Study On Intramolecular Cross Cycloaddition Of Straind Cycloalkanes And Application To Construct Medium-sized Carbocyclic Rings

Medium sized carbocyclic skeletons exist widely in natural products and can be used in the development of drug leader. The literature had reported a number of intramolecular cyclization, cycloaddition, fragmentation, ring expansion method and metal metathesis for the synthesis of medium sized rings, however, there is not a general and efficient method for the synthesis of medium sized carbocyclic skeletons. Because of its high efficiency, good regioselectivity and stereoselectivity, cycloaddition plays an important role in the synthesis of medium sized carbocyclic rings, especially the synthesis of eight membered carbocyclic rings. Our research was based on the intramolecular cross cycloadditon(IMCC) of strained cycloalkanes and carbonyls to construct medium sized carbocyclic skeletons.Firstly we developed the [3+2] IMCC of cobalt-alkynylcyclopropane 1, 1- diesters with carbonyls. The method could be used to build a series of oxa-[4.2.1] and [5.2.1] bridged seletons namely eight or nine membered carbocyclic rings. Cobalt-alkynyl complex namely Nicolas intermediate can be used as electron donating group stabilizing α-carbocation and activating the cyclopropane to favor the cycloaddition configurationally and conformationally. Subsequent transformation of cobalt-alkynyl complex and diesters was very rich and they could be used for the intermolecular Pauson-Khand reaction, [4+2] intermolecular cycloaddition and so on. These prepared skeletons are present in natural products such as kadsulignan L, myceopoxydiene and parvifoline.Secondly we attempted the [4+2] IMCC of cyclobutanones stabilized by 3-electron donating group with carbonyls. Until now cycloaddition of 3-alkoxy or amino cyclobutanone were common in the literature. Only one reported [4+2] IMCC of 3-phenyl cyclobutanones with carbonyls in the literature. We tried [4+2] IMCC of 3-phenyl cyclobutanones with carbonyls. And the reaction could be used to construct oxa-[3.3.1] skeletons namly eight membered carbocyclic rings.We developed an intramolecular cycloaddition of activated cyclopropanes and cyclobutanones with carbonyls catalyzed by Lewis acid. The mild reaction conditions and wide range substrates of this method made it can be used as a kind of synthetic strategy to construct medium sized carbocyclic rings. Also it can be explored as a method to synthesis complex skeletons of natural products.