Bimetallic Pt–Sn/γ-Al2O3catalyzed β-alkylation of secondary alcohols with primary alcohols under solvent-free conditions

Article abstract of DOI:10.1016/j.tetlet.2016.07.037

Heterogeneous bimetallic Pt–Sn/γ-Al₂O₃(0.5?wt% Pt, molar ratio Pt:Sn?=?1:3) was successfully utilized as the catalyst for direct β-alkylation of secondary alcohols with primary alcohols under solvent-free conditions. β-Alkylated secondary alcohols were obtained in moderate to high yields with water formed as the by-product through a hydrogen borrowing pathway. The present protocol provides a concise atom-economical and environmentally benign method for C–C bond formation.

Full text of DOI:10.1016/j.tetlet.2016.07.037

Tetrahedron Letters xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Bimetallic Pt–Sn/
c
-Al2O3 catalyzed b-alkylation of secondary alcohols
with primary alcohols under solvent-free conditions
⇑
Kaikai Wu, Wei He, Chenglin Sun, Zhengkun Yu
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, Liaoning 116023, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Heterogeneous bimetallic Pt–Sn/c-Al2O3 (0.5 wt% Pt, molar ratio Pt:Sn = 1:3) was successfully utilized as
Received 2 June 2016
Revised 7 July 2016
Accepted 11 July 2016
Available online xxxx
the catalyst for direct b-alkylation of secondary alcohols with primary alcohols under solvent-free
conditions. b-Alkylated secondary alcohols were obtained in moderate to high yields with water formed
as the by-product through a hydrogen borrowing pathway. The present protocol provides a concise
atom-economical and environmentally benign method for C–C bond formation.
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Alcohols
b-Alkylation
C–C bond formation
Hydrogen borrowing
Pt–Sn catalyst
Alcohols are very important in organic synthesis and chemical
industry. Traditional routes to access b-alkylated alcohols from
secondary alcohols usually require a multistep process involving
oxidation of the secondary alcohols, alkylation with alkyl halides,
and reduction of b-alkylated ketones. Alkylation of alcohol by
means of another alcohol as the alkylating agent has been consid-
ered as a green and direct method to attain b-alkylated alcohols.1
In the absence of a hydrogen acceptor or donor, such a process
can occur through a hydrogen borrowing pathway.2 Homogeneous
transition-metal catalysts such as ruthenium,3 iridium,4
palladium,5 and copper6 complexes have been reported to catalyze
direct C–C cross-coupling of secondary alcohols with primary alco-
hols to form b-alkylated alcohols or b-alkylated ketones without
using any hydrogen acceptor or donor, but the systems usually suf-
fer from limited scope of alcohols, difficulty in recycling the cata-
lyst, and need of a large amount of base. In order to overcome
some of the drawbacks of homogeneous catalysts, development
of efficient heterogeneous transition-metal catalyst systems has
recently been paid much attention for hydrogen borrowing
achieved using Ag6Mo10O33,
11 IrO2/Fe3O4,12 and SBA-15-supported
Ir/NHC complex13 catalysts under hydrogen borrowing conditions.
Recently, heterogeneous bimetallic catalysts have become
attractive in this area. Cao et al. reported Au–Pd/HT (Au:
Pd = 13:1) catalyzed synthesis of b-alkylated ketones from primary
and secondary alcohols through a facile hydrogen borrowing path-
way in the absence of basic additives.14 Such a catalyst could be
easily separated from the reaction mixture and reused for at least
three times without loss of its catalytic activity. Heterogeneous
bimetallic catalyst Pt–Sn/
dehydrogenation, reforming processes, and hydrogenation in pet-
roleum industry.15 We found that Pt–Sn/
-Al2O3 catalyst can be
c-Al2O3 has been well known for alkane
c
efficiently applied for the hydrogen-borrowing N-alkylation of
amines with alcohols or amines.16 Thus, we reasonably envisioned
that this catalyst might be utilized to promote the cross-coupling
between secondary and primary alcohols for the construction of
C–C bonds. Herein, we disclose direct b-alkylation of secondary alco-
hols with primary alcohols through a hydrogen borrowing pathway
using a Pt–Sn/c
-Al2O3 catalyst16 for the first time (Scheme 1).
