G Model
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M. Tao et al. / Chinese Chemical Letters xxx (2016) xxx–xxx
Scheme 1. Synthesis of chiral multidentate P3N4-type ligand.
ligand (R,R,R,R)-3 as a white solid in 90% yield, which features
2.1. Synthesis of chiral multidentate P3N4-type ligand
the HRMS signals at 1063.5117 (M+H). The 31P NMR spectrum of
(R,R,R,R)-3 in CDCl3 solution exhibited three singlets at
d
ꢀ15.84 (–
Chiral multidentate P3N4-type ligand (R,R,R,R)-3 was synthe-
sized as Scheme 1. A mixture of o-(diphenylphosphine)benzalde-
hyde (0.61 g, 2.1 mmol), (R,R,R,R)-1 (0.5 g, 0.97 mmol) and
anhydrous Na2SO4 (5.0 g) in CH2Cl2 (50 mL) was stirred at room
temperature for 2 days. The resulting yellow solution was filtered
and the solvent was removed under reduced pressure to give a pale
yellow solid (R,R,R,R)-2 (1.0 g, 97% yield). A solution of (R,R,R,R)-2
(1.0 g, 0.94 mmol) and NaBH4 (2.5 g, 66.0 mmol) in absolute
ethanol (120 mL) was refluxed with stirring for 42 h. The solution
was cooled to room temperature and H2O (30 mL) was added to
decompose excess NaBH4. The mixture solution was extracted
with CH2Cl2 (50 mL). Then, the combined extracts were washed
with saturated NH4Cl solution, H2O and saturated brine solution,
successively. The organic layers were combined and dried over
anhydrous Na2SO4, filtered. The solvent was removed under
reduced pressure to afford (R,R,R,R)-3 as a white solid in 90% yield
PPh2), ꢀ15.86 (–PPh2), and ꢀ25.81 (–PPh). Compound (R,R,R,R)-3
contains four chiral carbon atoms and seven possible coordination
sites, which is hopeful to exhibit unique performance in both
coordination chemistry and asymmetric catalysis.
Next, we are interested in the asymmetric catalytic behavior of
this novel chiral multidentate ligand (R,R,R,R)-3. Using i-PrOH as
hydrogen donor, we examined the ATH of propiophenone
catalyzed by combining (R,R,R,R)-3 with various iridium com-
pounds (Table 1). It can be seen that the ATH of propiophenone
proceeded smoothly to yield (S)-1-phenylpropanol under mild
conditions. Notably, the catalyst system generated in situ from
IrCl(CO)(PPh3)2 and (R,R,R,R)-3 gave 92% yield with 93% ee in just
half an hour at 40 8C (Table 1, entry 5), surpassing those
previously reported chiral PN4-type ligand (R,R,R,R)-1 [26]. Fur-
thermore, we performed the reaction at lower catalyst loading
(0.02 mol%), obtaining 61% yield with 90% ee (Table 1, entry 6).
These results showed that the chiral multidentate ligand
(R,R,R,R)-3 is highly effective for Ir-catalyzed enantioselective
reduction of propiophenone.
As we reported previously, adding an appropriate base is
important for the reaction of ATH in terms of both reactivity and
enantioselectivity [18]. Therefore, we examined the effect of the
amount of KOH on ATH of propiophenone with IrCl(CO)(PPh3)2/
(R,R,R,R)-3. It showed that no reaction carried out if the base was
absent or at low concentration. As the base concentration was
increased, both the reaction rate and ee increased greatly.
However, excess base decreased slightly the enantioselectivity
although the conversion increased (For more details, see the
Supporting information).
(0.9 g). Mp 113–116 8C. 1H NMR (400 MHz, CDCl3):
d 0.74 (d, 4H,
J = 8.7 Hz), 1.00 (d, 4H, J = 29.8 Hz), 1.48 (s, 4H), 1.85 (m, 8H), 2.01
(s, 4H), 3.63–3.82 (m, 4H), 3.83–4.00 (m, 4H), 6.61–6.80 (m, 4H),
6.93–7.32 (m, 31H), 7.49 (ddd, 6H, J = 28.2, 14.1, 7.0 Hz); 13C NMR
(100 MHz, CDCl3):
d 24.86, 31.02, 48.82, 60.47, 60.85 (d,
J = 6.13 Hz), 62.81, 63.05, 127.36, 128.68, 129.15 (d, J = 7.01 Hz),
132.28 (d, J = 26.97 Hz), 133.57, 134.22, 135.01, 135.63, 136.21 (d,
J = 9.48 Hz), 136.71 (dd, J = 4.03, 10.23 Hz), 144.40, 144.64, 145.43,
145.66; 31P NMR (162 MHz, CDCl3):
d
ꢀ15.84, ꢀ15.86, ꢀ25.81.
HRMS (ESI) Calcd. for [M+H]+: 1063.5126, Found: 1063.5117. ½a 2D0
ꢁ
ꢀ20.9 (c 0.2, CHCl3).
2.2. Typical procedure for ATH
Under nitrogen atmosphere, the catalyst precursor IrCl(-
CO)(PPh3)2 (3.9 mg, 0.005 mmol) and (R,R,R,R)-3 (5.3 mg,
0.005 mmol) were placed in a tube equipped with a Teflon-coated
magnetic stirring bar. i-PrOH was then added and the mixture was
stirred at 40 8C for 20 min. An appropriate amount of KOH/i-PrOH
solution was then added, and the mixture was continually stirred
for another 20 min. Next, ketone (0.5 mmol) was introduced and
the mixture was stirred at 40 8C for the required reaction time. At
the end of the reaction, the product was analyzed by GC using a
chiral CP-Chirasil-Dex CB column.
Table 1
Screening of catalysts for ATH of propiophenone.a
Entry
Iridium complex
Time (h)
Yield (%)b
ee (%)b
1
2
[IrCl(COD)]2
0.5
0.5
0.5
0.5
0.5
5
98
97
95
20
92
61
35
59
85
92
93
90
[IrHCl(COD)]2
[Cp*IrCl2]2
3
4
IrH(CO)(PPh3)3
IrCl(CO)(PPh3)2
IrCl(CO)(PPh3)2
5
6c
3. Results and discussion
a
Reaction conditions: propiophenone (1 mmol), iridium complex (0.005 mmol),
The condensation of chiral aminophosphine ligand (R,R,R,R)-1
and o-(diphenylphosphine)benzaldehyde proceeded in CH2Cl2 for
48 h, obtaining a pale yellow solid (R,R,R,R)-2 in 97% yield.
Reduction of (R,R,R,R)-2 with excess NaBH4 was carried out in
refluxing ethanol, giving the corresponding P3N4-type amine
(R,R,R,R)-3 (0.005 mmol), KOH (0.06 mmol), i-PrOH (10 mL), 40 8C.
b
Yield and ee were determined by GC analysis with a chiral CP-Chirasil-Dex CB
column.
c
Propiophenone (25 mmol), IrCl(CO)(PPh3)2 (0.005 mmol), (R,R,R,R)-3
(0.005 mmol), KOH (0.25 mmol).
Please cite this article in press as: M. Tao, et al., Novel chiral multidentate P3N4-type ligand for asymmetric transfer hydrogenation of