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Abstract
A powerful strategy to synthesize symmetrical as well as unsymmetrical di/triaryl methanes involve the Lewis/ Brønsted acid-catalyzed Friedel-Crafts arylation of aldehydes, and ketones. Though useful, this transformation is incompatible with electron-deficient arenes and is difficult to achieve for unsymmetrical substrates involving two different nucleophiles. Herein, we have developed a Friedel-Crafts arylation reaction of aliphatic as well as aromatic aldehydes and ketones with electron-deficient arenes in one pot as an efficient approach for the synthesis of symmetrical as well as unsymmetrical 1,1-di and triarylalkanes. The role of hexafluoroisopropanol (HFIP) in activating the aldehyde or ketone for the Friedel-Crafts process has been delineated through extensive NMR studies. The process has been utilized to synthesize various biologically important symmetrical 1,1-diarylalkanes like vibrindole A, and arundine and unsymmetrical triarylmethanes like phenanthrene containing antibreast cancer agent. Moreover, the synthesized molecules can be applied for various C–C, C–N, C–O bond formation reactions through benzylic C–H functionalization.
Supplementary materials
Title
Brønsted Acid Mediated Brønsted Acid-Catalyzed Friedel-Crafts Reactions of Aldehydes and Ketones with Arenes: A Mild Protocol for the Synthesis of Symmetrical/Unsymmetrical Di/Trisubstitutedmethanes.
Description
A powerful strategy to synthesize symmetrical as well as unsymmetrical di/triaryl methanes involve the Lewis/ Brønsted acid-catalyzed Friedel-Crafts arylation of aldehydes. Though useful, this transformation is incompatible with electron deficient arenes and is difficult to achieve for unsymmetrical substrates involving two different nucleophiles. Herein, we have developed a Friedel-Crafts arylation reaction of aliphatic as well as aromatic aldehydes with electron deficient arenes in one pot as an efficient approach for the synthesis of symmetrical as well as unsymmetrical 1,1-di and triarylalkanes. The role of hexafluoroisopropanol (HFIP) in activating the aldehyde for the Friedel-Crafts process has been delineated through extensive real-time NMR titration studies. The process has been utilized to synthesize various biologically important symmetrical 1,1-diarylalkanes like vibrindole A, and arundine and unsymmetrical triarylmethanes like phenanthrene containing antibreast cancer agent. Moreover, the synthesized molecules can be applied for various C–C, C–N, C–O and C-F bond formation reaction through benzylic C–H functionalization.
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