Study Of Tandem Ring Opening And Cycloaddition Reactions Of Electron Donating Vinyl Cyclopropanes And1-(1-Alkynyl) Cyclopropyl Ketones

Drug discovery based on using small orgaic molecules as probes is one of thehottest area in organic chemistry. Recent research shown that the high through-putscreen based on current small molecule collections seem to be less effective. Themain reason is the current commercial libraries used are too simple and lack of noveland complex molecules. Schrieber’s group shown that the structure complexity ofmolecule is correlated with protein-binding profile, which is a key feature for highvalue drugs. It means that synthesizing more complex molecules can enhance theprobability of drug discovery.The nature products and their analogs, based on thenatural characteristics, are rich in complex skeletons, functional groups andstereocenters. It always be the first consideration by both synthetic chemist and bybiochemists and viewed as the most important for organic chemistry.Many natural products have polycyclic structures, which on the one side increasethe success of searching new leading drugs, on the other side also increase thedifficulty of synthesis. Based on our research, vinyl cyclopropane (VCP) and alkynylcyclopropane (ACP) are two kinds of highly reactive synthons.With rationalmodification, they can launch many kinds of tandem reactions, which can be widelyused in synthetic fields.The cycloaddition reaction of ACP also exhibits extraordinaryabilities to serve as building blocks in polycyclic skeleton synthesis. However, thatkind of work is very limited in literature. So we propose that the field is very worth toexplore, and we finally discovered several kinds of new reactions.We successfully synthesized new vinyl cyclopropanes by installing electrondonationing groups on alkene part.Such kind of cyclopropane shown high reactivity,we found that it can proceedd tandem Mukaiyama-Aldol reaction/rearrangement toachieve (E)-4-oxo-6-phenylhex-5-en-1-yl benzoate derivative, we deeply studiedthe mechanism for this reactions and also explored the application for the reactions.1-alkynylcyclopropyl ketone (ACP) is a kind of high reactive synthonsdiscovered recently, which can be used for ring opening and cycloaddition reactions.Base on the literature, we discovered highly diasteroselective intermolecular [4+3]cycloadditions of1-alkynylcyclopropyl ketone and nitrones, we carefullystudied the mechanism and also discovered a “one-pot” method for the highefficiency synthesis of oxazepines derivitives.Bridged oxa-and aza-[n.2.1] and [n.3.1](n=2,3,4) skeletons widely distributesin nature and exhibits broad-ranging and important biological activities, due to thecomplexity, such kind of structures can only be synthesized by “target oriented”strategy, which is inefficiency. So a general method is always necessary to conctructsuch bridged structures, which may be meaningful fordrug screening.We designedand synthesized a new type ACP and investigated the cycloaddition reactions underdifferent lewis acid. Finally we successfully controlled two different cycloadditionreactions by switching the catalyst, and obtial two different bridged skeleton, whichcan be widely used in future.