One-pot synthesis of chiral alcohols from alkynes by CF3SO3H/ruthenium tandem catalysis

Article abstract of DOI:10.1039/c8ra02224k

A practical one-pot synthesis of chiral alcohols from readily available alkynes via tandem catalysis by the combination of CF₃SO₃H and a fluorinated chiral diamine Ru(ii) complex in aqueous CF₃CH₂OH is described. Very interestingly, the combination of fluorinated catalysts and solvent exhibits a positive fluorine effect on the reactivity and enantioselectivity. A range of chiral alcohols with wide functional group tolerance was obtained in high yield and excellent stereoselectivity under simple and mild conditions.

Full text of DOI:10.1039/c8ra02224k

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One-pot synthesis of chiral alcohols from alkynes
by CF SO H/ruthenium tandem catalysis†
3
3
Cite this: RSC Adv., 2018, 8, 14829
Huan Liu, Sensheng Liu, Haifeng Zhou, * Qixing Liu and Chunqin Wang
A practical one-pot synthesis of chiral alcohols from readily available alkynes via tandem catalysis by the
Received 14th March 2018
Accepted 12th April 2018
3 3 3 2
combination of CF SO H and a fluorinated chiral diamine Ru(II) complex in aqueous CF CH OH is
described. Very interestingly, the combination of fluorinated catalysts and solvent exhibits a positive
fluorine effect on the reactivity and enantioselectivity. A range of chiral alcohols with wide functional
group tolerance was obtained in high yield and excellent stereoselectivity under simple and mild conditions.
DOI: 10.1039/c8ra02224k
rsc.li/rsc-advances
Pot-economic reactions as alternatives to traditional multistep
synthetic procedures have received great attention. The signif- conditions, using 20 mol% triuoromethanesulfonic acid
2
icant benets of a one-pot reaction include simple starting (CF SO H) as the catalyst and 2,2,2-triuoroethanol (CF CH -
In 2016, a Markovnikov-type alkyne hydration under simple
3
3
3
1
9
materials and minimum isolation/purication processes. The OH) as the solvent was developed by Li and coworkers. It was
ꢁ
direct conversion of alkynes into alcohols is of great importance reported the CF
3
SO
3
could be counter anion of chiral Ru/
because of the readily available alkynes as well as the valuable diamine complexes, which were used as privileged catalysts
10,11
alcohols. However, the one-pot conversion of alkynes into for the AH or ATH of ketones.
alcohols through a tandem hydration/reduction process is still We reason that the conversion of alkynes into chiral alcohols
challengeable because of the conict of extrinsic reaction will be realized by tandem catalysis with CF SO H and chiral
3
3
2
conditions and the incompatible nature of the catalysts. The Ru/diamine complexes as the catalysts. Most importantly, it not
rst one-pot asymmetric synthesis of chiral alcohols from only makes the catalytic systems simple, but also cleverly avoids

