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Notably, for the photocleavages in the presence of
electron donor 8, products derived from the benzylic portion
of these substrates were not observed, apart from for the
reactions of 13 and 14 for which small amounts of 19 and 20
were isolated. To check whether this finding might be due to
the volatility (upon workup) of the toluenes that might be
expected from the benzylic radicals, a doping experiment was
conducted (Scheme 2). Ethyl ether 24 is the ethyl analogue of
the 3,4,5-trimethoxybenzyl example is 11.7 kJmolÀ1 more
favorable, again relative to the 4-methoxy case. In the real
situation, the reduction may be a little less straightforward if it
occurs as part of a donor–acceptor complex.
Our attention then turned to benzylalkyl ethers (Table 2),
which underwent slower cleavage than the corresponding
esters. Accordingly, we used 6 equivalents of electron donor 8
in DMF at room temperature for 72 h, with the same
irradiation source as used for the esters, that is, 2 ꢁ 100 W at
365 nm. 2-Methoxybenzyl ethers 29 and 33 (Table 2, entries 1
and 4), 3,5-dimethoxy ethers 31 and 35 (Table 2, entries 2 and
5), and trimethoxy ether 37 (Table 2, entry 7) cleaved to
afford the corresponding alcohols in moderate to good yield.
In contrast, the reduction of CF3 derivative 39 led to
decomposition, under identical conditions (Table 2, entry 8).
In this case, competition may arise between elimination of the
two benzylic groups—alkoxide and fluoride, with fluoride-
loss predominating (reduction of p-CF3C6H4CH3 with 8 also
led to decomposition).
Scheme 2. a) A doping experiment to investigate the reductive depro-
tection of benzyl esters. b) Radical trapping by the donor radical cation
26.
The major difference for the cleavage of the benzyl ethers
compared to that of the benzyl esters was that notable
Table 2: Reductive deprotection of benzyl ethers with electron donor 8.[a]
methyl ether substrate 22, from which no o-methox-
ytoluene (17) had been isolated. The expected
toluene from 24 is
[b]
o-ethoxytoluene (25). The reaction of 24 (1 equiv)
with the electron donor 8 was carried out under the
usual conditions except that the dopant, o-methox-
ytoluene 17, (1 equiv) was added at the start of this
reaction. As o-methoxytoluene 17 should have
similar volatility to its ethyl analogue 25, the
dopant ought to give a good indication of whether
product volatility was important. At the end of the
reaction, the carboxylic acid 23 (89% yield), and o-
methoxytoluene (17; 77% recovery) were isolated
from the organic fraction, but no o-ethoxytoluene
(25). This result indicates that o-ethoxytoluene was
not formed during this reaction. In fact, this outcome
is completely consistent with our recent report on the
rapid trapping of alkyl radicals in reactions of
electron donor 8;[8] in these reactions the substrate-
derived radical combines with the donor radical
Entry Benzyl Ar
ether
R
ArCH3
ROH[b] RSM [%]
1
2
3
29
31
32
2-(MeO)C6H4
3,5-(MeO)2C6H3
4-(MeO)C6H4
17 (23) 30 (73) 29 (8)
19 (34) 30 (64) 31 (9)
18 (0)
30 (10) 32 (65)
4
5
6
33
35
36
37
39
2-(MeO)C6H4
3,5-(MeO)2C6H3
4-(MeO)C6H4
3,4,5-(MeO)3C6H2 C11H23
4-(CF4)C6H4 C11H23
C10H21
C10H21
C10H21
17 (20) 34 (71) 33 (8)
19 (27) 34 (60) 35 (11)
18 (0)
20 (20) 38 (51) 37 (49)
21 (0) 38 (0) 39 (4)
34 (6) 36 (75)
7[c]
8[d]
[a] Reaction conditions: 8 (6 equiv), DMF, UV, RT, 72 h. [b] The values in
parentheses are the percent yields. [c] Inseparable mixture of 20 and 37. [d] 8
(3 equiv), 24 h gave 38 (0 %), 39 (63%). RSM=recovered starting material.
cation 26 to afford water-soluble products, for example, 27, in
an efficient example of the persistent radical effect.[10]
Returning our attention to the reaction of substrate 13, and
given that volatility is not likely to be an issue, an alternative
explanation for the small amounts of di- (19; 9%) and
trimethoxytoluenes (20; 11%) is that they arise from
a benzylic anion. Computation (B3LYP 6-31G*, modeled in
a DMF solvent continuum) of the energy changes going from
the respective benzyl radical to benzyl anion support this
hypothesis, at least qualitatively, as they show that the
reduction of the 4-MeOC6H4CH2 radical to its anion is the
least favorable, likely because of the + M mesomeric influ-
ence of the methoxy group. The reduction of the 2-methoxy
isomer is a little (-7.3 kJmolÀ1) more favorable. For the 3,5-
dimethoxy case, the transformation is -23.4 kJmolÀ1 more
favorable than for the 4-methoxy case, whereas the value for
amounts of the corresponding toluenes 17, 19, and 20 were
also formed. The reactions of p-methoxybenzyl ethers 32 and
36 were also examined (Table 2, entries 3 and 6), but gave rise
to very poor yields of fragmented products and good recovery
of the starting materials; this result that is reminiscent of the
findings of Ankner and Hilmersson for the reduction of some
p-methoxybenzyl substrates with SmI2.[2] The scope of our
investigation was extended to benzyloxycarbonyl-protected
amines 40 and 42, which underwent clean deprotection to give
their parent amines 41 and 43, respectively, under these
conditions (Scheme 3).
The different results for the reductive cleavage of benzylic
ethers and benzylic esters caused us to reflect on whether
fragmentation of benzylic ethers and benzylic esters occur
through the same intermediates. As noted above, our inves-
tigations indicate that the benzylic esters fragment through
2
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Angew. Chem. Int. Ed. 2013, 52, 1 – 5
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