Bis(phosphinite) with C2-symmetric axis; Effects on the ruthenium(II)-catalyzed asymmetric transfer hydrogenation of acetophenone derivatives

Article abstract of DOI:10.1055/s-0032-1317505

Chiral ruthenium catalyst systems generated in situ from [Ru(η⁶-p-cymene)(μ-Cl)Cl]complex and chiral Csymmetric bis(phosphinite) ligands based on amino alcohol derivatives were employed in the asymmetric transfer hydrogenation of aromatic ketones to give the corresponding optically active alcohols in high yield. The best results were obtained in the [Ru(η⁶-p-cymene)(μ-Cl)Cl]and (2S)-2-[benzyl(2-{benzyl[(2S)-1- [(diphenylphosphanyl)oxy]-3-phenyl propan-2-yl]amino}ethyl)amino]-3-phenylpropyl diphenylphosphinite or (2R)-2-[benzyl(2-{benzyl[(2R)-1-[(diphenylphosphanyl) oxy]-3-phenylpropan-2-yl]amino}ethyl)amino]-3-phenylpropyl diphenylphosphinite catalytic systems, which gave enantioselectivities of up to 93% ee and 99% conversion. Copyright

Full text of DOI:10.1055/s-0032-1317505

LETTER
▌2777
letter
Bis(phosphinite) with C2-Symmetric Axis; Effects on the Ruthenium(II)-
Catalyzed Asymmetric Transfer Hydrogenation of Acetophenone Derivatives
Asymmetric Transfer Hydrogenation of Acetophenone Derivatives
Murat Aydemir,* Feyyaz Durap, Cezmi Kayan, Akin Baysal, Yılmaz Turgut
Dicle University, Department of Chemistry, 21280 Diyarbakır, Turkey
Fax +90(412)2488300; E-mail: aydemir@dicle.edu.tr
Received: 19.07.2012; Accepted after revision: 28.09.2012
been extensively studied. Especially, catalysts derived
Abstract: Chiral ruthenium catalyst systems generated in situ from
from C2-symmetric amino alcohols have received much
attention and are used in many asymmetric catalytic reac-
tions; furthermore, they have been shown to be powerful
[Ru(η6-p-cymene)(μ-Cl)Cl]2 complex and chiral C2-symmetric
bis(phosphinite) ligands based on amino alcohol derivatives were
employed in the asymmetric transfer hydrogenation of aromatic ke-
tones to give the corresponding optically active alcohols in high yield. tools in the asymmetric reduction of prochiral ketones.16,17
The best results were obtained in the [Ru(η6-p-cymene)(μ-Cl)Cl]2
and (2S)-2-[benzyl(2-{benzyl[(2S)-1-[(diphenylphosphanyl)oxy]-3-
Because C2-symmetric amino alcohols often give high
levels of enantioselectivity in asymmetric reactions, as an
phenyl propan-2-yl]amino}ethyl)amino]-3-phenylpropyl diphe-
extension of our ongoing research program, we wanted to
nylphosphinite or (2R)-2-[benzyl(2-{benzyl[(2R)-1-[(diphenyl-
synthesize novel C2-symmetric bis(phosphinites) based
phosphanyl)oxy]-3-phenylpropan-2-yl]amino}ethyl)amino]-3-
phenylpropyl diphenylphosphinite catalytic systems, which gave en-
antioselectivities of up to 93% ee and 99% conversion.
on amino alcohol derivatives and use them with Ru(II)
precursors as catalysts in the asymmetric transfer hydro-
genation of aromatic ketones with i-PrOH under varying
conditions.
Key words: phosphinites, enantioselectivity, hydrogenation, ho-
mogeneous catalysis, ruthenium, ketones
The synthesis of the ligands was accomplished as illustrat-
ed in Scheme 1. First, the synthesis of L- and D-phenyl-
glycinol, and L- and D-phenylalaninol were accomplished
in one step from the corresponding phenylglycine or phe-
nylalanine according to procedures described in the liter-
ature,18,19 using NaBH4–I2 in anhydrous tetrahydrofuran
(THF). The conversions of phenylglycinol and phenylal-
aninol into the corresponding N-benzyl amino alcohol de-
rivatives were carried out at 110 °C, as shown in Scheme
1.20 The C2-symmetric chiral amino alcohols 13–16 were
synthesized from ethylene glycol ditosylate with an ex-
cess of 9–12 in the presence of Na2CO3 in good yields.
The structures of these chiral amino alcohols are consis-
tent with the data obtained from 1H NMR, 13C NMR, IR
spectra and elemental analyses (for details see the experi-
mental section).
Asymmetric transfer hydrogenation of ketones has recent-
ly emerged as an alternative method to asymmetric hydro-
genation for the production of chiral alcohols due to its
operational simplicity and ready availability of reduc-
tants.1–3 Chiral alcohols are very important building
blocks and synthetic intermediates in organic synthesis
and in the pharmaceutical industry.4,5 Catalytic asymmet-
ric synthesis using chiral metal complexes as catalyst pre-
cursors offers an ideal method for reducing ketones to
chiral alcohols.6,7 In general, the most easily designed and
the most abundant ligands are C2-symmetric bis(phos-
phines) due to their stereochemical redundancy. Signifi-
cantly fewer in number are other arrangements, such as
bidentate bis(phosphinites) systems.8,9 Phosphine ligands
have found widespread applications in transition-metal-
catalyzed asymmetric transformations.10,11 Phosphinites
provide different chemical, electronic, and structural
properties compared to phosphines. The metal–phospho-
rus bond is often stronger for phosphinites compared to
the related phosphines due to the presence of the electron-
withdrawing P-OR group. In addition, the empty σ*-orbit-
al of the phosphinite P(OR)R2 is stabilized, making the
phosphinite a better electron acceptor.12
The C2-symmetric chiral bis(phosphinite) ligands 17–24
were synthesized by hydrogen abstraction from the de-
scribed C2-symmetric chiral amino alcohols 13–16 by a
base (Et3N), and subsequent reaction with two equivalents
of Ph2PCl or (i-Pr)2PCl, in anhydrous toluene or CH2Cl2
under an argon atmosphere, respectively. The progress of
this reaction was conveniently followed by 31P-{1H}
NMR spectroscopy. The 31P NMR signals of the starting
materials PPh2Cl (δ = 81.0 ppm) and (i-Pr)2PCl (δ =
133.81 ppm) disappeared and new singlets appeared
downfield due to the phosphinite ligands. The new ligands
were characterized by 31P-{1H} NMR spectroscopy. Thus,
the 31P-{1H} NMR spectra of 17–24 showed no unexpect-
ed features and a singlet was observed in the spectrum of
each ligand due to the equivalent phosphorus nuclei.
