De Novo Assembly of Highly Substituted Morpholines and Piperazines

The
morpholine and piperazine with their remarkable physical and
biochemical properties are popular heterocycles in organic and medicinal
chemistry used in rational property design. However, in the majority
of cases these rings are added to an existing molecule in a building
block approach thus limiting their substitution pattern and diversity.
Here we introduce a versatile de novo synthesis of the morpholine
and piperazine rings using multicomponent reaction chemistry. The
large scale amenable building blocks can be further substituted at
up to four positions, making this a very versatile scaffold synthesis
strategy. Our methods thus fulfill the increasing demand for novel
building block design and nontraditional scaffolds which previously
were not accessible