alkynes via hydration/asymmetric transfer hydrogenation (ATH) the incompatible problem of different catalysts in one-pot
was reported by Xiao's group. In their process, formic acid was reaction. To continue our interest in asymmetric synthesis of
ꢀ
12
used as a solvent for the hydration step at 100 C, and then the chiral alcohols, we describe an easy operation process for
ATH was conducted at neutral conditions by adding a large a pot-economic synthesis of chiral alcohols from readily avail-
3
amount of NaOH (Scheme 1). Aer that, Sun and co-workers able alkynes via tandem catalysis under simple conditions,
described the same conversion catalyzed by the combination using CF SO H catalyzed hydration of alkynes in CF CH OH,
3
3
3
2
3
+
of salen–Co and a chiral ruthenium complex with the aid of followed by ATH with uorinated chiral diamine Ru(II) complex
4
H
2
SO
4
.
However, it is not applicable for electron-decient as the catalyst and sodium formate as the hydrogen source.
Initially, the hydration of phenylacetylene (2a) was carried
geneous bimetallic catalysts like Au–Ru and Au–Rh has also out with 20 mol% CF SO H as the catalyst and 2 mL of CF
been realized. In addition, the heterogeneous bimetallic cata- CH OH as the solvent in the presence of 2 equiv. of H
lytic systems like core–shell micellar supported Co/porphyrin monitored by gas chromatography (GC), 2a was converted to
alkynes. Subsequently, the similar transformation with homo-
5
6
3
3
3
-
9
2
2
O. As
7
ꢀ
13
and chiral rhodium/diamine complexes, large-pore meso- acetophenone quantitatively at 40 C for 6 h. Then, 0.5 mol%
porous silica supported Au/carbene and chiral ruthenium/ (S,S)-1a, 5 equiv. of HCOONa, and 2 mL of H O were added.
2
8
diamine dual complexes were also applied in this trans-
formation. Despite these achievements, it is highly desirable to
develop simple, efficient, and compatible catalytic systems
under mild conditions for the conversion of alkynes into chiral
alcohols from both a practical standpoint and an environ-
mental point of view.
Research Center of Green Pharmaceutical Technology and Process, Hubei Key
Laboratory of Natural Products Research and Development, College of Biological
and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002,
China. E-mail: zhouhf@ctgu.edu.cn
†
Electronic supplementary information (ESI) available. See DOI:
0.1039/c8ra02224k
1
Scheme 1 One-pot conversion of alkynes into chiral alcohols.
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a
a
Table 1 Optimization of the reaction conditions
Table 2 Substrate Scope
Entry
Cat.
Hydrogen source
Yield (%)
ee (%)
1
2
3
4
5
6
7
8
(S,S)-1a
(S,S)-1b
(S,S)-1c
(S,S)-1d
(S,S)-1e
(S,S)-1f
(S,S)-1g
(S,S)-1h
(S,S)-1h
(S,S)-1h
(S,S)-1h
HCOONa (5 equiv.)
HCOONa (5 equiv.)
HCOONa (5 equiv.)
HCOONa (5 equiv.)
HCOONa (5 equiv.)
HCOONa (5 equiv.)
HCOONa (5 equiv.)
HCOONa (5 equiv.)
HCOONa (5 equiv.)
41
<5
80
83
78
79
84
95
24
0
93
—
87
96
79
94
94
97
95
—
95
b
9
c
1
1
0
1
HCOOH/NEt
HCOOH/NEt
3
(5:2)
(1.1:1)
c
3
46
a
Reaction conditions: phenylacetylene (2a; 5 mmol), CF
3
SO
3
H (20
ꢀ
mol%), H
2
O (2 equiv.), CF
3
CH
2
OH (2 mL), 40 C, 6 h; then 0.5 mol%
2
O (2 mL) were added, 50
ꢀ
c
HCOOH/NEt
3
mixture was used, the data in the brackets are molar ratio.
ꢀ
The subsequent ATH was conducted at 50 C for 24 h,
affording the desired (S)-1-phenylethanol (3a) in 41% yield and
9
3% ee (Table 1, entry 1). Next, the chiral ruthenium/diamine
complexes including 1b–1h were screened. Interestingly, it
was found that a uorine effect on the reactivity and enan-
1
4
tioselectivity was observed in this tandem reaction. For
example, the uorinated chiral diamine Ru(II) complexes 1c–
1
h exhibit high reactivity and excellent enantioselectivity
(
entries 3–8). Among which, the best yield and ee value were
provided by the chiral N-pentauorobenzenesulfonyl-1,2-
diphenylethylenediamine Ru(II) complex (S,S)-1h, giving 3a
