An Efficient Approach to 2-CF3-Indoles Based on ortho-Nitrobenzaldehydes

Abstract

The catalytic olefination reaction of 2-nitrobenzaldehydes with CF3CCl3 afforded stereoselectively trifluoromethylated ortho-nitrostyrenes in up to 88% yield. The reaction of these alkenes with pyrrolidine permits preparation of α-CF3-β-(2-nitroaryl) enamines. Subsequent one pot reduction of nitro-group by Fe-AcOH-H2O system initiated intramolecular cyclization to afford 2-CF3-indoles. Target products can be prepared in up to 85% yields. Broad synthetic scope of the reaction was shown as well as some followed up transformations of 2- CF3-indole.

Synthesis and Reactions of 3-Halogenated 2-CF3-Indoles

“…Mono-and di-bromo derivatives were prepared in 58% and 56% yields calculating on two steps (Scheme 1). rated convenient approaches towards α-CF3-phenethylamines [48], CF3-enones [49][50][51], CF3-β-carbolines [52], 2-CF3-3-arylindoles [52], 2-CF3-3-benzylindoles [53] and unsubstituted 2-CF3-indoles [54,55]. We have also examined several electrophilic reagents for modification of 2-CF3-indoles at C-3 atom [55].…”

“…All reagents were of reagent grade and were used as such or were distilled prior to use. Enamine 1 [44] and indole 2 [54] were prepared as reported previously. Melting points were determined on an Electrothermal 9100 apparatus.…”

“…Recently we have proposed the synthesis of α-CF 3 -β-aryl enamines [44][45][46], which have been shown to be potent CF 3 -building blocks for the synthesis of various fluorinated compounds. Using α-CF 3 -β-aryl enamines, we have elaborated convenient approaches towards α-CF 3 -phenethylamines [47], CF 3 -enones [48][49][50], CF 3 -β-carbolines [51], 2-CF 3 -3arylindoles [51], 2-CF 3 -3-benzylindoles [52] and unsubstituted 2-CF 3 -indoles [53,54]. We have also examined several electrophilic reagents for modification of 2-CF 3 -indoles at C-3 atom [54].…”

“…Using α-CF 3 -β-aryl enamines, we have elaborated convenient approaches towards α-CF 3 -phenethylamines [47], CF 3 -enones [48][49][50], CF 3 -β-carbolines [51], 2-CF 3 -3arylindoles [51], 2-CF 3 -3-benzylindoles [52] and unsubstituted 2-CF 3 -indoles [53,54]. We have also examined several electrophilic reagents for modification of 2-CF 3 -indoles at C-3 atom [54]. 2-CF 3 -Indoles are perspective compounds for drug design.…”