Initially, the reaction of 1-phenylethanol (1a) with benzyl alco-
hol (2a) was carried out to optimize the reaction conditions
processes.7 Heterogeneous Ni/CeO2 and Pt/CeO2 exhibited high
catalytic activity for self-coupling of aliphatic alcohols to b-alky-
lated ketones in the absence of additives. Ag/Al2O3 promoted the
cross-alkylation of secondary alcohols with primary alcohols to
afford b-alkylated ketones in the presence of a catalytic amount
of Cs2CO3.10 b-Alkylation of secondary alcohols can also be
8
9
(Table 1). Using heterogeneous Pt–Sn/c-Al2O3 (I) (0.5 wt% Pt,
Pt/Sn = 1:1) (0.075 mol% Pt) as the catalyst and K3PO4 (0.5 equiv)
as the base at 145 °C in a sealed Pyrex glass screw-cap tube under
solvent-free conditions, 42% conversion was reached for 1a to form
the target b-alkylated product 3a as the major product and ketone
4a as the minor product (Table 1, entry 1). Increasing the Pt/Sn
molar ratio from 1:2 to 1:9 further improved the conversion of
⇑
Corresponding author. Tel./fax: +86 411 8437 9227.
E-mail address: zkyu@dicp.ac.cn (Z.K. Yu).
http://dx.doi.org/10.1016/j.tetlet.2016.07.037
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Wu, K. K.; et al. Tetrahedron Lett. (2016), http://dx.doi.org/10.1016/j.tetlet.2016.07.037

2
K.K. Wu et al. / Tetrahedron Letters xxx (2016) xxx–xxx
Table 2
OH
OH
Scope of primary alcohols (2)a,b
Pt-Sn/γ-Al2O3
(0.075 mol % Pt)
OH
Ar2
Ar1
+
Ar2
Ar1
catalyst III
K3PO4 (0.5 equiv), 155 o
-H2O
C
(0.075 mol % Pt)
K3PO4 (0.5 equiv)
OH
OH
+
R
OH
Ph
R
Ph
155 oC, 48 h
Scheme 1. Pt–Sn/c-Al2O3 catalyzed direct b-alkylation of secondary alcohols with
primary alcohols through a hydrogen borrowing pathway.
1a
2
3
OH
OH
OH
1a, and the best result (99% conversion for 1a with a 99:1 ratio of
3a:4a) was obtained using a Pt/Sn ratio of 1:3 (Table 1, entries
2–6). The best result was obtained with catalyst III (Pt/Sn = 1:3),
rendering formation of 3a in 93% isolated yield (Table 1, entry 3).
The high tin content in catalysts IV–VI (Pt/Sn = 1:5–1:9) may
partially block exposure of the Pt (0) metal surface required for
the hydrogen borrowing process, resulting in a lower reaction effi-
ciency (Table 1, entries 4–6). Elevating the reaction temperature to
155 °C led to 3a in 96% isolated yield (Table 1, entry 7). Lowering
the base amount to 0.3 equiv slightly deteriorated the conversion
of 1a (Table 1, entry 8). It was noted that the selectivity was
remarkably decreased by conducting the reaction in o-xylene sol-
vent (Table 1, entry 9). Other bases such as NaOtBu and KOAc were
not effective for the desired reaction (Table 1, entries 10 and 11).
3a, 96%
3b, 93%
3c, 85%
OH
OH
OH
O
O
OMe
3d, 25%
3e, 86%
3f, 82%
OH
OH
OH
Cl
Cl
3g, 90%
3h, 82%
3i, 80%
OH
OH
Somehow, both PtCl2 and Pt/
c
-Al2O3 did not show any catalytic
OH
activity for the reaction (Table 1, entries 12 and 13). It should be
noted that the reaction did not occur in the absence of K3PO4 base
(Table 1, entry 14).
