Methylene Thiazolidinediones as Alkylation Reagents in Catalytic C–H Functionalization: Rapid Access to Glitazones

Abstract

The straightforward and rapid incorporation of a thiazolidinedione scaffold into prefunctionalized (hetero)aromatic compounds is in demand for the development of antidiabetic glitazones and other pharmaceuticals. Herein, we report the unprecedented N- and O-directed C–H alkylation of various (hetero)arenes with methylene thiazolidinediones under rhodium(III) catalysis. The applicability of the developed protocol in challenging contexts is exhibited by the late-stage installation of a methylene thiazolidinedione moiety on the C–H bond of commercially available drug molecules. Combined mechanistic investigations aided the elucidation of a plausible reaction mechanism.

Transition-Metal-Catalyzed Directed C8–H Carbon–Carbon Bond Formation in Quinolines and 1,2,3,4-Tetrahydroquinolines

“…In addition, N-oxide DG assisted C8-H alkylation of QNs can be accomplished with methylene thiazolidinediones (Scheme 10B). 37 The reaction utilizes the combination of 2.5 mol % [Cp*RhCl2]2, 10 mol % AgSbF6 and 100 mol % PivOH. Further, organofluorine compounds represent versatile motifs in drug discovery and material sciences due to their unique physical and chemical properties.…”

“…In addition, N -oxide DG-assisted C8–H alkylation of QNs can be accomplished using a 5-methylenethiazolidine-2,4-dione utilizing a combination of 2.5 mol% [Cp*RhCl 2 ] 2 , 10 mol% AgSbF 6 and 100 mol% PivOH to give 2,4-dioxothiazolidin-5-ylmethyl-substituted QNOs (Scheme 10 B). 37 Organofluorine compounds represent versatile motifs in drug discovery and material sciences due to their unique physical and chemical properties. 38 The Rh(III)-catalyzed conjugate addition of β-CF 3 -enones with QNOs afforded C8-(3-aryl-3-oxo-1-(trifluoromethyl)propyl)-substituted QNOs (Scheme 10 C).…”

Synthesis of Mono- and Polyazole Hybrids Based on Polyfluoroflavones

“…Another equally important area of progress in the chemistry of flavones is the development of synthetic strategies for their modification. In addition, here, certain successes have recently been achieved, for example, its modification has been proposed by the Buchwald–Hartwig reaction [ 14 ], metal-catalyzed cascade rearrangements [ 15 , 16 ], electrochemical dimerization [ 17 ], CH-functionalization [ 18 ], etc. However, all of these transformations most often require expensive catalysts or complex installations.…”