Chiral β-amino alcohols continue to be of importance in
modern synthetic chemistry, not least because of their bi-
ological properties,13 but also because of their wide range
of synthetic applications.14,15 Hence, the asymmetric syn-
thesis of enantiomerically enriched amino alcohols has
The 31P-{1H} NMR spectra of the free ligands21,22 are
in line with the values previously observed for similar
compounds.23–26 Typical spectra of these ligands are il-
SYNLETT 2012, 23, 2777–2784
Advanced online publication: 09.11.2012
DOI: 10.1055/s-0032-1317505; Art ID: ST-2012-D0604-L
© Georg Thieme Verlag Stuttgart · New York
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6

2778
M. Aydemir et al.
LETTER
17 R1 = L-Ph, R2 = Ph
18 R1 = L-Ph, R2 = i-Pr
19 R1 = L-Bn, R2 = Ph
20 R1 = L-Bn, R2 = i-Pr
21 R1 = D-Ph, R2 = Ph
22 R1 = D-Ph, R2 = i-Pr
23 R1 = D-Bn, R2 = Ph
24 R1 = D-Bn, R2 = i-Pr
O
R1
H
*
OH
NH2
i
1 R1 = L-Ph; 2 L-Bn
3 R1 = D-Ph; 4 D-Bn
R1
N
N
R1
*
*
OPR2
R22PO
2
R1
*
OH
H
NH2
5 R1 = L-Ph; 6 L-Bn
7 R1 = D-Ph; 8 D-Bn
iv
R1
*
OH
NH
ii
H
R1
N
*
N
*
R1
iii
OH
HO
13 R1 = L-Ph; 14 L-Bn
15 R1 = D-Ph; 16 D-Bn
9 R1 = L-Ph; 10 L-Bn
11 R1 = D-Ph; 12 D-Bn
Scheme 1 Reagents and conditions: (i) NaBH4–I2, THF; (ii) PhCH2Cl, Na2CO3, 110 °C, 12 h; (iii) ethylene glycol ditosylate, Na2CO3, 110 °C,
12 h; (iv) Ph2PCl (2 equiv), Et3N (2 equiv), toluene (for 17, 19, 21, and 23); (i-Pr)2PCl (2 equiv), Et3N (2 equiv), CH2Cl2 (for 18, 20, 22, and 24).
lustrated in Figure 1 and Figure 2. Solutions of the li- 17–24 are not stable enough in common solvents that
gands in CDCl3, prepared under anaerobic conditions, contain trace amounts of water, the corresponding ru-
were unstable and decomposed rapidly to give the ox- thenium(II) complexes were synthesized in situ. The
ide and the hydrolysis product diphenylphosphinous starting ruthenium(II) complex, [Ru(η6-p-cymene)(μ-
acid [Ph2P(O)H; in 5 min).27 Furthermore, the 31P- Cl)Cl]2, was prepared from the reaction of commer-
{1H} NMR spectrum also revealed the formation of cially available α-phellandrene (5-isopropyl-2-meth-
PPh2PPh2 and P(O)Ph2PPh2, as indicated by signals at ylcyclohexa-1,3-diene) with RuCl3.29
ca. δ = –15.8 ppm as a singlet and δ = 35.2 ppm and δ
The excellent catalytic performance and the higher struc-
tural permutability of phosphinite-based transition metal
= –21.4 ppm as doublets (1JP–P = 224 Hz), respective-
ly.28 In addition, the 31P-{1H} NMR spectrum also
catalysts30–33 prompted us to develop new Ru(II) catalyst
revealed the formation of P(O)(i-Pr)2P(i-Pr)2, as indi-
systems with well-defined ligands.34–39 The most impor-
tant advantage of chiral phosphinite ligands over the cor-
responding phosphine ligands is the ease of preparation.
cated by signals at ca. δ = 66.3 ppm and δ = –13.5 ppm
as doublets (1JP–P = 279 Hz), respectively. Because
Figure 2 The 31P-{1H} NMR spectra of C2-symmetric chiral
bis(phosphinite) ligands 21–24
Figure 1 The 31P-{1H} NMR spectra of C2-symmetric chiral
bis(phosphinite) ligands 17–20
Synlett 2012, 23, 2777–2784
© Georg Thieme Verlag Stuttgart · New York

LETTER
Asymmetric Transfer Hydrogenation of Acetophenone Derivatives
2779
From a practical standpoint, it is of substantial interest to asymmetric transfer hydrogenation of acetophenone. The
develop highly effective chiral phosphinite ligands for catalysts were generated in situ prior to hydrogen transfer
asymmetric catalysis.40,41 Noyori and co-workers suggest- by heating a mixture of [Ru(η6-p-cymene)(μ-Cl)Cl]2 with
ed that the highly skewed position of the naphthyl rings in the appropriate ligand in anhydrous i-PrOH. Our aim here
BINAP was the determining factor for the ligand to be so was to compare the coordinating abilities of various func-
effective in asymmetric catalytic reactions.42 Comparison tionalized phosphinites in [Ru(η6-p-cymene)(μ-Cl)Cl]2
of the structure of BINAP with that of the less effective complexes in the catalytic asymmetric transfer hydroge-
BINAPO reveals two possible reasons for the difference nation. A comparison of the complexes with 17–24 as
in their effectiveness as chiral ligands in homogeneous ca- precatalysts for the asymmetric hydrogenation of aceto-
talysis:43 (1) The oxygen atom in BINAPO increases the phenone by i-PrOH in the presence of KOH is summa-
distance between the chiral binaphthyl moiety and the rized in Table 1. Catalytic experiments were carried out
PPh2 group. Consequently, there is less control of stereo- under argon atmosphere using standard Schlenk tech-
selectivity in the catalyst–substrate interaction. (2) The niques. These systems catalyzed the reduction of aceto-
presence of the C–O–P bond in BINAPO substantially in- phenone to the corresponding alcohol [(S)-, (R)-1-
creases the flexibility of the backbone and consequently phenylethanol] in the presence KOH as a promoter. To a
decreases the enantioselectivity of the catalyst. In our re- solution of ruthenium complex and chiral ligand in i-
cent pursuit of the design of new chiral and highly active PrOH, an appropriate amount of acetophenone, and
ligands, we have found an opportunity both to test these KOH/i-PrOH solutions were added, respectively, at room
hypotheses and to develop a class of effective chiral phos- temperature. The solution was stirred for several hours
phinite ligands.