O
N
N
3j, 94%
3k, 80%
3l, 20%c
Under the optimal conditions the reactions of 1a with a variety
of primary alcohols 2 were investigated (Table 2).17 Variation of
the methyl substituent at 3- and 4-positions on the aryl backbone
of 2 did not obviously affect formation of the target products 3b
and 3c (85–93%), while 2-methylbenzyl alcohol could not effi-
ciently undergo b-alkylation with 1a due to the increased steric
hindrance and the reaction only afforded 3d in 25% yield. Benzylic
alcohols bearing an electron-donating methoxy or 3,4-methylene-
dioxy substituent reacted with 1a to form products 3e (86%) and 3f
(82%), respectively. Chlorobenzyl alcohols, that is, 3- and
a
Conditions: 1a (5 mmol),
(0.5 equiv), 155 °C, 0.1 MPa N2, 48 h.
2 (5 mmol), catalyst III (0.075 mol% Pt), K3PO4
b
Yields refer to the isolated products.
Determined by GC analysis.
c
4-chlorobenzyl alcohols, also smoothly reacted with 1a to afford
products 3g (90%) and 3h (80%). The reaction of 1a with
1-naphthylmethanol efficiently occurred, forming 3i in 80% yield.
Although 2- and 4-pyridylme-thanols efficiently underwent the
Table 1
Screening of reaction conditionsa
OH
O
OH
conditions
+
Ph
OH
+
Ph
Ph
Ph
Ph
Ph
1a
2a
3a
4a
Entry
Catalyst
Pt/Sn (molar ratio)b
Conv. of 1ac (%)
3a:4ac
1
2
3
4
Pt–Sn/
Pt–Sn/
Pt–Sn/
Pt–Sn/
Pt–Sn/
Pt–Sn/
Pt–Sn/
Pt–Sn/
Pt–Sn/
Pt–Sn/
Pt–Sn/
PtCl2
c
c
c
c
c
c
c
c
c
c
c
-Al2O3 (I)
1:1
1:2
1:3
1:5
1:7
1:9
1:3
1:3
1:3
1:3
1:3
42
90
99
78
74
74
>99
98
>99
29
93:7
94:6
-Al2O3 (II)
-Al2O3 (III)
-Al2O3 (IV)
-Al2O3 (V)
-Al2O3 (VI)
-Al2O3 (III)
-Al2O3 (III)
-Al2O3 (III)
-Al2O3 (III)
-Al2O3 (III)
99:1 (93)d
99:1
5
99:1
99:1
6
7e
8f
99:1 (96)d
99:1 (92)d
73:27
9g
10g,h
11g,i
12
13
14j
88:12
n.r.
n.r.
n.r.
n.r.
Pt/c
-Al2O3
-Al2O3 (III)
Pt–Sn/
c
1:3
a
b
c
d
e
f
Conditions: 1a (5 mmol), 2a (5 mmol), catalyst (0.075 mol% Pt), K3PO4 (0.5 equiv), 145 °C, 0.1 MPa N2, 48 h. n.r. = no reaction.
The Pt content in all of the heterogeneous catalysts is 0.5 wt%.
Determined by GC analysis.
Isolated yield of 3a given in parentheses.
155 °C.
K3PO4 (0.3 equiv).
g
h
i
1a (1 mmol), 2a (1 mmol), catalyst (0.5 mol% Pt), K3PO4 (0.5 equiv), o-xylene (3 mL), 155 °C, 0.1 MPa N2, 48 h.
Using NaOtBu (0.5 equiv) instead of K3PO4.
Using KOAc (0.5 equiv) instead of K3PO4.
