Organocatalytic Enantioselective Synthesis of Tetrahydrofluoren-9-ones via Vinylogous Michael Addition/Henry Reaction Cascade of 1,3-Indandione-Derived Pronucleophiles

An
unprecedented organocatalytic enantioselective vinylogous Michael
addition/Henry cyclization cascade is presented for the synthesis
of highly substituted tetrahydrofluoren-9-ones 3 employing
novel 1,3-indandione-derived pronucleophiles 1a–g and nitroalkenes 2. Following a very simple
protocol, a wide range of products were obtained in good to excellent
yields and with excellent enantioinduction (43–98% yield, up
to 98% ee). The reaction proceeded with excellent diastereocontrol
despite the simultaneous generation of four stereogenic centers. Surprisingly,
when 2-(1-phenylethylidene)-1H-indandione (1h) was used as a pronucleophile, no cyclization was observed,
and only Michael addition adducts 4a–x were furnished in very good yields and excellent enantioselectivities.