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Chemistry Letters Vol.37, No.8 (2008)
Site- and Stereoselectivity in the Photochemical Oxetane Formation Reaction
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(Paterno–Buchi Reaction) of Tetrahydrobenzofuranols with Benzophenone:
¨
Hydroxy-directed Diastereoselectivity?
Youhei Yabuno, Yoshikazu Hiraga, and Manabu Abeꢀ
Department of Chemistry, Graduate School of Science, Hiroshima University,
1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526
(Received May 12, 2008; CL-080487; E-mail: mabe@hiroshima-u.ac.jp)
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The Paterno–Buchi reactions of tetrahydrobenzofuranols
¨
lective formation of oxetanes was postulated to be important
in controlling the site- and diastereoselectivity.7 Although site-
selectivity (double-bond selection) in a PB reaction of furans
is known to be largely dependent on reaction temperature,8 the
temperature effect on the selectivity was not examined in the lit-
eratures.7 Thus, thorough verification of ‘‘hydroxy-directivity’’
is needed in PB reactions of furan derivatives. The purpose of
this study is to clarify the site- and diastereofacial selectivity
of the oxetane formation in the PB reaction of benzophenone
with tetrahydrobenzofuran-7-ol (5) (Table 1) and with tetrahy-
drobenzofuran-4-ol (10) (Table 2). The intent was to determine
how the hydroxy group and its position on the ring system affect
site- and diastereoselectivity. In this study, the selectivities were
found to be largely dependent on the reaction temperature, and
not significantly affected by the position of the hydroxy group.
This implies that ‘‘hydroxy-directed selectivity’’ is not always
applicable for predicting the diastereoselectivity of photochem-
ical oxetane formation reactions of allylic alcohols.
with benzophenone were investigated to reveal site- and stereo-
selectivity in oxetane formation reactions. Both selectivities
were found to be largely dependent on the reaction temperature.
The trans selectivity increased with a decrease in temperature,
and the more-substituted oxetanes were selectively formed at
high temperature.
The photochemical [2 + 2] cycloaddition reaction of
carbonyl compounds with alkenes, the so-called Paterno–Buchi
¨
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(PB) reaction,1 is the most versatile method for preparing oxe-
tane derivatives, which are synthetically and biologically impor-
tant.2 Although the reaction involves an energized species, i.e. an
electronically excited carbonyl group (RCOꢀ), regio-, site-, and
stereoselective formation of oxetanes have been achieved within
the past two decades. In 2000, a threo-selective formation of ox-
etanes was found in the PB reaction of benzophenone (Ph2COꢀ)
with allylic alcohols 1 (Scheme 1).3 The diastereofacial selectiv-
ity was explained by the hydrogen-bonding interaction4 between
the hydroxy group and the incoming molecule, Ph2COꢀ. On the
other hand, it has shown that the reactive n, ꢀꢀ excited carbonyl
is a very electron-deficient species.5 We found that a trans-selec-
tive formation of the bicyclic oxetane in the PB reaction cyclic
allylic alcohol 2 in low temperature (Scheme 1).6 The trans
selectivity is apparently not consistent with hydroxy-directed
diastereoselectivity, i.e. cis selectivity. In the PB reaction of
furyl alcohols 3 and 4, the hydroxy-directed site- and stereose-
The experimental results of the photochemical reaction of
5 are summarized in Table 1. Bicyclic oxetanes 6 and 7 were
isolated and fully characterized by spectroscopic analyses.9
The cis and trans configurations were unambiguously deter-
1
mined using H NMR NOE measurement.9 Both isomers were
stable under irradiation conditions, and the ratios did not change.
The pinacol 8 and the oxidation product 9 were also detected as
minor products in the photochemical reaction. The mass balan-
ces of the photochemical reactions were quite high both in
toluene (Entries 1–5) and in DMSO (Entry 6), >84%. As found
in the reaction with allylic alcohol 2, the trans selectivity in bi-
cyclic oxetanes 6 and 7 increased with a decrease in temperature.
Thus, the trans selectivity observed in the PB reaction of 5 at low
temperature may not be explained by hydroxy-directed effect
(Entries 3–5). The site-selectivity, 6 vs. 7, was also largely de-
pendent on the reaction temperature. Thus, the more-substituted
oxetane 7 was selectively formed at high temperature, and the
chemical yield of less-substituted oxetane 6 increased with a
decrease in temperature, e.g. 6/7 = 14/86 at 60 ꢁC (Entry 1)
and 6/7 = 45/55 at ꢂ75 ꢁC (Entry 5). The temperature effect
on the site-selectivity was quite similar to the case of the PB re-
action of unsymmetrically substituted furan derivatives.8 When
the PB reaction was carried out in an aprotic polar-solvent,
DMSO, the highly trans selective formation of oxetanes 6 and
7 was observed (Entry 6), i.e. cis/trans-6,7 < 3/97. This result
implies that the steric factor plays an important role in control-
ling diastereofacial selectivity. Thus, the hydrogen-bonded
DMSO molecules would increase the size of the steric hindrance
of the hydroxy group. Next, we investigated the site- and diaster-
eoselectivity in the PB reaction of tetrahydrobenzofuran-4-ol
Ph2CO
hν
OH
OH
OH
O
R
O
R
R
+
Ph2CO*
Ph
Ph
Ph
Ph
1
erythro
threo
Ph2C=O*
Ph
H
Ph
O
O
OH
R
H
R
H
OH
O
OH
R
hν
O
O
OH
Ph2CO
Ph
OH
+
Ph
HO
cis
3
O
O
R
2
O
Ph
Ph
trans
O
4
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Scheme 1. Paterno–Buchi reactions of allylic alcohols.
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Copyright Ó 2008 The Chemical Society of Japan