in 95% yield and 97% ee (entry 8). Then, other uorinated
alcohols like hexauoro-2-propanol (HFIP) could also give the
desired product in 95% ee but with only 24% yield (entry 9).
Finally, other hydrogen sources were also examined. For and 12
example, no desired product was detected using an acidic
a
Reaction conditions: alkyne (5 mmol), CF
3
SO
3
H (20 mol%), H
2
O (2
ꢀ
equiv.), CF
HCOONa (5 equiv.), H
values were determined by HPLC analysis. Conditions were 70
3
CH
2
OH (2 mL), 40 C, 6 h, then add 0.5 mol% (S,S)-1h,
ꢀ
2
O (2 mL), 50 C, 24 h, isolated yield, the ee
b
ꢀ
C
c
h
for hydration step. HFIP was used ase
a
solvent.
d
ꢀ
Conditions were 70 C and 48 h for hydration step. Conditions
ꢀ
f
were 40 C and 48 h for hydration step. CF
equiv.), CF CH OH (2 mL), 70 C, 48 h, then add 1 mol% (S,S)-1h,
3
SO
3
H (40 mol%), H
2
O (4
HCOOH–NEt azeotrope (molar ratio F/T ¼ 5/2) as hydrogen
ꢀ
3
3
2
ꢀ
source (entry 10). By contrast, 3a was obtained in 46% yield HCOONa (10 equiv.), H
2
O (2 mL), 50 C, 48 h.
and 95% ee using slightly basic HCOOH–NEt
ratio F/T ¼ 1.1/1) as hydrogen source (entry 11). Based on
above results, the optimal reaction conditions were set as pot conversion of alkynes into chiral alcohols, the scope of
follow: 20 mol% CF SO H coupled with 0.5 mol% (S,S)-1h as various alkynes was then investigated. As summarized in Table
the catalysts, 5 equiv. of HCOONa as the hydrogen source, and 2, the internal aromatic alkynes were examined rst. For
3
mixture (molar
1
5
Having established a compatible catalytic system for the one-
3
3
CF CH OH/H O (v/v ¼ 1 : 1) as the solvent (entry 8).
examples, the reaction of phenylacetylene derivatives 2b–2e
3
2
2
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aryl moiety gives better yield and ee value, it may be ascribe to
the positive uorine effect between the uorinated solvent and
16
catalyst.
In summary, we have developed a simple and efficient
compatible catalytic system, using uorine-containing
BrØnsted acid (CF SO H) coupled with a uorinated chiral
diamine Ru(II) complex as catalysts, and uorinated alcohol
CF CH OH) as a solvent, which exhibits positive uorine effect
a
3
3
Scheme 2 Gram-scale reaction.
(
3
2
on the reactivity and enantioselectivity for the conversion of
alkynes into chiral alcohols. Furthermore, the gram-scale reac-
tion demonstrates its potential application.
bearing electron-donating groups (Me, Et, n-Pr, MeO) per-
formed smoothly under the optimized conditions, giving the
corresponding chiral alcohols 3b–3e in 74–95% yield and 92–
98% ee. By contrast, in the case of electron-decient phenyl-
acetylene derivatives 2f–2n bearing electron-withdrawing Conflicts of interest
2
groups (F, Cl, Br, NO ), the hydration step requires higher
temperature and longer time. Due to poor solubility of 4-bro-
There are no conicts to declare.
mophenylacetylene (2m) and 4-nitrophenylacetylene (2n) in
CF CH OH, the HFIP was used instead. In addition to phenyl- Acknowledgements
3
2
acetylene derivatives, the 2-ethynylnaphthalene (2o) could also
be converted to alcohol 3o in 89% yield and 88% ee successfully.
Next, the internal aromatic alkynes 2p–2s were also subjected to
this tandem reaction, and the corresponding alcohols 3p–3s
were isolated with 64–74% yield and 76–89% ee. Most impor-
We are grateful for the nancial support by the grants from the
National Natural Science Foundation of China (21202092) and
China Three Gorges University (KJ2014H008, KJ2014B084).
tantly, the direct conversion of 1,3-diethynylbenzene (2t) and Notes and references
1
,4-diethynylbenzene (2u) into chiral diols 3t and 3u was ach-
1
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propargyl alcohol (2x), and methyl phenylpropiolate (2y) were
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pot tandem process, a gram scale reaction with 3-uo-
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