Four-Electron Electrocyclic Ring-Opening/Intermolecular [4+2] Cycloadditions Of ?-Hydroxycyclobutenones:Stereoselective Synthesis Of Multiple Substituted ?-Lactams

By virtue of release of ring strains, the ring-opening process affords a powerful driving force to a number of interesting transformations of small ring compounds. As an unique family in transformations of all carbon four-membered ring compounds, the ring-opening and subsequent transformations of a-hydroxycyclobutenones are an attractive topic. The seminal studies from Moore and Liberskind discovered that, through a four-electron electrocyclic ring-opening process under thermal conditions, a-hydroxycyclobutenones can be readily transformed into an enol-ketene intermediate at high torquoselectivity. Moreover, depending on the structure of substituent, the intermediate can go through different subsequent transformations. For example, quinols and benzoquinones will be generated, respectively, through a 6?-electrocyclization process. As powerful strategies, these transformations have been used in synthesis of natural products. In addition, the enol-ketene intermediate can go through a carbonyl-ene reaction, an intramolecular [2+2] cycloaddition or an intramolecular [2+2] cycloaddition/rearrangement process. Although the various transformations of the enol-ketene intermediate are a very interesting field, to date, all reports on transformations of the intermediate, after the in situ generation from four-electron electrocyclic ring-opening of a-hydroxycyclobutenones, went through intramolecular pathways. Intermolecular pathways which would demonstrate more synthetic values in practical applications are rarely reported.In this paper, we deeply explored the intermolecular cycloaddition between imines and the enol-ketene intermediate. In conclusion, we have disclosed a four-electron electrocyclic ring-opening/intermolecular [4+2] cycloaddition of a-hydroxycyclobutenones under thermal conditions. This is the first report on the intermolecular cycloaddition of the extensively studied enol-ketene intermediate. With high stereoselectivity, this reaction affords a concise synthetic approach to multiple substituted ?-lactams.