2); δC (126 MHz, CDCl3) 152.91, 141.90,
139.78, 138.49, 137.76, 137.52, 137.03, 136.74, 136.58, 130.16, 129.85,
129.41, 128.66, 128.42, 128.34, 128.02, 127.81, 127.77, 127.71, 127.66,
127.60, 127.43, 127.27, 127.10, 107.38, 106.33, 105.98, 99.31, 77.26,
76.74, 67.27, 63.33, 62.99, 60.93, 56.24, 56.12, 49.09; m/z (ESI+)
735.1 ([M + H]+, 100%), 757.1 ([M + Na]+, 34%).
N-((S,S)-2-((3′,5′-Dimethoxy-[1,1′-biphenyl]-2-ylmethyl)-
amino)-1,2-diphenylethyl)-4-iodobenzenesulfonamide (18).
3′,5′-Dimethoxybiphenyl-2-carbaldehyde (20; 0.346 g, 0.73 mmol,
1 equiv), (S,S)-N-((S,S)-2-amino-1,2-diphenylethyl)-4-iodobenzene-
sulfonamide (0.196 g, 0.81 mmol, 1.16 equiv), and 4A-MS (0.442 g)
were added together in dry methanol (22 mL). Acetic acid (0.068 g,
1.13 mmol, 1.60 equiv) was injected, and the reaction mixture was
stirred at room temperature for 6 h and monitored by TLC.
Then sodium cyanoborohydride (0.186 g, 3 mmol, 4.09 equiv) was
added in one portion and the reaction mixture was stirred for 3 days.
The mixture was filtered through Celite, concentrated, suspended
in NaOH (1 M, 40 mL), and extracted with DCM (5 × 40 mL).
The combined organic extracts were washed with brine, dried
(anhydrous sodium sulfate), and concentrated under reduced pressure
to give the product (S,S)-18 as pink crystals (0.489 g, 0.69 mmol,
96.1%): TLC 20% ethyl acetate/79% petroleum ether/1% trimethyl-
amine; mp 71.7−74.6 °C; [α]D (S) 6.64 (c 0.20 in CHCl3); HRMS
found (ESI) [M + H]+ 705.1289, calc for C35H34IN2O4S 705.1279;
νmax 3258, 3061, 3027, 3002, 2934, 2836, 1590, 1453, 1418, 1333,
1203, 1151, 1055, 1026, 1006, 927, 815, 763, 729, 697 cm−1; δH
(500 MHz, CDCl3) 7.50 (2 H, d, J = 8.5, o-I−ArH), 7.30−7.33 (2 H, m,
ArH), 7.22−7.25 (1 H, m, ArH), 7.18−7.21 (1 H, m, ArH), 7.01−7.16
(8 H, m, ArH and o-SO2−ArH), 6.86 (2 H, d, J = 7.2, ArH), 6.76 (2 H,
d, J = 7.2, ArH), 6.47 (1 H, t, J = 2.3, o,o-H−Ar−(OMe)2), 6.36 (2 H,
d, J = 2.3, o,p-H−Ar−(OMe)2), 6.04 (1 H, br s, SO2NH), 4.23 (1 H, d,
J = 7.3, CH), 3.78 (6 H, s, (OCH3)2), 3.56−3.65 (2 H, m, N−CHH−
Ar and CH), 3.38 (1 H, d, J = 12.7, N−CHH−Ar), 1.56 (1 H, br s,
CH−NH−CH2); δC (126 MHz, CDCl3) 160.50, 143.05, 141.87,
N-((R,R)-2-((4′-Methoxy-[1,1′-biphenyl]-2-ylmethyl)amino)-
1,2-diphenylethyl)-4-iodobenzenesulfonamide Ruthenium(II)
Chloride Complex (14).
(R,R)-2-((4′-methoxy-[1,1′-biphenyl]-2-ylmethyl)amino)-1,2-dipheny-
lethyl)-4-iodobenzenesulfonamide (17; 0.402 g, 0.60 mmol, 1 equiv),
[Ru(C6H5CO2Et)Cl2]2 (0.193 g, 0.30 mmol, 0.5 equiv), and 4A-MS
(0.315 g) were added together in dry chlorobenzene (15 mL).
The reaction mixture was degassed, heated rapidly to 91 °C in a
preheated aluminum block, and stirred for 22 h, followed by mass
spectrometry, before the chlorobenzene was removed under vacuum.
The product was filtered through Celite and a silica plug in 10% IPA/
CHCl3. The crude product was purified by column chromatography
on silica (31 g of silica, first elution using 5−10% EtOAc/ 25−20%
hexane/70% DCM to remove the excess ligand and then gradient
elution 2−20% MeOH/28−10% hexane/70% DCM) to give the
I
DOI: 10.1021/acs.organomet.7b00731
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
product (R,R)-14 as a brown powder (0.268 g, 0.33 mmol, 55.7%):
mp 287.5 °C dec; [α]D 155.7 (c 0.004 in CHCl3); HRMS found (ESI)
[M + H]+ 775.0081, calcd for C34H30IN2O3RuS 775.0068; νmax 3462,
3435, 3057, 3027, 2932, 2835, 1541, 1453, 1248, 1134, 1080, 1002,
898, 805, 761, 723, 697 cm−1; δH (500 MHz, CDCl3) 7.64 (1 H, d, J =
6.9, ArH), 7.58 (1 H, t, J = 7.5, ArH), 7.43 (1 H, td, J = 7.5, 1.0, ArH),
7.35 (2 H, d, J = 8.4, o-I−ArH), 6.97−7.20 (7 H, m, ArH and o-SO2−
ArH), 6.77 (1 H, t, J = 7.3, ArH), 6.60 (3 H, t, J = 7.7, ArH), 6.38
(2 H, d, J = 7.3, ArH), 6.33 (1 H, dd, J = 5.8, 1.4, Ru−ArH), 5.89 (1 H,
dd, J = 6.6, 1.4, Ru−ArH), 5.40 (1 H, d, J = 5.8, Ru−ArH), 5.18 (1 H,
d, J = 6.4, Ru−ArH), 4.87 (1 H, d, J = 12.2, NH), 4.61 (1 H, dd, J = 14.1,
2.4, ArHCH−N), 4.19 (3 H, s, OCH3), 4.11 (1 H, d, J = 11.1, N−CH),
3.70−3.94 (1 H, m, ArHCH−N), 3.11 (1 H, t, J = 11.7, N−CH);
δC (126 MHz, CDCl3) 145.10, 138.07, 136.41, 135.67, 134.19, 132.43,
131.98, 130.87, 130.40, 130.08, 129.77, 129.40, 129.05, 128.95, 128.73,
128.57, 127.48, 126.84, 126.49, 95.81, 88.64, 81.31, 80.18, 77.26,
76.80, 76.75, 76.67, 75.36, 68.86, 57.38, 53.87; m/z (ESI+) 774.9
([M − Cl]+, 100%).
(S,S)-2-((3′,4′,5′-Trimethoxy-[1,1′-biphenyl]-2-ylmethyl)amino)-1,2-
diphenylethyl)-4-iodobenzenesulfonamide (19; 0.296 g, 0.40 mmol, 1
equiv), [Ru(C6H5CO2Et)Cl2]2 (0.13 g, 0.20 mmol, 0.5 equiv), and 4A-
MS (0.210 g) were added together in dry chlorobenzene (10 mL).
The reaction mixture was degassed, heated rapidly to 90 °C in a
preheated aluminum block, and stirred for 23 h, followed by mass
spectrometry, before the chlorobenzene was removed under vacuum.
The product was filtered through Celite and a silica plug in 10% IPA/
CHCl3. The crude product was purified by column chromatography
on silica (30.1 g of silica, first elution using 5−15% EtOAc/25−15%
hexane/70% DCM to remove the excess ligand and then gradient
elution 5−15% MeOH/25−15% hexane/70% DCM) to give the
product (S,S)-16 as a brown powder (0.184 g, 0.21 mmol, 52.5%):
HRMS found (ESI) [M + H]+ 835.0291, calcd for C36H34IN2O5RuS
835.0280; νmax 3524, 3510, 3446, 3180, 3057, 3026, 2931, 1729, 1568,
1454, 1419, 1346, 1223, 1111, 1003, 901, 808, 723, 697 cm−1; δH (500
MHz, CDCl3) 7.65 (1 H, d, J = 6.7, ArH), 7.50−7.60 (2 H, m, ArH),
7.33−7.44 (4 H, m, ArH), 7.30 (3 H, m, J = 8.7, ArH), 7.18 (2 H, m,
J = 6.8, ArH), 6.83−6.90 (1 H, m, ArH), 6.80 (1 H, d, J = 7.3, ArH),
6.74 (2 H, t, J = 7.4, ArH), 6.46 (2 H, d, J = 7.1, ArH), 4.87 (1 H, s,
Ru−ArH), 4.70 (1 H, d, J = 11.4, NH), 4.61 (1 H, d, J = 13.8, Ar−
CH2−N), 4.51 (3 H, br. s, OCH3), 4.42 (1 H, br s, Ru−ArH), 4.27 (3
H, br s, OCH3), 4.00 (4 H, br s, OCH3 and NCH), 3.73 (2 H, m, J =
13.7, Ar−CH2−N), 3.30 (1 H, t, J = 11.6, N−CH); δC (126 MHz,
CDCl3) 143.72, 139.62, 136.23, 135.37, 134.94, 133.72, 132.11,
131.47, 130.25, 130.19, 129.84, 129.69, 128.64, 128.40, 127.15, 126.70,
106.72, 106.18, 96.38, 91.39, 77.26, 76.75, 76.31, 69.25, 64.41, 60.92,
60.37, 59.19, 57.64, 57.20, 56.25, 54.87, 52.72; m/z (ESI+) 835.0
([M − Cl]+, 100%).
N-((S,S)-2-((3′,5′-Dimethoxy-[1,1′-biphenyl]-2-ylmethyl)-
amino)-1,2-diphenylethyl)-4-iodobenzenesulfonamide
Ruthenium(II) Chloride Complex (15).
