Recent developments and future prospects of visible-light photocatalysis in the late-stage functionalization of pharmaceuticals and natural bioactive compounds.

This review provides a comprehensive overview on the preparation and synthetic applications of functionalized isocyanides.

The possibility to harness aromatic isocyanides as visible-light photocatalysts in the α-amino C(sp³)–H functionalization is herein presented. Actually, the three-component cross-dehydrogenative coupling of aromatic tertiary amines with isocyanides and water leads to amide products under very mild conditions in high yields and with a good substrate scope. While the reaction with aromatic isocyanides proceeds upon direct photoexcitation, aliphatic isocyanides are able to form a photoactive electron–donor–acceptor complex with aromatic amines. Moreover, the use of a catalytic loading of an aromatic isocyanide promotes the oxidative coupling of N-phenyl-1,2,3,4-tetrahydroisoquinoline with an array of different (pro)nucleophiles in good to excellent yields, thus providing the proof-of-concept for the development of a new highly tunable class of organic visible-light photocatalysts.

The formation of the key short-lived intermediate nitrilium ion in the Passerini and Ugi reactions was recognized early in the discovery of these two-multicomponent transformations. Surprisingly, the idea of intramolecularly intercepting it, eluding the attack by the carboxylate, and thus interrupting the normal course of the reaction, was missed by chemists for several decades. In this review we describe, in an exhaustive manner, the reported synthetic approaches, which can be categorized as interrupted Passerini/Ugi reactions. Besides, the clear goal of this review is to show the potential of these transformations, whilst highlighting the underexplored combinations of reagents toward the identification of novel interrupted Passerini/Ugi reactions. 1 Introduction 2 The Interrupted Ugi Reaction 2.1 The Interrupting Functional Group is Present on the Amine Reactant 2.2 The Interrupting Functional Group is Present on the Isocyanide Reactant 2.3 The Interrupting Functional Group is Present on the Carbonyl Reactant 3 The Interrupted Passerini Reaction 3.1 The Interrupting Functional Group is Present on the Carbonyl Reactant 3.2 The Interrupting Functional Group is Present on the Isocyanide Reactant 4 Conclusions and Future Outlook