Abstract
Here we describe simple and efficient double Michael additions of aromatic and aliphatic
methyl ketones to electron deficient alkenes promoted on a surface of KF-alumina.
This one-pot procedure provides an easy access to a host of functionalized pimelate
esters, which can be subsequently converted in to 3-acylcyclohexanones.
Key words
double Michael additions - acetophenone - KF-alumina - pimelate esters - cyclohexanones
References
<A NAME="RD12104ST-1A">1a </A>
Bergman ED.
Ginsburg D.
Pappo R.
Org. React.
1959,
10:
179
<A NAME="RD12104ST-1B">1b </A>
Oare DA.
Heathcock CH.
J. Org. Chem.
1990,
55:
157
<A NAME="RD12104ST-1C">1c </A>
Perlmutter P.
Conjugate Addition Reaction in Organic Synthesis
Tetrahedron Organic Chemistry Series 9, Pergamon Press;
Oxford:
1992.
<A NAME="RD12104ST-2A">2a </A>
Oare DA.
Heathcock CH. In
Topics in Stereochemistry
Vol. 19:
Eliel EL.
Wilen SH.
John Wiley and Sons;
New York:
1989.
p.277
<A NAME="RD12104ST-2B">2b </A>
d’Angelo J.
Revial G.
Costa PRR.
Castro RN.
Antunes OAC.
Tetrahedron: Asymmetry
1991,
2:
199
<A NAME="RD12104ST-2C">2c </A>
List B.
Pojarliev P.
Martin HJ.
Org. Lett.
2001,
3:
2423
<A NAME="RD12104ST-2D">2d </A>
Alexakis A.
Andrey O.
Org. Lett.
2002,
4:
3611
<A NAME="RD12104ST-3">3 </A>
Smith MB.
March J.
March’s Advanced Organic Chemistry
5th ed.:
John Wiley and Sons;
New York:
2001.
p.1022
<A NAME="RD12104ST-4A">4a </A>
Bhardwaj CL.
Ireson JC.
Lee JB.
Tyler MJ.
Tetrahedron
1977,
33:
3279
<A NAME="RD12104ST-4B">4b </A>
Giardini A.
Lesma G.
Passarella D.
Perez M.
Silvani A.
Synlett
2001,
132
<A NAME="RD12104ST-4C">4c </A>
Hughes F.
Grossman RB.
Org. Lett.
2001,
3:
2911
<A NAME="RD12104ST-5A">5a </A>
Bergbreiter DE.
Lalonde JJ.
J. Org. Chem.
1987,
52:
1601
<A NAME="RD12104ST-5B">5b </A>
Ranu BC.
Bhar S.
Tetrahedron
1992,
48:
1327
<A NAME="RD12104ST-6A">6a </A>
Irie H.
Mizuno Y.
Taga T.
Osaki K.
J. Chem. Soc., Perkin Trans. 1
1982,
25
<A NAME="RD12104ST-6B">6b </A>
Clark JH.
Cork DG.
Robertson MS.
Chem. Lett.
1983,
1145
<A NAME="RD12104ST-6C">6c </A>
Yamawaki J.
Kawate T.
Ando T.
Hanafusa T.
Bull. Chem. Soc. Jpn.
1983,
56:
1885
<A NAME="RD12104ST-7">7 </A>
Forrester AR.
Irikawa H.
Thomson RH.
Woo SO.
King TJ.
J. Chem. Soc., Perkin Trans. 1
1981,
1712
<A NAME="RD12104ST-8A">8a </A>
Basu B.
Jha S.
Mridha NK.
Bhuiyan MMH.
Tetrahedron Lett.
2002,
43:
7967
<A NAME="RD12104ST-8B">8b </A>
Basu B.
Das P.
Bhuiyan MMH.
Jha S.
Tetrahedron Lett.
2003,
44:
3817
<A NAME="RD12104ST-9">9 </A>
Representative Experimental Procedure: A mixture of 4-methoxyacetophenone (300 mg, 2 mmol) and ethyl acrylate (600 mg, 6
mmol) was added in one portion to dry preformed KF-alumina (2 g) and the solid mixture
was stirred at 60 °C for 10 h. TLC was checked and the mixture was packed on a column
of silica gel and eluted with petroleum ether-EtOAc (9:1) to afford diethyl (4-methoxybenzoyl)
heptanedioate as colorless viscous oil (553 mg, 79%). IR (neat): 1735, 1680, 1588
cm-1 . 1 H NMR (300 MHz, CDCl3 ): δ = 1.22 (t, 6 H, J = 7.1 Hz, 2 OCH2 CH
3
), 1.80-1.88 (m, 2 H, 2 CH CH2 CO), 2.05-2.12 (m, 2 H, 2 CH CH2 CO), 2.19-2.41 (m, 4 H, 2 CH2 CH
2 CO), 3.56-3.63 (m, 1 H, COCH CH2 ), 3.87 (s, 3 H, OCH
3
), 4.10 (q, 4 H, J = 7.1 Hz, 2 OCH
2
CH3 ), 6.95 (d, 2 H, J = 8.8 Hz, ArH ), 7.99 (d, 2 H, J = 8.8 Hz, ArH ). 13 C NMR (75 MHz, CDCl3 ): δ = 14.0, 26.9, 31.5, 43.2, 55.3, 60.2, 113.8, 129.9, 130.6, 163.6, 172.9, 201.2.
<A NAME="RD12104ST-10A">10a </A>
Villemin D.
Ricard M.
Tetrahedron Lett.
1984,
25:
1059
<A NAME="RD12104ST-10B">10b </A>
Loupy A.
Petit A.
Hamelin J.
Texier-Boullet F.
Jacquault P.
Mathe D.
Synthesis
1998,
1213
For reviews see:
<A NAME="RD12104ST-11A">11a </A>
Ihara M.
Fukumoto K.
Angew. Chem., Int. Ed. Engl.
1993,
32:
1010
<A NAME="RD12104ST-11B">11b </A>
Grossman RB.
Synlett
2001,
13
<A NAME="RD12104ST-12">12 </A>
Schaefer JP.
Bloomfield JJ.
Org. React.
1967,
15:
1