4-Iodo-N-((R,R)-2-(3-(4-methoxyphenyl)propylamino)-1,2-
diphenylethyl)benzenesulfonamide (25).
(S,S)-(3′,5′-Dimethoxy-[1,1′-biphenyl]-2-ylmethyl)amino)-1,2-diphe-
nylethyl)-4-iodobenzenesulfonamide (18; 0.291 g, 0.41 mmol, 1 equiv),
[Ru(C6H5CO2Et)Cl2]2 (0.137 g, 0.21 mmol, 0.51 equiv), and 4A-MS
(0.228 g) were added together in dry chlorobenzene (10 mL).
The reaction mixture was degassed, heated rapidly to 90 °C in a preheated
aluminum block, and stirred for 23 h, followed by mass spectrometry,
before the chlorobenzene was removed under vacuum. The product
was filtered through Celite and a silica plug in 10% IPA/CHCl3.
The crude product was purified by column chromatography on silica
(30.8 g of silica, first elution using 5−10% EtOA/25−20% hexane/
70% DCM to remove the excess ligand and then gradient elution 5−
20% MeOH/25−10% hexane/70% DCM) to give the product (S,S)-
15 as a brown powder (0.154 g, 0.18 mmol, 44.4%): [α]D 152.1
(c 0.002 in CHCl3); HRMS found (ESI) [M + H]+ 805.0177, calcd for
C35H32IN2O4RuS 805.0166; νmax 3183, 3075, 3060, 3027, 2931, 2333,
2291, 1729, 1591, 1568, 1525, 1493, 1454, 1346, 1266, 1204, 1157,
1134, 1080, 1005, 901, 810, 761, 723, 697 cm−1; δH (500 MHz, CDCl3)
7.63 (1 H, d, J = 7.5, ArH), 7.54 (1 H, t, J = 7.5, ArH), 7.29−7.38
(4 H, m, ArH), 7.22−7.28 (4 H, m, ArH), 6.99−7.22 (5 H, m, ArH),
6.73−6.83 (3 H, m, ArH), 6.66 (2 H, t, J = 7.6, ArH), 6.50 (2 H, d, J =
7.3, ArH), 5.58 (1 H, s, Ru-H−Ar−o-(OMe)2), 4.78−4.87 (2 H,
m, Ru−ArH and NH), 4.58 (1 H, dd, J = 13.9, 1.8, ArHCH−N), 4.55
(1 H, s, Ru−ArH), 4.13 (3 H, s, OCH3), 4.10 (3 H, s, OCH3),
3.68−3.79 (2 H, m, ArHCH−N and N−CH), 3.36 (1 H, t, J = 11.7,
N−CH); δC (126 MHz, CDCl3) 144.82, 141.35, 138.71, 137.54,
137.44, 136.20, 135.37, 133.69, 132.43, 131.37, 130.00, 129.87, 129.69,
129.55, 128.90, 128.68, 128.51, 127.12, 126.42, 107.25, 106.96, 99.97,
96.07, 95.96, 94.56, 79.61, 77.28, 77.02, 76.77, 76.45, 68.90, 60.70,
57.81, 57.78, 57.19, 55.38, 52.47, 52.06; m/z (ESI+) 805.0
([M − Cl]+, 100%).
To a mixture of 3-(4-methoxyphenyl)propanol (0.278 g, 1.67 mmol,
1.6 equiv) and 2,6-lutidine (0.255 mL, 2.197 mmol, 2.10 equiv) in dry
DCM (10 mL) was added a solution of triflic anhydride (1 M in
DCM) (1.78 mL, 1.778 mmol, 1.70 equiv) dropwise at 0 °C under an
inert atmosphere. The resulting light pink solution was stirred at 0 °C
for 30 min and at room temperature for 60 min. The mixture was
again cooled to 0 °C. To this was added a solution of (S,S)-N-2-amino-
1,2-diphenylethyl)-4-iodobenzenesulfonamide (0.500 g, 1.046 mmol,
1.0 equiv) and TEA (0.349 mL, 2.510 mmol, 2.4 equiv) in dry DCM
(5 mL) dropwise at 0 °C. The resulting yellow mixture was stirred at
0 °C for 30 min and then at room temperature for 17 h. The reaction
mixture was diluted with DCM (15 mL) and washed with saturated
NaHCO3 solution (3 × 10 mL). The organic layer was separated,
washed with H2O (2 × 10 mL) and brine (10 mL), dried over
anhydrous Na2SO4, filtered, and concentrated to give the crude
compound. The crude compound was purified by column
chromatography on silica gel using EtOAc/petroleum ether (30/70)
as eluent to give the product. The product was triturated in n-pentane
(to remove traces of 2,6-lutidine). The solvent was evaporated to give
the pure compound (S,S)-25 as a white solid (0.439 g, 0.701 mmol,
28
67%): mp 122−124 °C; [α]D = +8.7 (c 0.505 in CHCl3); HRMS
found 627.1174, calcd for C30H31IN2O3S H+ 627.1173, error −0.1
ppm; νmax 3305, 3028, 2997, 2926, 2831, 1611, 1567, 1510, 1493,
1459, 1161, 811, 727, 701 cm−1; δH (400 MHz, CDCl3) 7.52 (2H, d,
J = 8.4, −CH of −SO2C6H4I), 7.18−7.04 (8H, m, ArH, −CH of
−SO2C6H4I), 6.98 (2H, d, J = 8.8, −CH of −C6H4(OCH3)), 6.96−
6.91 (4H, m, ArH), 6.79 (2H, d, J = 8.8, −CH of −C6H4 (OCH3)),
6.33 (1H, br s, -NHTs), 4.30 (1H, d, J = 7.4, −CHNHTs), 3.78 (3H, s,
−OCH3), 3.61 (1H, d, J = 7.4, −CHNH (CH2)3-), 2.53−2.40 (3H, m,
−NH−CHHCH2 CH2 −), 2.31−2.26 (1H, m, −NH−
CHHCH2CH2−), 1.74−1.59 (2H, m, −NH−CH2CH2CH2−), 1.28
(1H, br s, −NH (CH2)3-); δC (100 MHz, CDCl3) 157.75 (C), 139.83
N-((S,S)-2-((3′,4′,5′-trimethoxy-[1,1′-biphenyl]-2-ylmethyl)-
amino)-1,2-diphenylethyl)-4-iodobenzenesulfonamide
Ruthenium(II) Chloride Complex (16).
J
DOI: 10.1021/acs.organomet.7b00731
Organometallics XXXX, XXX, XXX−XXX

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Article
(C), 139.05 (C), 137.94 (C), 137.56 (2CH), 133.70 (C), 129.17
(2CH), 128.38 (4CH), 128.08 (2CH), 127.57 (CH), 127.48 (3CH),
127.24 (2CH), 113.75 (2CH), 99.29 (C), 67.49 (CH), 63.09 (CH),
55.24 (OCH3), 46.40 (CH2), 32.32 (CH2), 31.60 (CH2); m/z ESI-MS
[M + H]+ 627.1.
{4-Iodo-N-((R,R)-2-(3-(4-Methoxyphenyl)propylamino)-1,2-
diphenylethyl)benzenesulfonamide} Ruthenium Chloride
Complex (22).
silica gel using EtOAc/petroleum ether (26/74) as an eluent to give
the pure product (R,R)-26 as a light green solid (0.426 g, 0.714 mmol,
28
89%): mp 48−50 °C; [α]D = +9.29 (c 0.280 in CHCl3); νmax 3263,
3060, 3030, 2931, 2834, 2159, 1611, 1590, 1510, 1453, 1395, 1244,
1153, 838, 758, 697 cm−1; δH (400 MHz, CDCl3) 7.37 (2H, d, J = 8.4,
−CH of −SO2C6H4-), 7.28 (2H, d, J = 8.4, −CH of −SO2C6H4−),
7.15−7.02 (6H, m, ArH), 6.99 (2H, d, J = 8.4, −CH of −C6H4(OCH3)),
6.95−6.89 (4H, m, ArH), 6.80 (2H, d, J = 8.4, −CH of −C6H4(OCH3)),
6.37 (1H, br s, −NHTs), 4.27 (1H, d, J = 8.0, −CHNHTs), 3.78
(3H, s, -OCH3), 3.59 (1H, d, J = 8.0, −CHNH(CH2)3−), 2.55−2.40
(3H, m, −NH−CHHCH2CH2−), 2.32−2.26 (1H, m, −NH−
CHHCH2CH2−), 1.75−1.61 (2H, m, −NH−CH2CH2CH2−), 1.37
(1H, br s, −NH (CH2)3−), 0.26 (9H, s, −Si(CH3)3); δC (100 MHz,
CDCl3) 157.75 (C), 139.59 (C), 139.06 (C), 137.96 (C), 133.72 (C),
131.82 (2CH), 129.18 (2CH), 128.37 (2CH), 128.01 (2CH), 127.58
(CH), 127.53 (2CH), 127.50 (CH), 127.28 (2CH), 127.01 (CH),
126.83 (2CH), 113.76 (2CH), 103.38 (C), 97.76 (C), 67.71 (CH),
63.31 (CH), 55.23 (OCH3), 46.42 (CH2), 32.33 (CH2), 31.63 (CH2),
−0.194 (Si (CH3)3); m/z ESI-MS [M + H]+ 597.2.
(R,R)-2-(3-(4-Methoxyphenyl)propylamino)-1,2-diphenylethyl)-
benzenesulfonamide (25; 0.300 g, 0.479 mmol, 1.0 equiv) and
[(C6H5CO2Et)RuCl2]2 (0.154 g, 0.150 mmol, 0.5 equiv) were
dissolved in dry DCM (15 mL) under N2 and stirred at room
temperature for 30 min to give a brick red solution. The mixture was
concentrated on a rotary evaporator to give a dark orange residue.
