ABSTRACT
The identification of the beneficial pharmacokinetic properties of aza-spirocycles has led to the routine incorporation of these highly rigid and three-dimensional structures in pharmaceuticals. Herein, we report an operationally simple synthesis of spirocyclic dihydropyridines via an electrophile-induced dearomative semi-pinacol rearrangement of 4-(1'-hydroxycyclobutyl)pyridines. The various points for diversification of the spirocyclization precursors, as well as the synthetic utility of the amine and ketone functionalities in the products, provide the potential to rapidly assemble medicinally relevant spirocycles.
ABSTRACT
This report concerns the development of an efficient Sonogashira-type coupling of arylmethylsulfides and terminal alkynes to generate aryl alkyne motifs. Orthogonal reactivity between traditional Pd catalysts, and the Rh catalysts employed, results in the ability to selectively activate either the C-S bond or C-X bond through catalyst choice. The Rh-bisphosphine catalyst has further been shown to be able to effect a hydroacylation-Sonogashira tandem sequence, and in combination with further onward reactions has been used in the synthesis of heterocycles and polycyclic systems.
ABSTRACT
The first examples of ynamide hydroacylation are described. Using rhodium catalysis, linear ß-enaminone products are generated in high yield and excellent regioselectivity from the combination of aldehydes and ynamides. The enaminone products are subsequently used as a platform to construct a diverse array of substituted pyrazoles, pyrimidines, and isoxazoles in a two-step, one-pot sequence. It was found that with judicious choice of catalyst system it was possible to overturn the regioselectivity of the hydroacylation reaction to generate α-enaminone products.
