Synthesis of Dihydropyrrolizine and Tetrahydroindolizine Scaffolds from Pyrroles by Titanocene(III) Catalysis

Abstract

A synthetic approach to dihydropyrrolizine and tetrahydroindolizine scaffolds from pyrroles has been developed. The key step, a titanocene(III)-catalyzed radical arylation that proceeds by C-H functionalization is atom-economical and tolerates a large variety of functional groups. The reaction is therefore attractive for the swift assembly of functional and structural diversity.

Cp2TiX Complexes for Sustainable Catalysis in Single‐Electron Steps

“…Presumably, this is due to the sensitivity of 14S to Lewis‐acids. However, 4 is superior to 2 that resulted in a 57 % yield of 14P …”

“…[22] Epoxides 15S and 16S are substrates that are more critical (Scheme7). Compared to 8P and 10P-13P, the pyrrole 14P was obtainedi nalower yield of 71 %w ith 4.…”

“…However, 4 is superior to 2 that resulted in a5 7% yield of 14P. [22] Epoxides 15S and 16S are substrates that are more critical (Scheme7). The tricyclic core of 15P is fairly strained and therefore an efficient back electron transfer is mandatory to obtain ah igh yield of 15P.M oreover, 15P is somewhat sensitive to Lewis-acids and, therefore, ao verly Lewis acidic catalyst will result in product decomposition.…”

Synthesis of Tetrahydroquinoline‐Embedded Bridged Benzothiaoxazepine‐1,1‐dioxides

“…In 2009, Kobayashi and Harayama reported the synthesis of 3‐hydroxy‐4‐arylquinolin‐2(1 H )‐ones by leaving‐group‐assisted IFCEA cyclization . Gansäuer, Flowers, and coworkers recently reported the synthesis of N ‐alkyl tetrahydroquinolines by epoxide–arene cyclization involving homolytic aromatic substitution . However, an operationally simple method to access compounds of type 4 using the strategy outlined in Scheme has not been investigated.…”

Recent Advances in the Intramolecular Reactions of Epoxides with Arenes and Heteroarenes

“…[33] Very recently,H ildebrandta nd Gansäuer also reported the synthesis of dihydropyrrolizine andt etrahydroindolizine scaffolds from pyrroles through EACs that involved titanocene(III)catalyzed intramolecular radicala rylation (Scheme 28) through a5 -(arene-endo)-endo-epoxide cyclization reaction. [34] Once again, av ariety of functional groups were tolerated under these conditions. The proposed reaction mechanism was similar to that described in Scheme 26.…”