To this was added chlorobenzene (30 mL), and the mixture was
heated at 90 °C for 5 h. The reaction mixture was cooled to room
temperature and concentrated to give a dark brown residue. The solid
was scratched in diethyl ether, filtered, and dried to give a dark brown
solid. The solid was purified by column chromatography over Florisil
using DCM/MeOH (97/3 to 86/14) to give the compound as a
brown solid. The solid was recrystallized from MeOH to give pure
product (R,R)-22 as an orange solid (0.125 g, 0.164 mmol, 34%): mp
{N-((R,R)-2-(3-(4-Methoxyphenyl)propylamino)-1,2-dipheny-
lethyl)-4-(2-(trimethylsilyl)ethynyl)benzenesulfonamide}
Ruthenium Chloride Complex (23).
28
(R,R)-2-(3-(4-Methoxyphenyl)propylamino)-1,2-diphenylethyl)-4-(2-
(trimethylsilyl)ethynyl)benzenesulfonamide (26; 0.373 g, 0.626 mmol,
1.0 equiv) and [(C6H5CO2Et)RuCl2]2 (0.202 g, 0.313 mmol, 0.5 equiv)
were dissolved in dry DCM (15 mL) under N2 and stirred at room
temperature for 30 min to give a brick red solution. The mixture was
concentrated on a rotavap to give a dark orange residue. To this was
added chlorobenzene (30 mL), and the mixture was heated at 90 °C
for 5.5 h. The reaction mixture was cooled to room temperature and
concentrated to give a dark brown residue. The solid was scratched in
diethyl ether, filtered, and dried to give a dark brown solid. The solid
was purified by column chromatography over Florisil using DCM/
MeOH (97/3 to 86/14) to give the crude compound as a brown solid.
The solid was recrystallized from MeOH to give the pure complex
(R,R)-23 as an orange solid (0.094 g, 0.128 mmol, 20%): mp dec
>280 °C; [α]D28 = −328.33 (c 0.03 in CHCl3); HRMS found 697.1494,
calcd for C35H39N2O3RuSSi − Cl+ 697.1497, error −0.1 ppm; νmax
3190, 3051, 2936, 2917, 2156, 1533, 1465, 1454, 1257, 1181, 1041,
839, 814, 799, 760, 696 cm−1; δH (400 MHz, CDCl3) 7.31 (2H, d, J =
8.2, −CH of −SO2C6H4−), 7.16−7.07 (3H, m, ArH), 7.03 (2H, d, J =
8.4, −CH of −SO2C6H4−), 6.83−6.79 (3H, m, ArH), 6.68−6.64 (2H,
m, ArH), 6.55 (2H, d, J = 7.6, ArH), 5.55 (1H, d, J = 5.6, −CH of
Ru−Ar), 5.48 (1H, d, J = 5.6, −CH of Ru−Ar), 5.32 (1H, d, J = 6.0,
−CH of Ru−Ar), 5.28 (1H, d, J = 6.0, −CH of Ru−Ar), 4.30 (1H, d,
J = 11.2, −CHNTs), 4.06−3.99 (1H, m, -NH(CH2)3−), 3.96 (3H, s,
−OCH3), 3.62−3.56 (1H, m, −CHNH(CH2)3−), 2.81−2.75 (1H,
m, −NH−CHHCH2CH2−), 2.52−2.42 (1H, m, −NH−
CHHCH2CH2−), 2.24−2.48 (1H, m, −NH−CH2CH2CHH−),
2.34−2.26 (1H, m, −NH−CH2CH2CHH−), 2.13−1.95 (2H, m,
−NH−CH2CH2CH2−), 0.24 (9H, s, −Si(CH3)3); δC (100 MHz,
CDCl3) 146.67 (C), 138.45 (C), 136.21 (C), 134.65 (C), 130.72
(4CH), 128.72 (4CH), 128.41 (CH), 127.05 (2CH), 126.80 (2CH),
126.45 (CH), 123.15 (C), 104.97 (C), 96.68 (C), 91.18 (C), 84.62
(CH), 81.33 (CH), 78.79 (CH), 72.03 (CH), 68.84 (CH), 65.46
(CH), 56.80 (OCH3), 49.43 (CH2), 30.34 (CH2), 27.27 (CH2),
−0.006 (Si (CH3)3); m/z ESI-MS [M − Cl]+ 697.1.
dec >280 °C; [α]D = −164.54 (c 0.055 in CHCl3); HRMS found
727.0072, calcd for C30H30N2O3RuS − Cl+ 727.0067, error −1.4 ppm;
νmax 3198, 3051, 3027, 2925, 2872, 1572, 1533, 1509, 1465, 1454,
1279, 1266, 1255, 835, 796, 725, 694 cm−1; δH (500 MHz, CD2Cl2)
7.34 (2H, d, J = 8.3, −CH of −SO2C6H4I), 7.23−7.16 (3H, m, ArH),
7.10 (2H, d, J = 8.3, −CH of −SO2C6H4I), 6.96−6.86 (3H, m, ArH),
6.73−6.70 (2H, m, ArH), 6.60 (2H, d, J = 7.5, ArH), 5.55 (1H, d, J =
5.8, −CH of Ru−Ar), 5.51 (1H, d, J = 5.8, −CH of Ru−Ar), 5.37 (1H,
d, J = 6.0, −CH of Ru−Ar), 5.31 (1H, d, J = 6.0, −CH of Ru−Ar), 4.27
(1H, d, J = 11.0, −CHNTs), 4.00−3.96 (1H, m, −NH(CH2)3−), 3.96
(3H, s, −OCH3), 3.68−3.63 (1H, m, −CHNH(CH2)3−), 2.80−2.75
(1H, m, −NH−CHHCH2CH2−), 2.53−2.44 (2H, m, −NH−
CHHCH2CHH−), 2.34−2.29 (1H, m, −NH−CH2CH2CHH−),
2.16−2.10 (1H, m, −NH−CH2CHHCH2-), 2.02−1.93 (1H, m,
−NH−CH2CHHCH2-); δC (125 MHz, CD2Cl2) 147.61 (C), 138.96
(C), 136.87 (2CH), 136.80 (C), 135.27 (C), 129.45 (2CH), 129.21
(CH), 129.09 (4CH), 128.96 (CH), 127.64 (2CH), 126.83 (2CH),
95.45 (C), 91.85 (C), 85.34 (CH), 81.68 (CH), 79.63 (CH), 72.19
(CH), 69.13 (CH), 65.75 (CH), 57.19 (OCH3), 50.08 (CH2), 31.09
(CH2), 27.63 (CH2); m/z ESI-MS [M − Cl]+ 727.0.
N-((R,R)-2-(3-(4-Methoxyphenyl)propylamino)-1,2-dipheny-
lethyl)-4-(2-(trimethylsilyl)ethynyl)benzenesulfonamide (26).
In a glass tube, the diamine (R,R)-4-Iiodo-N-((R,R)-2-(3-(4-
methoxyphenyl)propylamino)-1,2-diphenylethyl)benzenesulfonamide
(25; 0.501 g, 0.8 mmol, 1.0 equiv), PdCl2(PPh3)4 (28 mg, 0.040 mmol,
0.05 equiv), and CuI (15.3 mg, 0.080 mmol, 0.1 equiv) were dissolved
in dry THF (10 mL) under an inert atmosphere followed by TEA
(2.5 mL). The resulting mixture was stirred for 5 min followed by
addition of trimethylsilylacetylene (0.382 mL, 2.71 mmol, 3.89 equiv).
The glass tube was sealed under an inert atmosphere, and the contents
were stirred at room temperature for 22 h. The reaction mixture
was filtered through Celite and washed with EtOAc (2 × 20 mL).
The filtrate was concentrated on a rotary evaporator to give a residue.
The crude compound was purified by column chromatography over
(R,R)-4-(2-(2-(2-Ethoxyethoxy)ethoxy)ethoxy)-N-1,2-
diphenylethyl)benzenesulfonamide.
K
DOI: 10.1021/acs.organomet.7b00731
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Organometallics
Article
To a mixture of (R,R)-DPEN (0.637 g, 3.00 mmol) and TEA (0.760 mL,
5.460 mmol, 1.82 equiv) in dry DCM (20 mL) was added a solution of
chloride C14H21ClO6S (1.056 g, 3.00 mmol, 1.0 equiv) in dry DCM
(10 mL) dropwise at 0 °C under an inert atmosphere. The resulting
light pink solution was stirred at 0 °C for 30 min and at room
temperature for 18 h. The mixture was concentrated on a rotary
evaporator to give a crude compound. The crude compound was
purified by column chromatography over silica gel using DCM/MeOH
(95/5) as eluent to give the pure product as an oil (1.380 g,
−OCH2CH2OCH2CH2OEt), 3.60−3.56 (3H, m, −CHNH(CH2)3−,
−OCH2CH2OCH2CH2OEt), 3.52 (2H, q, J = 7.2, −OCH2CH3), 2.54−
2.40 (3H, m, −NH−CHHCH2CH2−), 2.32−2.25 (1H, m, −NH−
CHHCH2CH2−), 1.73−1.61 (2H, m, −NH−CH2CH2CH2−), 1.45
(1H, br s, −NH(CH2)3−), 1.20 (3H, t, J = 7.2, −OCH2CH3); δC
(100 MHz, CDCl3) 161.59 (C), 157.72 (C), 139.26 (C), 138.26 (C),
133.78 (C), 131.86 (C), 129.17 (2CH), 129.12 (2CH), 128.28 (2CH),
127.90 (2CH), 127.55 (2CH), 127.46 (CH), 127.35 (2CH), 127.28
(CH), 114.20 (2CH), 113.73 (2CH), 70.88 (CH2), 70.71 (CH2), 70.62
(CH2), 69.79 (CH2), 69.41 (CH2), 67.73 (CH), 67.68 (CH2), 66.61
(CH2), 63.04 (CH), 55.22 (OCH3), 46.42 (CH2), 32.33 (CH2), 31.68
(CH2), 15.13 (CH3); m/z ESI-MS [M + H]+ 677.3.
