Study On The [3+2]/[2+1] Annulations Of Para-Quinone Methides

Spirocyclic skeletons not only exist in bioactive natural products,pharmaceutically active molecules and functional materials,but also play an important role in the synthesis of chiral ligands or catalysts and modern drug discovery.Among the various types of spirocyclic skeletons,spiro-cyclohexadienones have attracted wide attention from chemists owing to their DNA alkylation properties and their application as key intermediates in the construction of many complex natural products.Therefore,the development of simple and efficient methods to construct spiro-cyclohexadienones has become one of the research hotspots in modern organic chemistry.Due to their unique reactivities of 1,6-addition and domino 1,6-addition/cyclization,para-quinone methides have been proven as key synthons for the construction of spiro-cyclohexadienone skeletons and have important applications in the synthesis of spirocyclic compounds.In this thesis,a series of spiro-cyclohexadienones with potential biological activity have been synthesized by the [3+2]/[2+1] annulations of para-quinone methides.This thesis consists of the following three parts: The chapter one: The application of para-quinone methides in cycloaddition reactionsThe applications of para-quinone methides in the cyclization reactions are highlighted in this review,which consisted of the flollowing contents: [2+1],[3+2],[3+3],[4+1],[4+2],[4+3] and [5+2] annulation reactions.The chapter two: [3+2] Cycloaddition of para-quinone methides with nitrile iminesA [3+2] cycloaddition of para-quinone methides with nitrile imines under mild conditions has been achieved in this chapter.This protocol provides an efficient synthesis strategy for constructing the spiro-pyrazoline-cyclohexadienone products,which have potential biological activity,in good to excellent yields with excellent regioselectivity.The chapter three: Direct sulfide-catalyzed [2+1] annulation of para-quinone methides and bromidesAn efficient and direct sulfide-catalyzed [2+1] annulation of para-quinone methides(p-QMs)and bromides has been achieved in this chapter.This method provides an efficient strategy for the construction of a range of spiro-cyclopropanylcyclohexadienones in good to excellent yields with excellent diastereoselectivities,displaying good functional group tolerance as well as gram-scale capacity.