Iodine catalyzed one-pot multi-component reaction to CF3-containing spiro[indene-2,3′-piperidine] derivatives

In the presence of a catalytic amount of molecular iodine (0.1 equiv.), the one-pot multi-component reaction of ethyl trifluoroacetoacetate 1, indan-1,3-dione 2, ammonium acetate 3 and aromatic aldehyde 4 mainly gave the ethyl-6′-hydroxy-1,3-dioxo-2′,4′-diaryl-6′-(trifluoromethyl)-1,3-dihydrospiro[indene-2,3′-piperidine]-5′-carboxylate derivatives 5, along with the minor product 2-trifluoromethyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine derivatives 6. A plausible reaction mechanism for the formation of 5, 6 was presented. The structures of compounds 5, 6 were fully confirmed by 1H NMR, 19F NMR, MS, IR spectroscopies and elemental analysis or high resolution mass spectra (HRMS). Meanwhile, the representative 5a and 6h were further confirmed by XRD analysis.

A convenient synthesis of a series of ethyl-6′-hydroxy-1,3-dioxo-2′,4′-diaryl-6′-(trifluoromethyl)-1,3-dihydrospiro[indene-2,3′-piperidine]-5′-carboxylates 5, along with the minor product 2-trifluoromethyl-2,3,4,5-tetrahydro-1H-indeno [1,2-b]pyridine derivatives 6 from readily available starting materials via one-pot, multi-component reaction catalyzed by iodine is described.Figure optionsDownload as PowerPoint slideHighlights
► The manuscript reports the study of one-pot, four-component reaction catalyzed by iodine.
► The unexpected formation was attributed to the unique catalytic activity of iodine.
► The influence of the reaction and the scope and limitation were studied.
► The new fluorinated building-block strategy towards CF3-containing spiroheterocycles.