Organocatalytic Enantioselective Synthesis of Dihydropyrano‐ indole Derivatives Bearing Trifluoromethylated All‐Carbon‐ Substituted Stereocenters

Abstract

Malononitrile and isatin‐derived trifluoromethylacrylates underwent a Michael addition/cyclization reaction, a process that was catalyzed efficiently by a bifunctional squaramide to afford a range of dihydropyranoindole derivatives bearing trifluoromethylated all‐carbon‐substituted stereocenters in high yields (up to 99%) with excellent enantioselectivity (up to 98% ee). This transformation was also examined with ethyl cyanoacetate as a nucleophile using a bifunctional thiourea as catalyst affording moderate yields (up to 79%) and high enantioselectivity (up to 98% ee). One of the products has been used for the synthesis of a biologically interesting triazolopyrimidine derivative.magnified image

Squaramide Catalyzed Asymmetric Synthesis of Five‐ and Six‐Membered Rings

“…[61] Liu, Zhao and co-workers developed squaramide B' catalyzed cascade between isatin based trifluoromethyl acrylate 158 and malononitrile 107 in course of synthesizing dihydropyranoindole derivatives 159 bearing a trifluoromethylated quaternary stereocenter. [62] The reaction proceeds through sequential 1,4-addition, O-cyclization, imine-enamine tautomerism steps to afford the products with appreciable chemical yields and enantiocontrol. Electronic nature and position of the substituents in the aryl moiety of 158 had very little influence on the reaction.…”

Michael Addition of Aryl Thiols to 3-(2,2,2-Trifluoroethylidene)Oxindoles under Catalyst-Free Conditions: The Rapid Synthesis of Sulfur-Containing Oxindole Derivatives

“…Very recently, we synthesised a series of trifluoromethylated methylene oxindoles and further exploration revealed that these substrates underwent an organocatalytic Friedel-Craft alkylation/lactonisation reaction with naphthols or hydroxyindoles to give dihydrocoumarins in high stereoselectivities. 16,17 In continuation of our interest in the development of new methodologies for the synthesis of trifluoromethylated compounds, 18 we herein report a rapid thio-Michael addition of various thiols to trifluoromethylated 3-methylideneoxindoles under catalyst-free conditions.…”

A Morita–Baylis–Hillman Pathway to Wittig Products: One‐Pot Transformation of Nitroalkylideneoxindoles to Oxindolylidene‐Carboxylates

“…As in the case of glyoxalates, the trifluoropyruvate adducts 4a , 4e and 4f were obtained as single geometrical isomers ( E ‐isomers) though the reaction times were much longer. [ 20 ]…”