Categories: C-C Bond Formation > Oxygen-containing molecules > Carboxyl derivatives >
Synthesis of β-keto carboxylic acids, esters and amides
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Recent Literature
An (E)- and (Z)-stereocomplementary preparative method for α,β-disubstituted
α,β-unsaturated esters is performed via three general and robust reaction
sequences: Ti-Claisen condensation (formylation) of esters to give α-formyl
esters, (E)- and (Z)-stereocomplementary enol tosylation using
TsCl-N-methylimidazole-Et3N and LiOH, and stereoretentive
Suzuki-Miyaura cross-coupling.
H. Nakatsuji, H. Nishikado, K. Ueno, Y. Tanabe, Org. Lett., 2009,
11, 4258-4261.
Pentafluorophenylammonium triflate (PFPAT) successfully catalyzed the C-acylation of enol silyl ethers with acid chloride to produce various
β-diketones in good yield. Similarly, C-acylation of ketene silyl
acetals or ketene silyl thioacetals proceeded smoothly to provide
also thermodynamically unfavorable α,α-dialkylated β-keto (thio)esters in good yield.
A. Iida, J. Osada, R. Nagase, T. Misaki, Y. Tanabe, Org. Lett., 2007,
9, 1859-1862.
A Ti-crossed Claisen condensation between ketene silyl (thio)acetals and acid chlorides gave
α-monoalkylated (thio)esters and thermodynamically unfavorable
α,α-dialkylated β-keto (thio)esters in good yield. The protocol was extended to the
direct condensation of ketene silyl acetals with carboxylic acids.
A. Iida, S. Nakazawa, T. Okabayashi, A. Horii, T. Misako, Y. Tanabe, Org. Lett., 2006,
8, 5215-5218.
A. Iida, S. Nakazawa, T. Okabayashi, A. Horii, T. Misako, Y. Tanabe, Org. Lett., 2006,
8, 5215-5218.
Enamination of acetoacetamides with Boc-monoprotected ethylenediamine provides
β-enamino amides, which can be acylated at the α-carbon with excellent
selectivity. These C-acylated derivatives undergo domino fragmentation in acidic
media to give the corresponding β-keto amides accompanied by
2-methyl-4,5-dihydro-1H-imidazole.
P. Angelov, Synlett, 2010,
1273-1275.
P. Angelov, Synlett, 2010,
1273-1275.
Thioesters undergo chemoselective soft enolization and acylation by N-acylbenzotriazoles
on treatment with MgBr2ˇOEt2 and i-Pr2NEt
to give β-keto thioesters without prior enolate formation. The reaction is
conducted using untreated CH2Cl2 open to the air. The
coupled products can be converted directly into β-keto esters, β-keto amides,
and β-diketones under mild conditions.
G. Zhou, D. Lim, D. M. Coltart, Org. Lett.,
2008,
10, 3809-3812.
Aromatic, aliphatic, and heterocyclic aldehydes are successfully condensed with
ethyl diazoacetate in the presence of molybdenum(VI) dichloride dioxide as
catalyst to obtain the corresponding β-keto esters in high yields at room
temperature.
K. Jeyakumar, D. K. Chand, Synthesis, 2008,
1685-1687.
Aldehydes react readily with ethyl diazoacetate in the presence of 5 mol% of
NbCl5 in dichloromethane to produce the corresponding β-keto esters in good
yields with high selectivity. This method allows the preparation of
β-keto esters from various
aldehydes under mild reaction conditions.
J. S. Yadav, B. V. S. Reddy, B. Eeshwaraiah, P. N. Reddy, Tetrahedron, 2005,
61, 875-878.
The TiCl4-mediated reaction of esters with benzoyl chloride
gave α-benzoylated esters in high yields.
D. F. Taber, R. B. Sheth, P. V. Joshi, J. Org. Chem., 2005,
70, 2851-2854.
Chelated enolates are good nucleophiles for reactions with acyl halides and
imidazolides affording α-amino-β-keto esters. In most cases, the reactions are
over after a few minutes and preparatively useful yields are obtained,
independent of the protecting groups and electrophile used. With chloroformates
as acylating agents, various protected amino malonates become accessible.
K. Schultz, L. Stief, U. Kazmaier, Synthesis, 2012,
600-604.
A convenient two-step preparation of alkylidenepyrrolidines is reported.
M. C. Elliot, S. V. Wordingham,
Synthesis, 2006, 1162-1170.
