Step-Economical Photoassisted Diversity-Oriented Synthesis: Sustaining Cascade Photoreactions in Oxalyl Anilides to Access Complex Polyheterocyclic Molecular Architectures

Atom- and step-economy
in photoassisted diversity-oriented synthesis
(DOS) is achieved with a versatile oxalyl linker offering rapid access
to complex alkaloid mimics in very few experimentally simple steps:
(i) it allows for fast tethering of the photoactive core to the unsaturated
pendants, especially important in the case of (hetero)­aromatic aminesessentially
a one-pot reaction with no isolation of intermediates; (ii) the α-dicarbonyl
tether acts as a chromophore enhancer, extending the conjugation chain
and facilitating the “harvest” of the lower energy photons
for the primary and secondary photoreactions; (iii) it enhances the
quantum yield of intersystem crossing (ISC), i.e., it is capable of
sensitizing secondary photochemical processes in the cascade; and
(iv) the tether forms an additional heterocyclic moiety, imidazolidine-4,5-dione,
a known pharmacophore. The overall photoassisted cascade is an efficient
complexity-building process as quantified by computed step-normalized
complexity indices, leading to extended polyheterocyclic molecular
architectures comparable in complexity to natural products such as
paclitaxel while requiring only 2–4 simple synthetic steps
from readily available chemical feedstock.