Trichloroacetamides as powerful tools in radical chemistry for the synthesis of nitrogen heterocycles. A journey from tin to light Faïza Diaba, Gisela Trenchs, Alexandra G. Sandor University of Barcelona, Spain Trichloroacetamides tethered to alkenes have been used since the 1980s for the synthesis of nitrogen- containing heterocycles such as γ-lactams, as well as β- and δ-lactams, in a variety of radical processes (e.g., atom transfer and hydride transfer). 1 During the last decade we have demonstrated their versatility to access advanced intermediates toward the synthesis of natural compounds and bioactive small molecules. 2 In 2019 we reported an expeditious synthesis of b-lactams from N -tethered benzyl trichloroacetamides in the presence of RuCl 2 (PPh 3 ) 3 and under microwave activation. In this work the new C(sp 3 )-C(sp 3 ) bond formation takes place through an unprecedented “Ru”complex promoted activation of a benzylic position in a radical process. 3 Additionaly from N -tethered alkenyl trichloroacetamides, a diastereoselective Atom Transfer Radical Cyclization in the presence of a catalytic amount of RuCl 2 (PPh 3 ) 3 takes place diastereoselectively in a short reaction time providing the corresponding g- and d-lactams with good yields. Moreover, recently we have reported the first blue light-mediated synthesis of γ- and δ-lactams from trichloroacetamides in the presence of fac -Ir(ppy) 3 and under blue LEDs. This new non-contaminating approach allowed the synthesis of the above mentioned lactams under mild conditions, at ambient temperature, with extremely low loading of catalyst, in non-anhydrous green solvents and under air atmosphere. The investigation shed more light on the mechanism especially the involvement of the solvent in the last step of the cyclization process. 4
References 1. (a) Coussanes, G.; Vila, X.; Diaba, F.; Bonjoch, J. Synthesis 2017 , 49 , 1481. 2. Clark, A. J. C hem. Soc. Rev. 2002 , 31 , 1. 3. See inter alia: (a) Jansana, S.; Diaba, F.; Bonjoch, J. Org. Lett. 2019 , 21 , 5757. 4. Diaba, F.; Pujol-Grau, C.; Martínez-Laporta, A.; Fernández, I.; Bonjoch, J. Org. Lett. 2015 , 17 , 568.
5. Sandor, A.G.; Diaba, F. I nt. J. Curr. Res. 2019 , 11 , 6930. 6. Trenchs, G.; Diaba, F. Org. iomol. Chem. 2022 , 20 , 3118.
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