and then examined by capillary GC analysis. At room
temperature, transfer hydrogenation of acetophenone oc-
curred very slowly,44 with low conversion (up to 40%)
and moderate to high enantioselectivity (up to 80% ee) in
In a preliminary study, chiral ligands 17–24 combined
with [Ru(η6-p-cymene)(μ-Cl)Cl]2 were examined in the
Table 1 Transfer Hydrogenation of Acetophenone with i-PrOH Catalyzed by [Ru(η6-p-cymene)(μ-Cl)Cl]2-L
H
O
HO
[p-cymeneRuCl2]2, ligand
*
Entry
Ligand (L)
Sub./Cat./KOH Temp.
Time (h)a
Conversion (%)a,b ee (%)a,c
Config.d
TOF (h–1)e
1
2
3
4
5
6
7
8
17
18
19
20
21
22
23
24
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
24
24
24
24
24
24
24
24
32
14
30
10
36
12
32
14
76
70
80
74
74
69
78
72
S
S
S
S
R
R
R
R
<5
<5
<5
<5
<5
<5
<5
<5
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
100:1:0
100:1:0
100:1:0
100:1:0
100:1:0
100:1:0
100:1:0
100:1:0
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
1
1
1
1
1
1
1
1
<5
<5
<5
<5
<5
<5
<5
<5
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
17
18
19
20
21
22
23
24
17
18
19
20
21
22
23
24
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
2 (2)
4 (4)
2 (2)
4 (4)
2 (2)
4 (4)
2 (2)
4 (4)
95 (94)
98 (97)
99 (98)
96 (96)
98 (96)
98 (97)
97 (99)
96 (96)
78 (77)
73 (71)
88 (87)
76 (76)
80 (77)
75 (72)
90 (89)
82 (78)
S
S
S
S
R
R
R
R
48
25
50
24
49
25
49
24
a Values obtained with NaOH as base are given in parentheses.
b Determined by GC analysis (three independent experiments).
c Determined by capillary GC analysis using a chiral cyclodex B (Agilent) capillary column.
d Determined by comparison of the retention times of the enantiomers on the GC traces with literature values, (S) or (R) configuration was ob-
tained in all experiments.
e Referred to the reaction time indicated in column; TOF = (mol product/mol Ru(II)cat.) × h–1.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2777–2784

2780
M. Aydemir et al.
LETTER
all cases. During this period, the color changed from or- group resulted in an increase in both the conversion and
ange to deep-red. In addition, the ee values did not vary the enantioselectivity (Table 1). An examination of the re-
with time, as indicated by the results obtained with 17–24. sults shows clearly that the best enantioselectivity was
Furthermore, as can be inferred from the Table 1 (entries achieved when (2S)-2-[benzyl(2-{benzyl[(2S)-1-[(diphe-
9–16) the presence of base was necessary to obtain appre- nylphosphanyl)oxy]-3-phenylpropan-2-yl]amino}eth-
ciable conversions. The choice of base, such as KOH and yl)amino]-3-phenylpropyl diphenylphosphinite (19) and
NaOH, had little influence on the conversion or enantiose- (2R)-2-[benzyl(2-{benzyl[(2R)-1-[(diphenylphospha-
lectivity. In addition, optimization studies of the catalytic nyl)oxy]-3-phenylpropan-2-yl]amino}ethyl)amino]-3-
reduction of acetophenone in i-PrOH showed that good phenylpropyl diphenylphosphinite (23), were used as li-
activity was obtained with a base/ligand ratio of 5:1. Re- gand (up to 88 and 90% ee, respectively). These results in-
duction of acetophenone into (S)- or (R)-1-phenylethanol dicate that the structure of the bis(phosphinite) is a crucial
could be achieved in high yield by increasing the temper- factor for acceleration of the reaction. In the context of the
ature to 82 °C (Table 1, entries 17–24).
It is noteworthy that the catalytic system [Ru(η6-p-cy-
mene)(μ-Cl)Cl]2-L (L: 17–24) shows differences in reac-
results, it could be reasonably argued that the absolute
configuration of the product is governed by the carbon-
centered chirality.
tivity. Interestingly, the reaction rate could be enhanced Encouraged by the enantioselectivities obtained in these
by changing the nature of the substituents on the phospho- preliminary studies, we next extended our investigations
rus atom. Thus, replacing an isopropyl moiety by a phenyl to include asymmetric hydrogenation of substituted aceto-
Table 2 Asymmetric Transfer Hydrogenation of Substituted Acetophenones with the Catalyst Systems Prepared from [Ru(η6-p-cymene)(μ-
Cl)Cl]2 and C2-Symmetric Bis(phosphinite) Ligands 17–24a
Entry
Ligand (L) Substrate
Product
Time (h)
Conv. (%)b ee (%)c
Config.d
TOF (h–1)e
1
2
3
4
5
6
7
8
17
18
19
20
21
22
23
24
1
3
1
3
1
3
1
3
97
96
95
94
99
97
97
94
76
65
81
77
73
62
82
74
S
S
S
S
R
R
R
R
97
32
95
31
99
32
97
31
O
OH
*
F
F
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
2
4
2
4
2
4
2
4
98
99
97
96
98
97
97
96
77
67
83
76
77
67
83
76
S
S
S
S
R
R
R
R
49
25
49
24
49
24
49
24
O
OH
*
Cl
Cl
17
18
19
20
21
22
23
24
17
18
19
20
21
22
23
24
4
7
5
7
4
8
5
8
98
99
98
99
98
99
98
99
77
70
90
80
80
73
93
80
S
S
S
S
R
R
R
R
25
14
20
14
25
12
20
12
OMe OH
OMe
O
*
25
26
27
28
29
30
31
32
17
18
19
20
21
22
23
24
4
6
6
8
4
7
6
9 h
96
96
98
99
96
97
98
96
76
68
85
81
75
64
84
76
S
S
S
S
R
R
R
R
24
16
16
12
24
14
16
11
O
OH
*
MeO
MeO
a Reaction conditions: Catalyst (0.005 mmol), substrate (0.5 mmol), i-PrOH (5 mL), KOH (0.025 mmol), 82 °C, the concentration of acetophe-
none was 0.1 M.
b The purity was checked by NMR and GC analyses (three independent experiments); yields are based on aryl ketone.
c Determined by capillary GC analysis using a chiral cyclodex B (Agilent) capillary column (30 m × 0.32 mm × 0.25 μm film thickness).
d Determined by comparison of the retention times of the enantiomers on the GC traces with literature values.
e Referred to the reaction time indicated in column; TOF = (mol product/mol Ru(II)Cat.) × h–1.
