Table 1 TBN-initiated aerobic oxidative cleavage of styrenea
alcohol could be transformed to benzyl aldehyde and cinnamyl
aldehyde (entry 9). Unfortunately, aliphatic olefins did not work
using this protocol (entries 10–11), probably due to instability
of the radical intermediate derived from aliphatic olefins.
In the conventional two-step process, the cleavage of the
Yieldb (%)
Entry PO /MPa PO
/MPa
Conv.b (%) Aldehyde Acid
2 +CO2
2
1
0
1
1
1
1
1
1
1
1
1
1
1
0
1
1
4
2
1
6
0
0
21
9
7
6
0
0
0
C
C bond often involves the “diol or epoxide” intermediate3
2c
3
26
100
100
100
80
45
2
and subsequent oxidation to products. However, styrene ox-
ide or 1,2-dihydroxyethylbenzene remained intact under the
reaction conditions (Scheme 2).19 Accordingly, the reaction
pathway involving the “diol or epoxide” intermediate could be
excluded. On the other hand, the TBN-induced C C cleavage of
styrene was completely inhibited by adding TEMPO (entry 12,
Table 1), presumably indicating that the oxidation goes through
a free-radical pathway. Based on the previous reports and our
aforementioned results, a possible mechanism was proposed as
delineated in Scheme 3. As is well known, TBN can release
NO and the alkoxyl radical 1 under reaction temperature, and
nitrogen monoxide can subsequently react with an olefin to give
the nitryl-substituted compounds and oximes.16,17 As a result,
cleavage reaction of the C C bond with TBN/O2/CO2 system
probably could be initiated by the alkoxyl radical generated
in situ from TBN. The reaction of the radical 1 and molecular
oxygen affords the peroxide radical 2, which subsequently reacts
with an olefin like styrene to furnish the radical 3, followed by its
arrangement in combination with an oxygen radical to give the
carbonyl product and the radical 4. Furthermore, the primary
radical 1 can be regenerated from radical 4.
49
37
44
53
40
2
4
5
6
7
7
10
13
16
13
13
13
1
8
9d
10e
11f
12g
3
2
98
88
3
36
72
0.5
18
5
0
a Reaction conditions: styrene (0.5 mL, 4.35 mmol), TBN (11 mL,
2 mmol%), 80 ◦C, 12 h. b Determined by◦GC using bi◦phenyl as an
internal standard. c Without TBN. d T = 60 C. e T = 120 C. f t = 18 h.
g 2 mmol% TEMPO (2,2,6,6-tetramethyl-piperdine-1-oxy) was added.
To our delight, the yield of benzaldehyde reached 72% after
prolonging the reaction time to 18 h (entry 11). CO2 pressure
could play a crucial role in boosting the desired reaction as well
as noticeably improving the selectivity towards aldehyde, and
thus could allow this approach to be much more practically
viable in organic synthesis. Compressed CO2 could dissolve oxi-
dized products and small molecules like oxygen, alkoxy radicals
and NO, and thus prevent overoxidization/oligomerization.13,18
On the other hand, higher oxygen concentrations favor deeper
oxidation, resulting in a significant increase in the yield of
benzoic acid (entries 3–7). However, too much CO2 could dilute
the reaction species over 16 MPa of total pressure, and thus
result in slowing of the reaction (entry 8). Consequently, the
optimal pressure was found to be ca. 13 MPa. It is also worth
mentioning that there is often a white viscous solid, this being
oligomers of styrene generated in the range of 1–10 MPa (see
ESI†). In addition, high O2 pressure facilitates the reaction
with increasing yield of acid (entries 14, 15, Table S1, ESI†).
On the other hand, the reaction did not occur below 80 ◦C,
while the selectivity would become poor with further raising
of the temperature (entries 7, 9, 10). Therefore, an appropriate
temperature would be 80 ◦C. Furthermore, the amount of TBN
does not affect the reaction (entries 7, 11, 12, Table S1, ESI†).
This is understandable because TBN is assumed to serve as a
radical initiator.
Scheme 2 Oxidation reaction of epoxide or 1,2-diol with TBN/O2/
CO2.
The utility and generality of this metal-free process for the
aerobic cleavage of C C bonds were further examined. As
shown in Table 2, a series of aromatic olefins can be transformed
into the corresponding carbonyl compounds. Obviously, termi-
nal benzylic olefins showed good activity (entries 1–6). The p-
substituted styrene gave better results than styrene (entries 2, 3
vs. 1), whereas o- or m-substituted styrene showed slightly lower
activity (entries 4, 5). Notably, a-methyl styrene afforded the
ketone instead of the aldehyde as the predominant product in
a comparable yield after prolonging the reaction time to 24 h
(entry 6). On the other hand, internal benzylic olefins gave poor
results. The reaction almost returned only starting material at
80 ◦C in the case of methyl cinnamate (entry 7). The activity was
still not good even at 120 ◦C (entry 8). In addition, cinnamyl
Scheme 3 Proposed mechanism.
In summary, we developed a metal-free system comprising
tert-butyl nitrite, oxygen and compressed CO2 for aerobic
cleavage of benzylic C C bonds to carbonyl compounds.
Compressed CO2 could play a crucial role in boosting the desired
reaction as well as noticeably improving the selectivity towards
aldehyde, and thus could allow this approach to be much more
practically viable in organic synthesis. Furthermore, the alkoxyl
radical resulting from TBN is assumed to initiate the reaction.
542 | Green Chem., 2011, 13, 541–544
This journal is
The Royal Society of Chemistry 2011
©