Overview on the Recent Strategies for the Enantioselective Synthesis of 1, 1‐Diarylalkanes, Triarylmethanes and Related Molecules Containing the Diarylmethine Stereocenter

Abstract

There has recently been an increased interest in active pharmaceutical agents and various other molecules that contain the 1, 1‐diaryl stereocenter. This has led to the development of novel synthetic strategies to access molecules having this structural moiety. The current Review describes the variety of synthetic methodologies available for the enantioselective synthesis of 1, 1‐diarylethanes, triarylmethanes and related molecules with a 1, 1‐diaryl stereogenic center that were reported since 1995. The prime focus of the Review is on the formation of the 1, 1‐diarylmethine stereocenter either through the use of various enantioselective processes using chiral catalysts (the asymmetric catalytic approach) or through the use of chiral substrates and achiral catalysts. Resolution of racemic substrates is also required for the synthesis of this chiral molecule, but this approach is not covered in this Review. Moreover, comparative discussions on the future aspects of the synthesis of these molecules with a short comparison of the different available routes and possible areas of development are also presented.

Advances in The Catalytic Synthesis of Triarylmethanes (TRAMs)

“…The article by Panda in 2015, was the first which comprehended the synthetic methodologies of achiral diaryl/triaryl methanes followed by the report by Crudden in 2015 who has described the role of transition metals in the synthesis of triarylmethanes (TRAM's) . A recent report by Panda on the synthetic aspects of the molecules possessing 1,1‐diarylmethine also throws light on the stereoselective routes to 1,1‐diarylmethines . But the gargantuan extent of work has been carried out in the last few years demands to elicit the plethora of information in a systematic manner.…”

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.

“…1 For example, the indole alkaloid vibrindole A is an antimicrobial agent, letrozole, vorozole, and p-phenyl substituted bisindolyl methanes are used as anticancer agents, nafenopin is a peroxisome proliferator used as a hypolipidemic agent, beclobrate is a lipoprotein regulator. 1c-e The commonly used methods for the synthesis of this class of molecules involve a) transition metal catalyzed cross coupling of suitably activated benzylic systems with aryl or alkyl nucleophiles like boronic acids, Grignard reagents etc., [2][3][4][5][6] b) hydrogenation of the preformed 1,1-diaryl alkenes, 7 c) hydroarylation of styrenes, 8 and d) Friedel-Crafts alkylation of suitably substituted benzylic derivatives with arenes. 9 However, the said methods have various limitations.…”

Synthesis and Evaluation of Anticancer Activity of Pyrazolone Appended Triarylmethanes (TRAMs)

“…The central sp 3 hybridized carbon when attached to three aromatic groups constitutes an important class of molecules called triarylmethanes (TRAM's). [1][2][3][4] The TRAMs could further be classified as symmetrically substituted or unsymmetrically substituted depending on the nature of the aromatic groups attached to the central sp 3 methane carbon.…”

“…The central sp 3 hybridized carbon when attached to three aromatic groups constitutes an important class of molecules called triarylmethanes (TRAM's). [1][2][3][4] The TRAMs could further be classified as symmetrically substituted or unsymmetrically substituted depending on the nature of the aromatic groups attached to the central sp 3 methane carbon. TRAMs have gained tremendous attention due to their significant footsteps in pharmaceutical, dyes, building blocks for dendrimers, NLO materials, as well as fluorescent probes.…”