Current approaches to the synthesis of pyrrolo[2,1-a]isoquinolines (microreview)

Iron‐catalyzed oxidative [3+2] cycloaddition‐aromatization cascade: Synthesis of pyrrolo‐[2,1‐a]isoquinolines

“…Several solvents were then tested (entries 4-10) to improve product yield; solvents such as acetone, ethanol (EtOH), dichloromethane (DCM), acetonitrile (MeCN), methanol (MeOH), tetrahydrofuran (THF), and diethyl ether (Et 2 O) generated inferior 3a yields. Subsequently, several iron salts, that is, FeBr 3 , FeBr 2 , Fe(NO 3 ) 3 , FeCl 2 , NH 4 Fe (SO 4 ) 2, Fe 2 (SO 4 ) 3, Fe(OAc) 3 , and FeCl 3 Á6H 2 O were screened and no better results were observed (entries [11][12][13][14][15][16][17][18]. After this, anhydrous TBHP was tested and gave the same result (entry 19).…”

“…Since pyrrolo [2,1‐ a ] isoquinoline was first synthesized by Boekelheide and Godfrey in 1953 [6], various practical methods have emerged over the past 70 years, such as 1,3‐dipolar cycloaddition [7], oxidative dimerization [8], multicomponent cycloaddition [9], Michael coupling and condensation [10], and 1,5‐electrocyclization [11, 12]. In recent years, the direct oxidative “[3+2] annulation‐aromatization cascade of N ‐substituted tetrahydroisoquinolines” with dipolarophiles has become a powerful and flexible strategy for diverse pyrrolo [2,1‐ a ] isoquinoline synthesis due to its high atom‐ and step‐economy advantages.…”

Transannular Approach to 2,3-Dihydropyrrolo[1,2-b]isoquinolin-5(1H)-ones through Brønsted Acid-Catalyzed Amidohalogenation

“…The 2,3-dihydropyrrolo­[1,2- b ]­isoquinolin-5­(1 H )-one framework constitutes the central core of several families of bioactive compounds, some of them with relevant therapeutic potential (see Scheme ). In particular, this molecular architecture is the main structural feature of aromathecins, a family of topoisomerase I inhibitors that constitute promising chemotherapeutic agents against cancer, with some members already even approved for clinical uses . In addition, some other members of this family have been identified as highly active antiparasitic compounds which are able to selectively inhibit the phylogenetically unique topoisomerase IB present in the protozoan parasites Trypanosoma brucei, Trypanosoma cruzi, and the Leishmania species that cause African sleeping sickness (African trypanosomiasis) and Chagas disease (American trypanosomiasis).…”