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alyst could not be deactivated by supramolecular recognition
with PEG-300. We also performed the hydrogenation reaction
of compound 2a in a mixture of PEG-300/MeOH (Scheme 3)
and found that the hydrogenation reaction was switched “ON”
by simply adding a small amount of MeOH, which presumably
weakened the host–guest interactions. Based on these obser-
vations, encapsulation of the activated quinoline substrate by
PEG or long-chain OEG molecules might be the main reason
for the shutdown of the reaction.
Conclusion
In summary, we have investigated the asymmetric hydrogena-
tion reaction of quinoline derivatives in OEGs and PEGs cata-
lyzed by chiral ruthenium diamine complexes. In PEGs or long-
chain OEGs, the quinolines did not undergo hydrogenation,
owing to encapsulation inside PEG or OEG molecules through
host–guest interactions. The reactivity of the hydrogenation re-
action could be easily turned “on” by simply adding a small
amount of MeOH into the reaction mixture. The asymmetric
hydrogenation reactions of a range of 2-substituted quinoline
derivatives were achieved in short-chain 3-OEG with excellent
reactivities and enantioselectivities. In addition, catalyst recy-
cling and reuse were demonstrated in both pure 3-OEG and in
a biphasic 3-OEG/n-hexane system. Further efforts to extend
this solvent-controlled strategy to other asymmetric catalytic
reactions are underway.
Catalyst Recycling and Reuse
Another noteworthy feature of this catalytic system is the reus-
ability of the catalyst. Taking the asymmetric hydrogenation of
2-methylquinoline (2a) as a model reaction, we first examined
the recyclability of Ru catalyst (R,R)-1a in pure 3-OEG. Upon
completion of the hydrogenation reaction, the product was
separated by extraction with n-hexane. Then, the OEG phase
was directly recharged with compound 2a and subjected to
a second hydrogenation reaction under identical conditions.
As shown in Table 4, the ruthenium catalyst could be reused at
least six times without a clear loss of reactivity or enantioselec-
tivity.
Experimental Section
General Information
All of the experiments were performed under a nitrogen atmos-
phere by using standard Schlenk techniques or in a glove-box. All
of the solvents were treated prior to use according to the standard
methods. PEGs and short-chain OEGs were commercially available
and dried under reduced pressure by using a toluene azeotrope
prior to use. Long-chain OEGs (more than four EG units) were syn-
Table 4. Reuse of catalyst (R,R)-1a in the asymmetric hydrogenation of
[
a]
compound 2a in different solvent systems.
[9]
thesized according to a literature procedure. Silica gel was dried
at 3008C for 6 h prior to use. Other commercially available re-
agents were purchased from Alfa Aeser and Aldrich and used as re-
ceived without further purification. All of the ruthenium catalysts
[8,10] 1
[
b]
[c]
[d]
Run
Conversion [%]
Yield [%]
ee [%]
were synthesized according to a literature procedure.
H and
13
C NMR spectra were recorded at ambient temperature in CDCl
3
1
2
3
4
5
6
7
>99 (>99)
>99 (>99)
>99 (>99)
>99 (>99)
>99 (>99)
90 (94)
93 (94)
96 (95)
95 (96)
96 (94)
94 (93)
84 (89)
78 (77)
97 (97)
97 (97)
97 (97)
97 (97)
97 (96)
96 (96)
96 (95)
1
on a Bruker Model Advance DMX 300 Spectrometer ( H: 300 MHz;
13
C: 75 MHz) with tetramethylsilane (TMS) as an internal standard.
Enantiomeric excesses were determined by chiral HPLC analysis on
a Varian Prostar 210 liquid chromatograph. Optical rotations were
measured on a Rudolph Autopol VI polarimeter.
84 (82)
[
(
a] Reaction conditions: compound 2a (0.2 mmol), 3-OEG (1 mL), catalyst
R,R)-1a (1.0 mol%), H (50 atm), 258C, 24 h. [b] Determined by H NMR
2
General Procedure for the Asymmetric Hydrogenation of
Quinoline Derivatives in 3-OEG
1
spectroscopy. [c] Yield of the isolated product. [d] Determined by HPLC
analysis on a chiral stationary phase; data in parentheses were obtained
in a 3-OEG/n-hexane (1:1, v/v) biphasic catalytic system.
A 50 mL glass-lined stainless-steel reactor was charged with ruthe-
nium catalyst (R,R)-1a (0.002 mmol), substrate 2 (0.2 mmol), 3-OEG
(1 mL), and a magnetic stirrer bar under a N2 atmosphere in
a glove box. The autoclave was closed and the final pressure of
the hydrogen gas was adjusted to 50 atm after purging the auto-
clave several times with hydrogen gas. The reaction mixture was
stirred at RT for 20–30 h and, after carefully releasing the hydrogen
gas, the OEG phase was extracted with n-hexane (5ꢁ1 mL). The
combined n-hexane solution was concentrated under vacuum to
afford the crude product and the reaction conversion was deter-
Next, to further facilitate the catalyst recovery and decrease
the use of organic solvent, we studied a two-phase catalytic
system. Thus, a mixture of 3-OEG and n-hexane was used as
the reaction medium and, after the reaction was complete, the
product was easily separated by decantation. Similar results
were obtained by using this biphasic catalytic system com-
pared to pure 3-OEG (Table 4). Based on inductively coupled
plasma (ICP) analysis, we estimated that only 0.26% (in pure 3-
OEG) and 0.28% (in 3-OEG/n-hexane) of the ruthenium catalyst
had leached from the OEG phase during the second runs.
These results further demonstrated that OEGs are efficient re-
action media that can facilitate the immobilization and recy-
cling of homogeneous metallic catalysts.
1
mined by H NMR spectroscopy. Purification by column chromatog-
raphy on silica gel (petroleum ether/CH Cl , 1:1 v/v) gave the pure
2
2
product. Enantiomeric excess was determined by HPLC on a chiral
column (OD-H, OJ-H, AS-H, or AD-H). The absolute configuration of
[6b,11]
the product was assigned by comparison with literature data.
In the catalyst-recycling experiments, the recovered catalyst in 3-
OEG was directly reused in the next catalytic hydrogenation reac-
tion of the same substrate (2a) under identical reaction conditions.
&
&
Chem. Asian J. 2016, 00, 0 – 0
4
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!
Wang, Tianli
