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. 2025 Jun 13;30(12):2584.
doi: 10.3390/molecules30122584.

Photoexcited Palladium Complex-Catalyzed Isocyanide Insertion into Inactivated Alkyl Iodides

Andrea Messina  1 , Filippo Monticelli  1 , Tiziano Miroglio  1 , Anna Gagliardi  1 , Igor Viviani  1 , Luca Banfi  1 , Renata Riva  1 , Lisa Moni  1 , Andrea Basso  1 , Chiara Lambruschini  1
Affiliations

Photoexcited Palladium Complex-Catalyzed Isocyanide Insertion into Inactivated Alkyl Iodides

Andrea Messina et al. Molecules. .

Abstract

Isocyanides insertions represent an important transformation in the palladium-catalyzed reactions landscape. However, one of their most significant limitations is in the use of inactivated alkyl electrophiles. Palladium photocatalysis has been proven as a solid tool for the generation of alkyl radicals from alkyl halides, which may engage in subsequent transformations with a variety of reaction partners, closing the catalytic cycle. Herein, we report the mild three-component isocyanide insertions into inactivated alkyl iodides mediated by the catalytic activity of a photoexcited palladium complex. We investigated the scope of the reaction obtaining differently substituted secondary amides in good to high yields. We also investigated the mechanism, hypothesizing a key role of 4-(N,N-dimethylamino)pyridine in the outcome of the reaction.

Keywords: amide synthesis; isocyanide insertion; multicomponent reactions; palladium catalysis; photocatalysis; radical addition.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Scheme 1
Scheme 1
Typical CO (a) and isocyanides (b) insertion employing aryl halides as electrophiles; (c) three-component alkyl carbamoylation of alkenes; (d) multicomponent isocyanide insertion employing inactivated alkyl iodides as electrophiles catalyzed by photoexcited Pd species.
Figure 1
Figure 1
Scope of the reaction; conditions reported in Table 1; 100 mg scale of iodide; isolated yields.
Figure 2
Figure 2
Scope of the reaction. Comparison of the yields under conditions A (Table 1) and conditions B (Table 2, entry 6); 100 mg scale of iodide; isolated yields.
Figure 3
Figure 3
Gas Chromatography–Mass Spectrometry (GC–MS) of the radical-trapping experiment. The main peak is attributed to the adduct between TEMPO and the alkyl radical coming from 1 (tR = 9.30 min). The amide 2 has a tR = 8.665 min under the thermal method employed, but its peak is absent from the chromatogram.
Figure 4
Figure 4
On/off experiment. The yields of the amide 2 were determined by 1H NMR using 4-iodoanisole as an internal standard.
Scheme 2
Scheme 2
Proposed mechanism. Alternative pathways unlikely to happen are shown in grey.
See this image and copyright information in PMC

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