Synlett 2012, 23, 2777–2784
© Georg Thieme Verlag Stuttgart · New York

LETTER
Asymmetric Transfer Hydrogenation of Acetophenone Derivatives
2781
(5) and (2S)-2-(benzylamino)-3-phenylpropan-1-ol (6), (2R)-2-
(benzylamino)-2-phenylethan-1-ol (7), and (2R)-2-(benzylamino)-
3-phenylpropan-1-ol] (8)48 were prepared according to literature
procedures.
phenone derivatives. The results presented in Table 2
demonstrate that a range of acetophenone derivatives can
be hydrogenated with good to high enantioselectivities.
The catalytic reduction of acetophenone derivatives were
tested under the optimized conditions. Complexes 17–24
showed very high activity with most of the ketones, how-
ever, the position and electronic properties of the ring sub-
stituents influenced the hydrogenation results. The
introduction of electron-withdrawing substituents, such as
F and Cl, to the para-position of the aryl ring of the ketone
decreased the electron density of the C=O bond so that the
activity was improved, facilitating the hydrogenation.45,46
The presence of an electron-withdrawing group, such as a
fluoro group, on the para-position was helpful to obtain
excellent conversion and moderate to good enantioselec-
tivity (up to 82% ee, Table 2, entries 1–8), whereas the in-
troduction of an electron-donating substituent such as a
methoxy group on the para-position tended to lower ac-
tivity (<24 h–1), while maintaining satisfactory enantiose-
lectivity (entries 25–32). The introduction of an electron-
donating substituent such as a methoxy group to the or-
tho- or para-position decelerated the reaction (<25 h–1),
but substituents on the ortho-position especially increased
the enantioselectivity ratio (difference up to 10% ee),
more than substituents on the para-position (see Table 2).
Among all the selected ketones, the best result was ob-
tained in the reduction of o-methoxyacetophenone, giving
up to 93% ee (Table 2, entry 23). The results indicated that
strong electron-withdrawing substituents, such as fluoro
and chloro groups, were capable of achieving higher con-
version (up to 99 h–1), but with slightly lower enantiomer-
ic purity. Conversely, the most electron-donating
substituent (methoxy) led to lower conversions with high-
er ee values (Table 2).
IR spectra were recorded with a Mattson 1000 ATI UNICAM FT-
IR spectrometer as KBr pellets. 1H (400.1 MHz), 13C NMR (100.6
MHz), and 31P-{1H} NMR (162.0 MHz) spectra were recorded with
a Bruker AV 400 spectrometer, with δ referenced to external TMS
and 85% H3PO4, respectively. Elemental analysis was carried out
with a Fisons EA 1108 CHNS-O instrument. Melting points were
recorded with a Gallenkamp apparatus with open capillaries.
GC analyses were performed with a Shimadzu GC 2010 Plus Gas
Chromatograph equipped with cyclodex B (Agilent) capillary col-
umn (30 m × 0.32 mm, 0.25 μm film thickness). The GC parame-
ters for asymmetric transfer hydrogenation of ketones were as
follows: initial temperature 50 °C, initial time 1.1 min, solvent de-
lay 4.48 min, temperature ramp 1.3 °C/min, final temperature
150 °C, initial time 2.2 min, temperature ramp 2.15 °C/min, final
temperature 250 °C, initial time 3.3 min, final time 44.33 min, in-
jector port temperature 200 °C, detector temperature 200 °C, injec-
tion volume 2.0 μL.
Transfer Hydrogenation of Ketones; General Procedure
A flame-dried Schlenk flask was charged with [Ru(η6-p-cy-
mene)(μ-Cl)Cl]2 (0.005 mmol), excess bis(phosphinite) ligand
(0.02 mmol) and a stir bar. To these components was added i-PrOH
(5 mL, dried and degassed), and the resultant solution was heated to
82 °C for 20 min, followed by cooling to ambient temperature. A
solution of ketone (0.5 mmol) in i-PrOH (5 mL) was then added to
the catalyst mixture and the solution was heated to the desired tem-
perature (generally, 25 or 82 °C). The reaction was initiated by the
addition of a solution of KOH (2.5 mL, 0.1 M i-PrOH). As soon as
the reaction was complete, an aliquot of the solution (1 mL) was re-
moved by using a syringe and evaporated under reduced pressure.
The resultant oil was subjected to flash chromatography (silica gel
60; Et2O) and subsequent evaporation under reduced pressure yield-
ed clear liquids in each case. After this time a sample of the reaction
mixture was taken, diluted with acetone, and analyzed immediately
by GC. Reported conversions are related to the residual unreacted
ketone. 1H NMR spectral data for the resultant products were con-
sistent with previously reported results.
In conclusion, the [Ru(η6-p-cymene)(μ-Cl)Cl]2 and C2-
symmetric bis(phosphinite) systems demonstrate remark-
able catalytic activity and enantioselectivity in the asym-
metric transfer hydrogenation of acetophenone
derivatives. High conversion and good to excellent enan-
tioselectivity were obtained in the catalytic reaction. The
simplicity and efficiency clearly make it an excellent
choice of catalyst for the practical preparation of highly
valued alcohols through catalytic asymmetric transfer hy-
drogenation of ketones. Further studies are in progress to
improve both activity and enantioselectivity and to extend
the use of these novel ligands to other asymmetric catalyt-
ic reactions.
