Reduction of benzoyl tributylphosphonium chlorides by samarium diiodide as
a novel access to 4-benzoylbenzaldehydes
Hatsuo Maeda,* You Huang, Nagomi Hino, Yuji Yamauchi and Hidenobu Ohmori
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan
Received (in Cambridge, UK) 6th September 2000, Accepted 17th October 2000
First published as an Advance Article on the web 9th November 2000
Addition of samarium diiodide to a well-stirred THF
solution of benzoyl tributylphosphonium chlorides gen-
erated in situ from benzoyl chlorides and tributylphosphine
at 240 °C gave 4-benzoylbenzaldehydes as predominant
products from benzoyl chlorides without para-substituents,
while benzoyl chloride bearing p-methyl or chloro groups
was exclusively converted into the corresponding a-dike-
tone.
examined the reduction of 2 itself by SmI2 as a preliminary
study to develop the intermolecular reaction of an acyl radical or
acyl anion equivalent generated from 1 or 2, and obtained
interesting results different from those for the case of 3 itself.
We report herein that SmI2–reduction affords benzoylbenzalde-
hydes 4 as predominant products from 2 without para-
substituents and 5 exclusively from 2 bearing para-substituents
(Scheme 1).
It was reported that 4 can be prepared by the following
methods: (1) SmI2-induced coupling of benzaldehydes followed
by PDC oxidation;10 (2) benzylic bromination of 4-me-
thylbenzophenone followed by periodate oxidation;11 (3)
oxidative transformation of 4-methylbenzophenone into the
corresponding benzaldiacetate followed by acid hydrolysis,12,13
(4) photolysis of benzaldehyde–cyclodextrin complexes in the
solid state.12 However, the following factors seem to attenuate
their synthetic utilities: in the first method, the yields of
coupling products from substituted benzaldehydes were rather
low; it is unlikely that starting materials with a variety of
substituents for the second and the third methods are easily
available; the fourth method was applied only to unsubstituted
benzaldehyde and its generality is unknown. Thus, it is
worthwhile developing a simple and general method for
preparing 4, taking into consideration not only the drawbacks of
these methods but also the facts that 4 was used as an important
intermediate for synthesis of an HIV-1 integrase inhibitor11 and
antifungal agents.14
Recently it was found that the reduction potentials of alkanoyl-
and benzoyltributylphosphonium ions (1 and 2, respectively)
(Scheme 1), anodically generated from carboxylic acids and
tributylphosphine (Bu3P) or formed from acid chlorides and
Bu3P, are much more positive than those of the corresponding
acid chlorides;1,2 hence 1 and 2 are converted into aldehydes
without over-reduction to alcohols by reduction using a
cathode,1 Zn or Zn–Cu couple3 more feasibly than the
corresponding carboxylic acids or acid chlorides. In addition,
electrochemical reduction of 1 was shown to provide a novel
tool for the generation of acyl radical or acyl anion equivalents,
which are utilized in intramolecular C–C bond formation.4
However, the synthetically intriguing species generated from 1
or 2 have not been applied to intermolecular reactions. This is
probably because 1 and 2 are highly reactive acylating
reagents.4–6 During electrochemical generation of an acyl
radical or acyl anion equivalent from 1 or 2, excess of the
acylating reagent remains. Such circumstances may have
induced formation of a complex mixture in the cathodic reaction
of 1 or 2 with an electrophile or radical acceptor through
acylation of all anionic species generated during the elec-
trolysis. Thus, it is speculated that an immediate and total
transformation of 1 or 2 into the corresponding acyl radical or
acyl anion equivalent prevents such an undesired process. It was
reported that benzoyl chlorides 3 were reduced by samarium
diiodide (SmI2)7 as a one-electron reducing reagent, leading to
formation of the corresponding a-diketones (5).8,9 Based on the
reduction potentials, it was postulated that 2 will be more
feasibly reduced by SmI2 than the corresponding 3, namely, that
SmI2-reduction will satisfy the above requirement for the
reduced species of 2 to enter intermolecular reaction. Thus, we
The typical procedure is as follows: to a THF solution of 3
(1.0 mmol) cooled to 240 °C, Bu3P (1.1 mmol) was added
under an argon atmosphere and the resulting mixture was stirred
for 20 min. To the vigorously† stirred mixture, a THF solution
(0.1 M, 20 ml) of SmI2 was added using a syringe. After stirring
for 5 min at the same temperature, the reaction was quenched by
addition of 1 M HCl (5 ml). The entire mixture was poured into
H2O (20 ml) and extracted with ether (50 ml 3 3). The
combined organic layer was washed with 5% K2CO3 and brine
(40 ml each), and dried over MgSO4. After removal of the
solvent, the residue was subjected to column chromatography
(SiO2, hexane–AcOEt). Thus obtained products were charac-
1
terized by H-NMR, 13C-NMR, IR, and mass spectra or by
comparison with spectroscopic data in the literature.10,11,15 The
regiochemistry in 4b, 4c, 6, and 4f (cf. Table 1) was tentatively
assigned to be para with respect to the aldehyde groups, based
on the results for 2 with para-substituents as described below.
The results obtained for benzoyltributylphosphonium chlo-
rides 2 derived from several benzoyl chlorides 3 are shown in
Table 1. Reduction of phosphonium chloride 2a with SmI2
afforded keto aldehyde 4a as a sole product in an excellent yield
(run 1). Without in situ transformation into 2a, benzoyl chloride
was converted only to the corresponding a-diketone in 38%
yield under essentially the same conditions, suggesting that
reduction of 2 by SmI2 proceeds in a different manner from that
of 3 itself. Similarly, 2b and 2c bearing o- or m-methyl groups
were transformed into 4b and 4c, respectively, in excellent
yields, although formation of the corresponding a-diketone in
small amounts was noted (runs 2 and 3). In contrast to the case
of 2b and 2c, reduction of 2d with a p-methyl group resulted in
exclusive formation of a-diketone 5d (run 4), suggesting that
Scheme 1
DOI: 10.1039/b007226p
Chem. Commun., 2000, 2307–2308
This journal is © The Royal Society of Chemistry 2000
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