No base was used.
j
Please cite this article in press as: Wu, K. K.; et al. Tetrahedron Lett. (2016), http://dx.doi.org/10.1016/j.tetlet.2016.07.037

K.K. Wu et al. / Tetrahedron Letters xxx (2016) xxx–xxx
3
III
catalyst
OH
OH
OH
OH
Pt-Sn/γ-Al2O3
(0.075 mol %)
Ar2
OH
+
Ar1
Ar1
Ar2
+
Ph
OH
2a
R
Ph
R
K3PO4 (0.5 equiv)
155 oC, 48 h
1
3
[PtSn]
OH
OH
OH
OH
Cl
Ph
Ph
Ph
Ph
Ph
[PtSn]Hx
Br
Cl
O
O
aldol condensation
3n
3o
3a
, 96%
3m
, 70%
Ph
, 85%
OH
Ar2
, 83%
+
O
Ar1
Ar1
Ar2
OH
OH
Scheme 3. Proposed mechanism.
Ph
F
F3C
3p
3q
3r
, 40%
, 65%
, 91%
the reaction mixture by ICP-AES technology revealed no Pt metal
leaching into the liquid phase in each run reaction. A decrease in
the catalytic activity of catalyst III after recycling is attributed to
Scheme 2. Scope of secondary alcohols (1). Conditions: 1 (5 mmol), 2a (5 mmol),
catalyst III (0.075 mol% Pt), K3PO4 (0.5 equiv), 155 °C, 0.1 MPa N2, 48 h. Yields refer
to the isolated products.
the aggregation of Pt nanoparticles on the c-Al2O3 support during
the reaction, which reduces the available bare surface of Pt
particles catalytically active for the hydrogen borrowing process.
To gain insight into the reaction mechanism, a controlled exper-
iment was conducted (Eqn 1). Under the standard conditions the
1:1 molar ratio reaction of chalcone (5) and benzyl alcohol (2a)
achieved 20% for the starting substrates and formed nearly
equimolar amounts of the reduction product 3a (ꢀ20%) and
benzaldehyde (6, ꢀ20%) by 1H NMR analysis of the reaction
mixture. Thus, the reaction of 1 with 2 can be considered to occur
through a hydrogen borrowing pathway.
Table 3
Recycling of catalyst III from the reaction of 1a with 2aa
III
catalyst
OH
OH
K3PO4 (0.5 equiv)
Ph
OH
+
Ph
Ph
155 oC, 48 h
Ph
1a
2a
3a
Run
Conversion of 1ab (%)
Yieldc (%)
1
2
3
4
5
>99
>99
94
90
60
96
92
90
85
53
O
catalyst III
Ph
Ph
5 (5 mmol)
(0.075 mol % Pt)
3
OH
K PO (0.5 equiv)
4
+
PhCHO
ð1Þ
o
Ph
Ph
155 C, 48 h, N
conv. 20%
a
2
Conditions: 1a (5 mmol), 2a (5 mmol), catalyst III (0.075 mol% Pt), K3PO4
3a,~20%
6,~20%
(0.5 equiv), 155 °C, 0.1 MPa N2, 48 h.
Ph
OH
b
Determined by GC analysis.
Isolated yield.
c
2a (5 mmol)
A simplified mechanism is proposed in Scheme 3. Initially, the
precatalyst promotes oxidation of the secondary and primary alco-
hols to the corresponding ketone and aldehyde by generation of
the [PtSn]Hx hydride species. Then base-mediated cross-aldol
condensation of the in-situ formed ketone and aldehyde occurs to
b-alkylation with 1a to afford the corresponding target products 3j
and 3k (80–94%), 2-furfurylmethanol only demonstrated a poor
reactivity to form 3l in 20% yield. It is noteworthy that other
heteroarylmethyl alcohols such as 3-pyridylmethanol and
2-thiophenemethanol, and 2-phenylethanol did not undergo the
reactions with 1a under the same conditions.