Preparation of the Chiral, C2-Symmetric N-Benzyl Amino Alco-
hols and the Corresponding Chiral Bis(phosphinite) Ligands
(2S)-2-(Benzylamino)-2-phenylethan-1-ol (9): (S)-Phenylglycin-
ol (43.90 g, 320 mmol), benzyl chloride (10.13 g, 80 mmol), and an-
hydrous Na2CO3 (8.48 g, 80 mmol) were placed in a 250 mL two-
necked, round-bottomed flask. The mixture was stirred at 110 °C
for 12 h under dry Ar, then cooled to r.t. and CHCl3 (150 mL) was
added and the mixture was heated at reflux for 2 h. The CHCl3 layer
was separated from the solid phase, which was re-extracted with
CHCl3 (3 × 150 mL). The combined organic phase was dried over
anhydrous MgSO4, filtered, and evaporated. The product was then
distilled under reduced pressure (160–170 °C/0.8 mmHg) to give 9
(15.5 g, 85%); mp 83–84 °C; [α]D20 +56.9 (c 0.5, MeOH). 1H NMR
(CDCl3): δ = 7.28–7.37 (m, 10 H, ArH), 3.62–3.89 (m, 5 H, CH-N,
CH2OH and CH2Ph), 3.23 (br, 2 H, NH and OH). 13C NMR
(CDCl3): δ = 139.71, 139.19, 128.78, 128.52, 128.46, 127.86,
127.50, 127.30 (-CHC6H5 and -CH2C6H5), 66.49 (-CH2OH), 63.76
(-CH-N), 50.95 (-CH2Ph). IR (KBr): 3392 (OH), 3353 (NH), 3030
(CH), 2915, 2838 cm–1. Anal. Calcd for C15H17NO (227.3): C,
79.26; H, 7.54; N, 6.16. Found: C, 79.18; H, 7.47; N, 6.09.
Unless otherwise stated, all reactions were carried out under an at-
mosphere of argon using conventional Schlenk glassware; solvents
were dried using established procedures and distilled under argon
immediately prior to use. Analytical grade and deuterated solvents
were purchased from Merck. The starting materials L-, D-phenyl-
glycine, L-, D-phenylalanine, PPh2Cl, (i-Pr)2PCl and Et3N, pur-
chased from Fluka, and were used as received. [Ru(η6-p-
cymene)(μ-Cl)Cl]2,47 L-phenylglycinol [(2S)-2-amino-2-phenyle-
than-1-ol; 1], L-phenylalaninol [(2S)-2-amino-3-phenylpropan-1-
ol; 2], D-phenylglycinol [(2R)-2-amino-2-phenylethan-1-ol; 3], D-
phenylalaninol [(2R)-2-amino-3-phenylpropan-1-ol; 4],18 and N-
benzyl amino alcohols (2S)-2-(benzylamino)-2-phenylethan-1-ol
(2S)-2-(Benzylamino)-3-phenylpropan-1-ol (10): (S)-Phenylal-
aninol (48.40 g, 320 mmol), benzyl chloride (10.13 g, 80 mmol),
and anhydrous Na2CO3 (8.48 g, 80 mmol) were placed in a 250 mL
two-necked, round-bottomed flask. The mixture was stirred at
110 °C for 12 h under dry Ar, then cooled to r.t. and CHCl3 (150
mL) was added and the mixture was heated at reflux for 2 h. The
CHCl3 layer was separated from the solid phase, which was re-ex-
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2777–2784

2782
M. Aydemir et al.
LETTER
tracted with CHCI3 (3 × 150 mL). The combined organic phase was
dried over anhydrous MgSO4, filtered, and evaporated. The product
was then distilled under reduced pressure (165–170 °C/0.8 mmHg)
to give 10 (14.9 g, 77%); mp 54–56 °C; [α]D20 –11.1 (c 1.2, MeOH).
1H NMR (CDCl3): δ = 7.17–7.27 (m, 10 H, ArH), 3.57–3.99 (m,
4 H, -CH2OH and N-CH2-Ph), 2.99 (br, 1 H, CH-N), 2.80 (br, 2 H,
-CH2Ph), 2.14 (br, 2 H, NH and OH). 13C NMR (CDCl3): δ =
140.15, 139.17, 129.78, 129.75, 128.51, 128.14, 126.72, 126.40 (-
CH2C6H5 and -N-CH2C6H5), 53.32, 51.44 (-CH2OH and N-CH2-
Ph), 59.42 (-CH-N), 38.19 (-CH2Ph). IR (KBr): 3550 (OH), 3323
(NH), 3061 (CH), 3023, 2930, 2861, 1653 (C=C), 1601, 1523 cm–
1. Anal. Calcd for C16H19NO (241.3): C, 79.63; H, 7.94; N, 5.80.
Found: C, 79.59; H, 7.83; N, 5.76.
NCH2CH2N(a)], 2.30 [d, J = 9.2 Hz, 2 H, NCH2CH2N(b)], 13C
NMR (CDCl3): δ = 138.88, 135.63, 129.34, 129.08, 128.62, 128.35,
127.94, 127.29 (NCHPh and NCH2Ph), 64.37 (NCHPh), 61.06 (-
CH2OH), 55.04 (NCH2Ph), 47.40 (NCH2CH2N). IR (KBr): 3415
(OH), 3055, 3027 [aromatic υ(CH)], 2924, 2837 [aliphatic υ(CH)],
1487, 1451, 1407 [aromatic υ(C=C)], 1031 (C-0) cm–1. Anal. Calcd
for C32H36N2O2 (480.7): C, 79.97; H, 7.55; N, 5.83. Found: C,
79.68; H, 7.37; N, 5.61.
(2S)-2-[Benzyl(2-{benzyl[(2S)-1-hydroxy-3-phenylpropan-2-
yl]amino}ethyl)amino]-3-phenylpropan-1-ol (14): Compound 10
(24.13 g, 100 mmol), ethylene glycol ditosylate (6.18 g, 16.67
mmol), and Na2CO3 (3.03 g, 28.57 mmol) were stirred at 110 °C for
12 h under an Ar atmosphere. The mixture was cooled to r.t., CHCl3
(100 mL) was added and the mixture was heated at reflux for 2 h.
