Novel Approaches to Piperidine and Hydropyridine Derivatives

Three new modes of reactivity are reported between the reaction of an imine, but-3-en-2-ones and a Lewis acid. These are formal [2+2+2]-, [1+2+1+2]- and [4+2]- cycloadditions, deriving 1,1'-(1,2-dihydropyridine-3,5-diyl)diethanones, 1,1'-(1,4-dihydropyridine-3,5-diyl)diethanones and piperidin-4-ones and respectively. The [2+2+2]- and [1+2+1+2]-cycloadditions proceed when R3 = LG (leaving group), with the [1+2+1+2]-pathway dominating when the imine is easily hydrolysed within the reaction conditions. When R3 ≠ LG, the cycloaddition proceeds through different [4+2]-mechanistic pathways, dependent on how good a Michael acceptor the enone is. In addition, this work presents the asymmetric synthesis of aminoboronic acid. Its activity as a bifunctional organocatalyst was explored and it was found that partly due to boron-nitrogen chelation, this catalyst was inactive within the aza-Diels-Alder, aldol and Mannich reactions, although active within the Michael reaction. Nonetheless, this catalyst was found to be active when performing the aldol reaction in high concentrations, in order to predominantly afford double aldol products.