TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 1717–1719
A novel oxidative free radical reaction between
-hydroxy-1,4-naphthoquinone and b-enamino carbonyl
compounds
2
Che-Ping Chuang* and Yi-Lung Wu
Department of Chemistry, National Cheng Kung University, Tainan, 70101 Taiwan, ROC
Received 9 November 2000; revised 11 December 2000; accepted 15 December 2000
Abstract—The manganese(III) initiated oxidative free radical reaction between 2-hydroxy-1,4-naphthoquinone and b-enamino
carbonyl compound 2 is described. Enamine radical 5 can be generated effectively from the oxidation of enamine 2 by
manganese(III) acetate. Spirolactam 3 was prepared effectively from readily available 2-hydroxy-1,4-naphthoquinone and enamine
2. © 2001 Elsevier Science Ltd. All rights reserved.
Free radical reactions have become increasingly impor1-
tant in organic synthesis in the last two decades.
Electrophilic radicals produced from the mangane-
se(III) acetate oxidation of b-dicarbonyl compounds
lar addition followed by oxidation to give 7, which
undergoes either condensation to produce 4a (path a)
or oxidation to generate radical 8 (path b). This radical
8 undergoes 1,2-benzoyl group migration followed by
oxidation and intramolecular nucleophilic addition to
generate 3a. The generalities of this reaction are illus-
trated in Table 1. In all cases, spirolactam 3 was
prepared effectively from b-enamino ketone 2 (entries
a–g). On the contrary, with b-enamino ester 2h, the
1d–f,2
undergo efficient addition to a CꢀC double bond.
These reactions can be performed intermolecularly and
intramolecularly. The free radical addition of a carbon
2c–h,3
center radical to quinones has been reported.
Enamine radical 5 can be generated effectively from the4
oxidation of enamine 2 by manganese(III) acetate.
This report describes our results on the reaction
between 2-hydroxy-1,4-naphthoquinone and b-enamino
carbonyl compounds via the manganese(III) acetate
initiated oxidative free radical reaction.
3
yield of 3h is rather poor (entry h). With R =Me,
benzo[ f ]indole 4 was also formed as minor product
(except entries g and h). In these two cases, enamine 2
1
2
3
has larger substituents (R , R ). With R =n-Bu, this
reaction gave 3 as the only product. This is presumably
due to the rate of condensation (path a) decreasing as
‡
We began our studies with the reaction shown in
Scheme 1. When 2-hydroxy-1,4-naphthoquinone was
treated with b-enamino ketone 2a and manganese(III†)
acetate in acetic acid at room temperature, 3a and 4a
were obtained in 51 and 5% yields, respectively (Table
the size of substituents increases.
A typical experimental procedure is given for the prepa-
ration of 3a. A solution of 151 mg (0.86 mmol) of
2-hydroxy-1,4-naphthoquinone, 4-methylamino-3-pen-
ten-2-one [prepared from the reaction of 259 mg (2.59
mmol) of 2,4-pentanedione and 252 mg of 40% aqueous
methylamine (3.25 mmol) in 4 ml of ethanol at room
temperature for 24 h] and 924 mg (3.45 mmol) of
manganese(III) acetate in 10 ml of acetic acid was
stirred at room temperature for 24 h. The reaction
mixture was then diluted with 100 ml of ethyl acetate,
washed with 50 ml of saturated aqueous sodium
bisulfite, 3×50 ml portions of water, 3×50 ml portions
of aqueous saturated sodium bicarbonate, dried
1, entry a). A possible mechanism for this reaction is
outlined in Scheme 1. Initiation occurs with the man-
ganese(III) acetate oxidation of 2a to produce enamine
radical 5a. Enamine radical 5a undergoes intermolecu-
Keywords: manganese(III) acetate; oxidative; free radical; 2-hydroxy-
1
*
,4-naphthoquinone; b-enamino carbonyl compounds.
Corresponding author. Fax: +886-6-2740552;
e-mail:
†
A similar product has been prepared from the reaction between
2
2
-ethylamino-1,4-naphthoquinone and 2,4-pentanedione, see Ref.
h.
‡
Similar results have been reported, see Ref. 2h.
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02332-7
Chuang, Che-Ping