The CHCl3 layer was separated from the solid phase, which was re-
extracted with CHCl3 (2 × 50 mL). The combined CHCl3 layers
were dried (Na2SO4) and evaporated. After the excess amino alco-
hol 10 was distilled at reduced pressure (160–170 °C/0.1 mmHg),
the desired product was purified by flash column chromatography
on silica gel (toluene–EtOAc, 5:3) to give 14 (3.76 g, 44.3%); mp
(2R)-2-(Benzylamino)-2-phenylethan-1-ol (11): (R)-Phenylgly-
cinol (43.90 g, 320 mmol), benzyl chloride (10.13 g, 80 mmol), and
anhydrous Na2CO3 (8.48 g, 80 mmol) were placed in a 250 mL two-
necked, round-bottomed flask. The mixture was stirred at 110 °C
for 12 h under dry Ar, then cooled to r.t. and CHCl3 (150 mL) was
added and the mixture was heated at reflux for 2 h. The CHCl3 layer
was separated from the solid phase, which was re-extracted with
CHCl3 (3 × 150 mL). The combined organic phase was dried over
anhydrous MgSO4, filtered, and evaporated. The product was then
distilled under reduced pressure (160–170 °C/0.8 mmHg) to give
11 (14.2 g, 78.1%); mp 83–84 °C; [α]D20 –56.9 (c 0.5, MeOH). 1H
NMR (CDCl3): δ = 7.28–7.44 (m, 10 H, ArH), 3.86 (m, 1 H, CH-
N), 3.81 [m 1 H, CH2Ph(a)], 3.65 [m 1 H, CH2Ph(b)], 3.72 [m, 1 H,
CH2OH(b)], 3.61 [m, 1 H, CH2OH(b)]. 13C NMR (CDCl3): δ =
140.50, 140.06, 128.73, 128.49, 128.30, 127.71, 127.42, 127.13 (-
CHC6H5 and -CH2C6H5), 66.80 (-CH2OH), 63.85 (-CH-N), 51.23 (-
CH2Ph). IR (KBr): 3390 (OH), 3348 (NH), 3026 (CH), 2912,
2835 cm–1. Anal. Calcd for C15H17NO (227.3): C, 79.26; H, 7.54; N,
6.16. Found: C, 79.19; H, 7.49; N, 6.12.
20
1
106–108 °C; [α]D –28.6 (c 1.2, MeOH). H NMR (CDCl3): δ =
7.07–7.38 (m, 20 H, NCH2Ph and CHCH2Ph), 4.00 (br, 2 H,
CH2OH), 3.83 [d, J = 13.2 Hz, 2 H, NCH2Ph(a)], 3.49 [d, J =
10.8 Hz, 2 H, CH2OH(a)], 3.37 [m, 4 H, NCH2Ph(b) and
CH2OH(b)], 2.97 [m, 2 H, -CHN and 2 H, -CHCH2Ph(a)], 2.83 [d,
J = 8.8 Hz, 2 H, NCH2CH2N(a)], 2.53 [d, J = 7.6 Hz, 2 H,
NCH2CH2N(b)], 2.31 [m, 2 H, -CHCH2Ph(b)]. 13C NMR (CDCl3):
δ = 139.20, 138.84, 129.34, 128.97, 128.61, 128.60, 127.36, 126.24
(NCH2C6H5 and CHCH2C6H5), 62.54 (-CH-N), 60.57 (-CH2OH),
54.55 (NCH2Ph), 47.56 (NCH2CH2N), 31.51 (-CHCH2Ph). IR
(KBr): 3363 (OH), 3053, 3023 [aromatic υ(CH)], 2939, 2858 [ali-
phatic υ(CH)], 1489, 1452, 1411 [aromatic υ(C=C)], 1027 [υ(C-
0)] cm–1. Anal. Calcd for C34H40N2O2 (508.7): C, 80.28; H, 7.93; N,
5.51. Found: C, 80.18; H, 7.63; N, 5.44.
(2R)-2-(Benzylamino)-3-phenylpropan-1-ol (12): (R)-Phenylal-
aninol (48.40 g, 320 mmol), benzyl chloride (10.13 g, 80 mmol),
and anhydrous Na2CO3 (8.48 g, 80 mmol) were placed in a 250 mL
two-necked round-bottomed flask. The mixture was stirred at
110 °C for 12 h under dry Ar, then cooled to r.t. and CHCl3 (150
mL) was added and the mixture was heated at reflux for 2 h. The
CHCl3 layer was separated from the solid phase, which was re-ex-
tracted with CHCl3 (3 × 150 mL). The combined organic phase was
dried over anhydrous MgSO4, filtered, and evaporated. The product
was then distilled under reduced pressure (165–170 °C/0.8 mmHg)
(2R)-2-[Benzyl(2-{benzyl[(1R)-2-hydroxy-1-phenylethyl]ami-
no}ethyl)amino]-2-phenylethan-1-ol (15): Compound 11 (22.73
g, 100 mmol), ethylene glycol ditosylate (6.18 g, 16.67 mmol) and
Na2CO3 (3.03 g, 28.57 mmol) were stirred at 110 °C for 12 h under
an Ar atmosphere. The mixture was cooled, CHCl3 (100 mL) was
added at r.t., and the mixture was heated at reflux for 2 h. The CHCl3
layer was separated from the solid phase, which was re-extracted
with CHCl3 (3 × 25 mL). The combined CHCl3 layers were dried
(Na2SO4) and evaporated. After the excess amino alcohol 11 was
distilled at reduced pressure (150–160 °C/0.1 mmHg), the desired
product was purified by flash column chromatography on silica gel
20
to give 12 (14.2 g, 73.5%); mp 54–56 °C; [α]D +11.1 (c 1.2,
1
MeOH). H NMR (CDCl3): δ = 7.10–7.24 (m, 10 H, ArH), 3.64–
3.77 (m, 4 H, -CH2OH and N-CH2-Ph), 2.92 (br, 1 H, CH-N), 2.72
(br, 2 H, -CH2Ph), 2.14 (br, 2 H, NH and OH). 13C NMR (CDCl3):
δ = 140.07, 139.22, 129.32, 129.08, 128.53, 128.18, 126.14, 126.42
(-CH2C6H5 and -N-CH2C6H5), 53.35, 51.38 (-CH2OH and N-CH2-
Ph), 59.46 (-CH-N), 38.16 (-CH2Ph). IR (KBr): 3550 (OH), 3384
(NH), 3061 (CH), 3023, 2938, 2861, 1615 (C=C), 1561, 1525 cm–
1. Anal. Calcd for C16H19NO (241.3): C, 79.63; H, 7.94; N, 5.80.
Found: C, 79.60; H, 7.90; N, 5.76.
