KF-Alumina-Mediated Selective Double Michael Additions of Aryl Methyl Ketones: A Facile Entry to the Synthesis of Functionalized Pimelate Esters and Derivatives

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.

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. ¹H NMR (300 MHz, CDCl₃): δ = 1.22 (t, 6 H, J = 7.1 Hz, 2 OCH₂CH ₃ ), 1.80-1.88 (m, 2 H, 2 CHCH₂CO), 2.05-2.12 (m, 2 H, 2 CHCH₂CO), 2.19-2.41 (m, 4 H, 2 CH₂CH ₂CO), 3.56-3.63 (m, 1 H, COCHCH₂), 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). ¹³C 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