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 triarylmethane‐based 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.