Synthesis of N-Heterocycles via Intramolecular Pd-Catalyzed C-N Buchwald-Hartwig Reaction

Auxiliadora Prieto, In More Synthetic Approaches to Nonaromatic Nitrogen Heterocycles, 2022, A.M.M.F. Phillips (Ed.)., Wiley.

This chapter covers only the progress over the last 10 years in the synthesis of nonaromatic nitrogen-heterocycles through the use of intramolecular Pd-catalyzed N-arylation reactions. It describes the use of amide and tosylamide as coupling partner, respectively, and presents recent applications of intramolecular C—N coupling for the synthesis of nonaromatic heterocycles in natural products. Intramolecular Pd-catalyzed C—N coupling reaction has proven to be a convenient approach to the synthesis of different types of five-membered N-heterocycles, especially in the synthesis of indoline framework. Hydrazine derivatives have been shown to be suitable coupling partners for the intramolecular N-arylation reactions. In addition to Pd-catalyzed N-arylation of amide, the intramolecular arylation coupling of p-toluensulfonamide group has been reported. The practical applicability of Buchwald-Hartwig N-arylation in the macrocyclization of a complex peptide-based substrate were described for the first time in 2013 by Piersanti during the synthesis of (–)-epi-indolactam V.