J. CHEM. RESEARCH (S), 1999 505
Table 2 Oxidation of intermediate 3b with various oxidizing
agents
Although the intermediate adducts can be isolated, the acid
hydrolysis can be achieved more conveniently on the crude
reaction mixtures to a¡ord the desired ketones 5, through
a simple two step sequence.
Entry Solvent
Oxidizing systema
Ratio 4b:1b
1
2
3
4
5
6
7
THF
THF
THF
THF
THF
KMnO4
1:8
1:3
1:3
0
1:4
1:3
0
KMnO4 18-crown-6
DDQ
DDQc
Experimental
Compounds 1 were prepared by the procedure reported in reference
12.
NaMnO4 ÁH2O
THF/TMEDA NaMnO4 ÁH2O
Toluene
KMnO4 18-crown-6
General Procedure for the Preparation of Adducts 4 and Ketones 5.
Compound 1 (2 mmol) was dissolved in dry THF (50 mL) and cooled
at 78 8C. BunLi solution in hexanes (1.6 M, 1.25 ml, 2 mmol)
was added, followed by the addition of the desired nitroarene
(2 mmol). After 15 min a solution of DDQ (1.2 mmol) in THF
(20 mL) was added and the reaction mixture was allowed to warm to
room temperature overnight. Treatment with brine (50 mL) followed
by extraction with Et2O ꢀ2 Â 30 mL) and concentration of the
combined organic layers under reduced pressure gave a mixture
of the expected adduct 4 along with unchanged 1 and nitroarene as a
yellowish oil. The remaining oil was either subjected to £ash column
chromatography on silica gel (hexanes^ethyl acetate as eluent) to give
pure products (compounds 4a^4d) or used as a crude mixture for the
hydrolysis (compounds 4e^4i). Compound 4 was dissolved in a
15% solution of H2SO4 in 1,4-dioxane^water (4:1, 30 mL). The result-
ing solution was allowed to react at room temperature ꢀR1 Et or
under re£ux ꢀR1 Ph until the starting material was completely con-
verted. After removal of the solvent under vacuum, the residue was
dissolved in CH2Cl2 (30 mL), washed with aqueous 5% Na2CO3
ꢀ2 Â 30 mL), dried ꢀMgSO4 and the organic layer was concentrated
under reduced pressure. Puri¢cation of the crude reaction mixture
by £ash column chromatography on silica gel (hexanes^ethyl acetate
as eluent) a¡orded pure ketone 5.
a0.6 equiv. of oxidizer was employed. bDetermined by 1H NMR.
c1 equiv. of oxidizer was reacted.
While adducts 1a^1d are stable, the derived anions 2a^2d
undergo partial degradation upon standing at 78 8C how-
ever they are apparently stabilized by nitroarenes towards
decomposition and/or oxidation for up to 5 h at 78 8C.
Presumably, the equilibrium of compounds 2 and 3 pro-
vides su¤cient concentration of the sH adduct 3. The inter-
mediate sH adducts 3 are oxidized by the air dissolved
in the quenching solution. When anion 2a was treated with
DDQ in the presence of o-nitroanisole, 1a was recovered
quantitatively. Thus, the two conditions required for the
ONSH to proceed satisfactorily are ful¢lled.8
In an attempt to improve the yields, a range of alternative
oxidizing reagents were used with adduct 3b. Compound 1b
was lithiated with BunLi and the resulting anion then
treated with o-nitroanisole. The subsequent addition of
the oxidizer and warming the mixture to room temperature
a¡orded mixtures of product 4b and compound 1b in
the ratios reported in Table 2. However, none of the
reaction conditions tested compared favorably to the use
of DDQ.
We are grateful to 3M for ¢nancial support.
Received, 2nd February 1999; Accepted, 14th April 1999
Paper E/9/00891H
These data suggest that during the oxidation process the
hydrogen atom Ha in compounds 3 (Scheme 1) is converted
into an acidic proton which is transferred to the anion 2 at a
rate comparable with the oxidation. Furthermore, a highly
ionizing solvent favors the oxidation probably because of
an increased concentration of the sH adduct 3.
Tetrahydrofuran promotes the transformation 3 ! 4 as
opposed to toluene (entries 2 and 7), while the addition
of a complexing agent reinforces this e¡ect (entries 1
and 2, 6). Since increasing the reaction time did not improve
the conversion of the starting material, we assume that the
oxidation of intermediate 3 is a fast process. Attempts
to oxidize sH adduct 3 to 4 by adding the intermediate
3 to the oxidizer did not improve the conversion of 3, while
treating a two fold excess of the oxidizer with 3 resulted in
the quantitative isolation of the starting material (entry 4).
In conclusion, we have developed novel regiospeci¢c
syntheses of (p-nitroaryl) alkyl ketones and (p-nitroaryl)
aryl ketones starting from non-functionalized nitroarenes.
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