Synthesis of 2-trifluoromethyl chromenes via double carbonyl-ene reaction

A new protocol for the synthesis of diversely substituted 2-trifluoromethyl chromenes from the cyclization reaction of o-isopropenylphenols with trifluoroacetic anhydride has been developed, which proceeds via sequential trifluoroacetylation and double...

Organocatalyzed Beckmann Rearrangement of Cyclohexanone Oxime by Trifluoroacetic Anhydride in a Microreactor

An efficient method for the Beckmann rearrangement of cyclohexanone oxime (CHO) catalyzed by trifluoroacetic anhydride (TFAA) is proposed in this work. The effects of experimental parameters on the reaction rate are studied, including CHO concentration, TFAA/CHO ratio, temperature, and CPL concentration. The reaction rate shows a linear relationship with TFAA/CHO ratio and reduces with the increasing of CPL concentration. Based on the experimental data and the study of in-situ FTIR, a reaction mechanism is proposed and the equilibrium relationship between CPL and TFAA is established. A rate constant model is developed and is in good agreement with the experimental results. The TFAA/TFA catalytic system allows high conversion and reaction rate compared with other organic acids.

Radical Trifluoroacetylation of Alkenes Triggered by a Visible-Light-Promoted C−O Bond Fragmentation of Trifluoroacetic Anhydride

Trifluoromethyl ketones are not only found in drug like substances, but are also considered as key synthons for the preparation of various fluorinated heterocyclic molecules. Access to such trifluoromethyl ketone derivatives typically requires the incorporation of the trifluoromethyl group, or a surrogate moiety, at the beginning of a multi-step synthetic sequence. However, direct trifluoroacylation of alkenes could potentially provide a highly efficient and straightforward method for the synthesis of a,b-unsaturated trifluoromethyl ketones. Here we report a mild and operationally simple trifluoroacylation strategy of olefines, that utilizes trifluoroacetic anhydride as a low-cost and readily available reagent. This light-mediated process is fundamentally different from conventional methodologies and occurs through an trifluoroacyl radical mechanism promoted by a photocatalyst. Beyond simple alkenes, this method allows for chemo- and regioselective functionalization of small-molecule drugs and common pharmacophores.

Radical Trifluoroacetylation of Alkenes Triggered by a Visible-Light-Promoted C−O Bond Fragmentation of Trifluoroacetic Anhydride

Trifluoromethyl ketones are not only found in drug like substances, but are also considered as key synthons for the preparation of various fluorinated heterocyclic molecules. Access to such trifluoromethyl ketone derivatives typically requires the incorporation of the trifluoromethyl group, or a surrogate moiety, at the beginning of a multi-step synthetic sequence. However, direct trifluoroacylation of alkenes could potentially provide a highly efficient and straightforward method for the synthesis of a,b-unsaturated trifluoromethyl ketones. Here we report a mild and operationally simple trifluoroacylation strategy of olefines, that utilizes trifluoroacetic anhydride as a low-cost and readily available reagent. This light-mediated process is fundamentally different from conventional methodologies and occurs through an trifluoroacyl radical mechanism promoted by a photocatalyst. Beyond simple alkenes, this method allows for chemo- and regioselective functionalization of small-molecule drugs and common pharmacophores.

Access to Highly Substituted Pyrimidine N-Oxides and 4-Acetoxymethyl-Substituted Pyrimidines via the LANCA Three-Component Reaction–Cyclocondensation Sequence

The LANCA three-component reaction of lithiated alkoxy­allenes (LA), nitriles (N), and carboxylic acids (CA) smoothly provides β-alkoxy-β-ketoenamides in broad structural variety. The subsequent cyclocondensation of these compounds with hydroxylamine hydrochloride afforded a large library of pyrimidine N-oxides under mild conditions and in good yields. Their synthetic utility was further increased by the Boekelheide rearrangement leading to 4-acetoxymethyl-substituted pyrimidines. With trifluoroacetic anhydride the rearrangement proceeds even at room temperature and directly furnishes 4-hydroxymethyl-substituted pyrimidine derivatives. The key reactions are very robust and work well even in the presence of sterically demanding substituents.

Para-selective Hydroxylation of Alkyl Aryl Ethers

Para-selective hydroxylation of alkyl aryl ethers is established, which processes with ruthenium(II) catalyst, hypervalent iodine(III) and trifluoroacetic anhydride via a radical mechanism. This protocol tolerates a wide scope of substrates...