Radical addition-transfer of xanthates to 3,3,3-trifluoro-1-propene. A versatile and inexpensive access to trifluoromethyl substituted building blocks

A Simple and Modular Access to 4-Mercapto-4-methylpentanoic Acid: A Useful Building Block in Antibody-Drug Conjugates Research

“…Ethyl bromoacetate ( 20 ) was treated with potassium ethyl xanthate salt to give xanthate 21 in 97% yield, and we found after optimization, the intermolecular radical addition was best performed using 2.5 equivalents of isobutene ( 14 ) (9% in hexane) in the presence of 20 mol% of DLP in a sealed tube at 80 °C (Scheme 4 ). As in our previous study related to the use of 3,3,3-trifluoropropene, 15 the filling level of the sealed tube had a significant effect on the reaction conversion. 18 Under optimal filling we found that xanthate 21 was able to cleanly add to isobutene to give the new xanthate 22 in 56% isolated yield on a 5.0 g scale (see Supporting Information).…”

“…This olefin is a gas under standard conditions (boiling point of –6.9 °C) and we surmised our experience with the use of 3,3,3-trifluoropropene would be beneficial. 15 The addition of a xanthate derived from alkyl acetates was envisaged as an alternative one-electron strategy to synthesize this building block.…”

Application of Industrially Relevant HydroFluoroOlefin (HFO) Gases in Organic Syntheses

“…Under the optimized conditions trifluoropropene (1) reacted with 2,2-dichloro-1,1,1-trifluoroethane (10) in N,Ndimethylformamide (DMF) solvent with catalytic amount of CuCl and tris(2-pyridylmethyl)amine (TPMA) ligand. The desired product (11) was obtained only in 15% yield, probably owing to the electron withdrawing nature of the trifluoromethyl group. Accordingly, the substrates with electron donating group resulted higher yields.…”

“…The radical addition of xanthates 8 to 3,3,3-trifluoroprop-1-ene (1) was reported by Petit, Perez, and Delacroix in 2020. 11 Several xanthates were reacted with trifluoropropene 1 in ethyl acetate solvent at 80 °C in a pressure tube in the presence of dilauryl peroxide (DLP) as radical initiator (Scheme 1C). The yields varied between 28% and 78%, but the transformation was not fully optimized due to the technical difficulties of handling trifluoropropene gas.…”