Bronsted-Acid-Catalyzed One-Pot Synthesis of β,β-Diaryl Esters: Direct Regioselective Approach to Diverse Arrays of 3-Aryl-1-indanone Cores

A three-component, solvent-dependent, Bronsted-acid-catalyzed reaction of benzaldehydes, silyl enolates and arene nucleophiles has been developed for the synthesis of potential drug candidate 3-aryl-1-indanones. This reaction features the formation of three C-C bonds, high regioselectivity in a one-pot strategy, broad substrate generality, facile scalability (1.04g), high functional group tolerance and viable substrates. The beta-O-silyl ethers generated in-situ from the Mukaiyama aldol reaction were subjected to acid-catalyzed benzylic arylation with strong as well as weak nucleophiles, and the resultant beta,beta-diaryl esters can undergo a third C-C bond formation with excellent regioselectivity through intramolecular cyclization to afford the indanone products in the same pot. Detailed mechanistic insight leads to a feasible reaction pathway. This transformation opens up a practical and adaptable approach to producing a variety of synthetically valuable transformations and enable the synthesis of medicinally valuable (R)-tolterodine and (+)-indatraline.

Automated summary

A three-component, solvent-dependent, Bronsted-acid-catalyzed reaction has been developed for the synthesis of potential drug candidate 3-aryl-1-indanones. This reaction features high regioselectivity, broad substrate generality, easy scalability, and diverse starting materials. Detailed mechanistic insight leads to a feasible reaction pathway.