Development Of Some Asymmetric Sequential Cyclization Reactions Via Organocatalysis

Cascade reactions are defined as sequential transformations:two-step path is necessary for the formation of new chemical bonds, while the intermediate generated in the first step will be acted as a substrate in the next step. Cascade reactions distinctly superior in saving the experimental cast and time as well as reducing the job stress answered the call to the green chemistry and atom-economic construction. As we know, it is easy to construct a chiral center through a common Michael reaction, Aldol reaction, Mannich reaction, so cascade reaction seems no more mysterious. Cyclic compounds have been found in a large number of natural products, pharmaceuticals and pesticides. In consideration of less degree freedom in cyclic compounds, cyclization reaction is apt to the stereoselectivity control in the construction. Recently, many elegent works which exist to construct kinds of carbo-and heterocyclic compounds have been reported, including the Lewis acidic metal complexes or organic molecules catalyzed asymmetric Diels-Alder reactions, [3+2] cyclization reactions, [3+3] cyclization reactions as well as other asymmetric pathways. Although numerous achievements in cascade reaction, the development of new highly efficient, novel asymmetric synthetic methods to access these compounds has always provoked the interests of chemists. Here in, we present the first organocatalytic asymmetric [3+2] Michael/cyclization sequence of alpha-isothiocyanato imides, and esters with various unsaturated pyrazolones, affording the functionalized spiropyrazolones containing three adjacent chiral centers(up to 99% yield,20:1 d.r. and 99% ee). At the same time, we herein report the first catalytic asymmetric 1,5(6)-selective Michael/cyclization reaction of a-hydroxyimino cyclic ketones with γ,β-unsaturated a-keto esters to form ring-fused dihydropyrans with high levels of yield, enantio-and diastereoselectivity (up to 99% yield,20:1 d.r. and 99% ee).