Categories: C-N Bond Formation > Enamines
Synthesis of β-enamino esters, amides, and thioesters
Recent Literature
β-Keto esters efficiently react with a variety of amines in the presence of 0.1
equivalents of acetic acid as an inexpensive and environmentally benign catalyst
without any solvents under ultrasound to give good yields of the corresponding
β-enamino esters.
C. A. Brandt, A. C. M. P. da Silva, C. G. Pancote, C. L. Brito, M. A. B. da
Silveira, Synthesis, 2004,
1557-1558.
A green H2O-promoted solvent-free hydroamination of
electron-deficient terminal alkynes with secondary amines provides the
corresponding (E)-enamines in very good yields, whereas primary aromatic
amines afforded Z-configured products in moderate yields.
X. Y. Chen, L. Zhang, Y. Tang, S. Yuan, B. Zhu, G. Chen, X. Cheng, Synlett, 2020,
31,
878-882.
A wide range of β-enamino esters, thioesters, and amides can be formed using
carefully buffered conditions in the presence of hydroxybenzotriazole
derivatives. Illustrative syntheses of some heterocyclic systems are given,
including some related to protein-protein interface mimics.
D. Xin, K. Burgess, Org. Lett., 2014,
16, 2108-2110.
An efficient, mild Pd-catalyzed oxidative coupling of aromatic primary amines
and alkenes under molecular oxygen provides a rapid access to (Z)-enamines
with exceptional functional group tolerance and excellent regio- and
stereoselectivity. The resultant enamines could be conveniently transformed into
a series of N-containing heterocycles, thus illustrating its potential
applications in synthetic and medicinal chemistry.
X. Ji, H. Huang, W. Wu, X. Li, H. Jiang, J. Org. Chem., 2013,
78, 11155-11162.
The use of a planetary ball mill enables a solvent-free method for the addition
of amines to dialkylacetylendicarboxylates or alkylpropiolates. Conversion of
educts was quantitative within five minutes without use of any catalyst or base.
Beside the E-/Z-isomers, no side products were formed.
R. Thorwirth, A. Stolle, Synlett, 2011,
2200-2202.
Acid- or base-promoted condensation reactions of carbamates with β-alcoxyacrylates
provide N-monosubstituted
β-Aminoacrylates. Whereas the base-promoted reaction is E-selective, acid catalysis can selectively form
E or Z isomers depending on the solvent.
S. R. Pollack, A. Dion, J. Org. Chem., 2021, 86,
11748-11762.
Acid- or base-promoted condensation reactions of carbamates with β-alcoxyacrylates
provide N-monosubstituted
β-Aminoacrylates. Whereas the base-promoted reaction is E-selective, acid catalysis can selectively form
E or Z isomers depending on the solvent.
S. R. Pollack, A. Dion, J. Org. Chem., 2021, 86,
11748-11762.
A mild and operationally simple hydroamidation of electron-deficient terminal
alkynes by amides in the presence of a Pd-catalyst enables a stereoselective
synthesis of Z-enamides. Hydrogen bonding between the amido proton and
carbonyl oxygen of ester group maybe provides the extra stability to the Z-isomer
of an intermediate vinyl-palladium complex, which subsequently undergoes
protodepalladation and leads to the Z-enamide selectively.
N. Panda, A. K. Jena, J. Org. Chem., 2012,
77, 9407-9412.
The use of AgNTf2 as catalyst enables a facile, economic,
regioselective, and high-yielding protocol for the hydroamination of
unsymmetrical internal alkynes under mild reaction conditions. This strategy is
efficient to build complex structures from simple starting materials in an
environmentally compatible fashion.
X. Zhang, B. Yang, G. Li, X. Shu, D. C. Mungra, J. Zhu, Synlett, 2012, 23,
622-626.
A highly regioselective hydroamination of unsymmetrical electron-poor and
electron-rich alkynes with anilines is catalyzed by Au(I) under mild conditions.
In addition, applications toward indole syntheses are presented including an
example of a one-pot synthesis from a nonfunctionalized aniline.
S. Kramer, K. Dooleweerdt, A. T. Lindhardt, M. Rottländer, T. Skrydstrup, Org. Lett., 2009,
11, 4208-4211.