Ana G. Neo

Sequential five-component synthesis of spiropyrrolidinochromanones.

Herein we report a novel, diastereoselective, one-pot, two-step, sequential synthesis of highly functionalized natural product-like spiropyrrolidinochromanones. The process consists of an Ugi four-component condensation of 3-formylchromones with amines, isocyanides, and glyoxylic acids followed by a nucleophilic conjugate addition and intramolecular cyclization. The experimental simplicity and tolerance to a wide variety of substituents makes this method suitable for combinatorial synthesis.

Cyclopentathiadiazines, new heterocyclic materials from cyclic enaminonitriles

Indene and cyclopentene enaminonitriles were reacted with SCl2, iBu3N and NCS to give the first cyclopenta[1,2,6]thiadiazines that showed unusual characteristics, one as a NIR dye and another as a liquid crystal.

Enols as Feasible Acid Components in the Ugi Condensation

Heterocyclic enols are used for the first time as acid components in an Ugi-type multicomponent condensation. For that purpose, we have chosen enols containing a Michael acceptor, in order to facilitate an irreversible rearrangement of the primary Ugi adduct. The new four-component process leads readily and efficiently to heterocyclic enamines containing at least six elements of diversity.

A multicomponent approach to the synthesis of 1,3-dicarbonylic compounds

A general synthesis of 1,3-dicarbonylic compounds using multicomponent reactions of isocyanides is described. The process involves a Passerini three-component condensation of glyoxal derivatives, isocyanides and acetic acid, followed by metal mediated reductive or solvolytic removal of the acid component. Noteworthy, reductive deacetoxylation of Passerini glyoxylamide adducts was successfully achieved using photochemically activated SmI2. This procedure constitutes a novel convenient method for the direct synthesis of malonic retro-peptidic subunits.

Selective Synthesis of 3-Substituted Pyrrolidinones by Enol-Passerini and Anomalous Enol-Passerini Condensations

Enols are used for the first time in a condensation with aldehydes and isocyanides to selectively give three- or pseudo-four-component adducts, depending on the reaction conditions. These new transformations have proven to be a convenient alternative for the synthesis of biologically relevant pyrrolidinones containing peptidic or pseudo-peptidic groups on carbon 3. More importantly, this work attests to the utility of heterocyclic enols containing conjugated electron-withdrawing groups as useful reagents in isocyanide-based multicomponent reactions.

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

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