Regioselective Syntheses of 2,3,5-Trisubstituted Pyridines via 5-Chloro-3-fluoro-2-(methylsulfonyl)pyridine.

We report the high-yielding, large-scale, one-pot synthesis of two versatile building blocks (1-Cl and 1-Br) for the regioselective synthesis of a variety of 2,3,5-trisubstituted pyridines from inexpensive materials. These molecules are readily derivatized at positions 2, 3, and 5. These building blocks can also be used for the synthesis of fused pyrido-oxazines and for the synthesis of 2,3,4,5-tetrasubstituted pyridines.

Dearomatization of Cyclic Diphenylhydrazines: Harnessing the o-Semidine Rearrangement for the Synthesis of Spirocyclic Tetrahydroquinolines.

The synthesis of novel tetrahydroquinoline-containing spirocycles has been achieved through an acid-promoted dearomatization of cyclic diarylhydrazines. The reaction, proceeding through a dearomative o-semidine rearrangement, furnishes a stable, yet reactive spirocyclohexadieniminium ion, which can further be used as an electrophile or a diene in a one-pot sequence. These transformations efficiently produce novel diazaspirocycles and allow for further synthetic elaboration of the cyclohexadienamine products.

Synthesis and Spectrophotometric Analysis of 1-Azafluorenone Derivatives.

A new extension for the 'one pot' construction of diverse 1-azafluorene derivatives featuring a Diels-Alder/retro-Diels-Alder cycloaddition is reported. Conditions were also determined for oxidation to the derived azafluorenones. The spectrophotometric analysis of five different azafluorenones were performed. Moderate fluorescence was observed with azafluorenone derivatives that bear an imbedded pyridone motif; whereas those bearing substituted pyridines do not fluoresce.

Domino Reaction Sequence for the Synthesis of [2.2.2]Diazabicycloalkenes and Base-Promoted Cycloreversion to 2-Pyridone Alkaloids.

A new domino reaction sequence for the construction of 2-pyridone structures is reported. The reaction sequence begins with diacetyldiketopiperazine and proceeds via aldol condensation, alkene isomerization, and intramolecular Diels-Alder cycloaddition. The intermediate [2.2.2]diazabicycloalkene cycloadducts can be isolated or can engage in a base-accelerated extrusion of one lactam bridge to provide the 2-pyridone cycloreversion products. The operation leading to pyridone products can occur in one reaction vessel and proceeds at convenient temperatures.