28
2.614 mmol, 87%): [α]D = −11.15 (c 0.740 in CHCl3); HRMS
found 529.2354, calcd for C28H36N2O6S H+ 529.2367, error 1.6 ppm;
νmax 3280, 3062, 3030, 2972, 2868, 1594, 1580, 1495, 1453, 1323,
1301, 1255, 1179, 1094, 1054, 923, 832, 766, 698 cm−1; δH (400 MHz,
CDCl3) 7.34 (2H, d, J = 8.8, −CH of −SO2C6H4−), 7.18−7.14 (6H,
m, ArH), 7.11−7.09 (4H, m, ArH), 6.67 (2H, d, J = 8.8, −CH of
−SO2C6H4-), 6.01 (1H, br s, -NHTs), 4.35 (1H, d, J = 5.6, −CHNHTs),
4.11−4.08 (3H, m, −CHNH2, −C6H4−OCH2CH2O−), 3.85 (2H, t,
J = 4.8, −C6H4−OCH2CH2O−), 3.75−3.72 (2H, m, −OCH2CH2O−
CH2CH2OEt), 3.70−3.68 (2H, m, −OCH2CH2OCH2CH2OEt),
3.67−3.64 (2H, m, −OCH2CH2OCH2CH2OEt), 3.61−3.57 (2H, m,
−OCH2CH2OCH2CH2OEt), 3.52 (2H, q, J = 7.1, −OCH2CH3), 1.51
(2H, br s, −NH2), 1.20 (3H, t, J = 7.1, −OCH2CH3); δC (100 MHz,
CDCl3) 161.49 (C), 141.46 (C), 139.18 (C), 131.93 (C), 128.86
(2CH), 128.41 (2CH), 128.21 (2CH), 127.51 (CH), 127.37 (CH),
127.01 (2CH), 126.51 (2CH), 114.25 (2CH), 70.88 (CH2), 70.72
(CH2), 70.63 (CH2), 69.79 (CH2), 69.41 (CH2), 67.66 (CH2), 66.61
(CH2), 63.15 (CH), 60.52 (CH), 15.13 (CH3); m/z ESI-MS
[M + H]+ 529.2.
(R,R)-{4-(2-(2-(2-Ethoxyethoxy)ethoxy)ethoxy)-N-(2-(3-(4-
methoxyphenyl)-propylamino)-1,2-diphenylethyl)-
benzenesulfonamide} Ruthenium Chloride Complex (24).
(R,R)-4-(2-(2-(2-Ethoxyethoxy)ethoxy)ethoxy)-N-2-(3-(4-methoxy-
phenyl)-propylamino)-1,2-diphenylethyl)benzenesulfonamide (27;
0.203 g, 0.300 mmol, 1.0 equiv) and [(C6H5CO2Et)RuCl2]2
(0.097 g, 0.150 mmol, 0.5 equiv) were dissolved in dry DCM
(15 mL) under N2 and stirred at room temperature for 30 min to give
a brick red solution. The mixture was concentrated on a rotary evapo-
rator to give a dark orange residue. To this was added chlorobenzene
(20 mL), and the mixture was heated at 90 °C for 6 h. The reaction
mixture was cooled to room temperature and concentrated to give a
dark brown residue. The solid was scratched in diethyl ether, filtered,
and dried to give a dark brown solid. The solid was purified by column
chromatography over Florisil using DCM/MeOH (97/3 to 86/14) to
give (R,R)-24 as a brown solid. The solid was recrystallized from
MeOH to give the pure complex as an orange-brown solid (0.075 g,
(R,R)-4-(2-(2-(2-Ethoxyethoxy)ethoxy)ethoxy)-N-(2-(3-(4-
methoxyphenyl)propylamino)-1,2-diphenylethyl)-
benzenesulfonamide (27).
29
0.092 mmol, 30%): mp dec >180 °C; [α]D = +646.7 (c 0.003 in
CHCl3); HRMS found 777.2163, calcd for C38H47N2O7RuS − Cl+
777.2151, error −2.0 ppm; νmax 3191, 3059, 3027, 2865, 1725, 1594,
1536, 1510, 1494, 1453, 1248, 1124, 1081, 1038, 1011, 938, 906, 815,
801. 698 cm−1; δH (400 MHz, CDCl3) 7.31 (2H, d, J = 8.6, −CH of
−SO2C6H4−), 7.17−7.06 (3H, m, ArH), 6.85−6.74 (3H, m, ArH),
6.68−6.64 (2H, m, −ArH), 6.55 (2H, d, J = 7.2, ArH), 6.46 (2H, d,
J = 8.6, −CH of −SO2C6H4−), 5.55 (1H, d, J = 4.2, −CH of Ru−Ar),
5.47 (1H, d, J = 4.2, −CH of Ru−Ar), 5.34 (1H, d, J = 5.4, −CH of
Ru−Ar), 5.26 (1H, d, J = 5.4, −CH of Ru−Ar), 4.30 (1H, d, J = 10.8,
−CHNTs), 4.06−3.94 (6H, m, −C6H4−OCH2CH2O−, −OCH3,
−NH(CH2)3−), 3.81 (2H, t, J = 4.8, −C6H4−OCH2CH2O−),
3.72−3.65 (6H, m, −OCH2CH2OCH2CH2OEt), 3.61−3.57 (2H, m,
−OCH2CH2OCH2CH2OEt, −CHNH(CH2)3−), 3.52 (2H, q, J = 7.0,
−OCH2CH3), 2.82−2.72 (1H, m, −NH−CHHCH2CH2−), 2.51−2.37
(2H, m, −NH−CHHCH2CHH−), 2.33−2.27 (2H, m, −NH−
CH2CH2CHH−), 2.17−1.96 (2H, m, −NH−CH2CH2CH2−), 1.20
(3H, t, J = 7.0, −OCH2CH3); δC (100 MHz, CDCl3) 158.92 (C),
139.06 (C), 138.65 (C), 136.28 (C), 134.60 (C), 128.75 (2CH),
128.62 (6CH), 128.31 (CH), 126.92 (2CH), 126.16 (CH), 113.12
(2CH), 91.10 (C), 84.65 (CH), 81.49 (CH), 78.56 (CH), 72.15
(CH), 7.77 (CH2), 70.66 (CH2), 70.58 (CH2), 69.76 (CH2), 69.55
(CH2), 68.91 (CH), 67.40 (CH2), 66.59 (CH2), 65.52 (CH), 56.76
(OCH3), 49.36 (CH2), 30.22 (CH2), 27.30 (CH2), 15.12 (CH3); m/z
ESI-MS [M − Cl]+ 777.1.
To a mixture of the alcohol 3-(4-methoxyphenyl)propanol (0.266 g,
1.60 mmol, 1.6 equiv) and 2,6-lutidine (0.245 mL, 2.10 mmol,
2.10 equiv) in dry DCM (15 mL) was added a solution of triflic
anhydride (1 M in DCM) (1.7 mL, 1.70 mmol, 1.70 equiv) dropwise
at 0 °C under an inert atmosphere. The resulting light pink solution
was stirred at 0 °C for 30 min and at room temperature for 60 min.
The mixture was again cooled to 0 °C. To this was added a solution of
(R,R)-4-(2-(2-(2-ethoxyethoxy)ethoxy)ethoxy)-N-1,2-diphenylethyl)-
benzenesulfonamide (0.560 g, 1.0 mmol, 1.0 equiv) and TEA (0.334 mL,
2.40 mmol, 2.4 equiv) in dry DCM (10 mL) dropwise at 0 °C. The
resulting yellow mixture was stirred at 0 °C for 30 min and then at room
temperature for 17 h. The reaction mixture was diluted with DCM
(20 mL) and washed with saturated NaHCO3 solution (3 × 20 mL).The
organic layer was separated, washed with H2O (2 × 20 mL) and brine
(15 mL), dried over anhydrous Na2SO4, filtered, and concentrated to
give the crude compound. The crude compound was purified by column
chromatography over silica gel using EtOAc/petroleum ether (70/30)
as eluent to give a residue. The residue was triturated in n-pentane (to
remove traces of 2,6-lutidine), but there was no solid separation. The
solvent was evaporated to give pure compound (R,R)-27 as an oil
28
(0.510 g, 0.754 mmol, 75%): [α]D = −11.9 (c 0.470 in CHCl3);
HRMS found 677.3254, calcd for C38H48N2O7S H+ 677.3255, error 0.3
ppm; νmax 3262, 5062, 3029, 2864, 1594, 1580, 1511, 1495, 1453, 1300,
1244, 1149, 1093, 1030, 924, 830, 770, 698 cm−1; δH (400 MHz,
CDCl3) 7.39 (2H, d, J = 8.8, −CH of −SO2C6H4−), 7.15−7.12 (3H, m,
ArH), 7.06−7.02 (3H, m, ArH), 7.00 (2H, d, J = 8.6, −CH of
−C6H4OCH3), 6.94−6.88 (4H, m, ArH), 6.80 (2H, d, J = 8.6, −CH of
−C6H4OCH3), 6.70 (2H, d, J = 8.8, −CH of −SO2C6H4−), 6.26 (1H,
br s, −NHTs), 4.22 (1H, d, J = 8.0, −CHNHTs), 4.11−4.08 (2H, m,
−C6H4−OCH2CH2O−), 3.85 (2H, t, J = 5.0, −C6H4−OCH2CH2O−),
3.78 (3H, s, -OCH3), 3.74−3.72 (2H, m, -OCH2CH2OCH2CH2OEt),
3.70−3.68 (2H, m, -OCH2CH2OCH2CH2OEt), 3.67−3.64 (2H, m,
N-(2-((Biphenyl-2-yl)methylamino)ethyl)-4-methylbenzene-
sulfonamide.
To biphenylcarboxaldehyde (182 mg, 1.00 mmol) were added
activated molecular sieves (1 g) and anhydrous MeOH (6 mL). To
this were added TsEN (246 mg, 1.10 mmol) and acetic acid (50 μL).
