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Table 2 Solvent ratios for hydration of styrenea
Table 3 Control experiments for hydration of styrenea
Experiment 3/% 4/% 5/% 6/% Total [O]/% Selectivityb/%
No Pd
No Ru
0
0
57
0
12
0
0
0
10
0
1
0
0
82
2
84
5
0
1
0
0
0
0
0
83
69
84
18
0
0
99
73
100
51
0
No MeOH
i
No PrOH
No H2O
No BQ
MeOH : iPrOH : H2O 3/% 4/% 5/% 6/% Total [O]/% Selectivityc/%
0
a
6 : 3 : 1
4.5 : 4.5 : 1
3 : 6 : 1
39
61
74
66
30
80
1
3
6
3
2
5
11
17
10
13
16
6
0
0
0
0
0
0
51
81
90
82
48
91
97
96
93
96
97
94
Reaction conditions: 1% PdCl2(MeCN)2, 1% Shvo’s catalyst, 1.5 BQ,
0.083 M, 35 1C 4 h, 85 1C 30 h, MeOH : IPA : H2O 6 : 3 : 1. All other
conditions remain the same except for the reagent being omitted.
Markovnikov selectivity = (3 + 5)/(4 + 6) Â 100%.
b
3.6 : 5.4 : 1
2 : 2 : 1
3 : 6 : 1b
CuCl2, the Markovnikov selectivity decreased dramatically to 52%. As
a result, p-benzoquinone (BQ) was employed as the only reoxidant for
Pd(II) in the oxidation step. The optimum quantity of BQ was found to
be 1.5 equivalents. Despite the reaction being non-catalytic with
respect to BQ, BQ can easily be recovered from hydroquinone via
facile aerobic oxidation.18
a
Reaction conditions: 1% PdCl2(MeCN)2, 10% Shvo’s catalyst, 1.5 BQ,
b
0.083 M, 35 1C 4 h, 85 1C 30 h. 1% PdCl2(MeCN)2, 1% Shvo’s catalyst.
c
Markovnikov selectivity = (3 + 5)/(4 + 6) Â 100%.
catalyst combination, we went on to optimize the conditions required
for improving the selectivity for secondary alcohols. It was found that
at a high Shvo’s catalyst loading of 10 mol%, a high iPrOH content is
required to solubilize Shvo’s catalyst. When MeOH : iPrOH was 2 : 1,
the yield of 3 was only 39%. However, when MeOH : iPrOH was
changed to 1 : 2, the yield increased to 74%. This, however, was at
the expense of selectivity. At high alcohol yields, the selectivity was
poorer (Table 2). However, when the amount of Shvo’s catalyst was
decreased to 1 mol%, a 2 : 1 ratio of MeOH/iPrOH was able to give
80% 1-phenylethanol from styrene. This observation stems from
the relatively poor solubility of Shvo’s catalyst in MeOH, and the
addition of iPrOH is required to solubilize the precatalyst, A. Shvo’s
catalyst, in the active form, is the dissociated, monomeric Ru–H
species, B.16 In the heterogeneous form, most of the Shvo’s catalyst
remains in the non-activated A form. As such, when a large
quantity of Shvo’s catalyst (10 mol%) is used, much of it remains
undissolved in solution, giving little B for reduction of 5 to 3.
However, when the iPrOH content is high for the solubilisation of
A, more anti-Markovnikov product is formed, due to the attack of
the bulkier alcohol on the less hindered site of the terminal olefin
to form a vinyl ether that gets hydrolysed to aldehyde, 6, which gets
reduced to the primary alcohol, 4.1
(3)
Upon developing a suitable system for hydrating styrene, we went
on to combine both oxidation steps and reduction steps into one
single step by carrying out the entire tandem process at 85 1C. We also
probed the functional group tolerance of the catalytic system (eqn (3)).
It was found that the reported tandem hydration system is tolerant
to a wide variety of functional groups including esters, halides,
alkyls, nitro, trifluoroalkyl and naphthyl (Table 4). In particular,
p-chlorostyrene, 1f, produced 1-(4-chlorophenyl)ethanol in a high yield
of 83%. Acidic substrates such as 4-vinylbenzoic acid, 1j, produced a
poor yield of the corresponding alcohol, possibly due to premature
degradation of active Shvo’s catalyst B, in a highly acidic media.
Highly electron-withdrawing substituents on phenyl rings such as nitro
(1k) and bis(trifluoromethyl) (1l) tend to direct the selectivity toward
anti-Markovnikov instead, to result in the formation of 2-phenyl-
ethanol. This is due to the preferential coordination of Pd(II) to the
alpha carbon when the aryl group is highly electron-deficient.
A series of control experiments were also carried out and it
i
was found that both MeOH and PrOH were required to give a
high product yield. In the absence of H2O, small amounts of
oxidized products were obtained, likely from trace amounts of
moisture in the solvents. In the absence of BQ, the reaction did
not proceed at all. In the absence of Shvo’s catalyst or iPrOH as
the hydrogen source, no alcohols could be obtained (Table 3).
(4)
Aliphatic olefins such as 1-octene (2a) and 4-phenyl-1-butene (2f)
The reaction was also attempted on the bench to probe the effect were also hydrated using the tandem hydration system developed
of oxygen on the hydration system. However, it was found that Shvo’s (eqn (4)). With 1-octene, a much higher Markovnikov selectivity of
catalyst is very sensitive to oxygen in our system, despite being >99% could be obtained, with 2-octanol obtained in a yield of 71%
reported that Shvo’s catalyst is stable in air.11,16 This may be due to using 1 mol% catalyst. Isolation of the alcohol was difficult, resulting
the acidity of our reaction system which tends to destabilize the active in high loss of the product after purification. Gram-scale synthesis of
Ru hydride species, B. The reaction mixture was observed to turn deep 2-dodecanol was also attempted and 69% isolated yield could be
red rapidly, from yellow, when the reaction was carried out on the obtained (1.29 g 2-dodecanol from 0.01 mol 1-dodecene). The system
bench. A low alcohol yield of 24%, with 65% ketone, was obtained in is also tolerant to functional groups on the olefin chain such as
this case. The addition of CuCl2 to the reaction as a reoxidant for the ester, hydroxyl and carboxylic acid, despite the mildly acidic reaction
Pd(II) catalyst was also studied. However, in the presence of just 10% medium (Table 5). Esters in particular, such as ethyl-6-heptenoate
This journal is ©The Royal Society of Chemistry 2014
Chem. Commun., 2014, 50, 2608--2611 | 2609
Yang, Yongsheng
