Direct Assembly of Phthalides via Calcium(II)-Catalyzed Cascade ortho-C-Alkenylation/Hydroacyloxylation of 3-Aminobenzoic Acids with Alkynes in Hexafluoroisopropanol

Abstract

By virtue of a calcium­(II)/hexafluoroisopropanol cocatalytic system, the efficient and practical coupling of 3-aminobenzoic acids with alkynes has been realized, giving direct and regioselective access to the phthalide framework with good substrate/functional group compatibility. Mechanistic studies identified 3-amino-2-vinylbenzoic acid species as the active intermediate, thereby revealing an ortho-C-alkenylation/hydroacyloxylation cascade for this transformation.

Difunctionalization Processes Enabled by Hexafluoroisopropanol

“…Taking the same approach, the group of Wang designed a new strategy to obtain phthalide 3-aminobenzoic acids in a regioselective fashion (Scheme ). Not surprisingly, using HFIP as a solvent was indispensable and a Lewis acidic calcium catalyst proved optimal for this reaction. This approach combined the ortho -C alkenylation of anilines with an hydroacyloxylation of alkenes previously reported by our group .…”

“…The reaction was not limited to aliphatic alcohol nucleophiles but could also be extended to phenols (47) and carboxylic acids (48). Remarkably, by using enantiopure substrates as starting materials, the chiral information was completely transferred to the product (49).…”

Ca(NTf2)2/HFIP‐Mediated Direct and Mild Rearrangement of Cyclopropyl Carbinols to E‐Homoallylic Triflimides

“…By virtue of the established calcium catalysis, a variety of challenging transformations such as arylation, [10d,e] aza‐Piancatelli reaction, [10a,f] hydroacyloxylation, [10c] hydroamidation [10b] have been well addressed thus far. With our efforts, more recently we have also developed an ortho ‐C‐alkenylation/hydroacyloxylation sequence to assembly phthalides benefit from this Ca(NTf 2 ) 2 /HFIP co‐catalytic system [10h] . Inspired by these works and by designing the cyclopropyl carbinol species as the effector, we reasoned that, such Ca(NTf 2 ) 2 /HFIP‐based system should be able to induce the activation of the hydroxyl group in cyclopropyl carbinols and then to trigger a reasonable homoallylic rearrangement through readily ring‐opening of the cyclopropane moiety, followed by the (CF 3 SO 2 ) 2 N − addition to access the homoallylic triflimide framework (Scheme 1B).…”

Calcium(II)-Catalyzed Reductive Amination of Biomass-Derived Keto Acids to Functionalized Lactams under Solvent-Free Conditions

“…Such a strategy has been successfully applied to the hydroalkylation of pentafluorostyrene with m -xylene or diphenylamine for the synthesis of polyfluorinated molecules. More recently, we have also developed a Ca(NTf 2 ) 2 -catalyzed cascade o -C-alkenylation/hydroacyloxylation sequence to deliver lactones …”

“…More recently, we have also developed a Ca(NTf 2 ) 2 -catalyzed cascade o-C-alkenylation/hydroacyloxylation sequence to deliver lactones. 28 Inspired by these advances and as a continuation of our interest in developing novel calcium(II)-catalyzed transformations, we disclose herein a Ca(NTf 2 ) 2 -catalyzed and solvent-free reductive amination of keto acids into pyrrolidones with a special emphasis on highly electron-deficient polyfluoroanilines, in which hydrosilane was used as the viable reducing reagent. The robustness of this protocol has been further exemplified by the synthesis of polyfluorophenylsubstituted five-, six-, seven-, and eight-membered lactams with excellent chemospecificity.…”