DBSA‐Catalyzed Regioselective Dehydrative Friedel‐Crafts Arylation of CF₃‐Containing 3‐Indolyl(2‐thiophenyl)methanols with 2‐Substituted Indoles in Water

Abstract

A green and efficient regioselective dehydrative Friedel‐Crafts arylation of trifluorinated 3‐indolyl(2‐thiophenyl) methanols with 2‐substituted indoles, catalyzed by DBSA (dodecylbenzenesulfonic acid) in water is described. This simple and atom‐economical protocol features a unique regioselective 1,8‐addition, operational simplicity, mild conditions, excellent functional group compatibility, and environmental benignity.

Cross‐Dehydrogenative Coupling Reactions between Phenols and Hetarenes: Modern Trends in Cross‐Coupling Chemistry of Phenols

“…[69] Rao and co-workers later demonstrated that 3indolyl(2-thiophenyl)methanols bearing a CF 3 group can also undergo dehydration under acidic conditions, followed by the addition of nucleophiles such as indoles and phenols. [73] The main results of this crosscoupling reaction with phenols are illustrated in Scheme 26. The reaction proceeded at the C5 position of the thiophene moiety in the presence of a catalytic amount of dodecylbenzenesulfonic acid in water.…”

“…Rao and co‐workers later demonstrated that 3‐indolyl(2‐thiophenyl)methanols bearing a CF 3 group can also undergo dehydration under acidic conditions, followed by the addition of nucleophiles such as indoles and phenols [73] . The main results of this cross‐coupling reaction with phenols are illustrated in Scheme 26.…”

Synthesis of 2‐Phosphoryl‐3‐Monofluorovinylindoles under Catalyst‐ and Additive‐Free Conditions

“…However, to the best of our knowledge, the synthetic potential of difluoromethylated 3‐indolylmethanols remains untapped. With our continuing interest in exploring the dehydrative cross‐coupling reactions of fluorinated 3‐indolylmethanols, [19a,e] we herein describe a green and practical catalyst‐free approach for the synthesis of 2‐phosphoryl‐3‐monofluorovinylindoles via a cascade regioselective dehydrative phosphorylation/stereoselective defluorination process starting from easily accessible difluoromethylated 3‐indolylmethanols and H ‐phosphine oxides (Scheme 1e). Notably, this protocol features catalyst‐ and additive‐free conditions, excellent regio‐ and stereospecificity, broad substrate scope, and environmental benignity.…”

Brønsted Acid‐Catalysed Dehydrative Substitution Reactions of Alcohols

“…The method was extended to the use of 6‐indolylmethanols as substrates, providing the products with impressive enantioselectivity for a remote 1,8‐addition. Rao and co‐workers subsequently found that 2‐substituted indoles undergo regioselective 1,8‐addition into vinyliminium intermediates derived from dodecylbenzenesulfonic acid (DBSA) catalysed dehydration of trifluoromethyl 3‐indolyl(2‐thiophenyl)methanols [51] . A wide range of thiophene‐centred bisindole products can be produced in good yields from a range of both reaction partners.…”