O
CHO
R
O
R
OR'
R
N
R' R'
Et
2
NH
or
4
5
2 3
1
R–CH
2
CHO
CHO
O
O
O
+
4
Amine
6
7
TETRAHEDRON
LETTERS
Tetrahedron Letters 42 (2001) 2705–2707 Pergamon
Catalytic enamine reaction: an expedient 1,4-conjugate addition
of naked aldehydes to vinylketones and its application to
synthesis of cyclohexenone from Stevia purpurea
Hisahiro Hagiwara,
a,
* Tomoyuki Okabe,
b
Keisuke Hakoda,
b
Takashi Hoshi,
b
Hiroki Ono,
a
Vijayendra P. Kamat,
b,
Toshio Suzuki
b
and Masayoshi Ando
b
a
Graduate School of Science and Technology, Niigata University, 8050, 2 -nocho, Ikarashi, Niigata 950 -2181, Japan
b
Faculty of Engineering, Niigata University, 8050, 2 -nocho, Ikarashi, Niigata 950 -2181, Japan
Received 15 January 2001; revised 8 February 2001; accepted 9 February 2001
Abstract—Naked aldehydes directly add in a 1,4-manner to vinylketones in the presence of 0.2 equiv. of diethylamine in sealed
tubes to provide 5-keto aldehydes. © 2001 Elsevier Science Ltd. All rights reserved.
Enamines 2
1
have played an important role as very
versatile nucleophiles for mild carboncarbon bond
forming reactions. One of these nucleophilic reactions,
conjugate addition
2
of enamines 2 of aldehydes 1 to
a,b-unsaturated carbonyl compounds, has been a pow-
erful tool in the synthesis of g-formyl carbonyl com-
pounds (Scheme 1). As synthetic equivalents of
enamines 2, alkylenol or trimethylsilylenol ethers 3 of
aldehydes 1 have been employed for the 1,4-addition to
vinylketones in the presence of a Lewis acid.
3
Due to
the difficulty in controlling reactions of enolates or
enols of aldehydes, there had been no examples of
direct conjugate addition of naked aldehydes to
vinylketones so far until diethylamino(trimethyl)silane
(DEATMS)-mediated conjugate addition was
reported.
4
We delineate herein an alternative expedient
synthesis of 5-keto aldehydes 5 by 1,4-addition of
naked aldehydes 1 to 3-buten-2-one (MVK) 4 in the
presence of a catalytic amount of diethylamine (DEA).
The reaction of citronellal 6 with MVK 4 was employed
as a probe to find optimized reaction conditions
(Scheme 2, Table 1). A catalytic amount of DEA gave
a better yield than pyrrolidine when the reaction was
carried out in a sealed tube to prevent evaporation of
volatile DEA (Table 1, entries 1, 2 and 3). Among the
solvents investigated, MeCN and toluene gave the best
and comparable results (Table 1, entries 8 and 10).
With 0.1 equiv. of DEA, a certain amount of citronellal
6 was recovered (Table 1, entries 5, 6 and 7). Higher
temperature decreased the yield (Table 1, entry 9).
Thus, the optimized reaction was carried out simply by
Scheme 1.
Scheme 2.
Keywords : aldehydes; amines; catalysis; enamines; Michael reactions.
* Corresponding author. Fax: +81-25-262-7368; e-mail: hagiwara
@gs.niigata-u.ac.jp
On leave from Goa University, India.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII:S0040-4039(01)00247-7