Allylic amination of Passerini adducts. Application to the selective synthesis of chromone-substituted α-and γ-amino acid peptidic and retropeptidic units

Abstract

The first allylic amination of Passerini acetates is described, where both a and g-substitution products are obtained regioselectively from chromone derived adducts. While a-substitution occurs in THF, CuCl in methanol catalyses a tandem amination followed by a rearrangement leading to g-amino acid-derived chromones.

An easy synthesis of diversely functionalized 2H-chromenes and amido amines by an enol-Ugi reaction

“…26 Aminoamides are interesting synthetic targets, since they possess useful therapeutic properties. 13,27 Thus, development of simple straightforward and flexible syntheses of unprotected α-amino amides is still a challenging task. We believe that the apparently simple hydrolysis of enol-Ugi adducts 6 could provide a useful method for the synthesis of unprotected α-amino amides.…”

“…IR spectra were recorded as KBr pellets. Proton and carbon-13 nuclear magnetic resonance ( 1 H NMR or 13 C NMR) spectra were obtained on a 400 or 500 MHz spectrometer.…”

“…The assignments of signals in 13 C NMR were made using DEPT. Mass spectra (MS) and High Resolution Mass Spectra (HRMS) were recorded using Chemical Ionization (CI) with CH 4 or ESI-qTOF.…”

“…With this aim, we have effectively used multicomponent reactions of isocyanides for the one-pot synthesis of several chromene scaffolds. [12][13][14][15][16][17] In particular, we have synthesized biologically interesting 4-amino-2H-chromenes through the novel enol-Ugi reaction 18 of electron-deficient 4-hydroxycoumarins. 19 We reasoned that the introduction of a strongly electron-withdrawing α-ketoester group into the 3-position of 4-hydroxycoumarin would have the double effect of facilitating the enol-Ugi reaction of this enol and opening the possibility of performing post-condensation transformations leading to new chromene scaffolds.…”

Pyrrolidinodiones in Enol-Ugi, Enol-Passerini, and Anomalous Enol-Passerini Condensations

“…Thus, MCR involving isocyanides (IMCRs), such as the Passerini three-component condensation (P3CC; Scheme 1) [13] and the Ugi four-component condensation (U4CC; Scheme 1) [14], are extensively used to synthesize diversely functionalized substituted α-acyloxy-and α-acylamino amides, respectively [15][16][17]. Further structural diversity can be achieved through a wide variety of postcondensation transformations [18][19][20][21][22][23][24][25][26][27][28][29][30][31] or by the replacement of one of the reactant components with a new reagent that mimics its reactivity and chemical behavior [12]. We have recently discovered that enols can be used as acid components in Passerini-and Ugi-type multicomponent condensations [32][33][34][35].…”