Synthesis of Functionalized Azepines via Cu(I)-Catalyzed Tandem Amination/Cyclization Reaction of Fluorinated Allenynes

Abstract

An efficient method for the selective preparation of trifluoromethyl-substituted azepin-2-carboxylates and their phosphorous analogues has been developed via Cu(I)-catalyzed tandem amination/cyclization reaction of functionalized allenynes with primary and secondary amines.

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-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]. The method involves the initial transformation of α-arylpropargyl-α-amino esters into corresponding 5-aryl-2-(trifluoromethyl)-3,4-dihydro-2H-pyrrole-2-carboxylates [35] followed by rhodium(III)catalyzed C-H activation/[3+2]annulation with internal alkynes (Scheme 1c).…”

Synthetic Methods for Azaheterocyclic Phosphonates and Their Biological Activity: An Update 2004–2024

“…In this reaction, the first step is the formation of a copper acetylide, which undergoes a nucleophilic addition of the amine followed by a cyclization with the allene group. 428 Amide 856 was prepared from 4-fluoro-2-iodoaniline 854 and 2-nitroaryl carboxylic acid chloride 855. Using diethyl (cyanomethyl)phosphonate 248, an Ullmann type C−C coupling evoked a domino reaction through which an Ncontaining seven-membered ring was formed (Scheme 157).…”

“…Functionalized allenynes 851 can react under copper catalyst conditions with primary and secondary amines 852 to produce trifluoro methylated azepine-2-phosphonates 853 and their carboxylate analogues in moderate yields (Scheme ). In this reaction, the first step is the formation of a copper acetylide, which undergoes a nucleophilic addition of the amine followed by a cyclization with the allene group …”

Diastereoselective Synthesis of Highly Functionalized Proline Derivatives

“…Allenynes 2 have proved to be unique doubly unsaturated synthons that can afford a variety of the corresponding α-amino acid derivatives. Thus, the potential of 2 has been clearly revealed in their synthetic transformation under transition metal catalysis, e.g., during Pd-catalyzed Sonogashira coupling followed by intramolecular [2 + 2] cycloaddition [ 27 ] and a co-mediated Pauson–Khand reaction [ 26 ], Cu-catalyzed tandem amination/cyclization [ 28 ] and in intermolecular Ru-catalyzed dimerization [ 29 ] ( Scheme 1 B). Now we wish to disclose a highly diastereoselective pathway to new densely functionalized proline derivatives via a cascade reaction between allenynes 2 and tosylazide, which is involved in Cu(I)-catalyzed alkyne-azide [3 + 2]-cycloaddition, ketenimine rearrangement and Alder-ene cyclization ( Scheme 1 C).…”