Development of Transition‐Metal‐Free Lewis Acid‐Initiated Double Arylation of Aldehyde: A Facile Approach Towards the Total Synthesis of Anti‐Breast‐Cancer Agent

Abstract

This work describes a mild and robust double hydroarylation strategy for the synthesis of symmetrical /unsymmetrical diaryl-and triarylmethanes in excellent yields using Lambert salt (0.2-1.0 mol%). Despite the anticipated challenges associated with controlling selective product formation, unsymmetrical diaryl-and triarylmethanes products are obtained unprecedentedly. A highly efficient gram scale reaction has also been reported (TON for symmetrical product = 475 and for unsymmetrical product = 390). The synthetic utility of the methodology is demonstrated by the preparation of several unexplored diaryl-and triarylmethanebased biologically relevant molecules, such as arundine, vibrindole A, turbomycin B, and certain anti-inflammatory agents. A total synthesis of an anti-breast-cancer agent is also demonstrated. Control experiments, Hammett analysis, HRMS and GC-MS studies reveal the reaction intermediates and reaction mechanism.

Lewis Acid Promoted Homodimerization of Styrene Diols: An Efficient Approach toward 2-Phenylnaphthalenes

“…Furthermore, when this reaction was tried in chlorobenzene as a solvent instead of HFIP, only a trace of the desired product was obtained, and 4,4′-(2-phenylethane-1,1-diyl)bis(1,3-dimethoxybenzene) ( 8a ) was isolated as a significant product (Scheme 3 E). 15a This proved that the styrene diol is immediately converted into phenylacetaldehyde ( 4a ) in the presence of TMSOTf. This was confirmed by NMR analysis of the crude quenched reaction mixture from 1a , which showed characteristic triplet and doublet peaks at δ = 9.6 and 3.7 ppm, respectively [see the Supporting Information (SI) for more details].…”

“…After the activation of the aldehyde by the Lewis acid, the electron-rich additive, 1,3-dimethoxybenzene, attacks as a nucleophile to produce the monoarylated product B . 15a b Next, abstraction of a proton by the triflate ion generates alkene C in situ in the reaction medium. Alkene C is converted into the cationic intermediate D under the acidic conditions, as proposed by ­Vishwakarma and Bharate and their co-workers.…”

Silyl Cation-Initiated, Brønsted Acid-Catalyzed Strategy toward Unsymmetrical 3,3-Disubstituted 2-Oxindoles and Azonazine Cores

“…Furthermore, the silyl cation can also be utilized as a reactant, stoichiometric reagent, promoter, or catalyst for numerous processes . Recently, Hazra and his group have demonstrated Lambert salt-initiated Friedel–Crafts arylation of aromatic aldehydes and isatin derivatives as a milder strategy for synthesizing bioactive compounds . As a further advancement, we were interested in developing a benign and metal-free methodology for synthesizing unsymmetrical 3,3-disubstituted 2-oxindole.…”

One-Pot Sequential Synthesis of 3,3′- or 2,3′-Bis(indolyl)methanes by Using 1,3-Dithiane as the Methylene Source

“…For example, malassezin and ICZ are potent agonists of aryl hydrocarbon receptor (AhR) that played a critical role in immune cell differentiation and promoting intestinal immune function. Therefore, the development of synthetic methodologies toward these BIM motifs has been widely investigated in pharmaceutical discovery, organic synthesis, and material science …”