Page 180 - Advanced Organic Chemistry Part B - Reactions & Synthesis

152 Scheme 2.14. (Continued)

CHAPTER 2 11 k CO C H NaH COCHCO C H
2 2 5
2 2 5
Reactions of Carbon +CH (CH ) CO C H CH CH
3
2 2 5
2 2
Nucleophiles with N N 2 3 68%
Carbonyl Compounds
12 l (i-Pr) NMgBr
2
CO 2 C 2 H 5 + CH 3 CH 2 CO 2 C 2 H 5 COCHCO C H
2 2 5
51%
CH 3
a. R. R. Briese and S. M. McElvain, J. Am. Chem. Soc., 55, 1697 (1933).
b. B. E. Hudson, Jr., and C. R. Hauser, J. Am. Chem. Soc., 63, 3156 (1941).
c. P. S. Pinkney, Org. Synth., II, 116 (1943).
d. E. A. Prill and S. M. McElvain, J. Am. Chem. Soc., 55, 1233 (1933).
e. M. S. Newman and J. L. McPherson, J. Org. Chem., 19, 1717 (1954).
f. J. Yu, T. Wang, X. Liu, J. Deschamps, J. Flippen-Anderson, X. Liao, and J. M. Cook, J. Org. Chem., 68, 7565
(2003); P. Yu, T. Wang, J. Li, and J. M. Cook, J. Org. Chem., 65, 3173 (2000).
g. T. E. Jacks, D. T. Belmont, C. A. Briggs, N. M. Horne, G. D. Kanter, G. L. Karrick, J. L. Krikke, R. J. McCabe,
J. G. Mustakis, T. N. Nanninga, G. S. Risedorph, R. E. Seamans, R. Skeean, D. D. Winkle, and T. M. Zennie,
Org. Proc. Res. Develop. 8, 201 (2004).
h. R. N. Hurd and D. H. Shah, J. Org. Chem., 38, 390 (1973).
i. E. M. Bottorff and L. L. Moore, Org. Synth., 44, 67 (1964).
j. F. W. Swamer and C. R. Hauser, J. Am. Chem. Soc., 72, 1352 (1950).
k. D. E. Floyd and S. E. Miller, Org. Synth., IV, 141 (1963).
l. E. E. Royals and D. G. Turpin, J. Am. Chem. Soc., 76, 5452 (1954).
be done in nonnucleophilic solvents to avoid solvolysis of the acylating agent. The
use of these reactive acylating agents can be complicated by competing O-acylation.
Magnesium enolates play a prominent role in these C-acylation reactions. The
magnesium enolate of diethyl malonate, for example, can be prepared by reaction with
magnesium metal in ethanol. It is soluble in ether and undergoes C-acylation by acid
anhydrides and acyl chlorides. The preparation of diethyl benzoylmalonate (Entry 1,
Scheme 2.15) is an example of the use of an acid anhydride. Entries 2 to 5 illustrate
the use of acyl chlorides. Entry 3 is carried out in basic aqueous solution and results
in deacylation of the initial product.
Monoalkyl esters of malonic acid react with Grignard reagents to give a chelated
enolate of the malonate monoanion.

Mg 2+
R′O 2 CCH 2 CO 2 H + 2 RMgX – O O –
R′O O

These carbon nucleophiles react with acyl chlorides 220 or acyl imidazolides. 221 The
initial products decarboxylate readily so the isolated products are -ketoesters.

Mg 2+ O
– – RCOCl
O O
+ or R′O CCHCR
2
R′O O RCOIm
CH 3
CH3
220 R. E. Ireland and J. A. Marshall, J. Am. Chem. Soc., 81, 2907 (1959).
221
J. Maibaum and D. H. Rich, J. Org. Chem., 53, 869 (1988); W. H. Moos, R. D. Gless, and H. Rapoport,
J. Org. Chem., 46, 5064 (1981); D. W. Brooks, L. D.-L. Lu, and S. Masamune, Angew. Chem. Int. Ed.
Engl., 18, 72 (1979).