Introduction of Heteroatom-Based Substituents into 1,4-Dihydropyridines by Means of a Halogen-Mediated, Oxidative Protocol: Diamination, Sulfonylation, Sulfinylation, Bis-Sulfanylation, and Halo-Phosphonylation Processes

Abstract

The natural tendency of 1,4-dihydropyridines to undergo "biomimetic" oxidation to afford pyridinium salts can be switched off and, through the use of reagents that interact electrophilically with the enamine moiety present in the heterocyclic system, it is possible to promote alternative oxidations. In this way, efficient regio- and stereocontrolled synthetic methods have been developed that lead to diversely substituted di- and tetrahydropyridines. These include iodoazidation, diamination, bis-sulfonamidation, sulfonylation, sulfinylation, thiocyanation, sulfanylation, bis-sulfanylation, and halo-phosphonylation processes.

Recent developments in the chemistry of dihydropyridines

“…Following this electrophilic approach, sulfones 78, sulfoxides 79, sulfides 80, and thiocyanates 81 were also prepared (Scheme 22). 113 Other bond-forming oxidations affecting dihydropyridines have been described: the double phosphonylation of pyridinium salts to yield diphosphonates 82; 114 a double malonate addition to β-cyanopyridinium salts, a cascade process involving malonate ionic (nucleophilic) and radical reactions, to stereoselectively form tetrahydropyridines 83; 115 an allylic halogenation of the α-methyl groups of Hantzsch dihydropyridines (to give 84); 116 and the 1-aza-9-oxafluorene 85 formation on interaction of N-alkyl or acetyldihydropyridines with p-benzoquinones (Scheme 23). 117…”

Stereocontrolled Oxyselenation Studies on 1,4-Dihydropyridines: Synthesis of Trans-2-hydroxy (or Alkoxy) 3-Phenylseleno-1,2,3,4-tetrahydropyridines

“…In this way, efficient regio-and stereocontrolled synthetic methods have been developed that lead to diversely substituted tetrahydropyridines 3 (Scheme 2). [10] …”