Synthesis of Functionalized Isoquinolone Derivatives via Rh(III)-Catalyzed [4+2]-Annulation of Benzamides with Internal Acetylene-Containing α-CF3-α-Amino Carboxylates

Abstract

A convenient pathway to a new series of α-CF3-substituted α-amino acid derivatives bearing pharmacophore isoquinolone core in their backbone has been developed. The method is based on [4+2]-annulation of N-(pivaloyloxy) aryl amides with orthogonally protected internal acetylene-containing α-amino carboxylates under Rh(III)-catalysis. The target annulation products can be easily transformed into valuable isoquinoline derivatives via a successive aromatization/cross-coupling operation.

Asymmetric α-Fluoroalkyl-α-Amino Acids: Recent Advances in Their Synthesis and Applications

“…The Osipov group has been dedicating much effort to the synthesis and applications of alkyne-containing molecular scaffolds. Although they are always working on racemic mixtures, they demonstrated the relevance of such functional groups on α-CF 3 -α-amino acids that thus motivated the development of stereoselective strategies [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ].…”

Ru(II)-Catalyzed C(sp2)–H Activation Annulation: Synthesis of Fluorescent Benzoisoquinolonyl Acetate/Peptides from N-Arylamides and Ethyne at Room Temperature

“…The transition metal-catalyzed regioselective C–H activations of core aromatic/aliphatic molecules are extensively reported by installing directing groups . Various transition metal catalyst have been used for the synthesis of isoquinolone derivatives from aryl amide and ethyne molecules via C–H activation annulation. − A fascinating example is the atroposelective synthesis of biaryl by Rh­(III)-catalyzed C–H activation and intermolecular coupling with sterically hindered alkynes . Methoxybenzamide and vinylene carbonate, equivalent to acetylene, have also been utilized for the synthesis of isoquinolone derivatives by Rh­(III)-catalyzed C–H activation annulation at room temperature .…”

Synthesis of CF3-Containing Spiro-[Indene-Proline] Derivatives via Rh(III)-Catalyzed C-H Activation/Annulation

“…Recently, we have elaborated upon a convenient method for the preparation of novel α-CF 3 -substituted α-amino acid derivatives decorated with the pharmacophore isoquinolone [29,30] (Scheme 1a) and pirimidoindolone [31] (Scheme 1b) cores via Rh(III)catalyzed C-H activation/(4+2)-annulation of the aryl hydroxamates and indole carboxamides with orthogonally protected propargyl-containing α-amino acid derivatives.…”

“…Recently, we have elaborated upon a convenient method for the preparation of novel α-CF3-substituted α-amino acid derivatives decorated with the pharmacophore isoquinolone [29,30] (Scheme 1a) and pirimidoindolone [31] (Scheme 1b) cores via Rh(III)-catalyzed C-H activation/(4+2)-annulation of the aryl hydroxamates and indole carboxamides with orthogonally protected propargyl-containing α-amino acid derivatives. Now, in accordance with our current investigations focused on the development of efficient routes to new representatives of fluorinated α-amino acids and their multifunctional derivatives under metal catalysis [32][33][34], we want to report on a convenient regionselective approach to new CF 3 -containing spiro[indene-prolines].…”