Organic Letters
Letter
2
9
Swern oxidation of the resulting benzyl alcohol led to the
diol PPG releases both 1,2- and 1,3-diols efficiently. Moreover,
corresponding benzaldehyde, which was then converted to
dimethyl acetal 5. The reaction of PPG reagent 5 with various
diols 3a−g resulted in the photolabile acetals 1a−g in high
yields (Table 1). In the cases of diols 3c, 3e, and 3f, the
respective acetals were obtained as mixtures of two
diastereomers.
the acetals are stable neat or in organic solutions. For example,
in a control experiment, a solution of 1b (5 mM in CD OD)
3
was kept at 50 °C for 1 h, and no thermal decomposition could
1
be detected by H NMR analysis.
We recently demonstrated that the DEABn PPG differs from
the known 3,5-dimethoxybenzyl (DMBn) PPG, which was also
30
based on the meta effect. The latter releases only good leaving
groups such as carboxylate, carbonate, and carbamate. Herein
we also compared the 3-dimethylaminobenzylidene and 3,5-
dimethoxybenzylidene chromophores in releasing diols. Thus,
the commercially available 3,5-dimethoxybenzaldehyde (6) was
converted to the corresponding acetal 7 (Scheme 4). Its
Table 1. Installation of the New PPG and Release of Diols
reaction with diol 3e afforded dioxane 8 (ε
= 2600
(
MeOH)282 nm
−1
−1
M
cm ). UV spectra of 1e and 8 revealed a bathochromic
shift of 1e compared with 8 (Figure 1).
Scheme 4. Synthesis of Dioxane 8
a
Diol 3, PPG reagent 5, and camphorsulfonic acid (CAS) in toluene at
b
1
00−120 °C. Diol 3, PPG reagent 5, and CAS in chloroform at 66
Figure 1. UV−vis spectra of 1e and 8.
c
d
°C. Diol 3, PPG reagent 5, and CAS in DMF at 66 °C. A 5.0 mM
solution in methanol in 5 mm NMR tubes was irradiated for 30 min
with a 450 W medium-pressure mercury lamp equipped with a Pyrex
filter sleeve (λ > 300 nm) without deaeration. Isolated yields. Isolated
Irradiation of 8 for 30 min (with either a Pyrex filter sleeve (λ
300 nm) or a Vycor filter sleeve (λ > 220 nm)) could not
e
f
>
after derivatization.
−1
release diol 3e, while dioxane 1e (ε
= 2500 M
(
MeOH)304 nm
−1
cm ) released the diol in 89% yield (λ > 300 nm) (Table 1,
entry 5). These results confirmed again that one m-amino
group is more powerful than two m-methoxy groups in
facilitating the benzylic C−O cleavage, consistent with the
different reactivities of DEABn and DMBn observed in
Photolysis of acetals 1a−g in methanol released the
corresponding diols smoothly in good yields (Table 1). For
instance, irradiation of 1d (5.0 mM in CD OD) for 30 min
3
with a 450 W medium-pressure mercury lamp equipped with a
Pyrex filter sleeve (λ > 300 nm) without deaeration led to
complete conversion of 1d. The yield of the released diol 3d
21
releasing alcohols.
One advantage of the new diol PPG is that photolysis of the
new PPG does not change the PPG’s working chromophore, in
contrast to the 2-nitrobenzyl series of PPGs. We thus designed
a diol PPG that releases two diols from one chromophore. As
shown in Scheme 5, from diol 9, two steps led to diacetal 10. It
protected diol 3e to provide diacetal 11e in 86% yield.
Irradiation of 11e (5.0 mM in 2:1 MeOH/MeCN) for 30 min
1
reached 82% based on H NMR analysis. In a larger-scale run
(
5.0 mM in CH OH in multiple NMR tubes) under the same
3
irradiation conditions, the released 3d was isolated in 74% yield.
The PPG was also able to protect monosaccharide 3g in the
form of acetal 1g (ε(MeOH)308 nm = 2500 M cm , Φ = 0.08) in
high yield and release it in 94% yield (Table 1, entry 7). The
photoreactions can also take place in acetonitrile/water but
with lower efficiency. It is worth noting that unlike the
benzylidene-type diol PPGs obtained from 6-bromo-7-hydroxy-
−1
−1
released 3e in 74% yield. Diacetal 11g (ε
= 3400
(
MeOH)318 nm
−1
−1
M
cm , Φ = 0.07) was also prepared using the same
procedure. Its irradiation (5.0 mM in 5:2 MeOH/MeCN) for
30 min released methyl glucoside 3g cleanly in 94% yield.
However, the aldehyde 12g, isolated as a byproduct from the
reaction to prepare 11g, was inert under the irradiation
1
7
19
4
-formylcoumarin and salicylaldehyde, which show either
complete resistance to releasing 1,3-diols or notably lower
efficiency in releasing 1,3-diols than releasing 1,2-diols, the new
B
Org. Lett. XXXX, XXX, XXX−XXX