20
(toluene–EtOAc, 5:3) to give 15 (3.98 g, 49.7%); [α]D –59.2 (c
1
0.5, MeOH). H NMR (CDCl3): δ = 7.12–7.42 (m, 20 H, NCHPh
and NCH2Ph), 4.15 [m, 2 H, CH2OH(a)], 3.94 (m, 2 H, NCHPh),
3.82 [d, J = 13.2 Hz, 2 H, NCH2Ph(a)], 3.68 [m, 2 H, CH2OH(b)],
3.06 [d, J = 13.2 Hz, 2 H, NCH2Ph(b)], 2.94 [d, J = 8.8 Hz, 2 H,
NCH2CH2N(a)], 2.29 [d, J = 8.8 Hz, 2 H, NCH2CH2N(b)]. 13C
NMR (CDCl3): δ = 138.93, 135.67, 129.32, 129.06, 128.61, 128.34,
127.92, 127.27 (NCHPh and NCH2Ph), 64.34 (NCHPh), 61.06 (-
CH2OH), 55.05 (NCH2Ph), 47.44 (NCH2CH2N). IR (KBr): 3413
[υ(OH)], 3057, 3027 [aromatic υ(CH)], 2930, 2833 [aliphatic
υ(CH)], 1484, 1452, 1412 [aromatic υ(C=C)], 1033 [υ(C-O)]. Anal.
Calcd for C32H36N2O2 (480.7): C, 79.97; H, 7.55; N, 5.83. Found:
C, 79.78; H, 7.39; N, 5.59.
(2S)-2-[Benzyl(2-{benzyl[(1S)-2-hydroxy-1-phenylethyl]ami-
no}ethyl)amino]-2-phenylethan-1-ol (13): Compound 9 (22.73 g,
100 mmol), ethylene glycol ditosylate (6.18 g, 16.67 mmol) and
Na2CO3 (3.03 g, 28.57 mmol) were stirred at 110 °C for 12 h under
an Ar atmosphere. The mixture was cooled to r.t. and CHCl3 (100
mL) was added and the mixture was heated at reflux for 2 h. The
CHCl3 layer was separated from the solid phase, which was re-ex-
tracted with CHCl3 (3 × 25 mL). The combined CHCl3 layers were
dried (Na2SO4) and evaporated. After the excess amino alcohol 9
was distilled at reduced pressure (150–160 °C/0.1 mmHg), the
product was purified by flash column chromatography on silica gel
(2R)-2-[Benzyl(2-{benzyl[(2R)-1-hydroxy-3-phenylpropan-2-
yl]amino}ethyl)amino]-3-phenylpropan-1-ol (16): Compound 12
(24.13 g, 100 mmol), ethylene glycol ditosylate (6.18 g, 16.67
mmol) and Na2CO3 (3.03 g, 28.57 mmol) were stirred at 110 °C for
12 h under an Ar atmosphere. The mixture was cooled to r.t., CHCl3
(100 mL) was added, and the mixture was heated at reflux for 2 h.
The CHCl3 layer was separated from the solid phase, which was re-
extracted with CHCl3 (2 × 50 mL). The combined CHCl3 layers
were dried (Na2SO4) and evaporated. After the excess amino alco-
hol 12 was distilled at reduced pressure (160–170 °C/0.1 mmHg),
20
(toluene–EtOAc, 5:3) to give 13 (4.01 g, 50.1%); [α]D +59.2 (c
1
0.5, MeOH). H NMR (CDCl3): δ = 7.13–7.52 (m, 20 H, NCHPH
and NCH2PH), 4.16 [m, 2 H, CH2OH(a)], 3.94 (m, 2 H, NCHPh),
3.83 [d, J = 13.2 Hz, 2 H, NCH2Ph(a)], 3.69 [m, 2 H, CH2OH(b)],
3.07 [d, J = 13.2 Hz, 2 H, NCH2Ph(b)], 2.95 [d, J = 9.2 Hz, 2 H,
Synlett 2012, 23, 2777–2784
© Georg Thieme Verlag Stuttgart · New York

LETTER
Asymmetric Transfer Hydrogenation of Acetophenone Derivatives
2783
the desired product was purified by flash column chromatography
96.1%) as a white viscous oil. 31P-{1H} NMR (CDCl3): δ = 114.31
[s, O-P-(C6H5)2].
on silica gel (toluene–EtOAc, 5:3) to give 16 (3.52 g, 41.5%); bp
20
1
106–108 °C; [α]D +28.6 (c 1.2, MeOH). H NMR (CDCl3): δ =
6.94–7.28 (m, 20 H, NCH2Ph and CHCH2Ph), 3.70 [d, J = 13.2 Hz,
2 H, NCH2Ph(a)], 3.53 [t, J = 10.6 Hz, 2 H, CH2OH(a)], 3.26 [m,
4 H, NCH2Ph(b) and CH2OH(b)], 2.87 [m, 2 H, -CHN and 2 H, -
CHCH2Ph(a)], 2.71 [d, J = 8.4 Hz, 2 H, NCH2CH2N(a)], 2.39 [d, J
= 8.4 Hz, 2 H, NCH2CH2N(b)], 2.20 [m, 2 H, -CHCH2Ph(b)]. 13C
NMR (CDCl3): δ = 139.19, 138.84, 129.32, 128.96, 128.60, 128.58,
127.35, 126.22 (NCH2C6H5 and CHCH2C6H5), 62.56 (-CH-N),
60.66 (-CH2OH), 54.56 (NCH2Ph), 47.59 (NCH2CH2N), 31.52 (-
CHCH2Ph). IR (KBr): 3358 [υ(OH)], 3053, 3023 [aromatic υ(CH)],
2939, 2857 [aliphatic υ(CH)], 1488, 1452, 1411 [aromatic υ(C=C)],
1027 [υ(C-O)]. Anal. Calcd for C34H40N2O2 (508.7): C, 80.28; H,
7.93; N, 5.51. Found: C, 80.14; H, 7.64; N, 5.28.
