Synthesis of Substituted Tetrahydroindoloisoquinoline Derivatives via Intramolecular Pd-Catalyzed Alkene Carboamination Reactions

Abstract

Intramolecular Pd-catalyzed alkene carboamination reactions of substituted 2-allyl-N-(2-bromobenzyl)anilines are described. The substrates for these reactions are generated in two steps from readily available 2-allylanilines and 2-bromobenzaldehyde derivatives. The transformations afford substituted tetrahydroindoloisoquinolines, an uncommon class of fused bicyclic heterocycles, in good yield. The mechanism of these transformations is described, and a model that accounts for the observed product stereochemistry is proposed.

Recent Developments in Pd0‐Catalyzed Alkene‐Carboheterofunctionalization Reactions

“…Recently,A licea and Wolfe described an intramolecular Pd-catalyzedc arboamination reactiono fs ubstituted 2-allyl-N-(2-bromobenzyl)anilines (16)t hat generateds ubstituted tetrahydroindoloisoquinolines 17 in good yields (Scheme 5). [12] The requisite substrates (16)w ere synthesized through at wostep reductivea minationo f2 -bromobenzaldehyde derivatives with 2-allylanilines.S ubstrate 16 i,w hich contained an allylic methylg roup, was transformed into compound 17 i in good yield and diastereoselectivity (75 %yield, 18:1 d.r.) via transition state 18,w hilst substitution of the internal alkene carbon was also tolerated( 17 g).…”

Perfluorobutyl Iodide Mediated [1,2] and [2,3] Stevens Rearrangement for the Synthesis of Indolin‐3‐Ones

“…Products 2 a and 2 b were then transferred to azepinoindole derivative 3 a and tetrahydroindoloisoquinoline derivative 3 b via simple reduction of ketones. These two similar scaffolds are widely found in natural alkaloid products.…”

The syn/anti‐Dichotomy in the Palladium‐Catalyzed Addition of Nucleophiles to Alkenes

“…[ 67 , 68 ] In the most recent examples both amidation and arylation were carried out as intramolecular processes to produce polycyclic structures. [ 69 ] This area has also been reviewed. [ 70 ]…”