pyrimidines - enamides - multicomponent reaction
Significance
Reported is the synthesis of substituted 5-alkoxypyrimidines
from enamides which are derived through a stepwise three-component reaction
of alkoxyallenes, nitriles, and carboxylic acids. The mechanism
for this three-component reaction has been previously discussed
(H.-U. Reissig and co-workers Chem.
Eur. J. 2004, 10, 4283).
Of the two sets of conditions for the final pyrimidine formation,
that using ammonium acetate allowed the use of less equivalents
of ammonium salt and a slightly lower temperature. However, this
was not exclusively employed.
Comment
Pyrimidines are an important class of heteroaromatics which are,
or constitute part of, biological molecules and pharmaceuticals.
Consequently a large body of literature concerning their synthesis
is available (see Book below). The described method is an interesting
addition to this lexicon of methodologies. Since the three-component
reaction has been previously studied, optimization studies were
limited to the formation of the 5-alkoxypyrimidines with respect
to solvent, temperature and ammonia source. Additional utility was
demonstrated through de-benzylation of the 5-OBn derivative, conversion
into the corresponding nonaflate, and subsequent Sonogashira cross-coupling.
It was also demonstrated that the 6-Me group was easily oxidized
to the corresponding aldehyde.
Book
S. von Angerer, In Science of Synthesis, Vol.
16; Y. Yamamoto, Ed.; Thieme: Stuttgart, 2003,
379-572.