Next, the scope of secondary alcohols 1 was explored by means
of the reaction with benzyl alcohol (2a) (Scheme 2). The present
catalytic system could be tolerant with various functional groups
such as chloro, bromo, fluoro, trifluoromethyl, and methyl. Second-
ary alcohols bearing a 4- or 3-Me group underwent the reaction to
form the target products 3m and 3n (70–83%). 4-Bromo- and
4-fluorobenzyl alcohols reacted to afford 3o (85%) and 3p (65%),
respectively. Unexpectedly, 4-trifluoromethyl-benzyl alcohol effi-
ciently underwent the reaction to form 3q in 91% yield. However,
electron-donating 4-methyl-substituted secondary benzyl alcohol
exhibited a low reactivity to yield the target product 3r in 40% yield.
form
a,b-unsaturated ketone intermediate. Subsequent transfer
hydrogenation with [PtSn]Hx species yields the target alcohol.
In summary, an efficient heterogeneous bimetallic
Pt–Sn/c-Al2O3 catalyzed b-alkylation of secondary alcohols with
primary alcohols has been realized through a hydrogen borrowing
strategy. The present protocol provides a concise and environmen-
tally benign method for C–C bond formation.
Acknowledgements
We are grateful to the National Natural Science Foundation of
China (21472185).
Supplementary data
Then, the recyclability of the heterogeneous Pt–Sn/c-Al2O3 cat-
alyst was evaluated (Table 3). After the first run reaction of 1a with
2a was finished, catalyst III was filtered, washed with water to
remove K3PO4 salt, and subjected to calcination in air at 450 °C
for 4 h. The recovered catalyst was then reused in the second run
b-alkylation of 1a with 2a under the standard conditions. It should
be noted that after each run reaction was complete, the catalyst
was treated in the same fashion for the next run use. For the first
two run reactions, the catalyst almost remained the same catalytic
activity (Table 3, entries 1 and 2). In the third run obvious loss of
catalytic activity was observed, achieving 94% conversion for 1a
and 90 yield for 3a. In the fourth and fifth runs, the catalyst further
lost activity (Table 3, entries 4–5). Analysis of the supernatant from
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2016.07.037.
References and notes
1. Huang, F.; Liu, Z. Q.; Yu, Z. K. Angew. Chem., Int. Ed. 2016, 55, 862.
2. (a) Watson, A. J. A.; Williams, J. M. J. Science 2010, 329, 635; (b) Nixon, T. D.;
Whittlesey, M. K.; Williams, J. M. J. Dalton Trans. 2009, 753; (c) Guillena, G.;
Ramón, D. J.; Yus, M. Chem. Rev. 2010, 110, 1611.
3. For selected recent reports, see: (a) Bai, W.; Jia, G. C. Inorg. Chem. Acta 2015, 431,
234; (b) Jumde, V. R.; Gonsalvi, L.; Guerriero, A.; Peruzzini, M.; Taddei, M. Eur. J.
Org. Chem. 1829, 2015; (c) Wang, Q. F.; Wu, K. K.; Yu, Z. K. Organometallics 2016,
35, 1251.
Please cite this article in press as: Wu, K. K.; et al. Tetrahedron Lett. (2016), http://dx.doi.org/10.1016/j.tetlet.2016.07.037

4
K.K. Wu et al. / Tetrahedron Letters xxx (2016) xxx–xxx
4. For selected recent reports, see: (a) Obora, Y.; Anno, Y.; Okamoto, R.; Matsu-
15. (a) He, S. B.; Sun, C. L.; Bai, Z. W.; Dai, X. H.; Wang, B. Appl. Catal. A: Gen. 2009,
356, 88; (b) He, S. B.; Sun, C. L.; Du, H. Z.; Dai, X. H.; Wang, B. Chem. Eng. J. 2008,
141, 284; (c) Contreras-Andrade, I.; Vázquez-Zavala, A.; Viveros, T. Energy Fuels
2009, 23, 3835; (d) Lewandowski, M.; Sarbak, Z. Appl. Catal. B: Environ. 2008,
79, 313.
