Transition-Metal-Free Synthesis of Polyfunctional Triarylmethanes and 1,1-Diarylalkanes by Sequential Cross-Coupling of Benzal Diacetates with Organozinc Reagents

A variety of functionalized triarylmethane and 1,1-diarylalkane derivatives were prepared via a transition-metal-free, one-pot and two-step procedure, involving the reaction of various benzal diacetates with organozinc reagents. A sequential cross-coupling is enabled by changing the solvent from THF to toluene, and a two-step S(N)1-type mechanism was proposed and evidenced by experimental studies. The synthetic utility of the method is further demonstrated by the synthesis of several biologically relevant molecules, such as an anti-tuberculosis agent, an anti-breast cancer agent, a precursor of a sphingosine-1-phosphate (S1P) receptor modulator, and a FLAP inhibitor.

Automated summary

A variety of functionalized triarylmethane and 1,1-diarylalkane derivatives were successfully synthesized via a transition-metal-free, one-pot, two-step procedure, demonstrating the synthetic utility of the method for biologically relevant molecules. The sequential cross-coupling enabled by changing the solvent from THF to toluene and the proposed S(N)1-type mechanism were supported by experimental studies. The method was further demonstrated by the synthesis of several biologically relevant molecules, including an anti-tuberculosis agent, an anti-breast cancer agent, a precursor of a sphingosine-1-phosphate (S1P) receptor modulator, and a FLAP inhibitor.