Efficient Synthesis of a Series of Novel Octahydroquinazoline-5-ones via a Simple on-Water Urea-Catalyzed Chemoselective Five-Component Reaction

Multicomponent reactions
(MCRs) have become a powerful tool for
drug discovery and development owing to their advantages of fast and
efficient construction of a large library of products with complexity
and diversity. However, conventional MCRs usually proceed in environmentally
unfriendly organic solvents rather than in water, a green solvent
used by nature for biological chemistry. Herein, a simple and efficient
on-water urea-catalyzed chemoselective five-component reaction (5CR)
has been developed for the synthesis of a series of novel octahydroquinazoline-5-ones
(6), the derivatives of quinazolinones possessing diverse
biological activities. The molecular structure of 6{1,1,12} has been confirmed by single-crystal X-ray diffraction.
The 5CR can proceed at room temperature under normal atmospheric pressure
in good yields and afford a large library of octahydroquinazoline-5-ones
with various aromatic and aliphatic substituents at N-1, C-2, and
N-3. In addition, a green method has been developed for the synthesis
of enaminones, important intermediates in the 5CR and in synthetic
chemistry.