Carolyn L. Ladd

Synthesis of 2- and 2,3-substituted pyrazolo[1,5-a]pyridines: scope and mechanistic considerations of a domino direct alkynylation and cyclization of N-iminopyridinium ylides using alkenyl bromides, alkenyl iodides, and alkynes.

Direct functionalization and tandem processes have both received considerable recent interest due to their cost and time efficiency. Herein we report the synthesis of difficult to obtain 2-substituted pyrazolo[1,5-a]pyridines through a tandem palladium-catalyzed/silver-mediated elimination/direct functionalization/cyclization reaction involving N-benzoyliminopyridinium ylides. As such, these biologically important molecules are prepared in an efficient, high-yielding manner, only requiring a two-step sequence from pyridine. Aryl-substituted alkenyl bromides and iodides are effective ylide coupling partners. Mechanistic studies led to the use of terminal alkynes, which extended the scope of the reaction to include alkyl substitution on the unsaturated reactive site. The optimization, scope, and mechanistic considerations of the process are discussed.

Intramolecular sp3 Functionalization of Cyclopropyl α-Amino Acid-Derived Benzamides

Intramolecular Pd-catalyzed functionalization of cyclopropyl α-amino acid-derived benzamides proceeds without silver or pivalate additives. Both electronically and sterically diverse ethyl 1,2,3,4-tetrahydroisoquinolone-3-carboxylates were accessible in good to excellent yields.