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DOI: 10.1021/acs.organomet.7b00731
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The reaction mixture was stirred at room temperature for 5 h, and
then NaBH3CN (251 mg, 4.00 mmol) was added and the reaction
mixture stirred at room temperature overnight. After this the reaction
was filtered and the solid washed with DCM. The filtrate and DCM
washings were combined and dried under reduced pressure. The
residue was then dissolved in anhydrous DCM and washed with 1 M
NaOH(aq) solution. The DCM phase was separated, dried over
Na2SO4, and filtered, and the solvent was removed under reduced
pressure to give the product as a pale yellow viscous oil (134 mg, 0.35
mmol, 70%): HRMS (found (ESI) M+ + H 381.1632, calcd for
C22H25N2O2S (M) 381.1631; νmax 3272, 2858, 1477, 1450, 1322, 1155,
1091, 814, 775, 750, 703 cm−1; δH (300 MHz, CDCl3) 7.67 (2H, d J =
8.1, SO2CHAr), 7.43−7.11 (13H, m, ArH and NH overlapping), 3.58
(2H, s, ArCH2N), 2.84 (2H, dd J = 6.5 and 4.8, CH2NHSO2), 2.50
(2H, dd, J = 6.5 and 4.8, CH2NH), 2.40 (3H, s, CH3); δC (75 MHz,
CDCl3) 142.64 (CAr), 141.24 (CAr), 140.53 (CAr), 136.39 (CAr),
136.22 (CAr), 129.57 (CHAr), 129.04 (2 CHAr), 128.50 (CHAr),
128.27 (2 CHAr), 127.68 (2 CHAr), 126.95 (CHAr), 126.62 (CHAr),
126.55 (CHAr), 126.49 (2 CHAr), 50.06 (CH2), 46.65 (CH2), 41.60
(CH2), 20.92 (CH3); m/z (ESI) 381.0 (M+ + 1).
atmosphere for 4 h to form the imine. To this was added NaBH3CN
(0.351 g, 5.580 mmol, 4.0 equiv), and the resulting mixture was stirred
at room temperature for 18 h. The reaction mixture was filtered and
concentrated to give a residue. This was dissolved in DCM (60 mL)
and washed with 1 M NaOH (2 × 25 mL), dried over anhydrous
Na2SO4, filtered, and evaporated on a rotary evaporator to give the
crude product. The crude compound was purified by flash column
chromatography over silica gel using EtOAc/petroleum ether (7/3) to
give the product as an oil. The compound solidified on standing
overnight (0.643 g, 1.307 mmol, 93%): mp 66−68 °C; HRMS found
493.2878, calcd for C30H40N2O2S H+ 493.2883, error 1.0 ppm);
νmax 3277, 2961, 2930, 2869, 1599, 1456, 1424, 1333, 1320, 1301,
1163, 1154, 747, 699, 677 cm−1; δH (400 MHz, CDCl3) 7.41−7.33
(4H, m, ArH), 7.32−7.27 (4H, m, −ArH), 7.24−7.20 (1H, m, ArH),
7.14 (2H, s, m-CH of −SO2C6H2−), 4.95 (1H, br s, −NHSO2−),
4.17−4.07 (2H, m, o-CH(CH3)2), 3.66 (2H, s, −NHCH2-biphenyl),
2.94−2.85 (3H, m, p-CH(CH3)2, −SO2NHCH2CH2NH−), 2.58−2.55
(2H, m, −SO2NHCH2CH2NH−), 1.33 (1H, s, −SO2NHCH2CH2NH−),
1.25 (6H, d, J = 6.8, p-CH(CH3)2), 1.22 (12H, d, J = 6.8, o-CH (CH3)2);
δC (100 MHz, CDCl3) 152.52 (C), 150.28 (2C), 141.76 (C), 141.06 (C),
136.95 (C), 132.12 (C), 130.11 (CH), 129.05 (CH), 128.81 (2CH),
128.24 (2CH), 127.47 (CH), 127.16 (CH), 127.10 (CH), 123.68
(2CH), 50.83 (CH2), 47.29 (CH2), 41.88 (CH2), 34.10 (CH), 29.56
(2CH), 24.85 (4CH3), 23.57 (2CH3); m/z ESI-MS [M + H]+ 493.2.
{N-[2-(Biphenyl-2-yl)methylamino]ethyl-2,4,6-triisopropyl-
benzenesulfonamide} Ruthenium Chloride Complex (29).
{N-(2-((Biphenyl-2-yl)methylamino)ethyl)-4-methylbenzene-
sulfonamide} Ruthenium Chloride Complex (28).
N-(2-((Biphenyl-2-yl)methylamino)ethyl)-4-methylbenzenesulfona-
mide (0.450 g, 1.184 mmol, 1.0 equiv) and [(C6H5CO2Et)RuCl2]2
(0.381 g, 0.592 mmol, 0.5 equiv) were dissolved in dry DCM (40 mL)
under N2 and stirred at room temperature for 30 min to give a brick
red solution. The mixture was concentrated on a rotary evaporator to
give a dark orange residue. To this was added chlorobenzene (60 mL),
and the mixture was heated at 140 °C for 5.5 h. The reaction mixture
was cooled to room temperature and concentrated to give a dark
brown residue. The solid was scratched in diethyl ether, filtered, and
dried to give a dark brown solid. The solid was purified by column
chromatography over Florisil using DCM/MeOH (95/5 to 86/14) to
give the compound as a brown solid. The solid was recrystallized using
a mixture of MeOH and Et2O to give pure complex 28 as a brown
solid (0.105 g, 0.203 mmol, 14%): mp dec >184 °C; HRMS found
481.0524, calcd for C22H23N2O2SRu − Cl+ 481.0523, error −0.7 ppm;
νmax 3059, 2922, 2855, 1596, 1480, 1439, 1260, 1182, 1129, 811, 747,
704, 659 cm−1; δH (600 MHz, CDCl3) 7.74 (2H, d, J = 6.9, m-CH of
−SO2C6H4CH3), 7.52−7.40 (4H, m, ArH), 7.16 (2H, d, J = 6.9, o-CH
of −SO2C6H4CH3), 6.67 (1H, br s, −CH of Ru−Ar), 5.81 (1H, br s,
−CH of Ru−Ar), 5.68 (1H, br s, −CH of Ru−Ar), 5.28 (1H, br s,
−CH of Ru−Ar), 5.25 (1H, br s, −CH of Ru−Ar), 4.78 (1H, br d,
−CH2−NH−CHH−C6H4−), 4.49 (1H, br s, −CHNH−CH2−), 4.28
(1H, br d, −CH2−NH−CHH−C6H4−), 3.07 (1H, br d, -NHTs−
CHH−), 2.59 (1H, br s, −CHH−NH−CH2−C6H4−), 2.33 (4H, br s,
−NHTs−CHH−, −CH3), 2.14 (1H, br s, −CHH−NH−CH2−
C6H4−); δC (150 MHz, CDCl3) 140.49 (C), 140.40 (C), 134.69
(C), 132.36 (C), 131.24 (CH), 129.81 (CH), 129.74 (CH), 129.37
(CH), 128.66 (2CH), 127.13 (2CH), 93.04 (C), 92.28 (CH), 90.62
(CH), 81.27 (CH), 78.90 (CH), 77.47 (CH), 57.75 (CH2), 55.43
(CH2), 48.25 (CH2), 21.31 (CH3); m/z ESI-MS [M − Cl]+ 480.9.
N-[2-(Biphenyl-2-yl)methylamino]ethyl-2,4,6-triisopropyl-
benzenesulfonamide.
N-[2-(Biphenyl-2-yl)methylamino]ethyl-2,4,6-triisopropylbenzenesul-
fonamide (0.500 g, 1.016 mmol, 1.0 equiv) and [(C6H5CO2Et)RuCl2]2
(0.327 g, 0.508 mmol, 0.5 equiv) were dissolved in dry DCM (50 mL)
under N2 and stirred at room temperature for 30 min to give a brick
red solution. The mixture was concentrated on a rotary evaporator
to give a dark orange residue. To this was added chlorobenzene
(150 mL), and the mixture was heated at 140 °C for 3.0 h. The reaction
mixture was cooled to room temperature and concentrated to give a
dark brown residue. The solid was purified by column chromatography
over Florisil using EtOAc/MeOH/petroleum ether (60/2/38 to 60/8/32)
to give 29 as a brown solid. The solid was recrystallized using mixture
of MeOH and Et2O to give pure complex 29 as an orange solid (0.110 g,
0.175 mmol, 17%): mp dec >280 °C; HRMS found 593.1776, calcd for
C30H39N2O2SRu − Cl+ 593.1777, error −0.5 ppm; νmax 3189, 2960,
2947, 2864, 1598, 1455, 1437, 1267, 1246, 1123, 1055, 842, 816, 767,
748, 648 cm−1; δH (400 MHz, CDCl3) 7.53−7.47 (2H, m, ArH),
7.46−7.42 (1H, m, ArH), 7.39−7.38 (1H, m, ArH), 7.07 (2H, s, m-CH
of −SO2C6H2−), 6.83 (1H, t, J = 5.6,−CH of Ru−Ar), 6.03 (1H, t, J =
5.6,−CH of Ru−Ar), 5.77 (1H, t, J = 5.6,−CH of Ru−Ar), 5.39 (1H, d,
J = 5.6,−CH of Ru−Ar), 5.34 (1H, d, J = 5.6,−CH of Ru−Ar),
4.64−4.60 (1H, m, −NHCHH−biphenyl), 4.52−4.42 (2H, m,
o-CH(CH3)2), 4.40−4.31 (2H, m, −NHCHH−biphenyl), 2.90−2.83
(1H, m, p-CH(CH3)2), 2.73−2.70 (1H, m, −SO2NHCHHCH2NH−),
2.64−2.56 (2H, m, −SO2NHCHHCHHNH−), 2.31−2.22 (1H, m,
−SO2NHCH2CHHNH−), 1.23−1.20 (18H, m, o,p-CH(CH3)2); δC
(100 MHz, CDCl3) 150.60 (C), 150.42 (2C), 134.89 (C), 134.85 (C),
132.92 (C), 131.02 (CH), 129.85 (CH), 129.75 (CH), 129.51 (CH),
123.13 (2CH), 92.86 (C), 90.40 (CH), 89.49 (CH), 82.50 (CH), 78.87
(CH), 76.46 (CH), 58.03 (CH2), 55.96 (CH2), 48.07 (CH2), 33.97
(CH), 29.02 (2CH), 25.47 (2CH3), 24.81 (2CH3), 23.66 (2CH3); m/z
ESI-MS [M − Cl]+ 593.1.