(2R)-2-[Benzyl(2-{benzyl[(1R)-2-{[bis(propan-2-yl)phosphe-
nyl]oxy}-1-phenylethyl] amino}ethyl)amino]-2-phenylethylbis-
(propan-2-yl)phosphinite (22): (i-Pr)2PCl (0.067 g, 0.416 mmol)
was added to a stirred solution of 15 (0.100 g, 0.208 mmol) and
Et3N (0.043 g, 0.416 mmol) in CH2Cl2 (25 mL) at r.t. with vigorous
stirring. The mixture was stirred at room r.t. for 48 h, and the solvent
was removed under reduced pressure. After addition of anhydrous
toluene, the white precipitate (triethylammonium chloride) was fil-
tered off under argon and the remaining organic phase was dried in
vacuo to produce 22 (138 mg, 93.2%) as a white viscous oil. 31P-
{1H} NMR (CDCl3): δ = 150.29 [s, O-P-(i-Pr)2].
(2R)-2-[Benzyl(2-{benzyl[(2R)-1-[(diphenylphosphanyl)oxy]-3-
phenylpropan-2-yl]amino}ethyl)amino]-3-phenylpropyldiphe-
nylphosphinite (23): Chlorodiphenylphosphine (0.092 g, 0.394
mmol) was added to a stirred solution of 16 (0.100 g, 0.197 mmol)
and Et3N (0.040 g, 0.394 mmol) in toluene (25 mL) at r.t. with vig-
orous stirring. The mixture was stirred at r.t. for 1 h and the white
precipitate (triethylammonium chloride) was filtered off under ar-
gon and the remaining organic phase was dried in vacuo to produce
23 (165 mg, 95.9%) as a white viscous oil. 31P-{1H} NMR (CDCl3):
δ = 114.97 [s, O-P-(C6H5)2].
(2S)-2-{Benzyl[2-(benzyl{(1S)-2-[(diphenylphosphanyl)oxy]-1-
phenylethyl}amino)ethyl]amino}-2-phenylethyldiphenylphos-
phinite (17): Chlorodiphenylphosphine (0.097 g, 0.416 mmol) was
added to a stirred solution of 13 (0.100 g, 0.208 mmol) and Et3N
(0.043 g, 0.416 mmol) in toluene (25 mL) at r.t. with vigorous stir-
ring. The mixture was stirred at r.t. for 1 h and the white precipitate
(triethylammonium chloride) was filtered off under argon and the
remaining organic phase was dried in vacuo to produce 17 (172 mg,
92%) as a white viscous oil. 31P-{1H} NMR (CDCl3): δ = 115.19 [s,
O-P-(C6H5)2].
(2R)-2-[Benzyl(2-{benzyl[(2R)-1-{[bis(propan-2-yl)phospha-
nyl]oxy}-3-phenylpropan-2-yl]amino}ethyl)amino]-3-phenyl-
propylbis(propan-2-yl)phosphinite (24): (i-Pr)2PCl (0.063 g,
0.394 mmol) was added to a stirred solution of 16 (0.100 g, 0.197
mmol) and Et3N (0.040 g, 0.394 mmol) in CH2Cl2 (25 mL) at 0 °C
with vigorous stirring. The mixture was stirred at r.t. for 48 h, and
the solvent was removed under reduced pressure. After addition of
anhydrous toluene, the white precipitate (triethylammonium chlo-
ride) was filtered off under argon and remaining organic phase was
dried in vacuo to produce 24 (138 mg, 94.5%) as a white viscous oil.
31P-{1H} NMR (CDCl3): δ = 151.77 [s, O-P-(i-Pr)2].
(2S)-2-(Benzyl{2-[benzyl((1S)-2-{[bis(propan-2-yl)phospha-
nyl]oxy}-1-phenylethyl)amino]
ethyl}amino)-2-phenylethyl-
bis(propan-2-yl)phosphinite (18): (i-Pr)2PCl (0.067 g, 0.416
mmol) was added to a stirred solution of 13 (0.10 g, 0.208 mmol)
and Et3N (0.043 g, 0.416 mmol) in CH2Cl2 (25 mL) at r.t. with vig-
orous stirring. The mixture was stirred at r.t. for 72 h, and the sol-
vent was removed under reduced pressure. After addition of
anhydrous toluene, the white precipitate (triethylammonium chlo-
ride) was filtered off under argon and remaining organic phase was
dried in vacuo to give 18 (141 mg, 95%) as a white viscous oil. 31P-
{1H} NMR (CDCl3): δ = 154.24 [s, O-P-(i-Pr)2].
Acknowledgment
(2S)-2-{Benzyl[2-(benzyl{(2S)-1-[(diphenylphosphanyl)oxy]-3-
phenylpropan-2-yl}amino)ethyl]amino}-3-phenylpropyldiphe-
nylphosphinite (19): Chlorodiphenylphosphine (0.092 g, 0.394
mmol) was added to a stirred solution of 14 (0.100 g, 0.197 mmol)
and Et3N (0.04 g, 0.394 mmol) in toluene (25 mL) at r.t. with vigor-
ous stirring. The mixture was stirred at r.t. for 1 h and the white pre-
cipitate (triethylammonium chloride) was filtered off under argon
and remaining organic phase was dried in vacuo to produce 19 (166
mg, 97%) as a white viscous oil. 31P-{1H} NMR (CDCl3): δ =
114.68 [s, O-P-(C6H5)2].
Financial support from Tubitak (Project number: 108T060) is gra-
tefully acknowledged.
References and Notes
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(2S)-2-[Benzyl(2-{benzyl[(2S)-1-{[bis(propan-2-yl)phospha-
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propylbis(propan-2-yl)phosphinite (20): (i-Pr)2PCl (0.063 g,
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the solvent was removed under reduced pressure. After addition of
anhydrous toluene, the white precipitate (triethylammonium chlo-
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ring. The mixture was stirred at r.t. for 1 h and the white precipitate
(triethylammonium chloride) was filtered off under argon and the
remaining organic phase was dried in vacuo to produce 21 (170 mg,
© Georg Thieme Verlag Stuttgart · New York
Synlett 2012, 23, 2777–2784

2784
M. Aydemir et al.
LETTER
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Synlett 2012, 23, 2777–2784
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