TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6281–6284
Electroreductive intramolecular coupling of aromatic d- and
o-keto esters
Naoki Kise,* Kie Arimoto and Nasuo Ueda
Department of Biotechnology, Faculty of Engineering, Tottori University, Koyama, Tottori 680-8552, Japan
Received 24 May 2003; revised 17 June 2003; accepted 19 June 2003
Abstract—Electroreduction of aromatic d- and o-keto esters in the presence of chlorotrimethylsilane and triethylamine gave five-
and six-membered cyclized products. The products were transformed to the corresponding a-hydroxy ketones.
© 2003 Elsevier Ltd. All rights reserved.
Reductive intramolecular coupling of keto esters is a
useful method for the synthesis of cyclic ketones and
has been effectively realized by McMurry and Miller
with low-valent titanium as a reducing agent.1 Recently,
it has been reported that the reductive coupling of
aromatic d-keto esters with SmI2 produced cyclic 2-
hydroxycyclopentanones and 2-cyclopentenones.2 On
the other hand, electroreduction is an effective tool for
reductive cross-coupling of ketones with a variety of
functional groups. For instance, we have reported the
electroreductive intra- and intermolecular couplings of
ketones with nitriles,3 O-methyl oximes,4 and aromatic
rings.5 We wish to report herein that the electroreduc-
tion of aromatic d- and o-keto esters in the presence of
chlorotrimethylsilane (CTMS) gave five- and six-mem-
bered intramolecularly coupled products, respectively
(Scheme 1). This reaction provides a new method for
the synthesis of a-hydroxy cyclopentanones and a-
hydroxy cyclohexanones.
Conditions for the constant current electroreduction of
keto esters were surveyed with methyl 5-keto-5-
phenylpentanoate 1a using a divided cell, and the
results are summarized in Table 1. The cyclized prod-
ucts were obtained as a-trimethylsiloxy ketal 2a (about
2:1 mixture of two diastereomers) and a-trimethylsiloxy
ketone 3a together with ketone 4a. In the absence of
CTMS, complex mixtures were formed (run 1). The
presence of CTMS was crucial for the reductive
intramolecular coupling of 1a (run 2). Furthermore, the
addition of triethylamine significantly improved the
yields of the cyclized products (run 3).6 From the
results of runs 3–5, THF was the solvent of choice. As
a supporting electrolyte, tetrabutylammonium salts
were suitable (runs 3, 6–9). Among them, Bu4NClO4,
Bu4NBr, Bu4NPF6, and Bu4NCl gave almost the same
combined yields of 2a and 3a. The use of LiClO4,
however, brought about a considerably poor result (run
10). Although Pb seemed to be the best cathode mate-
Scheme 1.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01526-0