Preparation and cycloaddition reactions of enantiopure 2-(N-acylamino)-1,3-dienes for the synthesis of octahydroquinoline derivatives

Stille, Suzuki-Miyaura, and Sonogashira cross-coupling reactions were carried out with a glutarimide-derived vinyl phosphate, bearing a chiral auxiliary on the N atom, to prepare enantiopure 2-(N-acylamino)-1,3-dienes as partners in Diels-Alder reactions. The cycloadditions were performed with various dienophiles under thermal conditions, with or without Lewis acids. With maleimides, the preferential formation of endo cycloadducts was observed, whereas with acrylamides the exo approach prevailed. Furthermore, in the latter case, 6-substitued octahydro-quinolinones were obtained in accordance with the predicted regioselectivity. Since diastereopure compounds were in all cases obtained either by chromatography or by crystallization, and because of the easy access to a variety of boronic acids, to be used in the coupling step, this methodology is useful for the short synthesis of differently substituted, enantiopure octahydroquinolinones amenable to further transformation into decahydroquinolines possessing interesting biological activities.