1
412
Chemistry Letters Vol.36, No.12 (2007)
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Unusual Demethylation of O,O -Dimethyl Chlorothiophosphate with Aryllithiums
ꢀ
Nigel Ribeiro, Jin Maeda, Yasuhiro Ishida, Yuka Kobayashi, and Kazuhiko Saigo
Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo,
Hongo, Bunkyo-ku, Tokyo 113-8656
(Received September 10, 2007; CL-070987; E-mail: saigo@chiral.t.u-tokyo.ac.jp)
0
The reaction of O,O -dimethyl chlorothiophosphate with
aryllithiums took place easily to afford the corresponding
1
) n-BuLi (1.1 equiv.)
THF, −78 °C, 40 min
CH3
0
methylated aryl compounds in place of expected O,O -dimethyl
aryl(thiophosphonate)s.
O
O
2
3
) ClP(S)(OCH3)2
Br
2
−78 °C−rt, 4 h
+
) H O
3
The O-thiophosphorylation/phosphorylation of alcohols
0
with O,O -dialkyl chlorothiophosphates/chlorophosphates are
well-known reactions and were widely used for the synthesis
OH
OCH3
P OCH3
1
of pentavalent phosphorus atom-containing insecticides and
so on. On the other hand, Miller has reported that benzenethio-
S
late anion attacked the ꢀ-carbon of the ethyl group rather than
the pentavalent phosphorus atom of O,O -diethyl chlorothio-
1
0
2
phosphate to afford ethyl phenyl sulfide. Later, it has been
reported that the reactions of azaarenethiolate anions with
OH
6
0%
0
CH3
O,O -dimethyl chlorothiophosphate/chlorophosphate gave no
expected S-thiophosphorylated/phosphorylated products and
that the selective S-alkylation or S-preferential S/N-alkylation
3
Scheme 1. Methylation of 2-[3-(methoxymethoxy)propyl]-
0
3
of the azaarenethiols occured. These phenomena would be
phenyllithium with O,O -dimethyl chlorothiophosphate (demeth-
0
explained on the basis of the hard–soft acid–base principle; the
soft thiolate anions, polarized to a large extent, preferentially
attacked the alkyl ꢀ-carbon relatively softer than the pentavalent
ylation of O,O -dimethyl chlorothiophosphate).
a dry tetrahydrofuran solution (10 mL) of an aryl bromide
ꢂ
0
phosphorus atom in O,O -dialkyl chlorothiophosphates/chloro-
phosphates.
(4 mmol) at ꢁ78 C, and the mixture was stirred for 1 h at
ꢂ
0
ꢁ78 C. Then, O,O -dimethyl chlorothiophosphate (1.1 equiv.)
ꢂ
In this paper, we describe the nucleophilic attack of
0
was added to the solution at ꢁ78 C, and the reaction mixture
aryllithiums to the methyl carbon of O,O -dimethyl chlorothio-
phosphate, resulting in the methylation of the aryllithiums/the
demethylation of the thiophosphate.
was allowed to warm up to room temperature over a period of
4 h with stirring. After quenching the reaction with water,
followed by extraction with dichloromethane, the crude product
was purified by column chromatography on silica gel. The
results are summarized in Table 1.
In the course of our study on the development of enantiopure
O-alkyl arylphosphonothioic acids as efficient resolving agents
4
for 1-arylethylamine derivatives, we tried to synthesize a pre-
0
The reactions proceeded very smoothly to give the
corresponding methylated aryl compounds in 60–80% yields;
aryllithiums were found to be generally methylated with O,O -
dimethyl chlorothiophosphate without difficulty, namely, the
demethylation of O,O -dimethyl chlorothiophosphate could
easily occur with aryllithiums.
cursor of a cyclic phosphonothioic acid ester, O,O -dimethyl
[(3-hydroxypropyl)phenyl]thiophosphonate (1) by the reaction
of 2-[(3-methoxymethoxy)propyl]phenyllithium, generated in
0
0
situ from 1-bromo-2-[3-(methoxymethoxy)propyl]benzene (2)
0
and butyllithium, with O,O -dimethyl chlorothiophosphate.
0
However, the reaction, followed by the treatment with an
aqueous HCl solution to quench the reaction and to remove
the protecting group, gave an unexpected methylated product,
In contrast to the demethylation, the deethylation of O,O -
diethyl chlorothiophosphate did not occur at all with 2-naphthyl-
lithium, prepared from 2-bromonaphthalene (4) and t-butyllithi-
um. The reaction led to the formation of the thiophosphorylated
3-o-tolylpropan-1-ol (3), in 60% isolated yield, accompanying
the formation of only a small amount of 1 (Scheme 1). This
6
product 5, in 70% isolated yield (Scheme 2). Thus, the
0
0
result indicates that a demethylation of O,O -dimethyl chloro-
thiophosphorylation of aryllithiums/the dealkylation of O,O -
dialkyl chlorothiophosphate with aryllithium were strongly
thiophosphate underwent with the aryllithium. The result
prompted us to examine the present unusual demethylation fur-
ther, because no report described such a demethylation reaction
0
influenced by the alkyl group of O,O -dialkyl chlorothiophos-
phate. It is noteworthy that such dependence is a contrast to
the dealkylation with benzenethiolate anion.
Such switch in alkylation/thiophosphorylation for the reac-
0
2
with an aryllithium although the reactions of O,O -dialkyl
chlorothiophosphates/chlorophosphates with aryllithiums have
5
0
been fragmentally reported.
The reactions were carried out as follows: In order to
tion of aryllithiums with O,O -dialkyl chlorothiophosphate
would be explained by the hard–soft acid–base principle for
the substrate/reactant and/or by the steric repulsion between
the substrate/reactant: The rather soft arylic carbanions would
prepare an aryllithium, t-butyllithium (2.1 equiv.) in pentane
(
or butyllithium (1.1 equiv.) in hexane) was dropwise added to
Copyright Ó 2007 The Chemical Society of Japan
Ribeiro, Nigel