N-[2-(4′-Methoxy-1,1′-biphenyl-2-yl)methylamino]ethyl-
2,4,6-triisopropylbenzenesulfonamide.
To a mixture of N-2-(2,4,6-triisopropyl)benzenesulfonamido)-
ethylamine (0.500 g, 1.534 mmol, 1.10 equiv) and MS 4A (0.6 g) in
dry methanol (25 mL) was added biphenyl-2-carboxaldehyde (0.254 g,
1.395 mmol, 1.0 equiv) followed by acetic acid (three to four drops).
The mixture was stirred at room temperature under an inert
M
DOI: 10.1021/acs.organomet.7b00731
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Organometallics
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To a mixture of N-2-(2,4,6-triisopropyl)benzenesulfonamido)-
ethylamine (0.500 g, 1.534 mmol, 1.10 equiv) and MS 4A (0.6 g) in
dry methanol (25 mL) was added 4′-methoxy-[1,1′-biphenyl]-2-
carboxaldehyde (0.296 g, 1.395 mmol, 1.0 equiv) followed by acetic
acid (three to four drops). The mixture was stirred at room temper-
ature under an inert atmosphere for 4 h to form the imine. To this was
added NaBH3CN (0.351 g, 5.580 mmol, 4.0 equiv), and the resulting
mixture was stirred at room temperature for 18 h. The reaction
mixture was filtered and concentrated to give a residue. This was
dissolved in DCM (60 mL) and washed with 1 M NaOH (2 × 25 mL),
dried over anhydrous Na2SO4, filtered, and evaporated on a rotary
evaporator to give the crude product. The crude compound was purified
by flash column chromatography over silica gel using EtOAc/petroleum
ether (6/4) to give the product as an oil. The compound solidified on
standing overnight (0.728 g, 1.39 mmol, 99%).: mp 60−62 °C; HRMS
found 523.2294, calcd for C31H42N2O3S H+ 523.2989, error −0.7 ppm;
νmax 3291, 3244, 2961, 2929, 2834, 1610, 1600, 1459, 1445, 1164, 1098,
1072, 1016, 763, 706, 650 cm−1; δH (300 MHz, CDCl3) 7.33−7.21
(6H, m, ArH), 7.14 (2H, s, m-CH of −SO2C6H2−), 6.94 (2H, d, J =
12.0, −ArH), 4.97 (1H, br s, −NHSO2−), 4.19−4.05 (2H, m,
o-CH(CH3)2), 3.85 (3H, s, −OCH3), 3.66 (2H, s, −NHCH2-biphenyl),
2.95−2.82 (3H, m, p-CH(CH3)2, −SO2NHCH2CH2NH−), 2.60−2.57
(2H, m, −SO2NHCH2CH2NH−), 1.28 (1H, s, −SO2NHCH2CH2NH−),
1.25−1.2 (18H, m, o, p-CH(CH3)2); δC (75 MHz, CDCl3) 158.77
(C), 152.53 (C), 150.28 (2C), 141.41 (C), 137.11 (C), 133.35 (C),
132.12 (C), 130.31 (CH), 129.88 (2CH), 129.06 (CH), 127.20 (CH),
127.09 (CH), 123.68 (2CH), 113.67 (2CH), 55.25 (OCH3), 50.97
(CH2), 47.36 (CH2), 41.94 (CH2), 34.08 (CH), 29.57 (2CH), 24.85
(4CH3), 23.56 (2CH3); m/z ESI-MS [M + H]+ 523.2.
Asymmetric Hydrogenation Procedures. Asymmetric Transfer
Hydrogenation in Water. The catalyst (0.01 mmol) was placed in a
Schlenk tube under an inert atmosphere followed by HCOONa
(0.340 g, 5.0 mmol) and H2O (1 mL). The mixture was degassed three
times, and to this solution was added ketone (1 mmol) followed by
degassing two times. The mixture was stirred at 60 °C. The reaction
was monitored by chiral GC. For chiral GC analysis, the sample from
the reaction mixture was diluted with Et2O and H2O. The organic
layer was separated and filtered through a short column of silica using
hexane/EtOAc (1/1). The filtrate was analyzed by chiral GC. After
completion of the reaction, the reaction mixture was diluted with H2O
and extracted with Et2O (2 × 5 mL). The organic layers were
combined, dried over anhydrous Na2SO4, filtered, and concentrated to
give the crude compound. The crude compound was purified by flash
column chromatography to give the pure product.
Asymmetric Transfer Hydrogenation in FA/TEA. To a mixture of
the catalyst (0.002 mmol) in FA/TEA (5/2) (1.0 mL) was added
ketone (2.0 mmol), and the mixture was stirred at 60 °C for 24 h
under an inert atmosphere. The reaction was monitored by TLC. After
24 h, the reaction mixture was diluted with EtOAc and saturated
NaHCO3 solution. The organic layer was separated, washed with H2O,
dried over anhydrous Na2SO4, filtered, and concentrated to give a
1
brown residue. The crude compound was analyzed by H NMR to
give the conversion.
Reduction of Ketones with Hydrogen Gas. As an example,
acetophenone (100 mg, 0.83 mmol), catalyst (0.01 equiv, 1 mol %),
and iPrOH (0.5 mL) were placed in a small test tube containing a
stirrer bar. A solution of K2CO3 (5.8 mg, 0.042 mmol) in water
(0.2 mL) or TMAO (1 mol %) was added, and then the test tube was
sealed in a Parr hydrogenator and charged with hydrogen to 30 bar,
venting once. The sealed vessel was heated to the temperature
indicated and stirred for the time given in the table. At the end of this
time, the reaction mixture was cooled to room temperature, the
pressure was carefully released, and the sample was worked up and
analyzed as previously described.
{N-[2-(4′-Methoxy-1,1′-biphenyl-2-yl)methylamino]ethyl-
2,4,6-triisopropylbenzenesulfonamide} Ruthenium Chloride
Complex (30).
Data for the Reduction Products. (R)-1-Phenylethanol.
N-[2-(4′-Methoxy-1,1′-biphenyl-2-yl)methylamino]ethyl-2,4,6-triiso-
propylbenzenesulfonamide (0.500 g, 0.958 mmol, 1.0 equiv) and
[(C6H5CO2Et)RuCl2]2 (0.308 g, 0.479 mmol, 0.5 equiv) were
dissolved in dry DCM (50 mL) under N2 and stirred at room
temperature for 30 min to give a brick red solution. The mixture was
concentrated on a rotary evaporator to give a dark orange residue.
To this was added chlorobenzene (150 mL), and the mixture was
heated at 140 °C for 2.5 h. The reaction mixture was cooled to room
temperature and concentrated to give a dark brown residue. The solid
was purified by column chromatography over Florisil using EtOAc/
MeOH/petroleum ether (60/1/39 to 60/5/35) to give a brown solid.
The solid was recrystallized using a mixture of MeOH and Et2O to
give pure complex 30 as an orange solid (0.064 g, 0.097 mmol, 10%):
mp dec >270 °C; HRMS found 623.1886, calcd for C31H41N2O3SRu
− Cl+ 623.1883, error −1.3 ppm; νmax 3197, 2952, 2858, 1598, 1537,
1461, 1441, 1249, 1230, 1041, 1018, 860, 804, 770, 652 cm−1; δH
(600 MHz, CDCl3) 7.53−7.41 (3H, m, ArH), 7.35−7.33 (1H, m, ArH),
7.04 (2H, s, m-CH of −SO2C6H2−), 6.67 (1H, d, J = 5.2, −CH of
Ru−Ar), 5.82 (1H, d, J = 5.2,−CH of Ru−Ar), 5.63 (1H, d, J =
6.2,−CH of Ru−Ar), 5.35 (1H, d, J = 6.2,−CH of Ru−Ar), 4.93 (1H,
d, J = 14.0, −NHCHH−biphenyl), 4.60 (1H, br d, −NHCH2),
4.48−4.38 (2H, m, o-CH(CH3)2), 4.40−4.31 (1H, d, J = 14.0,
−NHCHH−biphenyl), 4.04 (3H, s, −OCH3), 2.88−2.78 (1H,
m, p-CH(CH3)2), 2.50 (2H, br d, −SO2NHCH2CH2NH−), 2.33
(1H, br d, −SO2NHCH2CHHNH−), 1.95−1.85 (1H, m,
−SO2NHCH2CHHNH−), 1.21 (6H, d, J = 6.8, p-CH(CH3)2), 1.17
(6H, d, J = 6.8, o-CH(CH3)2), 1.11 (6H, d, J = 6.8, o-CH(CH3)2); δC
(100 MHz, CDCl3) 150.60 (C), 150.35 (2C), 134.83 (C), 134.51 (C),
131.86 (C), 131.53 (CH), 129.89 (CH), 129.66 (2CH), 127.36 (C),
123.15 (2CH), 86.13 (C), 82.33 (CH), 81.76 (CH), 75.34 (CH),
70.31 (CH), 56.82 (OCH3), 56.59 (CH2), 54.04 (CH2), 47.83 (CH2),
33.92 (CH), 28.77 (2CH), 25.51 (2CH3), 24.65 (2CH3), 23.62
(2CH3); m/z ESI-MS [M − Cl]+ 623.1.
