Selective Assembly Of (E)-2,3-Disubstituted-N-Tosylacrylamides And Their Oxidative Cyclization Reactions

N-Sulfonylacrylamides are valuable compounds in organic synthesis beacuse these scaffolds not only are important units in medicinal and material science but also serve as versatile synthetic building blocks. Whereas significant progress has been achieved in the construction of this structural motif during the past decades, the stereocontrolled assembly of multisubstituted N-sulfonylacrylamides remains a challenging task. On the other hand, while transition-metal-catalyzed arene C-H functionalizations are among the most convenient and efficient methods for the synthesis of complex heterocycles from simple starting materials, the vinyl C(sp2)-H activation-triggered cyclization reactions have attracted relative limited attentions. Encouraged by our previous researches on the in situ generation of ynamido-metal intermediates, we present herein a new three-component reaction for the synthesis of (E)-2?3-disubstituted-N-sulfonylacrylamides via transient 2-sulfonyl-iminooxetanes. On this basis, the diverse chelation-assisted vinyl C(sp2)-H activation and cyclizations of (E)-2,3-disubstituted-N-tosyl-acrylamides have been exploited to deliver a variety of heterocyclic products. The details are summarized as following:1. A novel Cu-catalyzed three-component reaction of terminal alkyne, sulfonyl azide and aldehyde was developed, which afforded (E)-2,3-disubstituted-N-tosylacryl-amides in good yields with high stereoselectivity. This three-component reaction proceeded smoothly at room temperature with easy operation. A plausible mechanism for this approach has also been proposed. This method provides significant benefits toward the construction of a variety of (E)-2,3-disubstituted-N-tosylacrylamides.2. Isoquinolones represent one of the most important classes of heterocycles found in biologically active compounds. A concise and efficient method for the synthesis of 4H-pyrido[2,1-?]isoquinolin-4-one was developed, in the presence of [Cp*RhCl2]2 and Cu(OAc)2·H2O, from (E)-2,3-disubstituted-N-tosylacrylamides and alkynes. In this reaction, the incipient five-membered rhodacycle intermediate presumably undergoes migratory insertion into internal alkynes followed by C-N/C-C formation to deliver 4H-pyrido[2,1-?] isoquinolin-4-ones in high yields.3. We have presented the Rh(?)-catalyzed tunable oxidative C-H functionalization/ cyclization of readily available (E)-2,3-disubstituted-N-tosylacrylamides and diazo compounds, providing access to the selective synthesis of fully substituted a-pyrones and furans. It is found that acylsulfonamide groups are cabaple of serving as in situ removable directing groups, i.e. an oxidizing DGs or traceless DGs, to achieve the controllable transformation upon the judious selection of reaction conditions.