Catalytic Stereoselective Synthesis Of Fluorine-containing 1-Indanone Derivatives Via Tandem Nazarov Cyclization And Electrophilic Fluorination

Indanone derivatives are useful compounds serving as building blocks for the synthesis of natural products, medicines and agrochemicals, so fluorine-containing indanone compounds probably have more significant biologicalactivitives and great potential application values in drug design and synthesis. Although there have been a few reports on the synthesis of fluorine-containing indanone compounds by stepwise bond formation, there are no examples of catalytic tandem reactions for their construction with a single catalyst. In this discourse, we describe a Lewis acid-catalyzed tandem process of polarized enones for the synthesis of fluorine-containing 1-indanone derivatives via Nazarov cyclization and electrophilic fluorination reaction in good yield with excellent diastereoselectivity.Gratifyingly, the single regio- and stereoisomer was isolated from one of the tandem products by fractional recrystallization. X-ray structure analysis revealed the trans relationship between the F-atom andβ-substituent of the ketoester. The stereochemical assignment of the major isomer indicated that the trans-product was predominantly formed, and the cis attack of the subsequent fluorination to Nazarov cyclization intermediate was sterically restricted byβ-aromatic group.To acquire the optimized reaction conditions, we examined comprehensive experimental factors, such as electronic fluorinating reagents, catalysts, loads of catalyst, solvents and temperatures.Also we determined the scope of the tandem reaction by subjecting a series of alkylideneβ-ketoesters to the optimized reaction conditions,showing that the presence or position of electron-donating substituents on the phenyl ring of alkylidene moiety have a very limited effect on the stereoselection but a marked impact on the yield.