A Sustainable Multicomponent Pyrimidine Synthesis

Since
alcohols are accessible from indigestible biomass (lignocellulose),
the development of novel preferentially catalytic reactions in which
alcohols are converted into important classes of fine chemicals is
a central topic of sustainable synthesis. Multicomponent reactions
are especially attractive in organic chemistry as they allow the synthesis
of large libraries of diversely functionalized products in a short
time when run in a combinatorial fashion. Herein, we report a novel,
regioselective, iridium-catalyzed multicomponent synthesis of pyrimidines
from amidines and up to three (different) alcohols. This reaction
proceeds via a sequence of condensation and dehydrogenation steps
which give rise to selective C–C and C–N bond formations.
While the condensation steps deoxygenate the alcohol components, the
dehydrogenations lead to aromatization. Two equiv of hydrogen and
water are liberated in the course of the reactions. PN5P–Ir–pincer complexes, recently developed in our laboratory,
catalyze this sustainable multicomponent process most efficiently.
A total of 38 different pyrimidines were synthesized in isolated yields
of up to 93%. Strong points of the new protocol are its regioselectivity
and thus the immediate access to pyrimidines that are highly and unsymmetrically
decorated with alkyl or aryl substituents. The combination of this
novel protocol with established methods for converting alcohols to
nitriles now allows to selectively assemble pyrimidines from four
alcohol building blocks and 2 equiv of ammonia.