16. (a) He, W.; Wang, L. D.; Sun, C. L.; Wu, K. K.; He, S. B.; Chen, J. P.; Wu, P.; Yu, Z. K.
Chem. Eur. J. 2011, 17, 13308; (b) Wang, L. D.; He, W.; Wu, K. K.; He, S. B.; Sun, C.
L.; Yu, Z. K. Tetrahedron Lett. 2011, 52, 7103; (c) He, W.; He, S. B.; Sun, C. L.; Wu,
K. K.; Wang, L. D.; Yu, Z. K. Chin. J. Catal. 2012, 33, 717.
ura, T.; Ishii, Y. Angew. Chem., Int. Ed. 2011, 50, 8618; (b) Musa, S.; Ackermann,
L.; Gelman, D. Adv. Synth. Catal. 2013, 355, 3077.
5. Kose, O.; Saito, S. Org. Biomol. Chem. 2010, 8, 896.
6. (a) Miura, T.; Kose, O.; Li, F.; Kai, S.; Saito, S. Chem. Eur. J. 2011, 17, 11146; (b)
Liao, S.; Yu, K.; Li, Q.; Tian, H.; Zhang, Z.; Yu, X.; Xu, Q. Org. Biomol. Chem. 2012,
10, 2973.
7. (a) El-Molla, S. A. Appl. Catal. A: Gen. 2006, 298, 103; (b) Torres, G.; Apesteguia,
C. R.; Cosimo, J. I. D. Appl. Catal. A: Gen. 2007, 317, 161; (c) Kozlowski, J. T.;
Davis, R. J. ACS Catal. 2013, 3, 1588; (d) Shimizu, K. Catal. Sci. Technol. 2015, 5,
1412.
17.
A typical experimental procedure for the b-alkylation of secondary alcohols
with primary alcohols – synthesis of 3a: Under nitrogen atmosphere, to a 15-mL
Pyrex glass screw-cap tube were added 1-phenylethanol (1a: 0.613 g, 5 mmol),
benzyl alcohol (2a: 0.543 g, 5 mmol), K3PO4 (531 mg, 2.5 mmol), and Pt–Sn/
8. Shimura, K.; Kon, K.; Siddiki, S. M. A. H.; Shimizu, K. Appl. Catal. A: Gen. 2013,
462–463, 137.
9. Chaudhari, C.; Siddiki, S. M. A. H.; Shimizu, K. Top. Catal. 2014, 57, 1042.
10. Shimizu, K.; Sato, R.; Satsuma, A. Angew. Chem., Int. Ed. 2009, 48, 3982.
11. Cui, X. J.; Zhang, Y.; Shi, F.; Deng, Y. Q. Chem. Eur. J. 2011, 17, 1021.
12. Cano, R.; Yus, M.; Ramón, D. J. Chem. Commun. 2012, 48, 7628.
13. Wang, D.; Guo, X.-Q.; Wang, C.-X.; Wang, Y.-N.; Zhong, R.; Zhu, X.-H.; Cai, L.-H.;
Gao, Z.-W.; Hou, X.-F. Adv. Synth. Catal. 2013, 355, 1117.
14. Liu, X.; Ding, R. S.; He, L.; Liu, Y. M.; Cao, Y.; He, H. Y.; Fan, K. N. ChemSusChem
2013, 6, 604.
c-Al2O3 (catalyst III: 147 mg, 0.075 mol% Pt). The resultant mixture was stirred
in the sealed tube at 155 °C for 48 h. After cooled to ambient temperature, the
catalyst and base were removed by centrifugation and washed with Et2O
(2 ꢁ 5 mL). The combined supernatant was condensed under reduced pressure
and subject to purification by silica gel column chromatography (eluent:
petroleum ether (60–90 °C)/EtOAc = 20:1, v/v), affording product 3a as a white
solid (1.018 g, 96%).
Please cite this article in press as: Wu, K. K.; et al. Tetrahedron Lett. (2016), http://dx.doi.org/10.1016/j.tetlet.2016.07.037