This compound was prepared by the general procedure for ketone
reduction using acetophenone (73 mg, 0.61 mmol), catalyst (R,R)-14
(4.0 mg, 0.005 mmol), and FA/TEA (0.5 mL). Following solvent
removal, the product was isolated as a colorless oil (50 mg, 0.41 mmol,
68% yield, conversion >99%): [α]D = +47.4 (c = 0.50, CHCl3), 97%
ee (R), (lit.18 [α]D = +45.3 (c = 1.00, CHCl3) 98% ee (R)); δH
(300 MHz, CDCl3) 7.21−7.54 (5 H, m, ArH), 4.88 (1 H, q, J = 6.4,
CHOH), 1.97 (1 H, s, OH), 1.49 (3 H, d, J = 6.5, CH3); δC
(101 MHz, CDCl3) 145.82, 128.52, 128.33, 127.49, 125.39, 77.35,
77.03, 76.71, 70.45, 25.17. Conversion and enantiomeric excess were
determined by chiral GC analysis (CROMPAC CYCLODEXTRIN-β-
236M-19, 50 m × 0.25 mm × 0.25 μm, gas hydrogen, T = 110 °C,
P = 18 psi, FID temp 220 °C, injector temp 220 °C): ketone 11.8 min,
R isomer 17.6 min, S isomer 19.3 min.
(R)-1-(2-Methoxyphenyl)ethanol.
This compound was prepared by the general procedure for ketone
reduction using o-methoxyacetophenone (31; 73 mg, 0.49 mmol),
catalyst (R,R)-14 (4.0 mg, 0.005 mmol), and FA/TEA (0.5 mL).
Following solvent removal the product was isolated as a colorless oil
(48 mg, 0.31 mmol, 65% yield, conversion 97%): [α]D = +16.4 (c = 0.39,
CHCl3), 87% ee (R), (lit.18 [α]D = +16.0 (c = 1.00, CHCl3) 65%
ee (R)); δH (300 MHz, CDCl3): 7.11−7.48 (2 H, m, ArH), 6.75−7.08
(2 H, m, ArH), 4.97−5.22 (1 H, m, CHOH), 3.86 (3 H, s, OCH3),
2.52−2.71 (1 H, m, OH), 1.51 (3 H, d, J = 6.6, CH3); δC (101 MHz,
CDCl3) 156.52, 133.70, 133.56, 130.39, 128.27, 126.09, 120.81,
N
DOI: 10.1021/acs.organomet.7b00731
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
120.57, 111.60, 110.43, 77.44, 77.13, 76.80, 66.38, 55.49, 55.26, 31.84,
22.95. Conversion and enantiomeric excess were determined by
chiral GC analysis (CROMPAC CYCLODEXTRIN-β-236M-19,
50 m × 0.25 mm × 0.25 μm, gas hydrogen, T = 130 °C, P = 18 psi,
FID temp 220 °C, injector temp 250 °C): ketone 19.2 min, S isomer
23.7 min, R isomer 24.3 min.
(S)-2-Chloro-1-phenylethanol.
This compound was prepared by the general procedure for ketone
reduction using 2-chloroacetophenone (35; 77 mg, 0.50 mmol),
catalyst (R,R)-14 (4.1 mg, 0.005 mmol), and FA/TEA (0.5 mL).
Following solvent removal the product was isolated as a colorless oil
(46 mg, 0.29 mmol, 59% yield, >99% conversion): [α]D = +89.5 (c =
0.31, CHCl3), 97% ee (S), (lit.1f [α]D = +61.8 (c = 1.00, CHCl3) 96%
ee (S)); δH (300 MHz, CDCl3) 7.30−7.49 (5 H, m, ArH), 4.92 (1 H,
dt, J = 8.8, 3.3, CHOH), 3.76 (1 H, dd, J = 11.2, 3.4, CH2Cl), 3.66
(1 H, dd, J = 11.2, 8.8, CH2Cl), 2.62−2.73 (1 H, m, OH); δC (101 MHz,
CDCl3) 139.88, 129.73, 129.24, 128.65, 128.45, 126.12, 126.03, 77.32,
76.68, 74.05, 50.90. Conversion and enantiomeric excess were
determined by chiral GC analysis (CROMPAC CYCLODEXTRIN-
β-236M-19, 50 m × 0.25 mm × 0.25 μm, gas hydrogen, T = 130 °C,
P = 18 psi, FID temp 250 °C, injector temp 220 °C): ketone 24.2 min,
S isomer 29.9 min, R isomer 32.0 min.
(R)-1-(4-Methoxyphenyl)ethanol.
This compound was prepared by the general procedure for ketone
reduction using p-methoxyacetophenone (32; 76 mg, 0.50 mmol),
catalyst (R,R)-14 (4.0 mg, 0.005 mmol), and FA/TEA (0.5 mL).
Following solvent removal the product was isolated as a colorless oil
(55 mg, 0.36 mmol, 72% yield, 94% conversion): [α]D = +58.3 (c = 0.53,
CHCl3), 96% ee (R), (lit.19 [α]D = +56.8 (c = 1.00, CHCl3) 95%
ee (R)); δH (300 MHz, CDCl3): 7.28−7.35 (2 H, m, ArH), 6.84−6.95
(2 H, m, ArH), 4.87 (1 H, dd, J = 6.4, 2.6, CHOH), 3.82 (3 H, s,
OCH3), 1.79 (1 H, br. s, OH), 1.49 (3 H, d, J = 6.6, CH3); δC
(101 MHz, CDCl3) 158.79, 138.01, 130.51, 126.56, 113.68, 113.58,
77.32, 76.68, 69.73, 55.33, 55.14, 26.18, 24.92. Conversion and
enantiomeric excess were determined by chiral GC analysis
(CROMPAC CYCLODEXTRIN-β-236M-19, 50 m × 0.25 mm ×
0.25 μm, gas hydrogen, T = 130 °C, P = 18 psi, FID temp 220 °C,
injector temp 250 °C): ketone 28.7 min, R isomer 29.6 min, S isomer
31.0 min.
(R)-1-Phenylpropanol.
This compound was prepared by the general procedure for ketone
reduction using propiophenone (36; 69 mg, 0.52 mmol), catalyst
(R,R)-14 (4.0 mg, 0.005 mmol), and FA/TEA (0.5 mL). Following
solvent removal the product was isolated as a colorless oil (36 mg,
0.26 mmol, 51% yield, 99% conversion): [α]D = +69.7 (c = 0.39,
CHCl3), 94% ee (R), (lit.1f [α]D = +53.6 (c = 0.75, CHCl3) 98% ee
(R)); δH (400 MHz, CDCl3) 7.22−7.38 (5 H, m, ArH), 4.58 (1 H, t,
J = 6.4, ArCHOH), 1.91 (1 H, br s, OH), 1.68−1.88 (2 H, m, CH2),
0.91 (3 H, t, J = 7.5, CH3); δC (101 MHz, CDCl3) 144.57, 128.37,
127.47, 125.94, 77.32, 76.68, 76.00, 31.86, 10.11. Conversion and
enantiomeric excess were determined by chiral GC analysis
(CROMPAC CYCLODEXTRIN-β-236M-19, 50 m × 0.25 mm ×
0.25 μm, gas hydrogen, T = 130 °C, P = 18 psi, FID temp 250 °C,
injector temp 220 °C): ketone 30.7 min, R isomer 61.7 min, S isomer
66.2 min.
(R)-1-(2-Chlorophenyl)ethanol.
This compound was prepared by the general procedure for ketone
reduction using o-chloroacetophenone (33; 98 mg, 0.63 mmol),
catalyst (R,R)-14 (3.8 mg, 0.0025 mmol), and FA/TEA (0.5 mL).
Following solvent removal the product was isolated as a colorless oil
(60 mg, 0.38 mmol, 61% yield, >99% conversion): [α]D = +64.8 (c =
0.42, CHCl3), 88% ee (R), (lit.18 [α]D = +68.0 (c = 1.00, CHCl3) 98%
ee (R)); δH (300 MHz, CDCl3): 7.58 (1 H, d, J = 7.7, ArH), 7.31
(2 H, t, J = 7.8, ArH), 7.19 (1 H, td, J = 7.6, 1.5, ArH), 5.27 (1 H, q,
J = 5.8, CHOH), 2.48 (1 H, br s, OH), 1.48 (3 H, d, J = 6.5, CH3);
δC (101 MHz, CDCl3) 143.03, 131.53, 129.30, 128.30, 127.13, 126.35,
77.32, 76.68, 66.83, 23.44. Conversion and enantiomeric excess were
determined by chiral GC analysis (CROMPAC CYCLODEXTRIN-β-
236M-19, 50 m × 0.25 mm × 0.25 μm, gas hydrogen, T = 140 °C,
P = 18 psi, FID temp 250 °C, injector temp 220 °C): ketone 9.0 min,
R isomer 14.9 min, S isomer 16.9 min.
(R)-1-(Furan-2-yl)ethanol.
This compound was prepared by the general procedure for ketone
reduction using 2-acetylfuran (37; 118 mg, 1.08 mmol), catalyst (R,R)-
14 (8.1 mg, 0.010 mmol), and FA/TEA (0.5 mL). Following solvent
removal the product was isolated as a colorless oil (78 mg, 0.70 mmol,
65% yield, 99% conversion): [α]D = +24.7 (c = 0.36, CHCl3), 94% ee
(R), (lit.7 [α]D = +24.9 (c = 0.90, CHCl3) 98% ee (R)); δH (400 MHz,
CDCl3) 7.33−7.43 (1 H, m, CH furyl), 6.34 (1 H, dd, J = 3.2, 1.8, CH
furyl), 6.24 (1 H, d, J = 3.2, CH furyl), 4.80−4.95 (1 H, m, CHOH),
1.97 (1 H, br s, OH), 1.55 (3 H, d, J = 6.6, CH3); δC (101 MHz,
CDCl3) 157.58, 141.91, 110.11, 105.09, 77.32, 76.68, 63.64, 21.26.
Conversion and enantiomeric excess were determined by chiral GC
analysis (CROMPAC CYCLODEXTRIN-β-236M-19, 50 m ×
0.25 mm × 0.25 μm, gas hydrogen, T = 75 °C, P = 18 psi, FID temp
250 °C, injector temp 220 °C): ketone 16.3 min, R isomer 26.2 min,
S isomer 28.0 min.
