title: 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.
abstract: 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.
authors: Department of Chemistry, Université de Montréal, P.O. Box 6128, Station Downtown, Montréal, Québec, Canada H3C 3J7.
authors: James J
authors: JJ
authors: Mousseau
authors: James A
authors: JA
authors: Bull
authors: Carolyn L
authors: CL
authors: Ladd
authors: Angélique
authors: A
authors: Fortier
authors: Daniela
authors: D
authors: Sustac Roman
authors: André B
authors: AB
authors: Charette
mesh_terms: D000475:Alkenes / Q000737:chemistry; D000480:Alkynes / Q000737:chemistry; D001965:Bromides / Q000737:chemistry; D002384:Catalysis; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003500:Cyclization; D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007454:Iodides / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D010165:Palladium / Q000737:chemistry; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000378:metabolism; D012834:Silver / Q000737:chemistry
chemical_list: D000475:Alkenes; D000480:Alkynes; D001965:Bromides; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D007454:Iodides; D011720:Pyrazoles; D011725:Pyridines; D011954:Receptors, Dopamine; C118531:pyrazolopyridine; D012834:Silver; D010165:Palladium