Page 182 - Advanced Organic Chemistry Part B - Reactions & Synthesis

154 Acyl imidazolides are more reactive than esters but not as reactive as acyl halides.
Entry 7 is an example of formation of a -ketoesters by reaction of magnesium enolate
CHAPTER 2
monoalkyl malonate ester by an imidazolide. Acyl imidazolides also are used for
Reactions of Carbon acylation of ester enolates and nitromethane anion, as illustrated by Entries 8, 9, and
Nucleophiles with
Carbonyl Compounds 10. N-Methoxy-N-methylamides are also useful for acylation of ester enolates.
O O Li + 1) –78°C O
–
OCH 3
2) 25°C
CH (CH ) CN + CH 2 C CH (CH ) CCH CO C H
3
2 4
3
2
2 2 5
2 4
CH 3 OC H 3) HCl 82%
2 5
Ref. 222
Both diethyl malonate and ethyl acetoacetate can be acylated by acyl chlorides
using magnesium chloride and pyridine or triethylamine. 223
O
O O CR
MgCl 2 RCCl
C H O CCH CCH 3 C H O CCHCCH 3
2
2
2
2 5
2 5
pyridine
O
Rather similar conditions can be used to convert ketones to -keto acids by
carboxylation. 224
O O
MgCl , NaI H +
2
CH CH CCH CH 3 CH 3 CH CCHCH 3
2
2
2
3
CH CN, CO 2
3
Et N CO H
2
3
These reactions presumably involve formation of a magnesium chelate of the keto
acid. The -ketoacid is liberated when the reaction mixture is acidified during workup.
Mg 2+
– O O –
R O
R
Carboxylation of ketones and esters can also be achieved by using the magnesium
salt of monomethyl carbonate.
O O
DMF H +
CCH + Mg(O COCH ) CCH CO H
3
2
2
2
3 2
110°C
Ref. 225
222
J. A. Turner and W. S. Jacks, J. Org. Chem., 54, 4229 (1989).
223 M. W. Rathke and P. J. Cowan, J. Org. Chem., 50, 2622 (1985).
224 R. E. Tirpak, R. S. Olsen, and M. W. Rathke, J. Org. Chem., 50, 4877 (1985).
225
M. Stiles, J. Am. Chem. Soc., 81, 2598 (1959).