The Dark Side of Isocyanides: Visible-Light Photocatalytic Activity in the Oxidative Functionalization of C(sp3)-H Bonds.

Camilla Russo,Mariateresa Giustiniano,Jussara Amato,Gian Cesare Tron

doi:10.1021/acs.joc.1c02378

Camilla Russo, Mariateresa Giustiniano + Show 2 more

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https://doi.org/10.1021/acs.joc.1c02378

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Abstract

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.

Highlights

Isocyanides represent a class of very complex and fascinating compounds, thanks to their chameleonic electronic properties, which have been enabling, in the last decades, the development of well-defined and stimulating research areas.1 their unique reactivity features have been widely exploited in isocyanide-based multicomponent reactions2−4 and in Lewis acidcatalyzed migratory insertions into nucleophiles5−8
With the advent of the visible-light photocatalysis era,19−22 the somophile reactivity has been investigated in a plethora of transformations involving intramolecular cyclization of 2-isocyanobiphenyls and related analogues,16,17,23 as well as in two- or multicomponent reactions leading to amides, keto-amides, and other interesting molecular scaffolds.24−26 More in detail, these processes involve the formation of an imidoyl radical intermediate upon the addition of a radical species to isocyanide (Figure 1c)
While no bathochromic shift was observed for the mixture of 1 and DMA, we noticed that the absorption spectrum of 1 was characterized by two bands with λmax at 265 and 360 nm (Figure S1, Supporting Information). This observation prompted us to propose a mechanistic hypothesis entailing a catalytic role of isocyanide 1 upon its direct photoexcitation with visible light (Scheme 2)

Summary

Introduction

Isocyanides represent a class of very complex and fascinating compounds, thanks to their chameleonic electronic properties, which have been enabling, in the last decades, the development of well-defined and stimulating research areas. their unique reactivity features have been widely exploited in isocyanide-based multicomponent reactions− (nucleophile/carbene reactivity, Figure 1a) and in Lewis acidcatalyzed migratory insertions into nucleophiles− (electrophile reactivity, Figure 1b). Isocyanides represent a class of very complex and fascinating compounds, thanks to their chameleonic electronic properties, which have been enabling, in the last decades, the development of well-defined and stimulating research areas.1 Their unique reactivity features have been widely exploited in isocyanide-based multicomponent reactions− (nucleophile/carbene reactivity, Figure 1a) and in Lewis acidcatalyzed migratory insertions into nucleophiles− (electrophile reactivity, Figure 1b). While most of the current literature is based on these reactivity profiles, mainly triggered by either metal-based or organic visible-light photocatalysts as well as by thermal initiators (e.g., ditert-butyl peroxide, DTBP; tert-butyl hydroperoxide, TBHP; and so forth), processes involving the formation of imidoyl radical anions have been marginally reported (Figure 1d) The latter are considered quite unstable, albeit a recent involvement of their generation has been accounted upon photoinduced single-electron transfer (SET) from arylsulfinate anions following the formation of an EDA complex (EDA: electron donor−acceptor).

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Conclusion