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

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posted on 2017-10-20, 00:00 authored by Dmitry M. Kuznetsov, Andrei G. Kutateladze
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.