Catalytic Asymmetric Synthesis of Pyrroloindolines via a Rhodium(II)-Catalyzed Annulation of Indoles

Abstract

Herein we report the synthesis of pyrroloindolines via a catalytic enantioselective formal [3+2] cycloaddition of C(3)-substituted indoles. This methodology utilizes 4-aryl-1-sulfonyl-1,2,3-triazoles as carbenoid precursors and the rhodium(II)-tetracarboxylate catalyst Rh2(S-PTAD)4. A variety of aryl-substituted pyrroloindolines were prepared in good yields and with high levels of enantioinduction.

A Rh(II)-catalyzed multicomponent reaction by trapping an α-amino enol intermediate in a traditional two-component reaction pathway

“…For this designed reaction pathway, the most important competitive pathway is a two-component [3 + 2] cycloaddition that has been illustrated by Spangler et al . ( 47 ) for the efficient synthesis of pyrroloindoline architectures 5 via the combination of C(3)-substituted indole 2 and Rh(II)-associated 1-sulfonyl-1,2,3-triazoles (Scheme 2B). The authors suggested that the reaction was promoted via zwitterionic-type intermediate F from an α-imino rhodium carbene species.…”

Recent Developments in the Catalytic, Asymmetric Construction of Pyrroloindolines Bearing All-Carbon Quaternary Stereocenters

“…81 , Scheme 14). 40 In this reaction, the 4-aryl-1-sulfonyl-1,2,3-triazole serves as a precursor to a Rh-bound carbenoid. The authors speculate that the reaction proceeds through cyclopropanation of the indole C2-C3 bond to give 82 , followed by fragmentation of the cyclopropane and cyclization to form the dihydropyrrole ring.…”

Synthesis of 1-arylsulfonyl-1,2,3-triazoles from (Z)-arylvinyl bromides by sequential elimination–cycloaddition reaction

“…1,2 Serving as precursors for iminocarbenes, they have found widespread applications in the synthesis of biologically valuable heterocyclic compounds, such as imidazoles and pyrroles, via cycloaddition of nitriles, 3 alkynes, 4,5 allenes, 6 furans, 7 indoles, 8 and alkenes. 9 Accordingly, finding efficient synthesis methods of N-sulfonyltriazoles from easily accessible starting materials is a continuous necessity.…”