(R)-1-(4-Chlorophenyl)ethanol.
This compound was prepared by the general procedure for ketone
reduction using 4′-chloroacetophenone (34; 83 mg, 0.54 mmol),
catalyst (R,R)-14 (4.1 mg, 0.005 mmol), and FA/TEA (0.5 mL).
Following solvent removal the product was isolated as a colorless oil
(53 mg, 0.34 mmol, 63% yield, 99% conversion): [α]D = +51.7 (c =
0.23, CHCl3), 94% ee (R), (lit.20 [α]D = +56.4 (c = 1.00, CHCl3) 95%
ee (R)); δH (300 MHz, CDCl3): 7.21−7.40 (4 H, m, ArH), 4.87 (1 H,
q, J = 6.5, CHOH), 2.07 (1 H, br s, OH), 1.47 (3 H, d, J = 6.5, CH3);
δC (101 MHz, CDCl3) 144.20, 133.02, 128.56, 126.76, 77.32, 76.68,
69.69, 25.21. Conversion and enantiomeric excess were determined by
chiral GC analysis (CROMPAC CYCLODEXTRIN-β-236M-19,
50 m × 0.25 mm × 0.25 μm, gas hydrogen, T = 130 °C, P = 18 psi,
FID temp 250 °C, injector temp 220 °C) :ketone 15.6 min, R isomer
25.9 min, S isomer 28.7 min.
(R)-Cyclohexylethanol.
This compound was prepared by the general procedure for ketone
reduction using cyclohexyl methyl ketone (38; 61 mg, 0.48 mmol),
catalyst (S,S)-15 (4.2 mg, 0.005 mmol), and FA/TEA (0.5 mL).
Following solvent removal the product was isolated as a colorless oil
O
DOI: 10.1021/acs.organomet.7b00731
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
(38 mg, 0.29 mmol, 60% yield, 97% conversion): [α]D = −1.20
(c = 0.57, CHCl3), 71% ee (R), (lit.21 [α]D = −3.01 (c = 1.20, CHCl3)
87% ee (R)); δH (300 MHz, CDCl3) 3.54 (1 H, quin, J = 6.2, CHOH),
1.60−1.93 (6 H, m, Cy-CH2), 1.54 (1 H, s, OH), 1.17−1.35 (3 H, m,
Cy-CH2 and Cy-CH), 1.15 (3 H, d, J = 6.3, CH3), 0.83−1.09 (2 H, m,
Cy-CH2); δC (75 MHz, CDCl3) 77.43, 76.58, 72.15, 45.08, 28.65,
28.32, 26.47, 26.19, 26.10, 20.32. Enantiomeric excess was determined
by conversion to the acetate derivative (CP-CHIRASIL-DEX CB 50 m
x 0.25 mm x 0.25 μm, gas helium, T = 115 °C, P = 9 psi, det = FID
220 °C, injector temp 220 °C): ketone 24.6 min, S isomer 39.3 min, R
isomer 42.1 min.
(CROMPAC CYCLODEXTRIN-β-236M-19, 50 m × 0.25 mm ×
0.25 μm, gas helium, T = 125 °C, P = 15 psi, FID temp 250 °C,
injector temp 220 °C): ketone 67.9 min, R isomer 81.9 min, S isomer
84.3 min.
(R)-Chroman-4-ol.
This compound was prepared by the general procedure for ketone
reduction using 4-chromanone (42; 148 mg, 1.0 mmol), catalyst
(R,R)-11 (1.7 mg, 0.0025 mmol), and FA/TEA (0.5 mL). Following
solvent removal the product was isolated as a colorless oil (117 mg,
0.78 mmol, 78% yield, conversion 100%): [α]D = +64.63 (c = 0.55,
CHCl3), 99% ee (R), (lit.24 [α]D = +60.1 (c = 0.20, CHCl3) 96% ee
(R)); δH (300 MHz, CDCl3) 7.35−7.15 (2 H, m, ArH), 6.98−6.79 (2
H, m, ArH), 4.78 (1 H, d, J = 4.6, CHOH), 4.26 (2 H, d, J = 9.4, CH2),
2.21−1.95 (2 H, m, CH2), 1.92 (1 H, d, J = 4.6, OH); δC (75 MHz,
CDCl3) 154.71, 129.85, 124.44, 120.72, 117.21, 63.38, 62.05, 30.95.
Conversion and enantiomeric excess were determined by chiral HPLC
analysis: (IB, eluent hexanes/iPrOH 95/5, detector 250 nm, flow rate
1.0 mL/min): ketone 6.7 min, R isomer 9.0 min, S isomer 9.9 min.
The ketone response is 20.12 times greater than that for the alcohol.
(S)-1-Phenyl-2-phenoxyethanol.
This compound was prepared by the general procedure for ketone
reduction using α-OPh acetophenone (39; 425 mg, 2.0 mmol),
catalyst (R,R)-11 (3.5 mg, 0.005 mmol), and FA/TEA (1.0 mL).
Following solvent removal the product was isolated as a white solid
(323 mg, 1.51 mmol, 75% yield, conversion 100%): [α]D = +56.6 (c =
0.35, CHCl3), 93% ee (S), (lit.5b [α]D = +58.8 (c = 1.00, CHCl3) 95%
ee (S)); δH (300 MHz, CDCl3) 7.51−7.32 (4 H, m, ArH), 7.37−7.22
(2 H, m, ArH), 7.03−6.87 (3H, m, ArH), 5.13 (1 H, d, J = 9.1,
CH(OH)), 4.17−4.06 (1 H, m, CHH), 4.01 (1 H, t, J = 9.1, CHH),
2.78 (1 H, S, OH); δC (75 MHz, CDCl3) 158.51, 139.76, 129.71,
128.72, 128.34, 126.43, 121.46, 114.78, 73.44, 72.75. Conversion and
enantiomeric excess were determined by chiral HPLC analysis
(OD, eluent hexanes/iPrOH 90/10, detector 250 nm, flow rate
0.7 mL/min): ketone 21.9 min, R isomer 18.0 min, S isomer 31.1 min.
The ketone UV response is 12.35 times greater than that for the
alcohol.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the ACS
Publications website at DOI: 10.1021/acs.organomet.7b00731.
■
S
1H and 13C NMR spectra of new ligands and complexes,
chiral GC and HPLC of reduction products, and X-ray
crystallographic data for (R,R)-11 and 29 (PDF)
(R)-(4-Trifluoromethylphenyl)ethanol.
Accession Codes
CCDC 1571334−1571335 contain the supplementary crystal-
lographic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif, or by email-
ing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
This compound was prepared by the general procedure for ketone
reduction using 4-trifluoromethyl acetophenone (40; 376 mg,
2.0 mmol), catalyst (R,R)-11 (3.5 mg, 0.005 mmol), and FA/TEA
(1.0 mL). Following solvent removal the product was isolated as a
colorless oil (300 mg, 1.58 mmol, 79% yield, conversion 100%):
[α]D = +28.2 (c = 0.84, CHCl3), 95% ee (R), (lit.22 [α]D = +29.3
(c = 1.00, CHCl3) > 99% ee (R)); δH (300 MHz, CDCl3) 7.60 (2 H, d,
J = 8.0, ArH), 7.47 (2 H, d, J = 8.0, ArH), 4.94 (1 H, q, J = 6.6,
CH(OH)), 2.12 (1 H, s, OH), 1.49 (3 H, d, J = 6.6, CH3); δC
(101 MHz, CDCl3) 149.83, 129.92, 129.60, 125.78, 125.57 (q, J = 3.8),
69.95, 25.50. Conversion and enantiomeric excess were determined
by chiral GC analysis (CROMPAC CYCLODEXTRIN-β-236M-19,
50 m × 0.25 mm × 0.25 μm, gas hydrogen, T = 120 °C, P = 15 psi,
FID temp 250 °C, injector temp 220 °C): ketone 7.3 min, R isomer
15.0 min, S isomer 16.63 min.
AUTHOR INFORMATION
Corresponding Author
*M.W.: tel, (44) 24 7652 3260; e-mail, m.wills@warwick.ac.uk.
■
ORCID
Martin Wills: 0000-0002-1646-2379
Present Address
†College of Chemistry and Chemical Engineering, Qinzhou
University, Qinzhou, Guangxi 535011, People’s Republic of
China.
(R)-Tetralol.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This compound was prepared by the general procedure for ketone
reduction using α-tetralone (41; 146 mg, 1.0 mmol), catalyst (R,R)-11
(1.7 mg, 0.0025 mmol), and FA/TEA (0.5 mL). Following
solvent removal the product was isolated as a colorless oil (127 mg,
0.86 mmol, 86% yield, conversion 100%): [α]D = −34.4 (c = 0.57,
CHCl3), 99% ee (R), (lit.23 [α]D = −32.3 (c = 1.00, CHCl3) 98% ee
(R)); δH (300 MHz, CDCl3) 7.46−7.40 (1 H, m, ArH), 7.24−7.26
(2 H, m, ArH), 7.15−7.06 (1 H, m, ArH), 4.78 (1 H, d, J = 5.1,
CH(OH)), 2.91−2. 64 (2 H, m, CH2), 2.05−1.86 (2 H, m, CH2),
1.92−1.69 (2 H, m, CH2); δC (75 MHz, CDCl3) 138.93, 137.24,
129.14, 128.77, 127.71, 126.30, 68.29, 32.41, 29.38, 18.93. Conversion
and enantiomeric excess were determined by chiral GC analysis
We thank the Leverhulme Trust (grant number RPG-374) for
financial support to R.S. and EPSRC (grant nos. EP/D031168/1,
EP/G036993/1, and EP/M006670/1) for financial support
to S.G., K.E.J., and R.C.K. and K.E.J. Warwick University is
thanked for support of B.N.T. The X-ray diffraction instrument
was obtained through the Science City Project with support
from the AWM and funded in part by the ERDF.
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