Sc(OTf)₃-Catalyzed C2-Selective Cyanation/Defluorination Cascade of Perfluoroalkylated 3-Indolylmethanols and Application to the Synthesis of 3-Fluoro(perfluoroalkyl)-β-carbolines

Abstract

An unprecedented Sc­(OTf)3-catalyzed C2-selective cyanation/defluorination cascade of perfluoroalkylated 3-indolylmethanols with TMSCN is described, which provides a novel and practical strategy for the synthesis of structurally diverse 3-(2-cyano)-indolyl substituted gem-difluoroalkenes and β-fluoro-β-perfluoroalkylalkenes. The reaction features excellent regio- and stereoselectivity and broad substrate scope. Notably, the obtained gem-difluoroalkenes and β-fluoro-β-perfluoroalkylalkenes could be easily transformed into 3-fluoro­(perfluoroalkyl)-β-carbolines with excellent efficiency simply by treating them with Grignard reagents or DIBAL-H under mild reaction conditions.

The synthesis of indole-3-carbinols (I3C) and their application to access unsymmetrical bis(3-indolyl)methanes (BIMs) bearing a quaternary sp3-carbon

“…6 Moreover, these molecules are promising synthetic precursors for the construction of various simple to complex biologically important heterocyclic building blocks. 7…”

Brønsted Acid-Catalyzed Dehydrative Nazarov-Type Cyclization/C2–N1 Cleavage Cascade of Perfluoroalkylated 3-Indolyl(2-benzothienyl)methanols

“…4d,e Additionally, an elegant protocol for the synthesis of 2-cyclopentenones based on Lewis acid-catalyzed decarboxylative Nazarov cyclization of cyclic carbonate derivatives has also been accomplished by the group of Yamada. 7 Inspired by these pioneering works and as part of our ongoing efforts to explore the new reactivities of 3-indolylmethanols, 8,9 we envisioned that the easily accessible 3-indolyl(2-benzothienyl)methanols might serve as the functionalized divinyl carbinol surrogates to realize the dehydrative Nazarov-type cyclization/ C2−N1 bond cleavage cascade reaction under the appropriate conditions (Scheme 1b). 10 Herein, we disclose the details of this chemistry, which provides the first example in the field of dehydrative Nazarov-type cyclization involving the selective C2−N1 bond cleavage of indole.…”

Cascade Cyclization of Azadienes with Difluoroenoxysilanes: A One-Pot Formal [4 + 2] Approach to Fluorinated Polyfused Heterocycles

“…On the other hand, the construction of fluorine-containing molecules has also received wide attention for the fact that introducing fluorine(s) into parent compounds can strongly alter properties such as the bioactivity, lipophilicity, metabolic stability, and pharmacokinetics of drugs . However, compared with the various reports of the synthesis of these fused polyheterocyclic compounds, the method for accessing fluorine-containing pyridine-fused polyheterocycles has been much less exploited . Thus the development of novel and efficient methods for the rapid construction of fluorinated pyridine-fused polyheterocyclic products is highly desirable.…”