Intramolecular Diels-Alder Cycloaddition of Furan-Derived ß-Enamino Diketones: An Entry to Diastereoselective Synthesis of Polycyclic Pyrano[3,2-c]quinolin-5-one Derivatives.

A series of 1,3-cyclodiketone- and tetrahydroepoxyisoindole-fused ß-enamino dicarbonyl heterocycles were synthesized via a 1,4-diazabicyclo[2.2.2]octane-catalyzed, CH3NO2-mediated three-component reaction of 1,3-cyclodiketone, furfural, and allylamine in toluene. The target compounds were generated via the formation of ß-enamino diketone as a key intermediate, followed by intramolecular Diels-Alder cycloaddition. The prepared molecules bearing a quinoline-2,4-dione moiety could be further brominated with N-bromosuccinimide and diastereoselectively reduced by NaBH4 to afford pyrano[3,2-c]quinolin-5-one-derived heterocycles with six vicinal stereogenic centers.

Acid-catalyzed, regioselective [3 + 3] annulation of enaminones and α-substituted cinnamic acids: access to 3,4-dihydropyridones and 2-piperidinones.

An efficient strategy for the synthesis of structurally diverse 3,4-dihydropyridones and 2-piperidinones is reported. The former was prepared via acid-catalyzed Michael addition of enaminones to electron-deficient α-substituted cinnamic acids followed by lactamization, whereas the latter was synthesized by the same methodology except that cinnamic acids were replaced with coumarin 3-carboxylic acids. A unique regioselective reactivity of the enaminones toward different cinnamic acid derivatives is described.

Construction of 2-pyridones via oxidative cyclization of enamides: access to Pechmann dye derivatives.

An efficient protocol for the construction of structurally diverse 2-pyridone derivatives from imines and α,ß-unsaturated acid chlorides in a single operation is reported. The target compounds, including coumarin-8-oxoprotoberbine analogues and lamellarin G isomers, were prepared via thermal cyclization of the in situ generated enamides followed by thermal dehydrogenation. The cyclization of enamides was achieved by the introduction of an electron-withdrawing group on the α-carbon of acid chlorides. This methodology allows quick access to polycyclic Pechmann dyes via rare double oxidative cyclizations of dienamides under mild conditions.

Application of Dimedone Enamines as Protecting Groups for Amines and Peptides.

A simple protocol for the protection of amines was realized through a base-catalyzed one-pot reaction of dimedone, ß-nitroalkene, and amine. Employing this strategy, a variety of amines/amino acids were protected in excellent yields. These acid/base stable protected amines can be deprotected by either ethylene diamine or hydrazine hydrate under mild conditions. The practical application of this orthogonal protecting group was demonstrated by the synthesis of cyclic peptide melanotan II via SPPS.

Multicomponent Synthesis of 1,3-Diketone-Linked N-Substituted Pyrroles, Pyrrolo[1,2- a]pyrazines, Pyrrolo[1,4]diazepines, and Pyrrolo[1,4]diazocines.

A new methodology is developed for the efficient synthesis of 1,3-diketone-linked N-substituted pyrroles, pyrrolo[1,2- a]pyrazines, pyrrolo[1,4]diazepines, and pyrrolo[1,4]diazocines in good yields via a Yb(OTf)3-catalyzed, nitromethane-mediated reaction of primary amine/diamine, furfural, and 1,3-diketone. Possible mechanisms for these multicomponent reactions are also proposed.